Summary of COVID-19 studies
Studies
Meta Analysis
Hide extended summaries
RCT 4,652 low-risk participants, published days after completion, showing significantly lower PCR+ COVID-19 cases with HCQ/CQ prophylaxis, p = 0.0004. Authors include a meta-analysis of this and 11 other RCTs confirming significantly lower COVID-19 cases. Authors conclude that HCQ/CQ could have been deployed with benefit early in the pandemic. HCQ/CQ was well tolerated with no serious drug-related adverse events. There were significantly fewer severe adverse events with treatment. (Serious adverse events refer to serious outcomes while severe adverse events refer to intensity, e.g., severe headache). Authors note that "the primary outcome was subsequently changed to include seroconversion" rather than only PCR+ cases. The date of this change is not reported. The PCR+ results are the most reliable. Inclusion of seroconversion means that participants with asymptomatic COVID-19 and symptomatic non-COVID-19 infections will be counted as symptomatic COVID-19 cases...
Sep 2024, PLOS Medicine, https://journals.plos.org/plosone/article?id=10.1371/journal.pmed.1004428, https://c19p.org/schilling3
RCT 606 patients in Bangladesh for povidone iodine mouthwash/gargle, nasal drops and eye drops showing significantly lower death, hospitalization, and PCR+ at day 7.
Dec 2020, Bioresearch Communications, https://www.banglajol.info/index.php/BRC/article/view/54245, https://c19p.org/choudhury
RCT 995 outpatients showing significantly lower progression with early treatment within 48 hours using fluvoxamine, fluvoxamine+bromhexine, fluvoxamine+cyproheptadine, and niclosamide+bromhexine. 70% of patients received treatment within 12 hours of symptom onset. Treatments groups showed significantly lower long COVID (PASC). The combined treatment groups showed significantly lower viral load as early as day 3. The 3 combination arms were superior to fluvoxamine alone. The study was open-label. 593 out of 1,900 randomized participants did not receive the treatment, mostly due to inability to confirm eligibility, however baseline characteristics were similar for these patients. There was a very high hospitalization rate in the control arm. Authors note that the majority of cases were mild - the threshold for hospitalization may have been very low (in some places/times all cases were hospitalized). Authors also note that the patients requiring high flow oxygen all had the delta/alpha..
Mar 2024, eClinicalMedicine, 10.1016/j.eclinm.2024.102517, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00096-8/fulltext, https://c19p.org/wannigama
778 patient proxalutamide antiandrogen late treatment RCT: 78% lower mortality (p<0.0001), 45% improved recovery (p<0.0001), and 33% shorter hospitalization (p=0.0001).
RCT 778 hospitalized patients in Brazil, 423 treated with proxalutamide, showing significantly lower mortality and improved recovery with treatment. NCT04728802 and NCT05126628. Authors note that cases in this trial were predominantly the P.1 Gamma variant, for which proxalutamide may be more effective compared to other variants.
Dec 2021, Cureus, https://www.cureus.com/articles/80171-final-results-of-a-randomized-placebo-controlled-two-arm-parallel-clinical-trial-of-proxalutamide-for-hospitalized-covid-19-patients-a-multiregional-joint-analysis-of-the-proxa-rescue-androcov-trial, https://c19p.org/cadegiani10
PEP RCT 399 patients in Bulgaria showing significantly lower COVID-19 cases with ivermectin prophylaxis, and significantly lower cases with high viral load. No participant had severe symptoms, required oxygen, or was hospitalized. All patients with COVID-19 were treated with vitamin C and vitamin D. This trial makes the Cochrane analysis report statistically significant efficacy for prophylaxis, although they do not appear to have acknowledged this yet. There are currently 4 prophylaxis RCTs, and all 4 show statistically significant efficacy of ivermectin. Cochrane ignored them by simply choosing to only include post-exposure prophylaxis RCTs, even though they were included for the paxlovid analysis with many of the same authors. At the time there were no post-exposure RCTs and they knew that including any one of the 3 pre-exposure prophylaxis RCTs would show statistically significant efficacy.
Jan 2023, ECCMID 2023, https://www.medincell.com/wp-content/uploads/2024/03/Poster-SAIVE-April2023-OK3.pdf, https://c19p.org/desorthenin
Prophylaxis RCT for ivermectin and iota-carrageenan in Argentina, 117 healthcare workers treated with ivermectin and iota-carrageenan, and 117 controls, showing significantly lower cases with treatment. There were no moderate/severe cases with treatment vs. 10 in the control group. There were 4 cases with treatment (all mild) vs. 25 for the control group.
Jan 2021, American J. Therapeutics, https://journals.lww.com/10.1097/MJT.0000000000001433, https://c19p.org/ivercartuc
RCT 300 patients in Bangladesh, published 2 years after completion, showing significantly lower mortality with treatment at 28 days (not significant at 14 days). 1.2mg colchicine on day 1 followed by 0.6mg for 13 days.
Nov 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0277790, https://c19p.org/rahman3
RCT 180 hospitalized COVID-19 patients in Turkey showing faster reduction in inflammatory markers, improved pulmonary function, and lower rates of macrophage activation syndrome, respiratory failure and mortality with montelukast treatment (10mg or 20mg daily) in addition to standard care. The higher dose of 20mg daily showed greater improvement in pulmonary function compared to 10mg daily. There was no mortality in the montelukast groups compared to 6.7% mortality with standard care alone.
Jan 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27552, https://c19p.org/kerget2
RCT with 98 hospitalized moderate/severe patients treated with sabizabulin and 52 control patients, showing lower mortality with treatment. Sabizabulin 9mg for up to 21 days. For more discussion see [twitter.com, twitter.com, twitter.com].
Jul 2022, NEJM Evidence, https://evidence.nejm.org/doi/10.1056/EVIDoa2200145, https://c19p.org/barnette
RCT 379 mild COVID-19 cases showing significantly lower prevalence and severity of olfactory and gustatory dysfunction with budesonide nasal spray, chlorhexidine mouthwash, and saline nasal irrigation. The control group received no intervention, the saline group received saline nasal irrigation plus saline nasal spray and mouthwash, and the drug group received saline nasal irrigation plus budesonide nasal spray and chlorhexidine mouthwash. Saline nasal irrigation plus nasal spray and mouthwash were administered once and four times daily, respectively. Both treatment groups had significantly lower prevalence and severity olfactory and gustatory dysfunction. Prevalence was lower for the drug vs. saline group, without statistical significance.
Nov 2023, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcad262/7439598, https://c19p.org/jingnacl
Prospective study of 1,559,187 men in Sweden with cardiorespiratory fitness levels measured on military conscription, showing high cardiorespiratory fitness associated with lower risk of COVID-19 hospitalization, ICU admission, and death.
Jul 2021, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2021-051316, https://c19p.org/afgeijerstam
RCT 130 hospitalized COVID-19 patients in China, showing lower progression and improved recovery with Xiyanping injection (9-dehydro-17-hydro-andrographolide and sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate, which are derived from andrographis).
May 2021, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7141, https://c19p.org/zhang14
Retrospective 65,361 COVID-19 patients in South Africa, showing significantly lower hospitalization, ICU admission, ventilation, and mortality with exercise.
Feb 2022, British J. Sports Medicine, https://bjsm.bmj.com/content/early/2022/02/08/bjsports-2021-105159.long, https://c19p.org/steenkamp
RCT 470 patients with symptoms ≤7 days, showing significantly lower ICU admission and combined mortality/ICU admission with zinc treatment. Greater benefit was seen for patients treated within 3 days. 25mg elemental zinc bid for 15 days. See also [academic.oup.com] and the author's reply [academic.oup.com].
Nov 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac807/6795268, https://c19p.org/abdallah
RCT with 73 budesonide patients and 73 control patients, showing significantly lower combined risk of an ER visit or hospitalization, and lower risk of no recovery at day 14.
Feb 2021, Lancet Respiratory Medicine, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00160-0/fulltext, https://c19p.org/ramakrishnan
RCT 355 adults with COVID-19 or other upper respiratory tract infections (URTIs). For COVID-19 patients there was lower progression and faster symptom resolution with alkaline seawater nasal wash (pH ~8) 4 times daily for 21 days. There was significantly lower transmission for patients with the delta variant and for patients with high viral load. The seawater nasal wash was safe and well-tolerated.
Feb 2024, European Archives of Oto-Rhino-Laryngology, https://link.springer.com/10.1007/s00405-024-08518-y, https://c19p.org/degabory
RCT 268 male patients in Brazil, 134 treated with proxalutamide, showing significantly lower hospitalization and mechanical ventilation. This paper was retracted, however no specific reason is provided, the editors have ignored the authors, and the "external expert" was reportedly funded by Pfizer. For details see [twitter.com]. The retraction notice states: "The investigation found that the claims made in the conclusions were not adequately supported by the methodology of the study. In particular, as confirmed by an external expert, the process of allocation to treatment and control was not sufficiently random." The lack of any detail on what conclusion is not supported and why, or details of any issues in randomization, suggests the paper was censored rather than retracted. This study was censored.
Dec 2020, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.668698/abstract, https://c19p.org/mccoy
UK Biobank retrospective 412,596 people, showing severe COVID-19 and COVID-19 mortality inversely associated with self-reported walking pace.
Feb 2021, Int. J. Obesity, http://www.nature.com/articles/s41366-021-00771-z, https://c19p.org/yates
52,365 patient exercise study: 74% lower mortality (p=0.05), 58% lower severe cases (p=0.03), and 16% fewer cases (p=0.03).
Retrospective 212,768 adults in South Korea, showing lower risk of COVID-19 cases, severity, and mortality with physical activity. Notably, results for aerobic and muscle strengthening activities combined were much better than results for either one in isolation.
Jul 2021, British J. Sports Medicine, https://bjsm.bmj.com/content/early/2021/07/21/bjsports-2021-104203, https://c19p.org/lee6
25 patient nitric oxide ICU RCT: 90% lower mortality (p=0.03), 90% lower ventilation (p=0.03), 42% greater improvement (p=0.47), and 64% faster viral clearance (p=0.005).
RCT 29 ICU patients in India, showing improved clinical outcomes and faster viral clearance with inhaled nitric oxide treatment. The treatment group was younger (mean 54 vs. 66) and had more patients on NIV at baseline (29% vs. 18%).
Apr 2021, Infectious Microbes and Diseases, https://journals.lww.com/10.1097/IM9.0000000000000079, https://c19p.org/moni
Retrospective 2,028 COVID patients in the USA, showing significantly lower mortality, ventilation, ICU admission, and progression to ARDS with zinc use, defined as at least one dose from one week prior to admission to 48 hours after admission.
Dec 2021, Critical Care Medicine, https://journals.lww.com/ccmjournal/Citation/2022/01001/195__ZINC_USE_IS_ASSOCIATED_WITH_IMPROVED_OUTCOMES.161.aspx, https://c19p.org/mayberry
648 patient RCT pHOXWELL nasal spray in India, showing significantly lower IgGS+ and significantly lower symptomatic cases with treatment. pHOXWELL includes a combination of natural virucidal agents and is designed to mimic the fluid surrounding healthy cells. The spray included xylitol, zinc chloride, polyethylene glycol 400, poloxamer, disodium hydrogen phosphate, sodium chloride, hydroxypropyl methylcellulose, ginger oil, eucalyptus oil, basil oil, clove oil, sodium hydrogen carbonate, potassium dihydrogen phosphate, ethylenediaminetetraacetic acid, sodium hyaluronate, calcium chloride dihydrate, benzalkonium chloride, magnesium chloride hexahydrate, potassium chloride, and glycerol. The spray was administered up to three times per day (TID) 140 μl/nostril for 45 days, with a gap of 6-8 hours between doses.
Jul 2022, J. Clinical Virology, https://www.sciencedirect.com/science/article/pii/S1386653222001809, https://c19p.org/balmforthphx
648 patient RCT pHOXWELL nasal spray in India, showing significantly lower IgGS+ and significantly lower symptomatic cases with treatment. pHOXWELL includes a combination of natural virucidal agents and is designed to mimic the fluid surrounding healthy cells. The spray included xylitol, zinc chloride, polyethylene glycol 400, poloxamer, disodium hydrogen phosphate, sodium chloride, hydroxypropyl methylcellulose, ginger oil, eucalyptus oil, basil oil, clove oil, sodium hydrogen carbonate, potassium dihydrogen phosphate, ethylenediaminetetraacetic acid, sodium hyaluronate, calcium chloride dihydrate, benzalkonium chloride, magnesium chloride hexahydrate, potassium chloride, and glycerol. The spray was administered up to three times per day (TID) 140 μl/nostril for 45 days, with a gap of 6-8 hours between doses.
Jul 2022, J. Clinical Virology, https://www.sciencedirect.com/science/article/pii/S1386653222001809, https://c19p.org/balmforthxy
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seetp
N3C retrospective 39,616 COVID-19 patients with diabetes in the USA, showing lower mortality, ventilation, and hospitalization with metformin use.
Feb 2022, Diabetes Care, https://diabetesjournals.org/care/article/doi/10.2337/dc21-2186/144605/Glycemic-Control-and-Clinical-Outcomes-in-U-S, https://c19p.org/wong2
RCT 379 mild COVID-19 cases showing significantly lower prevalence and severity of olfactory and gustatory dysfunction with budesonide nasal spray, chlorhexidine mouthwash, and saline nasal irrigation. The control group received no intervention, the saline group received saline nasal irrigation plus saline nasal spray and mouthwash, and the drug group received saline nasal irrigation plus budesonide nasal spray and chlorhexidine mouthwash. Saline nasal irrigation plus nasal spray and mouthwash were administered once and four times daily, respectively. Both treatment groups had significantly lower prevalence and severity olfactory and gustatory dysfunction. Prevalence was lower for the drug vs. saline group, without statistical significance.
Nov 2023, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcad262/7439598, https://c19p.org/jing
RCT 73 outpatients with mild COVID-19 showing improved recovery and increased RBD/spike antibody response with 28 days of a multi-strain probiotic (Bifidobacterium (B.) lactis BI040, B. longum BL020, Lactobacillus (L) rhamnosus LR110, L. casei LC130, L. acidophilus LA120, 5 billion CFU total).
Jan 2024, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-023-00816-8, https://c19p.org/kolesnyk
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seetz
394 patient iota-carrageenan prophylaxis RCT: 80% fewer symptomatic cases (p=0.03).
Prophylaxis RCT with 394 healthcare workers, 196 treated with iota-carrageenan, showing significantly lower symptomatic cases with treatment. There were no deaths or hospitalizations. There was a significant number of PCR- symptomatic cases (7.6% treatment and 8.6% control). The two treatment cases occurred shortly after randomization - infection may have occurred before the start of treatment.
Apr 2021, Int. J. General Medicine, https://www.dovepress.com/efficacy-of-a-nasal-spray-containing-iota-carrageenan-in-the-postexpos-peer-reviewed-fulltext-article-IJGM, https://c19p.org/figueroa
RCT 152 outpatients, 80 treated with fluvoxamine showing lower progression with treatment (0 of 80 versus 6 of 72 control).
Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2773108, https://c19p.org/lenze
RCT 733 outpatients, 99% in the USA, showing lower hospitalization/death, and significantly reduced viral load with proxalutamide treatment. The viral clearance result is from [Ma]
Apr 2022, Kintor, Press Release, https://www.prnewswire.com/news-releases/kintor-pharmas-proxalutamide-demonstrated-reduction-in-hospitalizationmortality-for-patients-with-mild-to-moderate-covid-19-in-phase-iii-mrct-study-301518525.html, https://c19p.org/kintorpx3
94,731 patient exercise study: 74% lower mortality (p<0.0001) and 48% lower hospitalization (p<0.0001).
Retrospective 194,191 COVID-19 patients in the USA, showing lower risk of hospitalization and mortality with physical activity, with a dose response relationship.
Dec 2022, American J. Preventive Medicine, https://www.sciencedirect.com/science/article/pii/S0749379722005268, https://c19p.org/young
Observational prospective 5,541 patients, adjusted HCQ mortality odds ratio OR 0.36, p = 0.012. Adjusted hospitalization OR 0.57, p < 0.001. Zinc supplementation was used in all cases. Early treatment in ambulatory fever clinics in Saudi Arabia.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v1, https://c19p.org/sulaiman
RCT for ivermectin+doxycycline showing improvements in mortality, recovery, progression, and virological cure. 183 treatment and 183 control patients with no deaths in the treatment arm vs. 3 in the control arm (the 3 control deaths are not included in the analysis of other outcomes). Results may reflect the use of ivermectin, doxycycline, and potential synergistic effects of the combination. In the PRINCIPLE trial, no mortality benefit was seen for doxycycline alone [thelancet.com] (0.6% mortality with doxycycline vs. 0.2% control).
Oct 2020, J. Int. Medical Research, https://journals.sagepub.com/doi/10.1177/03000605211013550, https://c19p.org/mahmud
RCT 430 COVID+ patients in Japan, showing significantly lower viral infectivity from culture, and significantly faster PCR viral clearance with PVP-I. For days 2-4 the study compares treatment with PVP-I vs. water (on day 5 both groups received PVP-I). Most patients were asymptomatic. 4 times per day mouthwashing and gargling with 20mL of 15-fold diluted PVP–I 7% or water.
Nov 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-24683-8, https://c19p.org/matsuyama
RCT hospitalized patients in Bangladesh, showing faster recovery and viral clearance with favipiravir treatment.
May 2022, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170222000139, https://c19p.org/rahman2
1,214 patient metformin prophylaxis study: 59% lower mortality (p=0.01), 61% improved recovery (p=0.005), 64% greater improvement (p=0.009), and 56% higher hospital discharge (p=0.009).
Retrospective 1,214 COVID+ type 2 diabetes patients in Hong Kong, showing lower mortality and improved recovery with metformin use.
Mar 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.810914/full, https://c19p.org/wong
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. The ivermectin dosage was low for 42 days prophylaxis - only a single dose of 200µg/kg, with a maximum of 12mg. Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seet
Retrospective 10,429 outpatients in France, 8,315 treated with HCQ+AZ a median of 4 days from symptom onset, showing significantly lower mortality with treatment.
May 2021, Reviews in Cardiovascular Medicine, https://www.imrpress.com/journal/RCM/22/3/10.31083/j.rcm2203116, https://c19p.org/million4
PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group. Efficacy for symptomatic cases and severe cases is very similar. Adjusted results are provided only for symptomatic cases. See also [trialsitenews.com].
Aug 2020, J. Clinical and Diagnostic Research, https://www.jcdr.net/articles/PDF/14529/46795_CE[Ra]_F(Sh)_PF1(SY_OM)_PFA_(OM)_PN(KM).pdf, https://c19p.org/shouman
Retrospective 592,571 participants in the UK and USA with 31,815 COVID-19 cases, showing lower risk or COVID-19 cases and severity for higher healthful plant-based diet scores. Notably, the assocation was less evident with higher levels of physical activity.
Jun 2021, Gut, https://gut.bmj.com/content/70/11/2096, https://c19p.org/merino2
Retrospective 48,440 COVID-19 patients in the USA, showing significantly lower mortality, ICU admission, and hospitalization with exercise.
Apr 2021, British J. Sports Medicine, https://bjsm.bmj.com/content/55/19/1099, https://c19p.org/sallis
RCT for relatively low risk outpatients, 2235 treated with colchicine a mean of 5.3 days after the onset of symptoms, and 2253 controls, showing lower mortality, ventilation, and hospitalization with treatment. This study was submitted to NEJM which delayed for ~6 months and then said they were not interested, then to JAMA which delayed for ~6 months and then said they were not interested, and then to the Lancet which delayed for ~6 months and then said they were not interested, and finally was published in Lancet Respiratory Medicine [twitter.com].
Jan 2021, The Lancet Respiratory Medicine, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00222-8/fulltext, https://c19p.org/tardif
Retrospective 624,771 people with type 2 diabetes in the UK, showing lower COVID-19 mortality and hospitalization with metformin use.
Sep 2022, Diabetes, Obesity and Metabolism, https://onlinelibrary.wiley.com/doi/10.1111/dom.14872, https://c19p.org/zaccardi
RCT 90 vitamin D deficient moderate/severe COVID-19 ARDS patients in India, showing lower mortality with vitamin D treatment. 600,000IU nanoformulation cholecalciferol.
May 2022, J. Public Health, https://academic.oup.com/jpubhealth/advance-article-abstract/doi/10.1093/pubmed/fdae007/7591923?redirectedFrom=fulltext&login=false, https://c19p.org/singh7
RCT 93 patients in Thailand showing significantly faster clinical improvement with favipiravir treatment. 1800mg favipiravir bid day 1, 800mg bid 5-14 days until PCR-.
Jun 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.06.06.22275902v1, https://c19p.org/sirijatuphat2
173 patient chlorhexidine late treatment RCT: 85% improved viral clearance (p<0.0001).
RCT 294 hospitalized patients in the USA, showing faster oropharyngeal viral clearance with chlorhexidine. Results were better with a combination of oropharyngeal rinse and posterior oropharyngeal spray compared with the rinse alone.
Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jmv.26954, https://c19p.org/huang8
RCT 321 healthcare workers in Mexico, showing significantly lower SARS-CoV-2 infection with vitamin D prophylaxis. 4,000IU daily for 30 days. In comparison to [Jolliffe], this study used a higher dose, the participants had much higher exposure to SARS-CoV-2 patients, and the study was prior to vaccination. In [Jolliffe], 89% of participants had received a vaccine dose by the end of the study period, and the period overlapped with increasing solar UVB. For more discussion see [twitter.com].
Apr 2022, Archives of Medical Research, https://www.sciencedirect.com/science/article/abs/pii/S0188440922000455, https://c19p.org/villasiskeever
Prospective study of 657 COVID+ outpatients in Honduras, 594 accepting fluvoxamine treatment, showing significantly lower mortality and hospitalization with treatment.
Oct 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.1054644/full, https://c19p.org/pineda
RCT with 40 nitric oxide and 40 placebo patients in the UK, showing faster viral clearance and greater improvement with treatment.
May 2021, J. Infection, https://www.journalofinfection.com/article/S0163-4453(21)00251-6/fulltext, https://c19p.org/winchester
Retrospective 6,288 COVID+ patients and 125,772 matched controls in South Korea, showing significantly lower risk of COVID-19 infection and mortality with higher physical activity.
Apr 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/7/1539, https://c19p.org/cho
1,407 patient nitazoxanide prophylaxis RCT: 43% lower progression (p=0.02), 50% faster recovery (p=0.1), and 3% fewer cases (p=1).
RCT 1,407 healthcare workers and others at high risk of SARS-CoV-2 exposure, showing no difference in COVID-19 cases (13 in each group). There was lower symptom severity for nitazoxanide and a trend towards shorter illness duration. There is no publication, results are only available on clinicaltrials.gov, posted 3 years after completion (FDA pre-notice of noncompliance [fda.gov]).
Jun 2024, Romark, NCT04359680, https://clinicaltrials.gov/study/NCT04359680?term=NCT04359680&rank=1&tab=results, https://c19p.org/romark
RCT 120 hospitalized patients in India, 74 treated with spironolactone and dexamethasone, and 46 with dexamethasone, showing lower progression with treatment. Spironolactone 50mg once daily day 1, 25mg once daily until day 21.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277163, https://c19p.org/wadhwa
RCT 120 hospitalized patients in India, 74 treated with spironolactone and dexamethasone, and 46 with dexamethasone, showing lower progression with treatment. Spironolactone 50mg once daily day 1, 25mg once daily until day 21.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277163, https://c19p.org/wadhwasp
PSM retrospective in the USA, showing lower COVID-19 mortality and cases with vitamin D prophylaxis.
Nov 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-24053-4, https://c19p.org/gibbons
123,709 patient metformin prophylaxis PSM study: 25% lower mortality (p=0.001), 25% lower ventilation (p=0.01), 19% lower ICU admission (p=0.005), and 15% lower hospitalization (p<0.0001).
TriNetX retrospective 123,709 vaccinated patients with type 2 diabetes, showing significantly lower risk of COVID-19 mortality, mechanical ventilation, and hospitalization with metformin use. There was no significant difference for cases. The increasing benefit for more serious outcomes matches the results of studies to date.
May 2023, Diabetes Research and Clinical Practice, https://www.sciencedirect.com/science/article/pii/S0168822723004540, https://c19p.org/yen
RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The RCT included 101 outpatients showing significantly faster recovery with treatment. The retrospective study results are listed separately [Valerio-Pascua]. Long COVID results are from [Valerio-Pascua].
Oct 2022, Research Square, https://www.researchsquare.com/article/rs-2167465/v1, https://c19p.org/valeriopascua3
RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The RCT included 101 outpatients showing significantly faster recovery with treatment. The retrospective study results are listed separately [Valerio-Pascua]. Long COVID results are from [Valerio-Pascua].
Oct 2022, Research Square, https://www.researchsquare.com/article/rs-2167465/v1, https://c19p.org/valeriopascua3cpm
Retrospective study of calcitriol supplementation with chronic kidney disease patients in Catalonia showing lower cases, severe cases, and mortality with supplementation. A dose-response relationship was found for severe cases and mortality.
Apr 2021, Biomedicines, https://www.mdpi.com/2227-9059/9/5/509, https://c19p.org/oristrell
RCT inhaled budesonide with 80 moderate COVID-19 pneumonia patients. The budesonide group had significantly faster time to clinical improvement, fewer ICU admissions, shorter oxygen therapy duration, and lower mortality. Inhaled budesonide 400mcg twice daily for 14 days.
Sep 2023, Int. J. Academic Medicine and Pharmacy, https://academicmed.org/Uploads/Volume5Issue5/101.%20[1518.%20JAMP_Bhavani%20Vaidiyanathan]%20517-521.pdf, https://c19p.org/dhanger
RCT 1,557 critical patients, showing significantly lower mortality with aspirin, with 97.5% posterior probability of efficacy.
Mar 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2790488, https://c19p.org/bradbury
Retrospective 5,273 prostate cancer patients on androgen-deprivation therapy (ADT), and 37,161 not on ADT, showing lower risk of cases with treatment.
May 2020, Annals of Oncology, https://www.sciencedirect.com/science/article/pii/S0923753420397970, https://c19p.org/montopoli
Retrospective 21,232 patients in Argentina, 3,266 assigned to ivermectin treatment, showing lower mortality with treatment. Greater benefits were seen for patients >40, and a dose dependent response was found. For more discussion see [twitter.com].
Sep 2021, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2022.813378/full, https://c19p.org/mayer
RCT 50 hospitalized patients in Israel, 33 treated with curcumin, vitamin C, artemisinin, and frankincense oral spray, showing improved recovery with treatment.
May 2022, J. Cellular and Molecular Medicine, https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17337, https://c19p.org/hellou
Interim report on an RCT for prophylactic treatment with S. salivarius K12, showing significantly lower cases with treatment. Only patients with symptoms or known positive contacts were tested. Trial identification/registration details are not provided.
Mar 2021, Minerva Medica, https://www.minervamedica.it/en/journals/minerva-medica/article.php?cod=R10Y2021N04A0514, https://c19p.org/dipierro3
RCT 120 healthcare workers, 60 treated with quercetin phytosome, showing lower risk of cases with treatment. Quercetin phytosome 250mg twice a day.
Jan 2022, Life, https://www.mdpi.com/2075-1729/12/1/66/htm, https://c19p.org/rondanelli
Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Only 71.4% reported >70% adherence, limiting efficacy. QTc did not statistically significantly differ between baseline and follow-up readings (mean 379 vs 378ms, paired t-test p=0.387). Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seeth
Prospective study of 68,896 UK Biobank participants with COVID-19 showing adherence to a healthy lifestyle prior to infection, characterized by 10 factors including adequate physical activity and sleep, not smoking, and a healthy BMI, was associated with a significantly lower risk of mortality, hospitalization, and post-COVID multisystem sequelae. Risk decreased monotonically for increasing numbers of healthy lifestyle factors from 5-10. Reduced risks were evident across cardiovascular, metabolic, neurologic, respiratory, and other disorders over 210 days following infection, during both acute and post-acute phases, regardless of age, sex, ethnicity, test setting, vaccination status, or SARS-CoV-2 variant.
Jan 2024, Nature Communications, https://www.nature.com/articles/s41467-024-50495-7, https://c19p.org/wang24
Retrospective 3,214 veterans with cirrhosis comparing 1,607 participants taking ursodeoxycholic acid (UDCA) to 1,607 propensity score matched controls not taking UDCA. UDCA use was associated with significantly lower odds of SARS-CoV-2 infection, symptomatic COVID-19, moderate or worse COVID-19, and severe/critical COVID-19.
Apr 2023, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13630, https://c19p.org/john
PSM retrospective 64,349 COVID-19 patients in the USA, showing spironolactone associated with lower ICU admission. Authors also present In Vitro research showing dose-dependent inhibition in a human lung epithelial cell line.
Jul 2022, Cell Reports Methods, https://www.sciencedirect.com/science/article/pii/S2667237523001327, https://c19p.org/cousins
PSM retrospective 64,349 COVID-19 patients in the USA, showing spironolactone associated with lower ICU admission. Authors also present In Vitro research showing dose-dependent inhibition in a human lung epithelial cell line.
Jul 2022, Cell Reports Methods, https://www.sciencedirect.com/science/article/pii/S2667237523001327, https://c19p.org/cousinssp
Retrospective 556 diabetic patients in South Korea with COVID-19 showing lower risk of mechanical ventilation and death with metformin, lower risks of oxygen treatment and death with DPP-4 inhibitors, and increased risk of mechanical ventilation with sulfonylureas. The study used nationwide data to analyze the impact of common antidiabetic medications on COVID-19 outcomes. Authors note that South Korea had a policy early in the pandemic of hospitalizing nearly all confirmed COVID-19 patients regardless of severity.
Jan 2024, Endocrinology and Metabolism, http://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2024.1857, https://c19p.org/jang6
Retrospective 1,139 elderly COVID+ patients in the USA, 392 with pre-existing metformin use, showing significantly lower mortality, hospitalization, and ARDS with treatment.
Mar 2021, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://www.sciencedirect.com/science/article/pii/S187140212100045X, https://c19p.org/ghany
Open-label RCT with 419 patients in Iraq, 160 treated with Nigella Sativa, showing lower mortality and severe cases with treatment. Black seeds 40mg/kg orally once daily for 14 days.
Jan 2021, Indian J. Forensic Medicine & Toxicology, https://www.researchgate.net/publication/352134969_Clinical_Trial_of_Black_Seeds_Against_COVID_-19_in_Kirkuk_City_Iraq, https://c19p.org/alhaidari
Very small 42 PCR+ outpatient RCT in Mexico, 22 treated with vitamin D. Most patients had insufficient vitamin D levels, there were more symptoms in those with insufficient levels, and there were less cases with fever or with >3 symptoms at day 14 for treatment with vitamin D.
May 2021, Sánchez-Zuno, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/11/2378, https://c19p.org/sanchezzuno
RCT 179 hospitalized patients in Brazil, showing improved recovery with azvudine treatment.
Oct 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1215916/full, https://c19p.org/desouza2
Cluster RCT outpatients in Argentina showing significantly faster recovery with ivermectin. There were no deaths. Outpatients in Tucumán were assigned to the ivermectin group and outpatients from San Miguel de Tucumán and Gran San Miguel de Tucumán were assigned to the control group. All comorbidities, percentage of male patients, and age were higher in the ivermectin group, favoring the control group.
Mar 2021, Research, Society and Development, https://rsdjournal.org/index.php/rsd/article/view/30844, https://c19p.org/chahla
RCT with 55 patients treated with colchicine and 50 control patients, showing lower mortality and ventilation with treatment.
Jun 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767593, https://c19p.org/deftereos
4,922 patient metformin prophylaxis PSM study: 52% lower mortality (p=0.01), 54% lower ventilation (p=0.007), and 72% lower ARDS (p=0.04).
Retrospective 4,922 COVID-19 patients with type 2 diabetes in China, showing lower mortality with metformin and alpha-glucosidase inhibitor treatment and higher mortality with insulin treatment.
May 2024, Molecular Biomedicine, https://link.springer.com/10.1186/s43556-024-00183-1, https://c19p.org/xu13
PSM retrospective 64,349 COVID-19 patients in the USA, showing metformin associated with lower ICU admission and mechanical ventilation.
Jul 2022, Cell Reports Methods, https://www.sciencedirect.com/science/article/pii/S2667237523001327, https://c19p.org/cousinsmf
Quasi-randomized trial with 930 hospitalized patients, 447 treated with calcifediol, showing significantly lower ICU admission and death with treatment. Note that the randomization in this trial is by ward. Authors report that patients were allocated to empty beds available at admission time regardless of patient conditions, and that staff in all wards followed the same protocol. The earlier preprint for this article was censored by the Lancet. The Lancet reportedly requested a review from a Twitter user that posted negative comments [github.com]. The review provides useful feedback for the authors to improve the reporting of the cluster nature of the RCT, and to explain the delay in registration, however it is highly unusual to censor a preprint in this way. Authors responded to the issues raised here: [pubpeer.com]
Jan 2021, The J. Clinical Endocrinology & Metabolism , https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgab405/6294179, https://c19p.org/nogues
Prospective prophylaxis study with 3,532 healthcare workers, 2,199 receiving two-dose ivermectin prophylaxis, showing adjusted relative risk of confirmed COVID-19 with treatment 0.17 [0.12-0.23] p<0.001. 186 patients took only the first dose, and no significant difference was observed for this group. The same group published an earlier small study with 117 ivermectin patients. There were no serious adverse events. T/IM-NF/CM&FM/20/142.
Feb 2021, Cureus, https://www.cureus.com/articles/64807-prophylactic-role-of-ivermectin-in-severe-acute-respiratory-syndrome-coronavirus-2-infection-among-healthcare-workers, https://c19p.org/behera2
RCT with 52 colchicine patients and 51 control patients, showing lower risk of clinical deterioration with treatment. COL-COVID. NCT04350320.
Sep 2021, Int. J. General Medicine, https://www.dovepress.com/colchicine-in-recently-hospitalized-patients-with-covid-19-a-randomize-peer-reviewed-fulltext-article-IJGM, https://c19p.org/pascualfigal
305 patient N-acetylcysteine early treatment RCT: 80% lower hospitalization (p=0.25) and 83% improved recovery (p<0.0001).
RCT 304 low-risk outpatients, 229 treated with N-acetylcysteine, l-carnitine tartrate, nicotinamide riboside chloride, and serine, showing significantly faster recovery with treatment. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism were significantly improved in treated patients.
Jun 2021, Advanced Science, https://onlinelibrary.wiley.com/doi/10.1002/advs.202101222, https://c19p.org/altay
248 patient ivermectin late treatment study: 87% lower mortality (p=0.02), 89% lower ICU admission (p=0.007), 83% lower progression (p=0.0004), and 87% improved recovery (p=0.02).
Retrospective 115 ivermectin patients and 133 control patients showing significantly lower death and faster viral clearance. Some potential issues and the authors' response can be found in [sciencedirect.com, sciencedirect.com].
Sep 2020, Archivos de Bronconeumología, https://www.archbronconeumol.org/en-ivermectin-treatment-may-improve-prognosis-articulo-S030028962030288X, https://c19p.org/khan
40 patient hydrogen peroxide late treatment RCT: 46% lower need for oxygen therapy (p<0.0001), 36% faster recovery (p<0.0001), and 45% faster viral clearance (p<0.0001).
RCT 40 patients in India, showing improved recovery with nebulized hydrogen peroxide.
Apr 2022, J. South Asian Federation of Obstetrics and Gynaecology, https://www.jsafog.com/doi/10.5005/jp-journals-10006-1986, https://c19p.org/agrawal
RCT 183 mild COVID-19 outpatients in Saudi Arabia, 91 treated with Nigella Sativa, showing lower hospitalization and faster recovery with treatment. 500mg Nigella Sativa oil (MARNYS Cuminmar) twice daily for 10 days. NCT04401202.
Aug 2021, Complementary Therapies in Medicine, https://www.sciencedirect.com/science/article/pii/S0965229921001102, https://c19p.org/koshak
RCT low-risk (1 death in the control arm) patients in the USA, showing no significant differences with favipiravir. A majority of trial outcomes were modified after completion: [clinicaltrials.gov]. 44% of patients had no detectable viral load at baseline in the viral shedding sub-study. The primary outcome required 4 days of sustained clinical recovery and occurred after a median of 7 days, suggesting there was limited room for improvement in the population studied. The percentages for viral clearance at day 10 do not match any number of the reported group sizes. Authors write "of the six RCTs conducted", however there has been at least 24 other RCTs at the time of publication [c19favipiravir.com]. 1800mg bid day 1, 800mg bid days 2-10.
Sep 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac712/6692456, https://c19p.org/golan
754 patient HCQ late treatment RCT: 66% improved viral clearance (p<0.0001).
RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 appear to be reversed).
Feb 2021, Biochemistry Research Int., https://www.hindawi.com/journals/bri/2021/6685921/, https://c19p.org/purwati
RCT 41 patients in Brazil, 20 treated with a phthalocyanine derivative mouthwash, showing shorter hosptalization and lower ICU admission with treatment. One minute gargling/rinsing 5 times per day.
Oct 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-99013-5, https://c19p.org/dasilvasantos
RCT 200 patients showing improvements in clinical recovery and viral clearance with favipiravir. There is no paper available but results are posted in clinicaltrials.gov.
Nov 2020, NCT04542694, https://clinicaltrials.gov/ct2/show/results/NCT04542694?view=results, https://c19p.org/pushkar
RCT with 25 nitazoxanide patients and 25 control patients, showing improved virological and clinical outcomes with treatment. Authors also perform an in vitro study in Vero E6 cells showing 90% inhibition with 0.5µM, with no cytotoxicity. NCT04348409.
Jan 2021, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00261-3/fulltext, https://c19p.org/blum
RCT on calcifediol (25-hydroxyvitamin D) treatment for hospitalized COVID-19 patients showing significantly reduced intensive care unit admissions. All patients received standard care including HCQ+AZ. For additional analysis see Jungreis et al. [Jungreis].
Aug 2020, J. Steroid Biochemistry and Molecular Biology, 203, October 2020, https://www.sciencedirect.com/science/article/pii/S0960076020302764, https://c19p.org/entrenascastillo
RCT 49 hospitalized COVID-19 patients, 25 treated with curcumin and quercetin, shower lower mortality/ICU admission and improved recovery with treatment. All patients received vitamin D. 336mg curcumin, 520mg quercetin, and 18μg vitamin D3 daily for 14 days. The control arm received 20μg vitamin D3 daily. Baseline fever favored treatment while vaccination favored control.
Jun 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1137407/full, https://c19p.org/geraint
RCT 49 hospitalized COVID-19 patients, 25 treated with curcumin and quercetin, shower lower mortality/ICU admission and improved recovery with treatment. All patients received vitamin D. 336mg curcumin, 520mg quercetin, and 18μg vitamin D3 daily for 14 days. The control arm received 20μg vitamin D3 daily. Baseline fever favored treatment while vaccination favored control.
Jun 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1137407/full, https://c19p.org/gerain
490 patient ivermectin late treatment RCT: 69% lower mortality (p=0.09), 59% lower ventilation (p=0.17), 22% lower ICU admission (p=0.79), and 31% lower progression (p=0.29).
RCT 490 late stage (>65% lung change chest radiography at baseline) hospitalized patients in Malaysia, showing no significant differences. Mortality was 1.2% for ivermectin vs. 4% for control. If the same event rates continue, the trial would need to add ~13% more patients to reach statistical significance. i.e., by continuing the trial for ~2 weeks, there is a reasonable chance of the result being a statistically significant ~69% reduction in mortality, which would equate to ~4 million lives saved if adopted at the start of the pandemic. The mortality reduction is consistent with the results from all trials to date. While not reaching the significance threshold with the specified test, Bayesian analysis shows a 97% probability that ivermectin reduces mortality [normanfenton.com]. Authors describe the mortality results as "similar" and they are not mentioned in the visual abstract or the conclusion, suggesting substantial investigator bias with a preference for a null..
Nov 2021, JAMA, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2789362, https://c19p.org/lim
1,856 patient budesonide late treatment RCT: 39% lower mortality (p=0.45), 6% lower ventilation (p=1), 52% lower ICU admission (p=0.07), and 25% lower combined mortality/hospitalization (p=0.96).
Results from the PRINCIPLE trial, 1,073 treated with budesonide starting a median of 6 days after symptom onset, showing lower hospitalization/death, and faster recovery with treatment.
Apr 2021, The Lancet, https://www.sciencedirect.com/science/article/pii/S014067362101744X, https://c19p.org/yu3
89 patient ivermectin early treatment RCT: 70% lower hospitalization (p=0.34) and 62% improved viral clearance (p=0.02).
Double blind RCT for mild-moderate COVID-19 outpatients in Israel showing significantly faster reduction in viral load with treatment, and lower hospitalization with treatment. The one treatment hospitalization was a few hours after treatment and the patient improved and was discharged quickly. Authors also examine culture viability on days 2-6, with 13% positive in the ivermectin group vs. 48% in the control group. There were no safety issues. Ivermectin was taken one hour before a meal. Sheba IRB-7156/20.
Feb 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S120197122200399X, https://c19p.org/biber
RCT with 157 patients treated with honey and nigella sativa, and 156 control patients, showing significantly faster recovery and viral clearance. Honey (1gm/kg/day) plus encapsulated nigella sativa seeds (80mg/kg/day) orally in 2-3 divided doses daily for up to 13 days.
Nov 2020, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7640, https://c19p.org/ashraf2
Retrospective 445 elderly patients with severe asthma showing reduced risk of COVID-19 infection with montelukast treatment.
Sep 2020, J. Asthma, https://www.tandfonline.com/doi/full/10.1080/02770903.2020.1786112, https://c19p.org/bozek
Retrospective 168,370 hospitalized COVID-19 patients with diabetes in Japan showing lower mortality and reduced risk of acute kidney injury with biguanide (likely primarily or only metformin) use. Authors hypothesize that metformin's activation of AMPK in renal tubular epithelium may provide a protective effect against COVID-19-induced kidney damage.
Jul 2024, medRxiv, https://www.medrxiv.org/content/10.1101/2024.07.20.24310736v1, https://c19p.org/sugimoto
Retrospective 28,759 adult outpatients with mild COVID-19 in Iran, 7,295 treated with HCQ, showing significantly lower hospitalization and mortality with treatment.
Apr 2021, Int. Immunopharmacology, https://www.sciencedirect.com/science/article/pii/S1567576921002721, https://c19p.org/mokhtari
Prospective study of 68,896 UK Biobank participants with COVID-19 showing adherence to a healthy lifestyle prior to infection, characterized by 10 factors including adequate physical activity and sleep, not smoking, and a healthy BMI, was associated with a significantly lower risk of mortality, hospitalization, and post-COVID multisystem sequelae. Risk decreased monotonically for increasing numbers of healthy lifestyle factors from 5-10. Reduced risks were evident across cardiovascular, metabolic, neurologic, respiratory, and other disorders over 210 days following infection, during both acute and post-acute phases, regardless of age, sex, ethnicity, test setting, vaccination status, or SARS-CoV-2 variant.
Jan 2024, Nature Communications, https://www.nature.com/articles/s41467-024-50495-7, https://c19p.org/wang24sl
RCT 60 hospitalized patients in India, showing significantly greater clinical improvement with inhaled sodium bicarbonate. Nasal and oral inhalation of nebulized 50ml 8.4% sodium bicarbonate for 5 minutes twice daily for 5 days.
Mar 2021, Acta Scientific Orthopaedics, https://actascientific.com/ASOR/ASOR-04-0290.php, https://c19p.org/mody2
RCT 60 hospitalized patients in India, showing significantly greater clinical improvement with inhaled sodium bicarbonate. Nasal and oral inhalation of nebulized 50ml 8.4% sodium bicarbonate for 5 minutes twice daily for 5 days.
Mar 2021, Acta Scientific Orthopaedics, https://actascientific.com/ASOR/ASOR-04-0290.php, https://c19p.org/mody2sb
Retrospective 2,851,465 people with type 2 diabetes in the UK, showing lower mortality with existing metformin use. Results are subject to confounding by indication because metformin is typically used early in the progression of type 2 diabetes.
Mar 2021, The Lancet Diabetes & Endocrinology, https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00050-4/fulltext, https://c19p.org/khunti
Retrospective 28,048 COVID+ patients in Mexico, 7,898 receiving a treatment kit including low dose ivermectin, AZ, aspirin, and acetaminophen, shower lower mortality/hospitalization for those receiving the kit. Delivery of the treatment kit was based on availability in the medical units. Adherence is unknown and may be low. Adjusted results are only provided for combined mortality/hospitalization.
Jan 2022, Archives of Medical Research, https://www.sciencedirect.com/science/article/pii/S0188440922000029, https://c19p.org/dejesusascenciomontiel
For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - 1.17], vs. overall 0.89, possibly because the exposure events are identified faster in this context, versus home exposure where testing of the source may be more delayed. The trial is too small for significance here. If the trend continued this result would be significant at p<0.05 after about 25% more patients were added. There are 2 groups in this study: PCR+ at baseline (n=314) and PCR- at baseline (n=2000), which should be separated as they are different populations (primary outcome rates 18.6% and 22.2% compared to 3.0% and 4.3%). PCR+ already have COVID-19, so PEP analysis should be for the 2,000 PCR-, showing symptomatic COVID-19 of 4.3% (control) and 3.0% (treatment), RR 0.7, p=0.154. The paper has different RR values here, stating that they are adjusted for contact-level variables. It is not clear how they are computed - the adjusted RR for the overall sample is 4% lower, for..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2021801, https://c19p.org/mitjapep
Prophylaxis RCT 828 high-risk participants in South Africa, showing no significant difference with nitazoxanide and sofosbuvir/daclatasvir treatment. FLU-PRO results were available for 74% of the nitazoxanide arm compared to 54% of the control arm.
Aug 2022, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkac266/6661458, https://c19p.org/sokhela
RCT 35 hospitalized patients with viral pneumonia (34 with COVID-19) showing improved recovery with high-dose inhaled nitric oxide (iNO) treatment. The treatment group received intermittent inhalations of 150 ppm iNO for 40 minutes, 4 times daily for up to 7 days. The treatment group had significantly reduced oxygen support duration and a greater number of patients reaching oxygen saturation ≥93%. There was also a trend towards earlier hospital discharge in the iNO group, without statistical significance. The study was terminated early. There was no ICU admission or mortality in either group.
Jul 2024, Scientific Reports, https://www.nature.com/articles/s41598-024-68055-w, https://c19p.org/wolak
RCT 302 hospitalized COVID-19 patients showing lower mechanical ventilation but no significant difference in ICU admission or mortality with losartan treatment.
Dec 2022, SSRN Electronic J., https://www.ssrn.com/abstract=4278529, https://c19p.org/gotberg
Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including metformin. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/huntmf
Retrospective 571 type 2 diabetes patients with COVID-19 in China, showing lower combined mortality/mechanical ventilation with metformin.
Aug 2023, Diabetes, Metabolic Syndrome and Obesity, https://www.dovepress.com/effects-of-metformin-on-covid-19-patients-with-type-2-diabetes-a-retro-peer-reviewed-fulltext-article-DMSO, https://c19p.org/guo2
1,323 patient azithromycin late treatment RCT: 16% lower need for oxygen therapy (p=0.69), 9% lower hospitalization (p=0.87), and 7% improved recovery (p=0.23).
RCT 1,388 outpatients in the UK showing no significant benefit with azithromycin. There was no significant difference in time to first reported recovery or risk of hospitalization or death by 28 days with azithromycin compared to usual care alone. Only 31% of participants had PCR-confirmed SARS-CoV-2 infection.
Mar 2021, The Lancet, https://www.sciencedirect.com/science/article/pii/S014067362100461X, https://c19p.org/butler4az
RCT 201 hospitalized COVID-19 patients showing faster clinical improvement, less progression to mechanical ventilation or death, and shorter hospital stay with camostat mesylate compared to lopinavir/ritonavir. There was also a trend towards lower 29-day mortality with camostat. Authors note that the lopinavir/ritonavir dose likely did not reach effective levels, so it may be considered similar to a placebo group.
Jul 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.870493/full, https://c19p.org/karolyi
RCT 50 hospitalized COVID-19 pneumonia patients showing faster recovery with ultra-short wave diathermy (USWD). The USWD group received standard treatment plus USWD applied to the chest for 10 minutes twice daily for 12 days. The USWD group had significantly faster clinical recovery by 6.7 days, lower systemic inflammation, and better outcomes on the 7-point clinical status scale on days 21 and 28 compared to the control group receiving only standard treatment. There was no significant difference in SARS-CoV-2 viral clearance. Pulmonary fibrosis observed prior to treatment was recovered in most patients in both groups, alleviating concerns over potential harms of USWD. Baseline severe cases were more common in the treatment group, 52 vs. 28%.
Jan 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1149250/full, https://c19p.org/huang11
Retrospective 74,074 individuals with chronic liver disease in South Korea, showing lower risk of COVID-19 infection and related severe outcomes with ursodeoxycholic acid (UDCA) use. The risk reduction was dose-dependent, with greater benefits seen with higher UDCA exposure. Authors hypothesize that UDCA may reduce viral entry by downregulating the ACE2 receptor and modulate the cytokine storm implicated in severe COVID-19.
Aug 2024, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-024-02464-1, https://c19p.org/moon
Retrospective 2,882 patients in China, median age 62, 278 receiving HCQ, median 10 days post hospitalization, showing that HCQ treatment can reduce systemic inflammation and inhibit the cytokine storm, thus protecting multiple organs from inflammatory injuries, such as detoxification in the liver and attenuation of cardiac injury. IL-6 levels significantly reduced after HCQ treatment, p<0.05, and elevated after HCQ withdrawal. The significantly lower dose used here is potentially related to the different observations from the RECOVERY trial results. Authors suggest that treatment should be started as soon as possible. The 550 patients that were critically ill at baseline are reported in a separate paper. For the non-critically-ill patients at baseline, the proportion of patients that became critically ill was significantly lower for those treated with HCQ. For the subset of patients that started HCQ treatment early only 1.4% died versus 3.9% for HCQ started late and 9.1% for control..
Aug 2020, Science China Life Sciences, 2020 Aug 3, https://link.springer.com/article/10.1007/s11427-020-1782-1, https://c19p.org/yu2
Retrospective 100 COVID-19 patients in Bosnia and Herzegovina, showing lower symptom severity and faster recovery with a history of regular physical activity.
Jul 2023, Sports Science and Health, https://doisrpska.nub.rs/index.php/sportskenaukeizdravlje/article/view/9896, https://c19p.org/sebic
RCT 191 low risk (no mortality) outpatients in Spain, showing no significant differences with bromhexine. Authors note that "statistical differences between the study groups were observed in the percentage of patients treated with bronchodilators (p = 0.033) and receiving symptomatic treatment (p = 0.034), which were higher in the SOC alone group", but do not provide details or perform adjustments. There were more moderate/severe cases in the treatment group (9 vs. 5). Many results appear to be missing including: reduction in the severity of each symptom (0–10 NRS score) at days 4, 7, 14, and 28 as compared with baseline; proportion of patients with clinical improvement and time to clinical improvement; proportion of patients with disappearance of each symptom at days 4, 7, 14, and 28, and time to disappearance; proportion of asymptomatic patients at days 4, 7, 14, and 28. Bromhexine 48 mg/day for seven days. SOC included acetaminophen.
Dec 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/1/142, https://c19p.org/vilamendez
120 patient curcumin late treatment RCT: 86% lower mortality (p=0.24), 86% lower ventilation (p=0.24), 10% shorter hospitalization (p=0.4), and 32% faster recovery (p=0.001).
RCT with 60 hospitalized patients treated with Ayurcov and 60 control patients in India, showing improved viral clearance and faster symptom resolution in the mild/moderate group, but no significant differences in the severe group. Ayurcov contains curcuma longa, go ark, sphatika (alum), sita (rock candy), godugdham (bos indicus) milk, and goghritam (bos indicus ghee).
Mar 2022, Complementary Therapies in Medicine, https://www.sciencedirect.com/science/article/pii/S0965229922000267, https://c19p.org/sankhe2
864 patient HCQ late treatment study: 80% lower mortality (p<0.0001), 20% lower progression (p=0.43), and 31% faster viral clearance (p=0.26).
Retrospective 863 COVID-19 patients in Burkina Faso, showing lower mortality, lower progression for outpatients, and faster viral clearance with HCQ/CQ treatment. Only the lower mortality was statistically significant. NCT04445441.
Feb 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222001114, https://c19p.org/rouamba
RCT 56 severe COVID-19 patients, showing significantly decreased viral load with Sinomarin Plus Algae nasal irrigation. Sinomarin Plus Algae is a hypertonic seawater solution with algal and herbal natural ingredients with a pH of 7.5-8 [sinomarin.com]. The treatment group received nasal irrigation every 4 hours, 16 hours per day, for 2 days. Nasopharyngeal swabs were taken at baseline and 48 hours later to measure viral load. The treatment group showed a significant increase in cycle threshold values, indicating decreased viral load, while no difference was seen in the control group. The treatment was well tolerated with only mild adverse effects. Alkalinization is one possible mechanism of action - SARS-CoV-2 requires acidic pH for infection [Kreutzberger] and the solution has pH 7.5-8. Other possible mechanisms include antiviral activity of ingredients (e.g., fucoidan from Undaria pinnatifida) and physical removal of viral particles.
Jul 2023, J. Personalized Medicine, https://www.mdpi.com/2075-4426/13/7/1093, https://c19p.org/pantazopoulos
RCT 193 mechanically ventilated COVID-19 patients showing improved oxygenation at 48 hours but no difference in mortality with high-dose (80ppm) inhaled nitric oxide (NO) for 48 hours. The NO group had a higher proportion attaining PaO2/FiO2 > 300 mmHg and reduced rates of neurologic symptoms at 90 days. NO was associated with faster viral clearance. No serious adverse events were reported with NO.
Dec 2023, American J. Respiratory and Critical Care Medicine, https://www.atsjournals.org/doi/10.1164/rccm.202304-0637OC, https://c19p.org/difenza
RCT 50 hospitalized patients in the USA, 25 treated with calcitriol, showing significantly improved oxygenation with treatment. Mortality, intubation, ICU admission, and hospitalization time also favored treatment, while not reaching statistical significance with the very small sample size.
Sep 2021, Bone, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425676/, https://c19p.org/elamir
RCT 42 moderate COVID-19 inpatients showing significantly faster clinical and CT scan improvement with short-wave diathermy (SWD) treatment added to standard care, compared to placebo SWD plus standard care. 92.6% of the SWD group had clinical improvement at 14 days, compared to 69.2% in the control group. The SWD group also had significantly faster CT scan improvement. There was no significant difference in adverse events between groups, with only minor side effects like headache and dizziness reported.
Mar 2022, European J. Physical and Rehabilitation Medicine, https://www.minervamedica.it/index2.php?show=R33Y2022N01A0137, https://c19p.org/tian2
PSM retrospective 220,517 patients in Brazil,133,051 taking ivermectin as part of a citywide prophylaxis program, showing significantly lower hospitalization and mortality with treatment. Additional results are presented here: [odysee.com], including improved efficacy with analysis based on irregular/regular use, and a strong dose-response relationship. Confirmation from independent analysis of the raw data: [web.archive.org]. See [Mills] regarding [medrxiv.org].
Dec 2021, Cureus, https://www.cureus.com/articles/82162-ivermectin-prophylaxis-used-for-covid-19-a-citywide-prospective-observational-study-of-223128-subjects-using-propensity-score-matching, https://c19p.org/kerr
237 patient vitamin C early treatment RCT: 31% improved recovery (p=0.008).
RCT 237 patients in Turkey, 162 treated with IV vitamin C in addition to HCQ/AZ/zinc/vitamin D used for all patients, showing significantly faster recovery with the addition of IV vitamin C. 97% of patients were vitamin D deficient, and lower vitamin D levels were associated with ICU admission and longer hospital stay. Only 1 of 237 hospitalized patients died (average age 63, range 22-99) - a 70-year-old patient with heart and lung disease and severely deficient vitamin D levels (6 nmol/L). IV vitamin C (sodium ascorbate) was given as 50 mg/kg every six hours on day 1, followed by 100 mg/kg every six hours (four times daily, 400 mg/kg/day) for seven days. NCT04395768.
Nov 2021, Cureus, https://www.cureus.com/articles/76496-therapies-to-prevent-progression-of-covid-19-including-hydroxychloroquine-azithromycin-zinc-and-vitamin-d3-with-or-without-intravenous-vitamin-c-an-international-multicenter-randomized-trial, https://c19p.org/ried
RCT 114 patients in Egypt, 57 treated with ivermectin mucoadhesive nanosuspension intranasal spray, showing faster recovery and viral clearance with treatment. NCT04716569.
Jun 2021, Int. J. Nanomedicine, https://www.dovepress.com/clinical-biochemical-and-molecular-evaluations-of-ivermectin-mucoadhes-peer-reviewed-fulltext-article-IJN, https://c19p.org/aref
RCT 174 patients in India, 87 treated with AyurCoro-3 (turmeric, gomutra, potassium alum, khadisakhar, bos indicus milk, ghee), showing faster recovery with treatment. EC/NEW/INST/2019/245.
Aug 2021, J. Ayurveda and Integrated Medical Sciences, https://jaims.in/jaims/article/view/1386/1425, https://c19p.org/sankhe
RCT 202 patients in Iran, 102 treated with colchicine, showing lower hospitalization and improved clinical outcomes with treatment.
Feb 2022, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7319?af=R, https://c19p.org/pourdowlat
Retrospective 113,075 people in Israel, showing lower risk of COVID-19 cases with physical activity and a dose dependent response.
Nov 2022, European J. General Practice, https://www.tandfonline.com/doi/full/10.1080/13814788.2022.2138855, https://c19p.org/green
Prospective study of 61,557 adults aged 45+ years showing reduced risk of COVID-19 diagnosis and hospitalization for those meeting physical activity guidelines of ≥7.5 MET-hours/week before the pandemic compared to inactive individuals.
Feb 2024, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814993, https://c19p.org/munozvergara
Late treatment low risk population RCT showing lower progression to hospitalization or urgent care/ER visits with fluvoxamine, without statistical significance. There was no mortality and only three hospitalizations. Authors provide no details on the cause of hospitalization, but they appear to be unrelated to COVID-19. eFigure 5 shows no COVID-19 clinical progression to hospitalization (note that a hospitalization can be seen in the equivalent plot for the low dose arm), and the text indicates that the "COVID clinical progression scale simplified into a self-reported evaluation of home levels (limited vs not)". Note that the urgent care/ER visit outcome is also likely diluted due to inclusion of all-cause events, and could be statistically significant for only COVID-19 events. The sustained recovery outcome, which shows no difference, was a post-hoc creation used to hide efficacy for ivermectin, and is not logical for evaluating efficacy in this trial. The..
Sep 2023, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2812204, https://c19p.org/stewart8
Prospective survey based study with 14,335 participants, showing lower risk of viral symptoms with regular exercise.
Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253120, https://c19p.org/marcus
Retrospective 468,569 adults in the UK, showing significantly lower COVID-19 mortality with physical activity.
Aug 2021, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912100180X, https://c19p.org/ahmadi2
Open-label RCT 137 hospitalized COVID-19 patients, showing lower progression to ICU/step-down ICU and improved recovery with colchicine, both without statistical significance. The primary outcome was changed mid-trial due to the low number of patients progressing to severe disease.
May 2024, Cureus, https://www.cureus.com/articles/240800-colchicine-andor-naltrexone-for-hospitalized-covid-19-patients-not-requiring-high-levels-of-ventilatory-support-coltrexone-a-prospective-randomized-open-label-trial, https://c19p.org/gertner
3,462 patient azithromycin late treatment study: 67% lower mortality (p=0.0001).
Retrospective 3,462 hospitalized COVID-19 patients across 13 states in Nigiera, showing lower mortality with AZ. Authors note the worse results with a combination of CQ/HCQ and AZ, compared to either alone, may be related to the side effects becoming more significant for late stage patients.
May 2023, Nigerian Medical J., https://nigerianmedjournal.org/index.php/nmj/article/view/174, https://c19p.org/yilgwanazaz
RCT 226 ICU patients in Iran, showing lower mortality with melatonin treatment.
Nov 2022, Inflammopharmacology, https://link.springer.com/10.1007/s10787-022-01096-7, https://c19p.org/ameri
Retrospective 264 hospitalized COVID-19 patients in China showing lower risk of composite disease progression and all-cause mortality with azvudine treatment.
Nov 2024, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2024.1453234/full, https://c19p.org/xu17
441 patient HCQ late treatment RCT: 24% lower hospitalization (p=0.57) and 4% improved viral clearance (p=0.1).
Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients being over 5 days from the onset of symptoms. Adverse events were lower in the HCQ group compared to the control group. This trial appears to have been terminated at 45% enrollment while showing ≥70% probability of superiority. The futility threshold was not reported, but it would be highly unusual for it to be as high as 70% [doyourownresearch.substack.com]. The paper indicates the placebo was talc, however the trial protocol shows the "placebo" as vitamin C, for which there are 7 COVID-19 treatment studies as of April 2021 that collectively show significant efficacy. Results differ significantly from those reported prior to publication. Prior to publication, authors reported an RR for hospitalization or death of 1.0 [0.45-2.21] [ajtmh.org].
Apr 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779044, https://c19p.org/reis
RCT with 21 vitamin D and 22 placebo hospitalized patients in Belgium with vitamin D deficiency, showing significantly shorter hospitalization and improved clinical recovery with treatment.
Jul 2022, Nutrients, https://www.mdpi.com/2072-6643/14/15/3048, https://c19p.org/deniet
RCT 189 hospitalized COVID-19 patients showing lower mortality and faster recovery with spirulina. Spirulina treatment also resulted in greater reductions in inflammatory markers such as IL-6, TNF-a, IP-10, CRP, ESR, and ferritin. All patients received remdesivir. Spirulina contains many components including calcium spirulan, a sulfated polysaccharide shown to inhibit the replication of various enveloped viruses in vitro, and many nutrients showing benefits for COVID-19 including vitamins A, C, and D, selenium, and zinc.
Apr 2024, Frontiers in Immunology, https://www.frontiersin.org/articles/10.3389/fimmu.2024.1332425/full, https://c19p.org/aghasadeghispi
Retrospective 3,044 hospitalized COVID-19 patients in Italy, showing HCQ significantly associated with survival in light, mild, and moderate cases in multivariable analysis, but not in severe cases.
Apr 2021, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-021-02742-8, https://c19p.org/corradini
RCT 188 patients in Brazil, showing shorter hospitalization and improved outcomes with propolis, but without statistical significance. The incidence of secondary infections was significantly lower in the treatment group.
Oct 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-43764-w, https://c19p.org/silveira
Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including antihistamines. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/hunth1
RCT 20 hospitalized COVID-19 patients showing faster viral load reduction and lower oxygen use with metformin glycinate 620mg twice daily for 14 days compared to placebo. The in vitro portion demonstrated inhibition of viral replication and cytopathic effects with metformin glycinate pretreatment.
Aug 2022, Biomedicine & Pharmacotherapy, https://www.sciencedirect.com/science/article/pii/S0753332222006126, https://c19p.org/venturalopez
UK Biobank retrospective 196,154 participants with 11,288 COVID-19 cases, showing lower COVID-19 mortality, severity, and incidence for lower dietary inflammatory scores.
Dec 2022, SSRN Electronic J., https://www.ssrn.com/abstract=4300209, https://c19p.org/zhao6
Retrospective 224,190 type 2 diabetes patients in Russia, showing lower mortality with metformin use.
Aug 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.909874/full, https://c19p.org/shestakova
Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality.
Feb 2021, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445321000773, https://c19p.org/loratamayo
RCT 177 women in Brazil, 75 treated with proxalutamide, showing significantly lower hospitalization with treatment.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.06.21260086v1, https://c19p.org/cadegiani5
Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing lower mortality with metformin use. The study provides results for use before, after, and before+after. Before+after should more accurately represent prophylaxis up to COVID-19 infection (and continued use). Before included use up to 2 years before, and after included use up to 60 days later.
Dec 2021, BMJ Open, https://bmjopen.bmj.com/content/11/12/e050051.info, https://c19p.org/wallace
RCT 146 mild/moderate COVID-19 patients in Thailand, showing no significant difference in clinical outcomes. There were very few serious outcomes.
Aug 2023, Phytomedicine, https://www.sciencedirect.com/science/article/pii/S0944711323003793, https://c19p.org/siripongboonsitti3
Retrospective PSM analysis of pre-existing aspirin use in the USA, showing lower mortality with treatment.
Feb 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246825, https://c19p.org/osborne
Prospective study of 2,690 adults in the UK Biobank showing lower cardiorespiritory fitness associated with COVID-19 mortality.
May 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250508, https://c19p.org/christensen
PSM retrospective 3,998 hospitalized COVID-19 patients aged 60 years and older in China showing lower all-cause mortality, higher rate of discharge, and shorter time to viral clearance with azvudine treatment.
Dec 2024, Acta Pharmaceutica Sinica B, https://www.sciencedirect.com/science/article/pii/S2211383524004611, https://c19p.org/zhu9
RCT 156 patients in Japan, 107 treated with favipiravir, showing significant improvement in a composite outcome defined as the time to improvement in temperature, SpO2, CT findings, and recovery to PCR-.
Aug 2021, Infectious Diseases and Therapy, https://link.springer.com/article/10.1007/s40121-021-00517-4, https://c19p.org/shinkai
138,475 patient exercise study: 35% lower hospitalization (p=0.007).
UK Biobank retrospective 235,928 participants using walking pace as a proxy for physical fitness, showing lower risk of COVID-19 hospitalization with an average vs. slow walking pace.
Nov 2020, BMJ Open, https://bmjopen.bmj.com/content/10/11/e040402, https://c19p.org/ho
Retrospective 565 COVID-19 patients in India, showing lower mortality with HCQ+AZ treatment. Most patients (66%) had mild disease at baseline.
May 2023, The J. the Association of Physicians of India, https://pubmed.ncbi.nlm.nih.gov/37355843/, https://c19p.org/rathod2
RCT with 153 patients treated with a nitric oxide nasal spray, and 153 placebo patients, showing faster viral clearance with treatment. NO generated by a nasal spray (NONS) self-administered six times daily as two sprays per nostril (0.45mL of solution/dose) for seven days.
Jun 2022, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368222000464, https://c19p.org/tandon
PSM prospective study of 260 COVID-19 patients in Bulgaria, showing lower mortality, ventilation, and ICU admission with HCQ treatment.
Mar 2022, Infectious Disorders - Drug Targets, https://www.eurekaselect.com/article/121288, https://c19p.org/tsanovska
3,462 patient HCQ late treatment study: 93% lower mortality (p<0.0001).
Retrospective 3,462 hospitalized COVID-19 patients across 13 states in Nigiera, showing lower mortality with HCQ. Authors note that the improved results compared with many other late stage studies may be related to the dose and experience of the physicians - in other studies beneficial effects may be offset by the side effects of high cumulative doses in late stage patients. Authors also note the worse results with a combination of CQ/HCQ and AZ may be related to the side effects becoming more significant for late stage patients.
May 2023, Nigerian Medical J., https://nigerianmedjournal.org/index.php/nmj/article/view/174, https://c19p.org/yilgwan
Retrospective 1,657,800 COVID-19 hospitalizations in the USA including 13,095 patients with cannabis use disorder, showing lower risk of mortality with cannabis use disorder. The text and Table S2 have conflicting results for mortality: 0.45 [0.36-0.57] versus 0.43 [0.34-0.55].
Jan 2023, SSRN Electronic J., https://www.ssrn.com/abstract=4336513, https://c19p.org/mannumbethrenjithlal
Prospective UK Biobank analysis, showing a history of low physical activity associated with COVID-19 mortality.
Nov 2021, BMJ Open, https://bmjopen.bmj.com/content/11/11/e055003.info, https://c19p.org/hamrouni
Retrospective 282 adults recently vaccinated against poliovirus showing vitamin D supplementation associated with lower COVID-19 PCR+ cases, lower symptomatic cases, and shorter duration of symptoms.
Jan 2024, Vaccines, https://www.mdpi.com/2076-393X/12/2/121, https://c19p.org/comunale
PSM retrospective 32,864 hospitalized COVID-19 patients in China showing lower all-cause mortality and disease progression with azvudine treatment.
Nov 2024, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445324002901, https://c19p.org/ren2
RCT with 36 colchicine and 36 control patients, showing reduced length of hospitalization and oxygen therapy with treatment.
Aug 2020, RMD Open, https://rmdopen.bmj.com/content/7/1/e001455, https://c19p.org/lopes
Analysis of 1641 systemic autoimmune disease patients showing csDMARD (HCQ etc.) RR 0.37, p=0.015. csDMARDs include HCQ, CQ, and several other drugs, so the effect of HCQ/CQ alone could be higher. This study also confirms that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, OR 4.42, p<0.001 (this is the observed real-world risk which takes into account factors such as these patients potentially being more careful to avoid exposure). (results are for "definite + highly suspected" cases and the main result is presented in the paper as the OR for not taking csDMARDs, we have converted this to RR for taking csDMARDs).
Aug 2020, Clinical Rheumatology, https://link.springer.com/article/10.1007/s10067-020-05334-7, https://c19p.org/ferri
Retrospective 413 hospitalized COVID-19 patients with type 2 diabetes in China showing lower ICU admission, lower pneumonia incidence, and shorter hospital stay with metformin use.
Jun 2024, Translational Medicine of Aging, https://www.sciencedirect.com/science/article/pii/S2468501124000026, https://c19p.org/chen28
RCT 124 hospitalized COVID-19 patients in Brazil. The treatment groups received standardized green propolis extract (EPP-AF) at doses of 400mg/day or 800mg/day for 7 days, in addition to standard care. The EPP-AF groups had significantly shorter hospital stays post-intervention. The high dose EPP-AF group also had lower rates of acute kidney injury. No significant differences were seen for other outcomes like oxygen therapy duration or need for mechanical ventilation. The propolis adjunct treatment appeared safe with no discontinuations due to side effects.
Jun 2021, Biomedicine & Pharmacotherapy, https://www.sciencedirect.com/science/article/pii/S0753332221003115, https://c19p.org/silveira2
47% lower mortality with HCQ/CQ. Retrospective 1,271 patients with lung disease in Canada, China, Cuba, Ecuador, Germany, Italy and Spain, 83% treated with HCQ/CQ. Multivariable Cox regression HCQ/CQ mortality hazard ratio HR 0.53, p < 0.001.
Dec 2020, Archivos de Bronconeumología, https://www.sciencedirect.com/science/article/pii/S0300289620305354, https://c19p.org/signescosta
363 patient vitamin B9 prophylaxis RCT: 88% fewer cases (p<0.0001).
Cluster RCT 526 healthcare workers in Egypt, showing lower COVID-19 cases with folic acid supplementation, and a dose-response relationship. Each wave of health care workers was randomized within 14 day isolation periods, introducing potential confounding by time.
Nov 2022, Microbes and Infectious Diseases, https://mid.journals.ekb.eg/article_270589.html, https://c19p.org/farag
412 patient aspirin late treatment study: 47% lower mortality (p=0.02), 44% lower ventilation (p=0.007), and 43% lower ICU admission (p=0.007).
Retrospective 412 hospitalized patients, 98 treated with aspirin, showing lower mortality, ventilation, and ICU admission with treatment.
Mar 2021, Anesthesia & Analgesia, https://journals.lww.com/anesthesia-analgesia/fulltext/2021/04000/aspirin_use_is_associated_with_decreased.2.aspx, https://c19p.org/chow
Retrospective 2,184 hospitalized patients in the USA, 638 treated with famotidine, showing lower mortality with treatment.
Oct 2021, JGH Open, https://onlinelibrary.wiley.com/doi/10.1002/jgh3.12905, https://c19p.org/wagner
RCT 152 outpatients in Pakistan, 76 treated with quercetin phytosome, showing lower mortality, ICU admission, and hospitalization with treatment.
Jun 2021, Int. J. General Medicine, https://www.dovepress.com/possible-therapeutic-effects-of-adjuvant-quercetin-supplementation-aga-peer-reviewed-fulltext-article-IJGM#, https://c19p.org/dipierro
RCT with 103 indomethacin and 107 paracetamol patients, showing lower progression and improved recovery with indomethacin. Notably, improvements include faster resolution of cough. [Alkotaji] previously hypothesised the benefit of indomethacin for reducing cough via bradykinin inhibition.
Apr 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-10370-1, https://c19p.org/ravichandran
RCT 208 ICU patients in Bangladesh, showing improved recovery with famotidine. Famotidine 40mg (<60kg) or 60mg every 8 hours.
Aug 2022, World J. Clinical Cases, https://www.wjgnet.com/2307-8960/full/v10/i23/8170.htm, https://c19p.org/chowdhury2
PSM/IPTW retrospective 1,356 hospitalized COVID-19 patients with type 2 diabetes in China, showing lower mortality/hospice with metformin use.
Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-09639-2, https://c19p.org/ma5
Prophylaxis RCT with 59 zinc + doxycycline, 56 doxycycline, and 57 placebo healthcare workers, showing lower symptomatic cases and significantly improved Ct values with the addition of zinc to doxycycline treatment. Doxycycline 100mg/day and zinc 15 mg/day.
Jun 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222003496, https://c19p.org/stambouli
350 patient probiotics early treatment RCT: 50% fewer combined hospitalization/ER visits (p=0.13) and 20% faster recovery (p=0.1).
RCT 350 COVID+ outpatients in the USA, 174 treated with prebiotic KB109 (a microbiome metabolic therapy candidate), showing lower combined hospitalization, ER, and urgent care visits with treatment. NCT04414124.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.26.21254422, https://c19p.org/haran
Double-blind RCT 110 hospitalized moderate to severe COVID-19 patients showing significantly reduced ICU admission, shorter hospitalization, faster resolution of symptoms, and improved CRP and LDH levels with ivermectin treatment compared to placebo. No deaths occurred in either group. There were no serious adverse events. Note that preclinical research predicts synergistic effects with the standard treatment protocol used in both groups.
Apr 2024, Jundishapur J. Health Sciences, https://brieflands.com/articles/jjhs-146703, https://c19p.org/varnaseri
Retrospective 88 ventilated COVID-19 patients in Japan, 39 treated with ivermectin within 3 days of admission, showing significantly reduced incidence of GI complications and mortality, and increased ventilator-free days with treatment.
Dec 2021, J. Infection and Chemotherapy, https://www.jiac-j.com/article/S1341-321X(21)00360-3/fulltext, https://c19p.org/shimizu
Retrospective 17,396 PCR+ patients in the USA, showing lower mortality with metformin use.
Mar 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26873, https://c19p.org/bramante4
RCT 46 hospitalized patients with moderate COVID-19 pneumonia, 24 treated with N-acetylcysteine, showing significantly shorter hospitalization with treatment. NAC 1,200 – 1,500mg/day intravenously.
Feb 2021, Pulmonologiya, https://journal.pulmonology.ru/pulm/article/viewFile/2263/1813, https://c19p.org/gaynitdinova
RCT with 75 favipiravir patients and 75 control patients showing improved recovery with treatment.
Nov 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S120197122032453X, https://c19p.org/udwadia
147 patient curcumin long COVID RCT: 44% greater improvement (p=0.02).
RCT 147 long COVID patients in the UK, 56 treated with a phytochemical-rich concentrated food capsule, showing improved recovery with treatment. Treatment included curcumin, bioflavonoids, chamomile, ellagic acid, and resveratrol.
Mar 2022, COVID, https://www.mdpi.com/2673-8112/2/4/31, https://c19p.org/thomas3
Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity, depression, anxiety, stress, and poor health-related quality of life.
Nov 2023, Diseases, https://www.mdpi.com/2079-9721/11/4/165, https://c19p.org/pavlidousl
Retrospective 21,579 hospitalized COVID-19 patients mostly in the USA, showing lower risk of mortality and severity with existing aspirin use.
May 2022, Archivos de Bronconeumología, https://www.sciencedirect.com/science/article/pii/S0300289622005105, https://c19p.org/lal
Retrospective 4,396 hospitalized patients in Italy showing significantly lower mortality with HCQ treatment, and identifying greater efficacy for a subgroup of patients in clustering analysis.
Jan 2021, J. Healthcare Engineering, https://www.hindawi.com/journals/jhe/2021/5556207/, https://c19p.org/dicastelnuovo2
Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients. This study includes both outpatients and hospitalized patients.
Jun 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/pii/S1477893920302817, https://c19p.org/lagier
Prophylaxis study with 12,089 Indian healthcare workers, showing lower risk of COVID-19 cases with treatment, and increasingly lower risk for longer durations of HCQ prophylaxis. The appendices are not currently available.
Jun 2021, J. the Association of Physicians of India, June 2021, https://www.researchgate.net/publication/357700064_Hydroxychloroquine_for_SARS_CoV2_Prophylaxis_in_Healthcare_Workers_-_A_Multicentric_Cohort_Study_Assessing_Effectiveness_and_Safety, https://c19p.org/badyal
Retrospective 3,057 androgen deprivation therapy patients in the USA, and 36,096 control patients with cancer, showing lower risk of cases and severity with ADT.
Mar 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.774773/full, https://c19p.org/lee5
Retrospective 10,477 patients in Israel, showing lower risk of COVID-19 cases with existing aspiring use.
Feb 2021, The FEBS J., https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15784, https://c19p.org/merzon2
RCT 42 hospitalized moderate/severe COVID-19 patients in Iran, showing lower progression and improved recovery with nano-curcumin. Nano-curcumin 70mg bid for 14 days.
Apr 2023, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7844, https://c19p.org/sadeghizadeh
RCT 100 patients in India, 50 treated with ImmuActive (curcumin, andrographolides, resveratrol, zinc, selenium, and piperine), showing improved recovery with treatment.
Oct 2021, Evidence-Based Complementary and Alternative Medicine, https://www.hindawi.com/journals/ecam/2021/8447545/, https://c19p.org/majeed
Prospective study of 316 hospitalized patients in Uganda, 94 receiving fluvoxamine, showing significantly lower mortality and improved recovery with treatment.
Mar 2023, Molecular Psychiatry, https://www.nature.com/articles/s41380-023-02004-3, https://c19p.org/kirenga2
Retrospective 31,966 COVID+ patients using anti-hyperglycemic drugs in Italy, showing lower mortality and ICU admission with metformin use.
Jan 2022, Diabetes, Obesity and Metabolism, https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14648, https://c19p.org/ojedafernandez
RCT 30 hospitalized COVID-19 patients investigating the effectiveness of photobiomodulation (PBM) using a vest with near-infrared LEDs (simulating part of the sunlight spectrum). The treatment group showed shorter hospitalization, significant improvement in cardiopulmonary function, and improvements in leukocyte, neutrophil, and lymphocyte counts post-treatment. The treatment group had higher pneumonia severity at baseline. For more discussion see [youtube.com].
Dec 2022, J. Photochemistry and Photobiology B: Biology, https://www.sciencedirect.com/science/article/pii/S1011134422002342, https://c19p.org/pereira2
RCT 116 healthcare workers comparing 0.2% chlorhexidine mouthwash (n=36), 7.5% sodium bicarbonate mouthwash (n=40), and placebo (n=40) twice daily for 2 weeks, with symptoms followed for 4 weeks. There were lower symtoms and cases in both treatment groups, with statistical significance for chlorhexidine only. The treatments were stopped after two weeks, results may be better with continued use, more frequent use, and with the addition of nasal use.
Jan 2024, Iranian J. Nursing and Midwifery Research, https://journals.lww.com/jnmr/fulltext/2024/29010/a_comparison_of_the_effects_of_chlorhexidine_and.8.aspx, https://c19p.org/karami
Retrospective 7,539 patients with diabetes mellitus type 2 and chronic kidney disease in Croatia showing lower risk of SARS-CoV-2 infection with SGLT-2 inhibitors, metformin, and repaglinide use, and lower risk of COVID-19 hospitalization with SGLT-2 inhibitors and metformin use.
Mar 2024, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0301056, https://c19p.org/dimnjakovic
RCT 80 COVID-19 interstitial pneumonia patients in Italy, 40 treated with probiotics, showing significantly reduced gut inflammatory markers with treatment, and lower ICU admission and mortality, without statistical significance. Bifidobacterium lactis LA 304, lactobacillus salivarius LA 302, and lactobacillus acidophilus LA 201 bid for 10 days.
Jun 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/13/3758, https://c19p.org/saviano
334,374 patient aspirin prophylaxis PSM study: 46% lower mortality (p=0.001).
PSM retrospective 334,374 COVID-19 patients showing decreased risk of venous thromboembolism, including pulmonary embolism and deep vein thrombosis, but increased risk of arterial thromboembolic disorders, including ischemic stroke and acute ischemic heart disease, with aspirin use prior to COVID-19 diagnosis. The increased risk of arterial disease may be associated with preexisting cardiovascular disease for which aspirin was already prescribed. All cause mortality was lower in the aspirin group, however authors do not discuss this result.
Apr 2024, medRxiv, https://www.medrxiv.org/content/10.1101/2024.04.10.24305647, https://c19p.org/ware
Analysis of 39,915 patients with 1,768 COVID+ cases based on surveys in the Nurses' Health Study II, showing higher predicted vitamin D levels associated with lower risk of COVID-19 cases. There was significantly lower risk of hospitalization with vitamin D supplementation (≥400 IU/d), but no significant differences for cases based on supplementation.
Dec 2021, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqab389/6448988, https://c19p.org/ma2
Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity, depression, anxiety, stress, and poor health-related quality of life.
Nov 2023, Diseases, https://www.mdpi.com/2079-9721/11/4/165, https://c19p.org/pavlidoudt
Prospective trial of 768 COVID-19 outpatients in Mexico, 481 treated with ivermectin, AZ, montelukast, and aspirin, and 287 control patients with various treatments, showing significantly lower mortality and hospitalization, and significantly higher recovery at 14 days with treatment.
Feb 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221001004, https://c19p.org/limamorales
RCT 240 hospitalized patients with COVID-19 pneumonia, mean 9 days from the onset of symptoms, showing no significant differences with colchicine treatment. EudraCT 2020-001841-38.
Jun 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-13424-6, https://c19p.org/cecconi
PSM retrospective 878 hospitalized patients in the USA, 83 with existing famotidine use, showing significantly lower mortality with treatment.
Aug 2020, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000000832, https://c19p.org/mather
90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers.
Nov 2020, J. Marine Medical Society, https://www.marinemedicalsociety.in/preprintarticle.asp?id=300159, https://c19p.org/mathai
Retrospective 2017 hospitalized patients in India, showing lower mortality with zinc treatment.
Aug 2021, Lung India, https://journals.lww.com/lungindia/Fulltext/2022/01000/Clinical_features,_demography,_and_predictors_of.5.aspx, https://c19p.org/elavarasiz
RCT 500 patients in Brazil, showing improved recovery with a phthalocyanine derivative mouthwash and toothpaste. Toothbrushing for 2 minutes, three times per day, and gargling/rising (5ml) for one minute, three times a day, for 7 days.
Dec 2021, J. Evidence-Based Dental Practice, https://www.sciencedirect.com/science/article/pii/S1532338222001002, https://c19p.org/poleti
RCT with 189 patients showing significantly greater viral clearance with a single application of PVP-I. Authors recommend using PVP-I prophylactically in the nasopharynx and oropharynx. NCT04549376 [trialsjournal.biomedcentral.com].
May 2021, Indian J. Otolaryngology and Head & Neck Surgery, https://link.springer.com/article/10.1007/s12070-021-02616-7, https://c19p.org/arefin
RCT 3,622 (concurrent and eligible) COVID-19 outpatients in the UK showing significantly faster recovery with favipiravir, and significantly greater full recovery at 3, 6, and 12 months. Authors note: "From 16 Dec 2021, a minority of extremely clinically vulnerable patients could also access antiviral treatment or a monoclonal antibody infusion". However, there is no information on treatments provided or procedures for determining eligibility. This change invalidates hospitalization/death data after 16 Dec 2021. Hospitalization/death events occured in a small minority of patients and are expected to be strongly biased towards the extremely clinically vulnerable patients. Patients randomized to usual care are more likely to obtain alternative treatment. During the trial extension period sotrovimab was the most common treatment, with paxlovid and molnupiravir also being used [england.nhs.uk]. Sotrovimab showed very high efficacy during this period [Behzad, De Vito]. It..
Aug 2024, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445324001828, https://c19p.org/hobbs
Analysis of COVID-19 cases vs. widespread prophylactic use of ivermectin for parasitic infections showing significantly lower incidence of COVID-19 cases.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304684, https://c19p.org/hellwig
HCQ decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City.
Jun 2020, J. Gen. Intern. Med., https://link.springer.com/article/10.1007/s11606-020-05983-z, https://c19p.org/mikami
RCT of 1,000 people showing lower risk of COVID-19 infection with HCQ prophylaxis. There was no significant difference in side effects or adherence, no severe side effects, and blinding was well maintained. There are now PrEP RCTs, showing significant efficacy for COVID-19 cases with .
Jan 2024, Social Determinants of Health, https://journals.sbmu.ac.ir/sdh/article/view/43032, https://c19p.org/chouhdari
RCT 120 outpatients in Turkey, showing improved reduction in viral load with PVP-I nasal irrigation. PVP-I prepared with hypertonic alkaline solution had better results. [Kreutzberger] show that SARS-CoV-2 requires acidic pH to infect cells, therefore alkalinization may add additional benefits. All patients received favipiravir. PVP-I 1% 4 times per day.
Oct 2022, Authorea, https://www.authorea.com/users/337860/articles/592062-effect-of-the-povidone-iodine-hypertonic-alkaline-solution-and-saline-nasal-lavage-on-nasopharyngeal-viral-load-in-covid-19?commit=bcb03d2ad8d86742ebd473271b70f5ab7211094d, https://c19p.org/karaaltin
Propensity matched retrospective prophylaxis study of healthcare workers in the Dominican Republic showing significantly lower cases with treatment, and no hospitalization with treatment (versus 2 in the PSM matched control group). The cases with treatment were mostly in the first week, with only one case in the second and third weeks, and none in the fourth week. There were no severe side effects. In post-hoc analysis, as the treatment group discontinued treatment over time, their protection also decreased. NCT04832945.
Apr 2021, Cureus, https://www.cureus.com/articles/63131-ivermectin-as-a-sars-cov-2-pre-exposure-prophylaxis-method-in-healthcare-workers-a-propensity-score-matched-retrospective-cohort-study, https://c19p.org/morgenstern2
RCT 342,183 adults in Bangladesh showing lower COVID-19 cases with a community-level mask promotion and distribution intervention. The reduction in symptoms and seroprevalence was larger with surgical masks compared to cloth masks, and in older adults. Villages were randomly assigned to receive free cloth or surgical masks along with education and promotion of mask-wearing, or no intervention. Author do not report any information on the severity of cases.
Jan 2022, Science, https://www.science.org/doi/10.1126/science.abi9069, https://c19p.org/abaluck
Small prophylaxis RCT with 25 treatment and 25 control health care workers, showing lower PCR+, symptomatic cases, and hospitalization with treatment, although not statistically significant with the small sample size.
Mar 2021, Interdisciplinary Perspectives on Infectious Diseases, https://www.hindawi.com/journals/ipid/2022/4693121/, https://c19p.org/mikhaylov
2075 hospital patients in Spain showing HCQ reduces mortality 52%, odds ratio OR 0.39, p<0.001, after adjustment for age, gender, temperature > 37 °C, and saturation of oxygen < 90% treatment with azithromycin, steroids, heparin, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, and date of admission (model 4).
Sep 2020, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-020-02505-x, https://c19p.org/ayerbe
IPTW retrospective 141 COVID-19 patients (83% hospitalized), 71 treated with colchicine and 70 matched control patients, showing lower mortality and faster recovery with treatment.
Mar 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248276, https://c19p.org/manenti
Retrospective 116 patients with D levels < 30ng/mL, 58 treated with vitamin D 100,000IU daily for two days, and 58 matched controls, showing significantly lower mortality with treatment.
May 2022, Healthcare, https://www.mdpi.com/2227-9032/10/5/956, https://c19p.org/fiore2
RCT 293 outpatients in Mexico, 147 treated with a probiotic composed of three L. plantarum strains (KABP022, KABP023 and KABP033) and one P. acidilacti strain (KABP021), showing improved recovery with treatment. There were no hospitalizations or deaths.
May 2021, Gut Microbes, https://www.tandfonline.com/doi/pdf/10.1080/19490976.2021.2018899, https://c19p.org/gutierrezcastrellon
Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including colchicine. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/hunto
100% reduction in hospitalization and cases with early treatment using HCQ+AZ+zinc. Brief report on healthcare workers in Bulgaria. 0 hospitalizations with treatment vs. 2 for control 0 PCR+ at day 14 with treatment vs. 3 for control 33 treatment patients and 5 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297520301657, https://c19p.org/simova
RCT 24 patients with olfactory dysfunction post-COVID-19 in Hong Kong, showing significantly improved recovery with the addition of vitamin A to aerosolised diffuser olfactory training. 25,000IU vitamin A for 14 days.
Jun 2023, Brain Sciences, https://www.mdpi.com/2076-3425/13/7/1014, https://c19p.org/chung
Early terminated RCT with 164 aspirin and 164 control patients in the USA with very few events, showing no significant difference with aspirin treatment for the combined endpoint of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, and hospitalization for cardiovascular or pulmonary indication. There was no mortality and no major bleeding events among participants that started treatment (there was one ITT placebo death).
Oct 2021, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2785218, https://c19p.org/connors
Prospective study of 103 hospitalized patients in Italy, showing very high prevalence of vitamin D deficiency, and increased severity for lower vitamin D levels. Vitamin D supplementation was significantly less common for cases.
Jun 2021, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06281-7, https://c19p.org/campi
Small 72 patient RCT of ivermectin and ivermectin + doxycycline showing faster recovery with ivermectin. The ivermectin + doxycycline group uses only a single dose of ivermectin vs. 5 daily doses for the ivermectin group. PCR testing was only done weekly after day 7, therefore hospitalization time may not match symptomatic recovery. Ivermectin group: 12mg daily for 5 days Ivermectin + doxycycline: 12mg ivermectin single dose, 200mg doxycycline + 100mg bid 4 days
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325066, https://c19p.org/ahmed
435 patient HCQ prophylaxis RCT: 51% fewer symptomatic cases (p=0.79) and 27% fewer cases (p=0.31).
Early terminated healthcare worker prophylaxis RCT in Spain, showing lower risk of symptomatic cases with HCQ prophylaxis, without statistical significance due to the small number of events.
Aug 2022, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X22003706, https://c19p.org/polo
PSM retrospective 898,303 hospitalized COVID-19 patients in the USA, 16,324 on spironolactone, showing lower mortality and ventilation with spironolactone use.
Mar 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.02.28.23286515v1, https://c19p.org/cousins2
PSM retrospective 898,303 hospitalized COVID-19 patients in the USA, 16,324 on spironolactone, showing lower mortality and ventilation with spironolactone use.
Mar 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.02.28.23286515v1, https://c19p.org/cousins2sp
Retrospective 546 COVID+ patients in the USA, showing lower risk of hospitalization with higher consumption of vegetables.
Oct 2022, American J. Lifestyle Medicine, http://journals.sagepub.com/doi/10.1177/15598276221135541, https://c19p.org/reis6
Retrospective 650,317 COVID-19 patients in Japan showing lower risk of severe COVID-19 with metformin use.
Sep 2024, Discover Public Health, https://ete-online.biomedcentral.com/articles/10.1186/s12982-024-00225-7, https://c19p.org/sakamaki
RCT 189 hospitalized patients showing lower mortality, ICU admission, and intubation with metformin, statistically significant only for intubation. Treatment patients may have also taken metformin prior to admission. Authors note that patients receiving metformin prior to the study were not matched, and diabetes and hyperlipidemia differed between groups.
Jul 2022, Advanced Pharmaceutical Bulletin, https://apb.tbzmed.ac.ir/Article/apb-33452, https://c19p.org/shaseb
Retrospective 2,796 hospitalized diabetes patients with COVID-19 in France, showing lower mortality with metformin use.
Feb 2021, Diabetologia, https://link.springer.com/article/10.1007/s00125-020-05351-w, https://c19p.org/wargny
621 patient povidone-iodine early treatment RCT: 91% lower hospitalization (p=0.06), 15% faster recovery (p=0.008), 68% improved viral clearance (p<0.0001), and 92% lower transmission (p<0.0001).
RCT with 200 patients and 421 contacts, with 100 patients and their contacts treated with nasal and oropharyngeal sprays containing povidone-iodine and glycyrrhizic acid, showing significantly faster viral clearance and recovery, and significantly lower transmission. SOC included vitamin C and zinc. The spray active ingredients included a compound of glycyrrhizic acid in the form of ammonium glycyrrhizate 2.5 mg/ml plus PVI 0.5% for oropharyngeal and dipotassium glycyrrhizinate 2.5 mg/ml plus PVI 0.5% for nasal spray. Patients were advised to concomitantly use oropharyngeal and nasal sprays 6 times per day. They were instructed to abstain from food, drink, and smoke for 20min, particularly after oropharyngeal spray. The oropharyngeal spray bottle contains an atomizer that ends with a long arm applicator to insert inside the mouth cavity and can be directed up, down, right, or left to cover the entire pharyngeal area.
Apr 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.863917/full, https://c19p.org/elsersy
Retrospective 1,470 healthcare workers in India, showing significantly lower risk of symptomatic COVID-19 with ivermectin prophylaxis.
May 2021, J. the Indian Medical Association, https://onlinejima.com/read_journals.php?article=683, https://c19p.org/mondal
Retrospective 857 hospitalized type 2 diabetes patients showing lower mortality with pre-admission metformin use. Authors report no significant difference in mortality with in-hospital metformin use, but do not report the actual result.
Nov 2024, Diabetes and Vascular Disease Research, https://journals.sagepub.com/doi/10.1177/14791641241288390, https://c19p.org/chertokshacham2
RCT with 112 mild and moderate COVID-19 patients in India, showing lower mortality, ventilation, and ICU admission, although not statistically significant due to the small number of events. There was no mortality in the treatment arm (55 patients) versus 7% (4 of 57) in the control arm. The PCR result is subject to confounding by biased loss of followup, with 23 lost in the treatment group and 13 in the control group, and 8 more people in the treatment group discharged before day 6.
Jan 2021, J. Pharmacy & Pharmaceutical Sciences, https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/32105, https://c19p.org/ravikirti
PSM retrospective 900 hospitalized COVID-19 patients in China showing lower risk of disease progression and death with azvudine treatment.
Jan 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.01.23.23284899, https://c19p.org/shen3
53% reduction in PCR+ with high-dose cholecalciferol supplementation. RCT with 16 treatment patients and 24 control patients. 25(OH)D levels at day 14 were 52 ng/ml vs. 15 ng/ml in the intervention and control group.
Nov 2020, Postgraduate Medical J., https://pmj.bmj.com/content/early/2020/11/12/postgradmedj-2020-139065.full, https://c19p.org/rastogi
RCT 75 patients in Brazil, showing significantly lower viral load with phthalocyanine mouthwash and nasal spray. The combination was more effective than mouthwash alone.
Jun 2023, German Medical Science GMS Publishing House, https://www.egms.de/en/journals/gms/2023-21/000321.shtml, https://c19p.org/coladosimao
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3h
RCT 471 mild COVID-19 patients in Pakistan showing no significant differences in clinical improvement and viral clearance between HCQ, azithromycin, oseltamivir, and combinations. Mortality was significantly lower in HCQ vs. non-HCQ arms. The best results for viral clearance and clinical improvement were seen with the combination of all treatments. There was no placebo group (the study compares different combinations of treatments). No serious adverse events were reported. All patients had mild COVID-19 and the paper indicates early treatment, however time from onset is not reported and minimal baseline information is provided.
Mar 2024, Pakistan J. Medical Sciences, https://www.pjms.org.pk/index.php/pjms/article/view/8757, https://c19p.org/azhar
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/beherai
Case control study with 307 severe COVID-19 ICU patients and 307 matched COVID-19 outpatients in Brazil, showing significantly higher risk of severe cases with low physical activity.
May 2023, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775323002518, https://c19p.org/cardoso
Chronic treatment with HCQ provides protection against COVID, odds ratio 0.51 (0.37-0.70). The actual benefit is likely to be larger becasue research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall. Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure.
Jun 2020, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26286, https://c19p.org/ferreira
PSM retrospective SLE/RA patients in the USA, showing lower COVID-19 cases with HCQ prophylaxis.
Jun 2023, Studies in Health Technology and Informatics, https://ebooks.iospress.nl/doi/10.3233/SHTI230489, https://c19p.org/finkelstein
RCT with 39 bromhexine and 39 control patients showing lower mortality, intubation, and ICU admission with treatment. The treatment group received bromhexine hydrochloride 8 mg three times a day for two weeks. All patients received SOC including HCQ.
Jul 2020, Bioimpacts, https://bi.tbzmed.ac.ir/Article/bi-23240, https://c19p.org/ansarin
Low dose low-risk patient HCQ PEP RCT, showing lower symptomatic cases with treatment, without statistical significance. There were no moderate or severe cases. HCQ 800mg on day one followed by 400mg once weekly for 3 weeks.
Jan 2023, Scientific Reports, https://www.nature.com/articles/s41598-022-26053-w, https://c19p.org/dhibar2
Randomized controlled trial of 82 mild COVID-19 outpatients showing significantly greater reduction in cough and lower inflammatory markers at day 7. Symptomatic improvement was significant at day 7 when combining all symptoms reported, but not for other symptoms individually. There was no progression to severe pneumonia in either group.
Feb 2024, OBM Integrative and Complementary Medicine, https://www.lidsen.com/journals/icm/icm-09-01-013, https://c19p.org/prasoppokakorn
Retrospective 377 patients, 73% reduction in mortality with HCQ+AZ, adjusted hazard ratio HR 0.27 [0.17-0.41]. Mean age 71.8. No serious adverse events. Subject to incomplete adjustment for confounders.
Sep 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1111/cts.12860, https://c19p.org/lauriola
Retrospective 215 patients with chronic hepatitis B in China, showing lower risk of COVID-19 infection, milder symptoms, and faster recovery with ursodeoxycholic acid (UDCA) treatment.
Mar 2024, J. Clinical Hepatology, https://www.lcgdbzz.org/en/article/doi/10.12449/JCH240309, https://c19p.org/cui2
OpenSAFELY retrospective 11,305 primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) patients showing lower risk of COVID-19 hospitalization or death with ursodeoxycholic acid (UDCA) treatment.
Dec 2023, Communications Medicine, https://www.nature.com/articles/s43856-024-00664-y, https://c19p.org/costello
Retrospective 1,212 patients in the USA with a history of seizure-related conditions, showing patients treated with CBD100 had significantly lower incidence of COVID-19 cases compared to a matched control group. In Vitro study showing CBD inhibits SARS-CoV-2 with Vero E6 and Calu-3 cells. Mouse study showing CBD significantly inhibited viral replication in the lung and nasal turbinate. Authors note that CBD does not inhibit ACE2 expression or the main viral proteases, inhibition occurs after viral entry. Authors stress several limitations for use at this time, including purity, quality, and the formulation of products, and potential lung damage based on administration method. Authors recommend clinical trials, but do not mention the existing RCT by Crippa et al.
Jan 2022, Science Advances, https://www.science.org/doi/10.1126/sciadv.abi6110, https://c19p.org/nguyen
HCQ 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administration of HCQ significantly ameliorates inflammatory cytokine secretion and that COVID-19 patients should be administrated HCQ as soon as possible. 42 patients with HCQ 1-4 days from diagnosis, 48 with HCQ 5+ days from diagnosis.
Jul 2020, Infection & Chemotherapy, 2020, https://icjournal.org/DOIx.php?id=10.3947/ic.2020.52.3.396, https://c19p.org/hong
HCQ decreases mortality from 26.4% to 13.5% (HCQ) or 20.1% (HCQ+AZ). Propensity matched HCQ HR 0.487, p=0.009. Michigan 2,541 patients retrospective. Before propensity matching the HCQ group average age is 5 years younger and the percentage of male patients is 4% higher which is likely to favor the treatment and the control respectively in the before-propensity matching results. Some reported limtiations of this study are inaccurate [ijidonline.com]. Corticosteroids were controlled for in the multivariate and propensity analyses as were age and comorbidities including cardiac disease and severity of illness. Age was an independent risk factor associated with mortality. HCQ was independently associated with decreased mortality, distinct from the steroid effect. 91% of all patients began treatment within two days of admission. HCQ was used throughout the study period, limiting time bias. Patients assigned to HCQ group had moderate and severe illness at presentation, which would favor..
Jun 2020, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext, https://c19p.org/arshad
Retrospective 14,921 hospitalized patients in Spain, showing lower mortality with HCQ treatment.
Jan 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261711, https://c19p.org/lavillaolleros
Retrospective 300 hospitalized patients in Saudi Arabia showing HCQ adjusted odds ratio aOR 0.12, p < 0.001.
Nov 2020, Diabetes Research and Clinical Practice, https://www.sciencedirect.com/science/article/pii/S0168822720307956, https://c19p.org/sheshah
Retrospective 13,585 COVID+ patients in the USA, showing lower mortality with metformin use, but no significant difference for ventilation, ICU admission, and hospitalization.
Oct 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0275787, https://c19p.org/morrison
Retrospective 272 nursing home residents showing significantly improved survival after establishing a treatment program including HCQ with or without lopinavir/ritonavir and with the addition of adjuvant and antimicrobial treatments depending on circumstances. HCQ (114 patients), HCQ+LPV/RTV (18 patients), and HCQ+AZ (7 patients). Dosage details are in the supplementary appendix.
Jul 2020, J. Gerontol. A Biol. Sci. Med. Sci., https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glaa192/5879759, https://c19p.org/bernabeuwittel
Prophylaxis study with 334 low-risk healthcare workers in India, showing significantly lower risk of cases with treatment. Symptomatic patients received PCR results, but only some asymptomatic patients did, so there may have been additional asymptomatic cases. There were no severe adverse events.
Jul 2020, J. Family Medicine and Primary Care, https://journals.lww.com/10.4103/jfmpc.jfmpc_1177_21, https://c19p.org/kadnur
RCT 182 COVID-19 exposed patients, 91 treated with daily probiotic Lactobacillus rhamnosus GG starting a median of 3 days from exposure, showing lower symptomatic COVID-19 with treatment. There were no hospitalizations or deaths.
Jan 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.01.04.21268275, https://c19p.org/wischmeyer
Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including vitamin D. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/hunt
RCT 158 severe condition patients in Iraq, 82 treated with melatonin, showing lower mortality, thrombosis, and sepsis with treatment.
Oct 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221007980, https://c19p.org/hasan
RCT 100 outpatients in the USA, showing lower hospitalization and progression with resveratrol, without statistical significance.
Jun 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-13920-9, https://c19p.org/mccreary3
ICMR seroprevalence survey of 500 healthcare workers in India, 279 taking HCQ prophylaxis, showing a significantly lower risk with treatment, and lower severity.
Sep 2020, ResearchGate, https://www.researchgate.net/publication/344221734_Sero-survey_for_health-care_workers_provides_corroborative_evidence_for_the_effectiveness_of_Hydroxychloroquine_prophylaxis_against_COVID-19_infection, https://c19p.org/yadav3
UK Biobank retrospective including 43,610 type 2 diabetes patients, showing lower mortality with metformin use within matched type 2 diabetes patients.
May 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.05.19.23290214, https://c19p.org/araldi
PSM retrospective 804 high-risk, nonhospitalized adults with mild to moderate COVID-19 in China. The study compared outcomes between 317 patients who received azvudine with 487 patients who received standard supportive treatment only. The azvudine group had a lower rate of disease progression (composite of death or COVID-19 hospitalization) at 28 days, as well as a lower rate of COVID-19 hospitalization specifically after adjusting for factors. In addition, azvudine shortened the duration of fever if given within 3 days of symptom onset. However, azvudine treatment was associated with a higher incidence of adverse effects, including mainly mild gastrointestinal and nervous system effects.
Jul 2023, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.28947, https://c19p.org/yang8
RCT hospitalized patients in India, 224 treated with atorvastatin, 225 with aspirin, and 225 with both, showing lower serum interleukin-6 levels with aspirin, but no statistically significant changes in other outcomes. Low dose aspirin 75mg daily for 10 days.
Jul 2022, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-022-07570-5, https://c19p.org/ghati
Small RCT with low-risk patients in the USA showing no significant differences in overall recovery. Minimal details on outcomes are provided in the preprint. Authors note significantly faster resolution of respiratory symptoms when treatment increased vitamin D levels. Baseline vitamin D was relatively high, mean 37±1 ng/mL, 95% >20ng/mL, leaving little room for improvement. Treatment delay is not specified but is likely relatively late based on the symptoms at baseline, PCR testing delay, and exclusion with FLU-PRO scores <1.5. ER/urgent care data from clinicaltrials.gov.
Feb 2022, Nutrition, https://www.sciencedirect.com/science/article/pii/S0899900722003100, https://c19p.org/bishop
RCT late stage patients with COVID-19 pneumonia, 202 treated with nitazoxanide and 203 placebo patients, showing improved recovery, but no significant difference in mortality.
Apr 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.844728/full, https://c19p.org/rocco2
381 patient nigella sativa late treatment RCT: 61% lower ICU admission (p=0.28), 70% shorter hospitalization (p=0.001), and 67% improved recovery (p=0.001).
RCT 358 hospitalized patients in Iran, 184 receiving treatment with a combination of nigella sativa and several other herbal medicines, showing shorter hospitalization time and improved recovery with treatment. IR.TUMS.VCR.REC.1399.024.
Oct 2021, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7277, https://c19p.org/karimi
Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity, depression, anxiety, stress, and poor health-related quality of life.
Nov 2023, Diseases, https://www.mdpi.com/2079-9721/11/4/165, https://c19p.org/pavlidou
Analysis of 241 adults >65yo in Belgium, showing lower risk of COVID-19 with a history of physical activity.
Oct 2021, Aging Clinical and Experimental Research, https://link.springer.com/10.1007/s40520-021-01991-z, https://c19p.org/lengele
80 patient favipiravir late treatment study: 69% lower pneumonia (p=0.04) and 71% improved viral clearance (p=0.03).
Comparison of 35 FPV patients and 35 LPV/RTV patients, showing significant improvements in chest CT and faster viral clearance with FPV.
Mar 2020, Engineering, https://www.sciencedirect.com/science/article/pii/S2095809920300631, https://c19p.org/cai
Retrospective 520 COVID-19 patients in Spain, showing significantly lower mortality with a history of physical activity.
Mar 2022, Infectious Diseases and Therapy, https://link.springer.com/article/10.1007/s40121-021-00418-6/fulltext.html, https://c19p.org/salgadoaranda
Retrospective 421 hospitalized COVID-19 patients with type 2 diabetes in India, showing significantly lower mortality with metformin use compared to other antidiabetic medications.
Nov 2024, Annals of Medicine, https://www.tandfonline.com/doi/full/10.1080/07853890.2024.2425829, https://c19p.org/somasundaram
499 patient favipiravir late treatment RCT: 26% lower mortality (p=0.24), 24% lower ventilation (p=0.21), and 6% improved recovery (p=0.53).
PIONEER very late treatment RCT showing lower mortality and mechanical ventilation with favipiravir, without statistical significance. The conclusion "favipiravir is not efficacious in treating hospitalised adult patients with COVID-19" is incorrect. Authors show 26% and 24% lower mortality and mechanical ventilation. While these results are not statistically significant, they predict efficacy, and cannot be used to rule out efficacy. Favipiravir 1,800mg bid day 1, 800mg bid days 2-10.
Sep 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S221326002200412X, https://c19p.org/shah5
RCT 143 healthcare workers in Iran, showing lower cases with HCQ prophylaxis, statistically significant only for moderate/severe cases. Baseline details are not provided.
Jan 2023, Advanced Biomedical Research, https://www.advbiores.net/article.asp?issn=2277-9175;year=2023;volume=12;issue=1;spage=3;epage=3;aulast=Nasri, https://c19p.org/nasri
RCT 140 patients, 70 treated with curcumin and piperine (for absorption), and 70 treated with probiotics, showing faster recovery, lower progression, and lower mortality with curcumin.
May 2021, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2021.669362/full, https://c19p.org/pawar
PSM matched analysis from consecutive hospitalized patients, with 33 colchicine and 33 control matched patients, showing lower mortality with treatment.
Sep 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/9/2961, https://c19p.org/brunetti
Prospective cohort study of hospitalized patients in the USA, 34 treated with colchicine, showing lower mortality and intubation with treatment.
Oct 2020, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2020/8865954/, https://c19p.org/sandhu
COVID-OUT remotely operated RCT, showing lower combined ER/hospitalization/death with metformin. Results for other treatments are listed separately - ivermectin , fluvoxamine . The "control" group includes patients receiving active treatments fluvoxamine and ivermectin. Control arm results are very different between treatments, for example considering hospitalization/death, this was 1.0% for ivermectin vs. 2.7% for overall control, however it was 1.3% for the ivermectin-specific control. 394 control patients are shared. The rate for the non-shared 261 metformin control patients is 5%, compared to 1.3% for ivermectin control patients. The metformin arm started earlier, however it is unclear why the difference in outcomes is so large. Results were delayed for 6 months with no explanation, with followup ending Feb 14, 2022. Adherence was very low, with 77% overall reporting 70+% adherence. Numbers for 100% adherence are not provided. Multiple outcomes are missing, for example time to..
Aug 2022, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2201662, https://c19p.org/covidoutmf
Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality. mortality at 28 days relative risk RR 0.54 [0.21-1.42] combined mortality/intubation at 28 days relative risk RR 0.74 [0.33-1.70] If not stopped early and the same trend continued, statistical significance would be reached on 28 day mortality after ~550 patients (1,300 patients were planned). Mortality results are not provided for subgroups. For the subgroups receiving AZ: No safety concerns were identified. This study has been presented as negative, however the results do not support that conclusion.
Oct 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X21001403, https://c19p.org/dubee
197 CQ patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events.
May 2020, National Science Review, https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa113/5848167, https://c19p.org/huangnsr
PSM retrospective 1072 hospitalized patients with COVID-19 pneumonia in China, showing lower mortality with azvudine treatment.
Jul 2023, Acta Pharmaceutica Sinica B, https://www.sciencedirect.com/science/article/pii/S2211383523002575, https://c19p.org/zong
Retrospective diabetic COVID-19 patients in Italy, showing lower risk of hospitalization with metformin use.
Jun 2023, Nutrition, Metabolism and Cardiovascular Diseases, https://www.sciencedirect.com/science/article/pii/S0939475323002491, https://c19p.org/piarulli
Retrospective study of 287 nursery school children in Italy, 186 treated with S. salivarius K12 probiotic. The probiotic group had significantly lower rates of COVID-19, bronchitis, sinusitis, and laryngitis as well as lower antibiotic use. The study was registered retrospectively and details of COVID-19 diagnosis are not provided. Parents that administer the treatment may also use other treatments or take other actions that reduce risk for their children.
Sep 2023, Minerva Medica, https://www.minervamedica.it/index2.php?show=R10Y9999N00A23092804, https://c19p.org/dipierro7
RCT 44 treatment and 43 control patients with vitamin D levels <30ng/ml, showing significant reduction in inflammatory markers with treatment of 60,000IU vitamin D per day for 8 days (10 days for BMI >25). Death and ICU admission was lower in the treatment group but not statistically significant. Randomization was simple alternation, with the allocation officer unaware of which group patients were being assigned to as detailed in the study. An earlier version of this study was censored based on incorrect claims from an anti-treatment researcher. For discussion see [c19early.org].
Jul 2022, Archives of Clinical and Biomedical Research, https://www.fortunejournals.com/articles/effect-of-short-term-high-dose-oral-vitamin-d-therapy-on-the-inflammatory-markers-in-patients-with-covid-19-disease.html, https://c19p.org/lakkireddy
Retrospective 270 moderate/severe hospitalized COVID-19 patients, showing lower mortality with high (25 g/day) or low-dose (2 g/day) intraveneous vitamin C.
Nov 2024, Inflammopharmacology, https://link.springer.com/10.1007/s10787-024-01597-7, https://c19p.org/uz
RCT 23 early COVID-19 outpatients showing significantly improved reduction in viral load and significantly faster viral clearance with povidone-iodine nasal spray compared to placebo. The study was underpowered due to low recruitment, enrolling only 23 patients from a target of 144. Authors report generally mild symptoms and a 6% benefit over placebo on symptom scores (AUC symptom score days 2–5) without statistical significance, but do not provide details. Notably, no benefit was seen for rapid antigen test positivity, which is unable to distinguish viable and non-viable virus. The relatively poor diagnostic information from viral positivity using methods that cannot distinguish viable virus may present misleading results in many COVID-19 studies. Treatment 8 times daily for a total of 20 doses.
Mar 2024, The Laryngoscope, https://onlinelibrary.wiley.com/doi/10.1002/lary.31430, https://c19p.org/friedland2
568 patient exercise study: 71% lower severe cases (p=0.001).
Retrospective 568 convalescent COVID-19 patients in Poland, showing lower risk of severe cases with regular physical activity in the 3 months before COVID-19.
Dec 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034122003495, https://c19p.org/kapusta
Retrospective 1,606 SLE patients showing lower risk of severe COVID-19 outcomes with HCQ/CQ use.
Feb 2022, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2022/02/15/annrheumdis-2021-221636.long, https://c19p.org/ugartegil
RCT 60 outpatients with mild COVID-19 showing improved viral clearance with hypertonic alkaline (pH 9.3) nasal irrigation. All patients received HCQ. The nasal irrigation group had no hospitalizations, while 3 patients in the control group required hospitalization, associated with viral load increase at day 3.
Nov 2021, Laryngoscope Investigative Otolaryngology, https://onlinelibrary.wiley.com/doi/10.1002/lio2.686, https://c19p.org/yilmaz4
21,026 patient famotidine prophylaxis PSM study: 36% fewer cases (p<0.0001).
PSM retrospective in South Korea, showing lower risk of COVID-19 cases with H2RA (including famotidine) and PPI use, but no significant difference in severe outcomes (results provided for the combined groups only).
Mar 2023, J. Korean Medical Science, https://jkms.org/DOIx.php?id=10.3346/jkms.2023.38.e99, https://c19p.org/kim11
Retrospective propensity score matched cohort study of 225 chronic liver disease patients on UDCA therapy matched to 225 controls without UDCA in China. UDCA use was associated with lower COVID-19 infection rate (85% vs 94%), lower maximum temperature, less severe symptoms, shorter recovery time (5 vs 7 days median), and lower risk of infection on regression (OR 0.32). The results rely on patient self-report rather than lab confirmed COVID-19 diagnosis.
May 2023, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2023.1178590/full, https://c19p.org/li26
Prospective multicenter study of 209 severe hospitalized COVID-19 patients in China showing improved 28-day composite outcomes, faster viral clearance, and higher PaO2/FiO2 levels with azvudine plus dexamethasone compared to dexamethasone alone.
Nov 2024, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2024.1390098/full, https://c19p.org/zhang39
RCT 155 hospitalized patients showing no significant differences with camostat.
Sep 2022, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02518-7, https://c19p.org/kinoshita
PSM retrospective 6,217 hospitalized patients in Spain, showing lower mortality with HCQ. The higher efficacy reported with obesity is consistent with the greater efficacy predicted for higher cholesterol [Yuan].
Sep 2022, Anti-Infective Agents, https://www.eurekaselect.com/204783/article, https://c19p.org/nunezgil2
Small RCT for severe COVID-19 comparing the addition of ivermectin to SOC (low dose HCQ+AZ+favipiravir), with 30 treatment and 30 control patients in Turkey, showing lower mortality and faster clinical recovery. Authors also investigate the presence of gene mutations that alter ivermectin metabolism, predicting that ivermectin can be used safely without serious side effects in patients without MDR-1/ABCB1 and/or CYP3A4 gene mutation, and recommending monitoring and appropriate treatment if necessary when sequencing is unavailable. NCT04646109.
Jan 2021, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06104-9, https://c19p.org/okumus
100% reduction in cases with HCQ+zinc post-exposure prophylaxis. Brief report for healthcare workers in Bulgaria. 0 cases with treatment vs. 3 for control. 156 treatment patients and 48 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297520301657, https://c19p.org/simovapep
82,069 patient fluvoxamine prophylaxis PSM study: 28% fewer cases (p<0.0001).
TriNetX PSM retrospective 82,069 OCD patients, showing lower risk of COVID-19 with fluvoxamine use.
Oct 2022, The Primary Care Companion For CNS Disorders, https://www.psychiatrist.com/pcc/ocd/protective-effect-fluvoxamine-covid-19-obsessive-compulsive-disorder-real-world-case-control-study/, https://c19p.org/diaz3
Retrospective 8,075 hospitalized patients, 4,542 low-dose HCQ, 3,533 control. 35% lower mortality for HCQ (17.7% vs. 27.1%), adjusted HR 0.68 [0.62–0.76]. Low-dose HCQ monotherapy was independently associated with lower mortality in hospitalized patients. Patients exposed to others therapies (TCZ, AZ, LPV/RTV) were excluded. Statistical analysis was performed by an independent group. Calendar time of prescription and immortal time bias was taken into account. Corticosteroids prescriptions was low in both groups.
Aug 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920303423, https://c19p.org/catteau
79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. No cardiac side effects. Retrospective 518 patients (141 treated, 377 control).
Jul 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304258, https://c19p.org/derwand
11,672 patient melatonin prophylaxis study: 58% fewer cases (p<0.0001).
Retrospective 11,672 patients tested for COVID-19 with 818 testing positive, showing significantly lower risk with melatonin use.
Jun 2020, Chest, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286244/, https://c19p.org/jehi
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3ib
RCT 105 hospitalized patients with mild-to-moderate COVID-19, evaluating the efficacy and safety of local thermotherapy (heating pads applied to the chest for 90 minutes twice daily for 5 days) to prevent disease progression, compared to standard care alone. The thermotherapy was well-tolerated with no significant adverse events. Reduction in NEWS-2 score was significantly faster with treatment. There was lower progression and mortality with treatment, without statistical significance. The study was underpowered due to early termination. The temperature used may be too low. Lung temperature is expected to be lower than the external skin surface temperature measured on the thorax, due to heat diffusion and dissipation that occurs in transferring thermal energy across the tissue layers of skin, adipose, muscle, connective tissue and bone between the heating pad and the lung. The treatment group had greater severity at baseline, NEWS-2 7 vs. 5, and PH-COVID-19 high-risk 7.5% vs. 0%...
Dec 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1256197/full, https://c19p.org/mancillagalindo2
RCT with 80 colchicine and 80 control patients, showing improved recovery with treatment. SOC included vitamin C, vitamin D, and zinc.
Apr 2022, Annals of Medicine and Surgery, https://www.sciencedirect.com/science/article/pii/S2049080122003533, https://c19p.org/gorial2
RCT 205 hospitalized patients showing no significant benefit with camostat. There was a trend towards lower risk of ICU admission or death in the camostat group (10% vs. 18% for placebo), but the study was not powered for this endpoint. Viral load and inflammatory markers were not significantly different between groups. The study was underpowered due to faster than expected clinical improvement.
May 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537021001292, https://c19p.org/gunst
Retrospective 2,070 hospitalized patients in the USA, showing lower mortality with aspirin treatment.
Sep 2021, Anesthesiology, https://pubs.asahq.org/anesthesiology/article-abstract/doi/10.1097/ALN.0000000000003999/117698/Treatments-Associated-with-Lower-Mortality-among?redirectedFrom=fulltext, https://c19p.org/zhao5
Retrospective 5,338 individuals with confirmed contact with a COVID-19 patient, showing lower risk of COVID-19 with exercise.
Jun 2023, Sports Medicine - Open, https://sportsmedicine-open.springeropen.com/articles/10.1186/s40798-023-00592-6, https://c19p.org/schmidt3
96 patient RCT showing faster resolution of post-COVID anosmia with an ivermectin nanosuspension nasal spray.
Sep 2022, Infection and Drug Resistance, https://www.dovepress.com/possible-role-of-ivermectin-mucoadhesive-nanosuspension-nasal-spray-in-peer-reviewed-fulltext-article-IDR, https://c19p.org/aref2
91% reduction in COVID-19 cases with ivermectin prophylaxis. 118 healthcare workers in Bangladesh, 58 receiving ivermectin 12mg monthly, showing RR 0.094, p < 0.0001.
Dec 2020, European J. Medical and Health Sciences, https://ejmed.org/index.php/ejmed/article/view/599, https://c19p.org/alam2
Update: we have not received details for treatment delay. An author reports that treatment initiation time was not recorded: [osf.io]. Conflicting estimates are provided in a comment of the article and independent analysis, with reports indicating missing data in the dataset. Also see [medrxiv.org] (companion PEP trial), and Pullen et al. [ncbi.nlm.nih.gov], which shows shipping delay for these trials of 19 - 68 hours. Only one third of participants completed enrollment weekdays between 8:00am and 4:00pm, with 44% outside of these hours during the week, and 22% during the weekend. With enrollment up to 4 days after symptom onset, this implies delivery 19 - 164 hours after onset (19 hours would require instantaneous enrollment). ~70 to 140 hour (inc. shipping) delayed outpatient treatment with HCQ showing lower hospitalization/death and faster recovery, but not reaching statistical significance. There was one hospitalized control death and one non-hospitalized HCQ death. It is unclear..
Jul 2020, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M20-4207, https://c19p.org/skipper
Retrospective 1,675,593 patients in the Jeonbuk CDM cohort and 8,528,533 patients in the NHIS cohort, showing ursodeoxycholic acid (UDCA) intake associated with significantly lower risk of COVID-19 infection and severe COVID-19.
Aug 2024, JMIR Public Health and Surveillance, http://preprints.jmir.org/preprint/59274/accepted, https://c19p.org/lee16
62 patients. RCT showing significantly faster recovery with HCQ. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% of treated patients and 16% of control patients.
Mar 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3, https://c19p.org/chenrct
117 patient camostat late treatment RCT: 8% lower progression (p=1) and 40% higher hospital discharge (p=0.04).
RCT 117 hospitalized patients with moderate COVID-19 pneumonia in Japan, showing a shorter time to discharge with favipiravir, camostat, and ciclesonide combination therapy compared to favipiravir monotherapy. Subgroup analysis showed greater benefit in patients ≤60 years old and those with less severe disease not requiring oxygen. There were no significant differences between groups in clinical findings, laboratory values, or adverse events. The mortality numbers in the main results table and the text are different, without explanation.
Jun 2022, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537022002140, https://c19p.org/terada
Retrospective 164 COVID-19 patients and 188 controls in China, showing the risk of severe cases associated with lack of sleep.
Nov 2021, Nature and Science of Sleep, https://www.dovepress.com/reduced-sleep-in-the-week-prior-to-diagnosis-of-covid-19-is-associated-peer-reviewed-article-NSS, https://c19p.org/huang5sl
Retrospective 200 severe condition hospitalized patients in Italy, 88 treated with probiotic Sivomixx, showing lower mortality with treatment.
Jan 2021, Frontiers in Medicine, https://internal-journal.frontiersin.org/articles/10.3389/fnut.2020.613928/full, https://c19p.org/ceccarelli
Retrospective 3,729 rheumatic disease patients showing lower risk of mortality with HCQ/CQ use (HCQ/CQ vs. no DMARD therapy).
Jan 2021, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/80/7/930, https://c19p.org/strangfeld
RCT 55 mild/moderate patients in China, showing shorter hospitalization with sodium bicarbonate nasal irrigation and oral rinsing. Oral rinse with 5% sodium bicarbonate solution three times daily. Nasal irrigation two times with the solution entering through one nostril and exiting from the other. 30–40mL of solution was used every time and irrigation was performed for at least 30s. Details of randomization are not provided.
Mar 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1145669/full, https://c19p.org/wang12
RCT 55 mild/moderate patients in China, showing shorter hospitalization with sodium bicarbonate nasal irrigation and oral rinsing. Oral rinse with 5% sodium bicarbonate solution three times daily. Nasal irrigation two times with the solution entering through one nostril and exiting from the other. 30–40mL of solution was used every time and irrigation was performed for at least 30s. Details of randomization are not provided.
Mar 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1145669/full, https://c19p.org/wang12sb
Retrospective patients with rheumatologic conditions showing zero of 10,703 COVID-19 deaths for HCQ patients versus 7 of 21,406 propensity matched control patients (not statistically significant). The average age of HCQ patients is slightly lower 64.8 versus 65.4 control. COVID-19 cases OR 0.79, p=0.27. There are several significant differences in the propensity matched patients that could affect results, e.g., 20.9% SLE versus 24.7%.
Sep 2020, Lancet Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30305-2/fulltext, https://c19p.org/gentry
262 patient colchicine late treatment study: 85% lower mortality (p<0.0001).
Retrospective 122 colchicine patients and 140 control patients in Italy, showing lower mortality with treatment.
Sep 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/79/10/1286, https://c19p.org/scarsi
Retrospective 100 COVID+ elderly nursing home patients, HCQ+AZ mortality 11.4% vs. control 61.9%, RR 0.18, p<0.001. Median age 85.
Sep 2020, European Geriatric Medicine, https://link.springer.com/article/10.1007/s41999-020-00432-w, https://c19p.org/heras
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin D prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimer
Retrospective 64,892 veterans with diabetes in the USA, showing lower mortality with existing metformin use.
Oct 2021, Diabetes Care, https://care.diabetesjournals.org/content/early/2021/10/06/dc21-1351.article-info, https://c19p.org/wander
87 patient dutasteride antiandrogen early treatment RCT: 62% improved recovery (p=0.009).
RCT 130 outpatients in Brazil, 54 treated with dutasteride, showing faster recovery with treatment. All patients received nitazoxanide. There were no hospitalizations, mechanical ventilation, or deaths. Some percentages for viral clearance in Table 3 do not match the group sizes, and a third-party analysis suggests possible randomization failure. 34110420.2.0000.0008.
Jan 2021, Cureus, https://www.cureus.com/articles/50511-early-antiandrogen-therapy-with-dutasteride-reduces-viral-shedding-inflammatory-responses-and-time-to-remission-in-males-with-covid-19-a-randomized-double-blind-placebo-controlled-interventional-trial-eat-duta-androcov-trial---biochemical, https://c19p.org/cadegiani7
1,991 patient alcohol study: 50% fewer cases (p=0.05).
Retrospective survey of 1,997 college students in the USA, showing higher risk of COVID-19 cases with alcohol consumption.
Feb 2022, JMIR Mental Health, https://mental.jmir.org/2022/2/e34645, https://c19p.org/gilleyac
Retrospective 452 participants in Luxembourg, showing lower risk of moderate cases with higher physical activity.
Apr 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2021-057863, https://c19p.org/malisoux
Analysis of 3,947 participants in Vietnam, showing significantly lower risk of COVID-19-like symptoms with physical activity and with a healthy diet. The combination of being physically active and eating healthy reduced risk further compared to either alone. The analyzed period was Feb 14 to Mar 2, 2020, which may have been before testing was widely available.
Sep 2021, Nutrients, https://www.mdpi.com/2072-6643/13/9/3258, https://c19p.org/nguyen2
Retrospective 188 hospitalized patients in Brazil, showing lower risk of mortality with metformin use. Authors note that, although pre-hospital metformin use improved clinical parameters at admission, continuous use during hospitalization is essential. Patients that used pre-hospital metformin therapy but interrupted the treatment during hospitalization showed higher mortality than those that continued metformin therapy.
Jul 2021, Diabetology & Metabolic Syndrome, https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-021-00695-8, https://c19p.org/tamura
636 patients. HCQ+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.
Apr 2020, Prevent Senior Institute, São Paulo, Brazil, https://pgibertie.com/wp-content/uploads/2020/04/2020.04.15-journal-manuscript-final.pdf, https://c19p.org/esper
RCT 300 hospitalized COVID-19 patients in Pakistan receiving either 4,000 IU vitamin D3 supplementation or standard care daily for 14 days. The vitamin D group had significantly faster time to clinical improvement (7 vs 9 days) and shorter length of stay (9 vs 11 days). 65% of patients were vitamin D deficient at baseline.
Jun 2023, Biological and Clinical Sciences Research J., https://bcsrj.com/ojs/index.php/bcsrj/article/view/322, https://c19p.org/salman
Retrospective 3,451 hospitalized patients, 30% reduction in mortality with HCQ after propensity adjustment, HR 0.70 [0.59 - 0.84].
Aug 2020, European J. Internal Medicine, https://www.sciencedirect.com/science/article/abs/pii/S0953620520303356, https://c19p.org/dicastelnuovo
Retrospective 288 hemodialysis patients in Spain, 137 with existing vitamin D treatments (94 with paricalcitol), showing lower mortality with treatment. There was no significant difference in outcomes based on serum levels, however authors do not separate patients that received vitamin D treatment.
Jul 2021, Nutrients, https://www.mdpi.com/2072-6643/13/8/2559, https://c19p.org/jimenez
Small RCT 22 hospitalized COVID-19 patients with cardiovascular disease in Argentina showing lower mortality, ventilation, and ICU admission with vitamin D treatment, without statistical significance. Treatment was associated with lower levels of inflammatory markers IL-6, IL-8 and TNF-α, higher levels of anti-inflammatory IL-10, and improvements in gut microbiome markers. 10,000 IU/day vitamin D3 for 10 days.
Jun 2024, Hipertensión y Riesgo Vascular, https://www.sciencedirect.com/science/article/pii/S1889183724000564, https://c19p.org/sanz
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297521000792, https://c19p.org/cadegiani
52 patient RCT in the USA with nigella sativa component thymoquinone, showing improved recovery with treatment. There was a significantly faster decline in the total symptom burden, and a significant increase in CD8+ and helper CD4+ central memory T lymphocytes. The treatment group contained 5 more vaccinated patients and 7 more overweight patients. Authors also present in vitro results showing an inhibitory effect with five SARS-CoV-2 variants including omicron.
May 2022, Pathogens, https://www.mdpi.com/2076-0817/11/5/551, https://c19p.org/bencheqroun
Retrospective 318 pregnant women, 54 COVID+ and 264 healthy controls, showing lower risk of COVID-19 with vitamin D supplementation, and with higher vitamin D levels.
Dec 2022, Cukurova Anestezi ve Cerrahi Bilimler Dergisi, https://dergipark.org.tr/en/doi/10.36516/jocass.1185181, https://c19p.org/sengul
Retrospective 351 hospitalized COVID-19 patients with pre-existing cardiovascular diseases in China, showing lower mortality with azvudine treatment.
Mar 2024, Advanced Science, https://onlinelibrary.wiley.com/doi/10.1002/advs.202306050, https://c19p.org/wu10
Retrospective 283 COVID-19+ diabetes patients in China, showing lower mortality with existing metformin treatment.
May 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/configurable/content/journals$002ftpmd$002f103$002f1$002farticle-p69.xml?t:ac=journals%24002ftpmd%24002f103%24002f1%24002farticle-p69.xml, https://c19p.org/luo3
Retrospective phone survey of 1,486 Parkinson's disease patients in Italy, showing lower risk of COVID-19 cases with vitamin D supplementation. This paper also presents a case control study of PD patients and family member control patients.
Jun 2021, Movement Disorders, https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28176, https://c19p.org/fasano
Small RCT 116 mITT patients in the USA, 59 treated with favipiravir, showing no significant differences with treatment.
Nov 2021, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac312/6572081, https://c19p.org/holubar
Analysis of 868 patients on renal replacement therapy. Statistically significant reduction in mortality with HCQ for patients on dialysis (OR 0.47, p=0.005). No statistically significant change was found for transplant patients (the result is not given but likely the sample size is too small - the number of transplant patients was half the number of dialysis patients).
Apr 2020, Nefrología, https://www.sciencedirect.com/science/article/pii/S201325142030050X, https://c19p.org/sanchezalvarez
Retrospective 638 matched hospitalized patients in the USA, 319 treated with aspirin, showing lower mortality with treatment.
Jan 2021, American J. Hematology, https://onlinelibrary.wiley.com/doi/10.1002/ajh.26102, https://c19p.org/meizlish
Retrospective 5,712 COVID-19 patients in the USA, showing higher risk of COVID-19 hospitalization with a history of physical inactivity.
May 2021, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2020-044052, https://c19p.org/lobelo
Retrospective 932 patients showing that the addition of zinc to HCQ+AZ reduced mortality / transfer to hospice, ICU admission, and the need for ventilation.
May 2020, J. Medical Microbiology, https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.001250, https://c19p.org/carlucciz
Retrospective 6,462 liver cirrhosis patients in South Korea, with 67 COVID+ cases, showing significantly lower cases with spironolactone treatment. Death and ICU results per group are not provided.
Feb 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.629176/full, https://c19p.org/jeon
Retrospective 6,462 liver cirrhosis patients in South Korea, with 67 COVID+ cases, showing significantly lower cases with spironolactone treatment. Death and ICU results per group are not provided.
Feb 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.629176/full, https://c19p.org/jeonsp
Retrospective 4,868 elderly COVID-19 patients in Japan, showing higher risk of severe cases with poor physical activity status.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277144, https://c19p.org/tsuzuki3
Retrospective 1,040 outpatients in China showing lower COVID-19 cases, less severe symptoms, and shorter symptom duration with ursodeoxycholic acid (UDCA) use.
Jul 2024, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2024.1381830/full, https://c19p.org/li36
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3mf
Retrospective 976 mild to moderate COVID-19 outpatients in Thailand showing significantly lower household transmission with favipiravir treatment of index cases.
Dec 2024, J. Virus Eradication, https://www.sciencedirect.com/science/article/pii/S2055664024001912, https://c19p.org/siripongboonsitti7
Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including anti-androgens. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/huntaa
Retrospective 207 hospitalized patients in Turkey, 37 with vitamin D levels <30ng/ml treated with a single dose of 300,000IU vitamin D, showing lower mortality with treatment.
Sep 2021, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7390&category_id=171&option=com_virtuemart&vmcchk=1&Itemid=1, https://c19p.org/yildiz
Retrospective survey of 938 COVID-19 recovered patients in Brazil, showing lower hospitalization with physical activity. NCT04396353.
Sep 2021, J. Science and Medicine in Sport, https://www.jsams.org/article/S1440-2440(21)00136-5/fulltext, https://c19p.org/desouza
Randomized controlled trial of 111 hospitalized COVID-19 patients in Iran showing significantly shorter hospital stay, higher oxygen saturation, and lower respiratory rate at discharge with azithromycin plus hydroxychloroquine and lopinavir/ritonavir compared to hydroxychloroquine and lopinavir/ritonavir alone. There were no significant differences in ICU admission, intubation, or mortality, although there was a trend towards lower ICU admission with azithromycin (3.6% vs. 12.7%, p = 0.07). Patients with prior cardiac disease were excluded. The study is limited by the small sample size and open-label design.
Oct 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920303411, https://c19p.org/sekhavatiaz
RCT 180 hospitalized COVID-19 patients showing improved cough frequency and severity with gabapentin and gabapentin/montelukast compared to dextromethorphan, with the combination being more efficacious. The gabapentin/montelukast group had a significantly greater reduction in cough frequency (measured by the Breathlessness, Cough, and Sputum Scale) compared to the gabapentin alone group. There was no significant difference between the two groups in cough severity reduction measured by Visual Analog Scale.
Jul 2022, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13529, https://c19p.org/soltani2
RCT with 56 cholecalciferol and 54 control hospitalized patients with vitamin D insufficiency or deficiency in Russia, showing positive effects on immune status. The median age in the treatment group was 7 years lower and deficiency was less common, while baseline treatment group CT lung involvement and supplemental oxygen use was higher in the treatment group. Treatment increased vitamin D levels and neutrophil and lymphocyte counts, decreased CRP levels, and was associated with a decrease in CD38++CD27 transitional and CD27−CD38+ mature naive B cells and an increase in CD27−CD38− DN B cells.
Jun 2022, Nutrients, https://www.mdpi.com/2072-6643/14/13/2602, https://c19p.org/karonova5
RCT 63 mild COVID-19 patients showing lower progression and improved viral clearance with andrographis, without statistical significance.
Jul 2021, Archives of Internal Medicine Research, https://www.fortunejournals.com/articles/efficacy-and-safety-of-andrographis-paniculata-extract-in-patients-with-mild-covid19-a-randomized-controlled-trial.html, https://c19p.org/wanaratna
Prospective study with 125 favipiravir patients and 125 patients declining favipiravir treatment, showing lower mortality and improved recovery with treatment. All patients received vitamin C, D, and zinc. Favipiravir 3200mg day 1, followed by 600mg bid days 2-10.
May 2022, Int. J. Applied Sciences: Current and Future Research Trends, https://ijascfrtjournal.isrra.org/index.php/Applied_Sciences_Journal/article/view/1235, https://c19p.org/qadir
Analysis of 39,915 patients with 1,768 COVID+ cases based on surveys in the Nurses' Health Study II, showing higher UVA/UVB exposure associated with lower risk of COVID-19 cases.
Dec 2021, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqab389/6448988, https://c19p.org/ma2sun
Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (p=0.001) and mortality (p=0.38) with HCQ.
Feb 2021, Revue des Maladies Respiratoires, https://www.sciencedirect.com/science/article/pii/S0761842521000383, https://c19p.org/ouedraogo
Prospective analysis of 95 Lupus Nephritis patients in Romania, showing lower risk of COVID-19 with HCQ use.
Sep 2022, Biomedicines, https://www.mdpi.com/2227-9059/10/10/2423, https://c19p.org/obrisca
Retrospective 1,274 outpatients, 47% reduction in hospitalization with HCQ with propensity matching, HCQ OR 0.53 [0.29-0.95]. Sensitivity analyses revealed similar associations. Adverse events were not increased (2% QTc prolongation events, 0% arrhythmias).
Aug 2020, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-05773-w, https://c19p.org/ip
523 patient vitamin D late treatment study: 80% lower mortality (p=0.001).
80% lower mortality with cholecalciferol booster therapy. Retrospective 986 hospitalized patients in the UK finding that cholecalciferol booster therapy, regardless of baseline serum levels, was associated with a reduced risk of mortality in acute COVID-19 inpatients. Primary cohort of 444 patients, adjusted mortality odds ratio aOR 0.13, p < 0.001. Validation cohort of 541 patients, adjusted mortality odds ratio aOR 0.38, p = 0.018.
Dec 2020, Nutrients, https://www.mdpi.com/2072-6643/12/12/3799, https://c19p.org/ling
Retrospective 537 patients in Spain, 79 treated with calcifediol, showing significantly lower mortality with treatment. The treated group had a higher risk of comorbidity, whereas the control group had lower O2 saturation, higher CURB-65, and higher ARDS (severity measures were included in the multivariate analysis).
May 2021, Nutrients, https://www.mdpi.com/2072-6643/13/6/1760, https://c19p.org/alcaladiaz
RCT with 77 nitazoxanide, 70 sofosbuvir/ledipasvir, and 73 SOC patients in Egypt, showing faster viral clearance with nitazoxanide and with sofosbuvir/ledipasvir. There was no mortality or progression to severe COVID-19 or ICU admission. Nitazoxanide 500mg qid for 14 days. SOC included vitamin C and zinc.
May 2022, Arab J. Gastroenterology, https://www.sciencedirect.com/science/article/pii/S1687197922000326, https://c19p.org/medhat
Retrospective 219 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment.
Jan 2021, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2020.600439/full, https://c19p.org/crouse
Retrospective 383 hospitalized COVID-19 patients in Argentina showing signifcantly lower mortality and shorter hospital stay with nebulized sodium ibuprofenate compared to 195 contemporaneous controls. The treatment appears to be the same as detailed in [Kalayan], which reports a pH of 8.5. [Kreutzberger] showed that SARS-CoV-2 requires an acidic pH (between 6.2-6.8) for membrane fusion and cell entry, even when the viral spike protein is primed by proteases like TMPRSS2. Efficacy seen here may be more due to alkalinization, which shows more consistent higher efficacy than ibuprofen in studies to date. Baseline SpO2 was significantly different for the patients on mechanical ventilation at baseline.
Aug 2021, Infectious Diseases and Therapy, https://link.springer.com/10.1007/s40121-021-00527-2, https://c19p.org/salvaph
Retrospective 40 favipiravir patients in Kazakhstan and 40 controls, showing faster recovery and viral clearance with treatment.
Aug 2021, , https://newjournal.ssmu.kz/upload/iblock/026/6_15_4_23_2021.pdf, https://c19p.org/kulzhanova
Retrospective 120 hospitalized COVID-19 patients with persistent cough in India, showing faster resolution of cough, shorter duration of oxygen support, and shorter hospitalization with inhaled budesonide treatment compared to standard of care alone.
Mar 2022, Int. J. Scientific Development and Research, https://mail.ijsdr.org/viewpaperforall.php?paper=IJSDR2203020, https://c19p.org/bhandari2
Retrospective 1,915 rheumatic disease patients with COVID-19 in Argentina, showing lower mortality, severe oxygen requirement, and hospitalization with CQ/HCQ (antimalarial) use in unadjusted results, statistically significant only for severe oxygen requirement.
Oct 2022, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-022-06393-8, https://c19p.org/isnardi
Prospective analysis of 32,249 women, showing lower risk of PASC with a healthy lifestyle, in a dose-dependent manner. Participants with 5 or 6 healthy lifestyle factors had significantly lower COVID-19 hospitalization and PASC. BMI and sleep were independently associated with risk of PASC.
Feb 2023, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2800885, https://c19p.org/wang10ex
Retrospective 4,631 hospitalized patients in New York, showing higher mortality with remdesivir, and lower mortality with HCQ. Authors suggest that increased mortality during the first epidemic wave was partly due to strain on hospital resources.
Aug 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac436/6675651, https://c19p.org/bowen
Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 [0.45-0.92].
Dec 2020, The Lancet Regional Health - Europe, https://www.sciencedirect.com/science/article/pii/S2666776220300193, https://c19p.org/taccone
Retrospective analysis of retirement homes, HCQ+AZ >= 3 days mortality OR 0.37, p=0.02. 1,690 elderly residents (mean age 83), 226 infected residents, 116 treated with HCQ+AZ >= 3 days. Detection via mass screening also showed significant improvements (16.9% vs. 40.6%, OR 0.20, p=0.001), suggesting that earlier detection and treatment is more successful.
Aug 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920304301, https://c19p.org/ly
Retrospective 3,038 bariatric surgery patients in Israel, showing higher risk of SARS-CoV-2 infection with vitamin D deficiency, and lower risk with physical activity.
Jun 2023, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/12/4054, https://c19p.org/frishex
Retrospective 2,011 hospitalized patients in France, median age 67, showing lower mortality with HCQ+AZ, and further benefit with the addition of zinc.
Jun 2021, Therapeutics and Clinical Risk Management, https://www.dovepress.com/outcomes-of-2111-covid-19-hospitalized-patients-treated-with-hydroxych-peer-reviewed-fulltext-article-TCRM, https://c19p.org/lagier2
Retrospective study of the 31 onchocerciasis-endemic countries using the community-directed treatment with ivermectin (CDTI) and the 22 non-endemic countries in Africa, showing significantly lower mortality per capita in the countries using ivermectin.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.26.21254377v1, https://c19p.org/tanioka
Retrospective 2,224 healthcare workers in India, showing lower risk of seropositivity with HCQ prophylaxis, without statistical significance.
Jul 2022, Indian J. Community Medicine, http://www.ijcm.org.in/text.asp?2022/47/2/202/350357, https://c19p.org/yadav4
RCT 98 hospitalized patients in the USA, 49 treated with aspirin and dipyridamole, showing improved results with treatment, but without statistical significance.
Jan 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0274243, https://c19p.org/singla
122 patient camostat late treatment PSM study: 69% lower mortality (p=0.001), 10% lower ventilation (p=1), and 17% longer hospitalization (p=0.35).
Retrospective 371 critically ill COVID-19 patients showing lower mortality with camostat mesylate treatment.
Apr 2021, Intensive Care Medicine, https://link.springer.com/10.1007/s00134-021-06395-1, https://c19p.org/sakr
Retrospective 439 severe COVID-19 hospitalized patients with hypertension, 201 receiving a supervised exercise program, showing significantly lower mortality with exercise. Exercise included of aerobic, breathing, and musculoskeletal exercises, 3 to 4 times per week. There were significantly more control patients on beta-adrenergic blockers and thiazide diuretics. There are many possible mechanisms of action, including improved circulation, stress reduction, hormone regulation, improved sleep, increased antioxidant levels, and increased nitric oxide levels in the respiratory system. Over-exercising may be detrimental and lead to impaired immune function.
Feb 2023, J. Applied Physiology, https://journals.physiology.org/doi/10.1152/japplphysiol.00544.2022, https://c19p.org/fernandez
4+ doses of HCQ associated with a significant decline in the odds of getting infected, dose-response relationship exists.
May 2020, Indian J. Medical Research, https://www.ijmr.org.in/article.asp?issn=0971-5916;year=2020;volume=151;issue=5;spage=459;epage=467;aulast=Chatterjee, https://c19p.org/chatterjee
Retrospective 378 hospitalized patients in Spain, showing lower mortality with N-acetylcysteine treatment.
Jul 2023, Revista Clínica Española, https://www.sciencedirect.com/science/article/abs/pii/S2254887423000929, https://c19p.org/galindoandugar
Retrospective 65 elderly COVID-19 patients and 65 matched controls, showing lower vitamin D levels associated with more severe lung involvement, longer disease duration, and higher mortality. Vitamin D supplementation was less common in the COVID-19 group compared to the control group.
Feb 2021, Nutrients, https://www.mdpi.com/2072-6643/13/3/717, https://c19p.org/sulli
Retrospective 73 familial Mediterranean fever patients with COVID-19 in Turkey, showing significantly higher risk of hospitalization for respiratory support with non-adherence to colchicine treatment before the infection.
Jul 2022, Modern Rheumatology, https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roac074/6647632, https://c19p.org/avanogluguler
Prospective study of zinc supplementation with 104 patients randomized to receive 10mg, 25mg, or 50mg of zinc picolinate daily, and a matched sample of 96 control patients from the adjacent clinic that did not routinely recommend/use zinc, showing significantly lower symptomatic COVID-19 with treatment.
Dec 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.756707/full, https://c19p.org/gordon
Retrospective 355 diabetic hospitalized COVID-19 patients in the Philippines, showing lower mortality with metformin use.
Oct 2021, J. the ASEAN Federation of Endocrine Societies, https://www.asean-endocrinejournal.org/index.php/JAFES/article/view/1155, https://c19p.org/ong
Retrospective healthcare workers in six countries with exposure to COVID-19 patients, showing lower risk of moderate/severe COVID-19 with plant-based diets.
Jun 2021, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/257, https://c19p.org/kim4
PSM observational study with a database of 26,779 patients in the USA, showing significantly lower risk of PCR+ with melatonin usage.
Nov 2020, PLOS Biology, https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000970, https://c19p.org/zhou2
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3u
Retrospective 890 cancer patients with COVID-19, adjusted mortality HR for HCQ/CQ 0.41, p<0.0001. Confirmed SARS-CoV-2 infection was required, which may help focus on more severe cases. Analysis with Cox proportional hazard model. Potential unmeasured confounders.
Aug 2020, Cancer Discovery, https://cancerdiscovery.aacrjournals.org/content/early/2020/08/18/2159-8290.CD-20-0773, https://c19p.org/pinato
Early terminated HCQ PrEP RCT with 62 HCQ and 65 placebo patients, showing 82% lower cases with treatment, p = 0.12. If the trial is continued and the same event rate is observed, statistical significance will be reached after adding about 16 patients per arm.
May 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261980, https://c19p.org/rojasserrano
Open label RCT late stage hospitalized patients in Brazil with 14 colchicine and 16 SOC patients, showing lower mortality and improved recovery with treatment, without statistical significance. Authors note that the colchicine group had one patient with SOFA ≥7 vs. zero for SOC, however both groups had one patient intubated and SOC had more patients not requiring high-flow oxygen (12 vs. 8). The journal version of this paper falsely states: "Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective". The pre-print more accurately represents the improved but not statistically significant results: "The colchicine arm presented the lowest mortality rate (0%), while the low dose IL-2 had the highest (21.4%) by day 28 post-enrollment. The frequency of adverse events was lowest in the colchicine group (7.3%). None of the differences observed was statistically significant. Interpretation: Colchicine added to SOC performed better than Ixekizumab, low-dose..
Apr 2022, Revista da Sociedade Brasileira de Medicina Tropical, http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822023000100317&tlng=en, https://c19p.org/pimentabonifacio
PEP RCT with 372 close contacts of COVID+ patients, 187 treated with bromhexine, showing significantly lower cases with treatment. IRCT20120703010178N22.
Dec 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3989849, https://c19p.org/tolouian2
Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum of 5 days treatment.
Apr 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/9/1951, https://c19p.org/derosa
Retrospective 5,146 hospitalized COVID-19 patients in Argentina, showing lower mortality associated with nebulized ibuprofen (NaIHS) treatment. Doubly robust inverse probability weighting estimators were used to control for confounding. Authors emphasize the need for randomized controlled trials. The treatment appears to be the same as detailed in [Kalayan], which reports a pH of 8.5. [Kreutzberger] showed that SARS-CoV-2 requires an acidic pH (between 6.2-6.8) for membrane fusion and cell entry, even when the viral spike protein is primed by proteases like TMPRSS2. Efficacy seen here may be more due to alkalinization, which shows more consistent higher efficacy than ibuprofen in studies to date.
May 2022, National Bureau of Economic Research, http://www.nber.org/papers/w30084.pdf, https://c19p.org/calonicoph
Retrospective 1,082 severely and critically ill COVID-19 patients in China showing lower 60 day mortality with azvudine. Mortality was also lower with paxlovid, but without statistical significance, and health related quality of life was significantly lower for paxlovid patients at 60 days.
Jul 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/7/1859, https://c19p.org/shao4azv
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127.
Feb 2021, Infectious Disease Reports, https://www.mdpi.com/2036-7449/14/2/20, https://c19p.org/beltrangonzalezh
Prospective quasi-randomized (patient choice) study with 125 outpatients, 77 treated with fluvoxamine, showing lower death/ICU admission (0 of 77 vs. 2 of 48), lower hospitalization (0 of 77 vs. 6 of 48), and faster recovery with treatment. Note that 12 treatment patients were added but are not reflected in the table in the paper (because the numbers had been previously published and the IRB did not allow updating the table).
Jan 2021, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab050/6124100, https://c19p.org/seftel
Retrospective 280 hospitalized patients showing lower mortality with ivermectin (13.3% vs 24.5%), propensity matched odds ratio OR 0.47 [0.22-0.99], p=0.045.
Oct 2020, Chest, https://www.sciencedirect.com/science/article/pii/S0012369220348984, https://c19p.org/rajter
RCT 68 patients in Italy showing improved viral clearance with raloxifene.
Jun 2022, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537022001808, https://c19p.org/nicastri
Analysis of nutrient intake and COVID-19 outcomes for 3,996 people in Iran, showing lower risk of COVID-19 hospitalization with sufficient vitamin A, vitamin C, and selenium intake, with statistical significance for vitamin A and selenium.
May 2023, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13632, https://c19p.org/vaisise
RCT 180 moderate hospitalized COVID-19 patients in Egypt, showing lower ICU admission and shorter hospitalization with ibuprofen compared with acetaminophen.
Apr 2023, The Open Anesthesia J., https://openanesthesiajournal.com/VOLUME/17/ELOCATOR/e258964582303020/, https://c19p.org/sobhy
Retrospective 1,500 COVID+ patients in Bangladesh, showing lower risk of severe cases with good sleep.
Sep 2021, Infection and Drug Resistance, https://www.dovepress.com/lifestyle-and-comorbidity-related-risk-factors-of-severe-and-critical--peer-reviewed-fulltext-article-IDR, https://c19p.org/mohsin
Retrospective 1,500 COVID+ patients in Bangladesh, showing higher risk of severe cases with alcohol/smokeless tobacco/substance abuse.
Sep 2021, Infection and Drug Resistance, https://www.dovepress.com/lifestyle-and-comorbidity-related-risk-factors-of-severe-and-critical--peer-reviewed-fulltext-article-IDR, https://c19p.org/mohsinac
Retrospective 15,103 hospitalized COVID-19 patients in France showing lower mortality with hydroxyzine use.
Dec 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/24/5891, https://c19p.org/sanchezrico2
Retrospective 266 COVID-19 ICU patients in India, showing significantly lower mortality with PVP-I oral gargling and topical nasal use, and non-statistically significant higher mortality with ivermectin and lower mortality with remdesivir.
Dec 2021, Cureus, https://www.cureus.com/articles/73667-determinants-of-outcome-among-critically-ill-police-personnel-with-covid-19-a-retrospective-observational-study-from-andhra-pradesh-india, https://c19p.org/jamirp
Vitamin D3 supplementation during or just before COVID-19 was associated with 68% lower mortality and less severe COVID-19 in frail elderly. Retrospective 66 French nursing home residents, mean age 87.7, 9 control patients, and 57 that received an oral bolus of 80,000 IU vitamin D3 either in the week following the suspicion or diagnosis of COVID-19, or during the previous month. 17.5% mortality in the treatment group and 55.6% in the control group.
Oct 2020, The J. Steroid Biochemistry and Molecular Biology, https://www.sciencedirect.com/science/article/pii/S096007602030296X, https://c19p.org/annweiler
80 patient RCT with 40 patients treated with a comprehensive regimen of nutritional support, showing significantly lower mortality with treatment. Treatment contained cholecalciferol, vitamin C, zinc, spirulina maxima, folic acid, glutamine, vegetable protein, selenium, resveratrol, omega-3 fatty acids, l-arginine, magnesium, probiotics, and B-complex IV. Adherence was strictly monitored.
Oct 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/19/3/1172/htm, https://c19p.org/lealmartinez
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3c
RCT 14,892 late stage patients, 7,351 treated with aspirin, showing slightly improved discharge and hospitalization time, and no significant difference for mortality. Results are limited due to low dose (150mg daily), very late treatment (9 days post symptom onset), and 96% concurrent use of low molecular weight heparin. Greater benefits were seen for non-LMWH patients, and for very late (<= 7 days from onset) vs. extremely late (>7 days) treatment. For more discussion see [web.archive.org].
Nov 2021, RECOVERY Collaborative Group, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673621018250, https://c19p.org/recoverye
Retrospective 15,968 hospitalized patients in Spain showing a significant reduction in mortality associated with the prescription of vitamin D, especially calcifediol, within 15-30 days prior to hospitalization.
Apr 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-02701-5, https://c19p.org/loucera
Retrospective 9,748 COVID-19 patients in the USA showing lower hospitalization with turmeric extract.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejant
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizimf
Retrospective database analysis of 65,149 in South Korea, showing significantly lower cases with existing N-acetylcysteine treatment. The journal version of this paper does not present the N-acetylcysteine results.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.04.20089904v2, https://c19p.org/huhnac
RCT 165 low-risk mild COVID-19 patients in Thailand receiving either 180mg/day of Andrographis paniculata extract or placebo for 5 days. No significant difference was found between groups for disease progression, though A. paniculata showed lower progression. Most symptoms improved similarly between groups, though A. paniculata provided faster relief for headaches and loss of smell. All patients recovered with 14 days. The main side effect was mild diarrhea.
Nov 2023, Research in Pharmaceutical Sciences, https://journals.lww.com/10.4103/1735-5362.389947, https://c19p.org/kanokkangsadal
Small prophylaxis study of 208 healthcare workers in Turkey, 138 with high risk exposure received HCQ, while 70 with low and medium risk exposure did not. COVID-19 cases were lower in the treatment group, relative risk RR 0.43, p = 0.026. Since the control group had lower risk, the actual benefit may be larger.
Sep 2020, Medical J. Bakirkoy, 280-6, https://cms.galenos.com.tr/Uploads/Article_47752/BTD-16-280-En.pdf, https://c19p.org/polat
RCT 100 outpatients in Pakistan, 50 treated with ivermectin, showing faster recovery with ivermectin. All patients received AZ, zinc, vitamin C, vitamin D, and paracetemol. Details of randomization were not provided. No mortality or hospitalization was reported.
May 2021, The Professional Medical J., http://theprofesional.com/index.php/tpmj/article/view/5867, https://c19p.org/faisal
Retrospective 1,000 COVID+ hospitalized patients in India, showing lower mortality with famotidine and remdesivir in multivariable logistic regression.
Feb 2022, Indian J. Clinical Practice, https://ijcp.in/Admin/CMS/PDF/6.%20OriginalResearch_IJCP_Feb2022.pdf, https://c19p.org/siraj
HCQ prophylaxis RCT reporting statistically significant lower cases when pooling results with the COVID PREP RCT, OR 0.74 [0.55-1.0] p = 0.046. There were no significant safety issues. The trials were both terminated early resulting in a loss of power, however the combination shows statistically significant efficacy of HCQ. Note that this result has been censored in the journal version, see [medrxiv.org]. The journal paper still shows the COVID PREP paper in the reference list, but the analysis and discussion has been deleted. The journal version falsely states: "The prophylactic use of HCQ by HCW was safe but not effective", whereas the paper actually estimates OR 0.75, which becomes statistically significant OR 0.74 when pooled with COVID PREP. The preprint contains a different version: "...but did not produce a clinically useful treatment". It's unclear why ~25% fewer cases would not be useful. They also state "This is one of several negative studies"..
Aug 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S120197122300019X, https://c19p.org/naggie
RCT with 131 24mg ivermectin, 130 12mg ivermectin, and 130 placebo patients, showing no significant differences in outcomes. Lower ventilation and hospitalization was seen with treatment, in a dose-dependent manner, but not reaching statistical significance with the small number of events.
Jun 2022, Respirology, https://onlinelibrary.wiley.com/doi/10.1111/resp.14318, https://c19p.org/mirahmadizadeh
Retrospective, 550 critically ill patients. 19% fatality for HCQ versus 47% for non-HCQ, RR 0.395, p=0.002. The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 pg/mL to 5.2 pg/mL (p<0.05) at the end of the treatment in the HCQ group but there was no change in the control group.
May 2020, Science China Life Sciences, 2020 May 15, 1-7, https://link.springer.com/article/10.1007%2Fs11427-020-1732-2, https://c19p.org/yu
In Silico study followed by PSM analysis of the National COVID Cohort Collaborative data in the USA, showing 27% lower mortality with metformin use.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.22.21254110, https://c19p.org/alamgir
Retrospective 926 patients in Senegal, 674 treated with HCQ+AZ, showing significantly higher hospital discharge at day 15 with treatment.
Jun 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/13/2954, https://c19p.org/taieb
Retrospective 28,093 COVID+ patients in the USA, showing lower risk of hospitalization with metformin use.
Sep 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-96720-x, https://c19p.org/ando
RCT with 30 nanocurcumin and 30 control patients in Iran, showing lower mortality and improved recovery, without statistical significance, and improved NK cell function. 160mg nanocurcumin for 21 days.
Sep 2022, European J. Pharmacology, https://www.sciencedirect.com/science/article/pii/S0014299922005283, https://c19p.org/abbaspouraghdam
Retrospective 126 patients in Turkey, showing lower risk of PCR+ at day 14 with favipiravir treatment.
Jun 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7706&category_id=179&option=com_virtuemart, https://c19p.org/usanmakoban
RCT in India with low risk patients, comparing 24mg ivermectin, 12mg ivermectin, and placebo showing non-statistically significant improvements in recovery and PCR+ status (day 5 both arms, day 7 24mg only) with treatment, and showing greater improvement for the higher dose arm. Viral load decline was similar in all arms - absolute values are lower for ivermectin in a dose-dependent manner, however the baseline value for the ivermectin groups was lower, leaving less room for change. There were no deaths or use of mechanical ventilation. There were no serious adverse events. Note that our pre-specified protocol prioritizes clinical outcomes over PCR results.
Feb 2021, J. Infection and Chemotherapy, https://www.sciencedirect.com/science/article/pii/S1341321X21002397, https://c19p.org/mohan
Retrospective 228 hospitalized COVID-19 patients, median age 78, showing significantly lower risk of ICU admission and severe cases with vitamin D prophylaxis. NCT04877509.
Apr 2022, Nutrients, https://www.mdpi.com/2072-6643/14/8/1641, https://c19p.org/parant
PSM retrospective 6,781 hospitalized patients ≥50 years old in the USA who were on pre-hospital antiplatelet therapy (84% aspirin), and 10,566 matched controls, showing lower mortality with treatment.
Aug 2021, J. Thrombosis and Haemostasis, https://onlinelibrary.wiley.com/doi/abs/10.1111/jth.15517, https://c19p.org/chow2
RCT 48 hospitalized patients in China showing faster clinical recovery and viral clearance with CQ/HCQ.
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.19.20136093v1, https://c19p.org/chen
Retrospective 76 COVID-19 patients, 46 treated with intravenous high-dose vitamin C, showing lower mortality and improved oxygen requirements with treatment. Dosage was 6g intravenous infusion per 12hr on the first day, and 6g once for the following 4 days.
Feb 2021, Aging, https://www.aging-us.com/article/202557/text, https://c19p.org/gao3
Observational prospective 254 hospitalized patients, HCQ+AZ mortality odds ratio OR 0.36, p = 0.04. Ventilation OR 0.20, p = 0.008.
Sep 2020, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906720303365, https://c19p.org/heberto
RCT 150 hospitalized patients in Pakistan showing 26% faster recovery, p < 0.0001. 36% lower mortality, not statistically significant due to the small number of events. Dosage was 50 mg/kg/day of intravenous vitamin C.
Nov 2020, Cureus, https://www.cureus.com/articles/45284-the-role-of-vitamin-c-as-adjuvant-therapy-in-covid-19, https://c19p.org/kumari
RCT 214 low risk (no hospitalization) healthcare workers in China, showing no significant differences with vitamin D2 prophylaxis using two bolus treatments. Patients with higher vitamin D levels (across both groups) were less likely to be infected. The trial only lasted one month. Two thirds of the cases occurred within the first week, when treatment may have minimal impact on vitamin D levels (calcifediol or calcidiol may be more effective due to delays in conversion). Cases were lower in the intervention group during the last two weeks, after treatment is likely to have increased levels significantly. Regular rather than bolus treatment, longer term treatment, or alternative forms of vitamin D (e.g., calcifediol/calcidiol) may be more effective. Authors report that "4.5% of subjects were lost to follow-up" (1% and 7.6% per group). Figure 2 shows 2 and 0 patients at risk at day 28. This is inconsistent with the reported infection rates and loss to followup, raising..
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-024-66267-8, https://c19p.org/wang14
Retrospective 586 diabetic hospitalized COVID-19 patients in Turkey, showing lower mortality with existing metformin use.
Oct 2021, Irish J. Medical Science, https://link.springer.com/article/10.1007/s11845-021-02823-9/fulltext.html, https://c19p.org/saygili
RCT with 54 favipiravir, 51 HCQ, and 52 SOC hospitalized patients in Bahrain, showing no significant differences. Viral clearance improved with both treatments, but did not reach statistical significance with the small sample size.
Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-08794-w, https://c19p.org/alqahtani2
76 patient alkalinization ICU study: 76% lower mortality (p=0.0001).
Analysis of 76 ICU patients in Brazil, 44 treated with bronchoalveolar lavage using 3% sodium bicarbonate, showing significantly lower mortality with treatment. Bronchoalveolar lavage with 10ml of sodium bicarbonate solution directly into the tube (closed circuit), 500μl for each lung segment, followed by aspiration of the solution, performed every 6 hours for 7 days.
Dec 2021, Brazilian J. Development, https://brazilianjournals.com/ojs/index.php/BRJD/article/view/40521, https://c19p.org/soares
76 patient sodium bicarbonate ICU study: 76% lower mortality (p=0.0001).
Analysis of 76 ICU patients in Brazil, 44 treated with bronchoalveolar lavage using 3% sodium bicarbonate, showing significantly lower mortality with treatment. Bronchoalveolar lavage with 10ml of sodium bicarbonate solution directly into the tube (closed circuit), 500μl for each lung segment, followed by aspiration of the solution, performed every 6 hours for 7 days.
Dec 2021, Brazilian J. Development, https://brazilianjournals.com/ojs/index.php/BRJD/article/view/40521, https://c19p.org/soaressb
Retrospective 112,269 hospitalized COVID-19 patients in the USA, showing lower mortality with aspirin treatment.
Mar 2022, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790439, https://c19p.org/chow3
RCT 60 hospitalized COVID-19 patients with type 2 diabetes showing quercetin treatment decreased levels of inflammatory markers (interleukin-6, CRP, ferritin), reduced length of hospital stay, and improved capillaroscopy measures compared to standard care. Quercetin was administered at 0.5g intravenously once daily for 10 days. The authors hypothesize the benefits may be due to the anti-inflammatory, antioxidant and endothelium-protective effects of quercetin,
Dec 2024, Wiadomości Lekarskie, https://www.wiadomoscilekarskie.pl/Effectiveness-of-the-quercetin-use-in-patients-with-COVID-19-with-concomitant-type,191875,0,2.html, https://c19p.org/tylishchak
Prospective study of 106 IBD patients in Italy, showing lower risk of IgG positivity with vitamin D supplementation. Vitamin D levels below 30 ng/mL were associated with a higher probability of symptomatic cases.
Dec 2022, Nutrients, https://www.mdpi.com/2072-6643/15/1/169, https://c19p.org/denicolo
PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with aspirin (not reaching statistical significance) and famotidine, and improved results from the combination of both.
Mar 2021, Signal Transduction and Targeted Therapy, https://www.nature.com/articles/s41392-021-00689-y, https://c19p.org/murafm
Retrospective 1,979 nurses in the USA, showing lower risk of long COVID with better sleep quality.
May 2023, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2805380, https://c19p.org/wang17
PrEP RCT showing lower cases with HCQ prophylaxis. The trial was halted after 47% enrollment, p < 0.05 would be reached at ~75% enrollment if similar results continued. HR 0.66/0.68 for full medication adherence, 0.72/0.74, p = 0.18/0.22 overall (1x/2x dosing). Efficacy for first responders was higher, OR 0.32, p = 0.01. First responders had a much higher incidence, allowing greater power, and reducing the effect of confounders such as misdiagnosis of other conditions or survey issues. Performance is similar to the control arm for the first 3 weeks. The effect may be greater with a dosage regimen that achieves therapeutic levels faster [tandfonline.com]. ~40% of participants suspected they might have had COVID-19 before the trial, the effect in people without prior COVID-19 may be higher. Research shows the treatment used in the control arm (folic acid) may have significant efficacy for COVID-19 [Deschasaux-Tanguy, Farag], so the true effectiveness of HCQ may be higher than observed...
Sep 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1571/5929230, https://c19p.org/rajasingham
Retrospective 42 hospitalized PCR+ COVID-19 pneumonia patients treated with NAC, and a matched control group of 40 patients, showing significantly lower severe respiratory failure and significantly lower mortality with treatment. NAC 600 mg bid orally for 14 days.
Jun 2021, Infectious Diseases, https://www.tandfonline.com/doi/full/10.1080/23744235.2021.1945675, https://c19p.org/assimakopoulos
Retrospective 167 severe COVID-19 patients showing lower mortality with ursodeoxycholic acid (UDCA). Timing and duration of treatment is unknown - UDCA patients may have been on UDCA since before COVID-19.
Jun 2024, Microorganisms, https://www.mdpi.com/2076-2607/12/7/1269, https://c19p.org/zheng10
Retrospective 111 hospitalized COVID-19 pneumonia patients treated with colchicine and 111 matched controls, showing lower mortality with colchicine treatment.
Mar 2023, Eur. J. Hosp. Pharm., https://ejhp.bmj.com/lookup/doi/10.1136/ejhpharm-2023-eahp.56, https://c19p.org/villamanan
Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases for HCQ users.
May 2021, Authorea, https://www.authorea.com/doi/full/10.22541/au.162257516.68665404, https://c19p.org/korkmaz
Retrospective 580 hospitalized COVID+ patients in Cameroon, showing lower mortality with HCQ+AZ treatment.
Mar 2022, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/pii/S1477893922000382, https://c19p.org/ebongue
179 patient colchicine late treatment RCT: 81% lower mortality (p=0.03), 87% lower ICU admission (p=0.002), and 35% shorter hospitalization (p<0.0001).
RCT 179 hospitalized COVID-19 patients showing lower mortality, ICU admission, and hospitalization duration with colchicine plus phenolic monoterpenes compared to standard care alone. The intervention group received 0.8 mg/day colchicine and 45 mg/day phenolic monoterpenes extracted from nigella sativa and Trachyspermum ammi in addition to standard care (lopinavir/ritonavir). No serious side effects were reported. Baseline SpO2 was significantly lower in the control group, although there was no significant difference in severity according to NIH guidelines.
Mar 2024, Heliyon, https://www.sciencedirect.com/science/article/pii/S2405844024034042, https://c19p.org/vaziri
RCT 140 patients showing lower progression and improved recovery with propolis plus Hyoscyamus niger L.syrup.
Nov 2023, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.8047, https://c19p.org/kosari2
Retrospective 103 outpatients in Greece, showing lower risk of progression with fluvoxamine 100mg bid for 10 days. 2 patients (4%) in the fluvoxamine group had clinical deterioration compared to 8 patients (16%) in the standard care group (p<0.05). After adjusting for confounders, fluvoxamine was associated with a lower risk of clinical deterioration (adjusted OR 0.12, p=0.02). Fluvoxamine was also associated with improved lymphocyte count. Control patients were during Sep-Nov 2021, and treatment patients Nov-Dec 2021, introducing potential confounding by time due to changes in variants, although the change in risk during this period is expected to be relatively low.
Aug 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/8/2073, https://c19p.org/tsiakalos
Retrospective 95 people in Poland, showing significantly lower risk of COVID-19 with higher consumption of fruits, vegetables, and nuts. Diets with higher consumption of fruits, vegetables, and nuts had a significantly lower dietary inflammatory index.
Jan 2022, Nutrients, https://www.mdpi.com/2072-6643/14/2/350, https://c19p.org/jagielski
Retrospective 5,194 participants in Spain with 382 COVID-19 cases, showing lower risk of COVID-19 with high adherence to a Mediterranean diet, with statistical significance only when excluding healthcare professionals.
Jan 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2021.805533/full, https://c19p.org/perezaraluce
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihic
Retrospective 288 hospitalized COVID-19 patients in Italy, showing lower mortality and shorter hospitalization with calcifediol. Results may underestimate the benefits because only higher risk patients with vitamin D deficiency received supplementation. Treated patients also had significantly higher BMI. 83% of patients had vitamin D insufficiency (levels <30 ng/mL). Lower vitamin D levels correlated with higher inflammation markers. Patients with severe vitamin D deficiency (<10 ng/mL) had significantly higher mortality compared to those with levels >10 ng/mL.
Jul 2023, Nutrients, https://www.mdpi.com/2072-6643/15/15/3392, https://c19p.org/mingiano
164 patient exercise study: 91% lower mortality (p=0.09) and 70% lower severe cases (p=0.03).
Retrospective 164 COVID-19 patients in China, showing physical inactivity associated with an increased risk of severe COVID-19.
Jun 2021, Therapeutic Advances in Respiratory Disease, https://journals.sagepub.com/doi/10.1177/17534666211025221, https://c19p.org/yuan2
PEP retrospective 625 university students in Thailand offered nitric oxide nasal spray, showing significantly lower cases for students that chose to use the treatment.
Apr 2022, SaNOtize, https://sanotize.com/clinical-trials-covid/, https://c19p.org/sanotizepep
Retrospective 221 COVID-19 patients showing an association between high-risk obstructive sleep apnea and COVID-19 severity.
Oct 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/21/6415, https://c19p.org/atceken
Retrospective 948 intubated patients, 196 treated with melatonin, showing lower mortality with treatment.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.15.20213546v1, https://c19p.org/ramlall
Prospective study of 41,012 UK Biobank participants, showing higher risk of COVID-19 cases with ultra-processed food consumption.
Aug 2022, European J. Nutrition, https://link.springer.com/10.1007/s00394-022-02982-0, https://c19p.org/zhou7
RCT 44 hospitalized patients in Iran, 24 treated with melatonin, showing faster recovery with treatment. There was no mortality.
Jun 2021, Archives of Medical Research, https://www.sciencedirect.com/science/article/pii/S0188440921001417, https://c19p.org/farnoosh
1,497 patient fluvoxamine late treatment RCT: 30% lower mortality (p=0.24), 22% lower ventilation (p=0.33), 22% lower hospitalization (p=0.1), and 32% fewer combined hospitalization/ER visits (p=0.004).
Together Trial showing significantly lower hospitalization/extended ER visits with fluvoxamine treatment. Adherence was only 73.2%. Symptom onset was unspecified or >= 4 days for 57% of patients. The schedule of study activities specifies treatment administration only one day after randomization, adding an additional day delay. Overall mortality is high for the patient population. Results may be impacted by late treatment, poor SOC, and may be specific to local variants [science.sciencemag.org, thelancet.com]. Per-protocol analysis shows significantly improved results in this trial, however this may be subject to bias - the probability of adherence may be related to the probability of the outcome. Regarding the combined hospitalization/extended ER observation outcome, authors have noted that at the study sites, extended medical observation was essentially equivalent to being hospitalized. “These were not standard emergency rooms but instead were COVID-19 emergency centers that were..
Aug 2021, The Lancet Global Health, https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext, https://c19p.org/reis2
Retrospective 375 patients in China, 179 treated with probiotics (Bifidobacterium, Lactobacillus, and Enterococcus), showing improved clinical outcomes with treatment.
Aug 2021, Therapeutic Advances in Gastroenterology , https://journals.sagepub.com/doi/full/10.1177/17562848211035670, https://c19p.org/zhang3
Retrospective 131 hospitalized COVID-19 patients with type 2 diabetes, showing lower mortality with metformin treatment and acarbose treatment.
Sep 2021, Endocrinology, Diabetes & Metabolism, https://onlinelibrary.wiley.com/doi/10.1002/edm2.301https://onlinelibrary.wiley.com/doi/pdf/10.1002/edm2.301, https://c19p.org/li18
Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients, that positive PCR may simply reflect detection of inactive (non-infectious) viral remnants, that an alternative dosage regimen may be more effective, and that medication adherence was unknown. HCQ dosing was 600mg/day for 1 week, therapeutic levels may not be reached for several days. There were no deaths or serious adverse events. Viral load was already very high at baseline.
Nov 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303898, https://c19p.org/omrani
Retrospective 72 pediatric patients showing HCQ associated with a shorter duration of fever (p=0.023), less progression (p=0.016), and fewer return visits to the ER (p=0.017).
Nov 2020, Annals of Pediatrics, https://www.sciencedirect.com/science/article/pii/S1695403320304768, https://c19p.org/lopez2
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297521000792, https://c19p.org/cadegianin
RCT 827 children aged 1-6 years in daycare in Finland analyzing the effectiveness of daily Streptococcus salivarius K12 oral probiotic use for 6 months in preventing acute otitis media (AOM). The probiotic group did not have a significantly lower rate of AOM requiring antibiotics compared to placebo. A secondary outcome shows no significant difference in COVID-19, with only 2 and 3 cases in the treatment and placebo groups.
Nov 2023, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2811238, https://c19p.org/sarlin
RCT 45 hospitalized high-risk pediatric patients requiring supplemental oxygen in Mexico, showing lower mortality, ventilation, and intensive care with vitamin D treatment, however there were less severe and critical cases at baseline in the treatment group.
Jul 2022, Frontiers in Pediatrics, https://www.frontiersin.org/articles/10.3389/fped.2022.943529/full, https://c19p.org/zuritacruz
150 patient nigella sativa ICU RCT: 6% lower mortality (p=0.87), 62% lower ventilation (p=0.01), and 23% lower ICU admission (p=0.74).
Open label randomized trial of 150 ICU patients in Bangladesh, showing shorter ICU stay and lower requirements for increased oxygen support including mechanical ventilation with nigella sativa treatment, but no significant difference in mortality. The large baseline difference in convalescent plasma usage suggests an error or randomization problem.
Aug 2023, Bangladesh Critical Care J., https://www.researchgate.net/publication/376207383_Role_of_Nigella_Sativa_black_cumin_seedsas_an_adjunct_therapy_in_treating_severe_and_critical_COVID_-19_infection_compared_to_those_with_standard_therapy_An_open_label_randomized_clinical_trial, https://c19p.org/faruq
69 residents of a French care home, median age 90, were treated with ivermectin for a scabies outbreak. 3,062 residents in 45 nearby comparable homes were used as controls. 7 of 69 treated patients had probable or certain COVID-19, with no serious cases and no deaths. In comparable care homes in the same district, matched by age and socio-economic level, there was 22.6% COVID-19 and 5% death.
Nov 2020, Annals of Dermatology and Venereology, https://www.sciencedirect.com/science/article/pii/S015196382030627X, https://c19p.org/bernigaud
Retrospective 2,919 non-hospitalized COVID-19 patients in Brazil showing remaining physically active before and after COVID-19 infection reduces the probability of experiencing long COVID symptoms, particularly those affecting the musculoskeletal, neurological and respiratory systems.
Dec 2023, BMC Sports Science, Medicine and Rehabilitation, https://bmcsportsscimedrehabil.biomedcentral.com/articles/10.1186/s13102-023-00782-5, https://c19p.org/rocha
PSM retrospective 1,620 hospitalized patients in the USA, 84 with existing famotidine use, showing lower risk of combined death/intubation with treatment.
May 2020, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34706-5/fulltext, https://c19p.org/freedberg
Retrospective 733 hospitalized COVID-19 patients with diabetes in the USA, showing lower risk of severity with metformin use.
Nov 2022, J. Community Hospital Internal Medicine Perspectives, https://scholarlycommons.gbmc.org/jchimp/vol12/iss6/5, https://c19p.org/milosavljevic
73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, p = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression but not the effect size.
Dec 2020, Aging, https://www.aging-us.com/article/202307/text, https://c19p.org/cangiano
Retrospective 31,260 COVID-19 cases and 125,039 matched controls, showing lower risk of COVID-19 with previous azithromycin use.
Mar 2023, Antibiotics, https://www.mdpi.com/2079-6382/12/3/587, https://c19p.org/dugotaz
Retrospective 328 COVID-19 patients with type 2 diabetes in China, showing significantly lower risk of ARDS with existing metformin use.
Mar 2021, Diabetes Research and Clinical Practice, https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(20)30876-7/fulltext, https://c19p.org/jiang2
Retrospective 164 COVID-19 patients and 188 controls in China, showing lower risk of cases with regular exercise.
Nov 2021, Nature and Science of Sleep, https://www.dovepress.com/reduced-sleep-in-the-week-prior-to-diagnosis-of-covid-19-is-associated-peer-reviewed-article-NSS, https://c19p.org/huang5
HCQ prophylaxis RCT with 201 weekly HCQ patients, 197 daily HCQ patients, and 200 control patients, concluding the prophylaxis is safe. There were no grade 3 or 4 AEs, SAEs, ER visits, or hospitalizations. There was only 4 confirmed cases, 2 in the placebo arm and one in each HCQ arm. 60% of patients had exposure at baseline. HCQ 400mg weekly or HCQ 200mg daily after a loading dose of 400mg on day 1.
Dec 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221012431, https://c19p.org/mckinnon
Retrospective 8,297 adults from the UK Biobank showing the habitual use of vitamin D supplements significantly associated with lower risk of COVID-19 cases. Note that the information on vitamin D supplement use was collected a median of 10 years before the COVID-19 tests, so usage may have changed significantly.
Jan 2021, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqaa381/6123965, https://c19p.org/ma
HOPE-COVID-19 PSM retrospective 7,824 patients, comparing prophylactic anticoagulation with and without additional treatment with aspirin in hospitalized patients, showing lower mortality with aspirin treatment.
Jun 2022, J. the American Heart Association, https://www.ahajournals.org/doi/10.1161/JAHA.121.024530, https://c19p.org/santoro3
Low dose prospective PEP study with 132 HCQ patients and 185 control patients, showing significantly lower COVID-19 cases with treatment. There were no serious adverse events. HCQ 800mg on day one followed by 400mg once weekly for 3 weeks.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304350, https://c19p.org/dhibar
RCT 68 post-COVID-19 outpatients showing improvement in cough severity measures with montelukast treatment. The montelukast group had a greater reduction in number of cough paroxysms per day, cough severity visual analog scale, cough severity index, and improved cough quality of life scores compared to the control group. The montelukast group also had a shorter duration of cough.
Sep 2022, The Egyptian J. Bronchology, https://ejb.springeropen.com/articles/10.1186/s43168-022-00154-6, https://c19p.org/mohamedhussein
Small RCT showing significantly improved recovery with intranasal chlorpheniramine maleate. Authors also perform an In Vitro study showing efficacy with a highly differentiated three-dimensional model of normal, human-derived tracheal/bronchial epithelial cells.
Dec 2022, Medical Research Archives, https://esmed.org/MRA/index.php/mra/article/view/2752, https://c19p.org/sanchezgonzalez2
Small RCT showing significantly improved recovery with intranasal chlorpheniramine maleate. Authors also perform an In Vitro study showing efficacy with a highly differentiated three-dimensional model of normal, human-derived tracheal/bronchial epithelial cells.
Dec 2022, Medical Research Archives, https://esmed.org/MRA/index.php/mra/article/view/2752, https://c19p.org/sanchezgonzalez2cpm
Retrospective of 132 hospitalized patients. HCQ+AZ(52)/AZ(28) significantly reduced death/ICU, HR=0.45, p=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay from admission to treatment 0.7 days.
Aug 2020, Int. J. Antimicrobial Agents, 2020, https://www.sciencedirect.com/science/article/pii/S0924857920303125, https://c19p.org/davido
RCT 76 hospitalized patients, showing improved recovery with nanocurcumin. Authors note that pure curcumin is limited due to rapid metabolism, low bio-availability, weak aqueous solubility, and systemic deletion, and that the nanocurcumin formulation used improves curcumin’s solubility, stability, half-life, and bioavailability. The dropout rate was higher in the curcumin group, in part due to discontinuation for side effects. Authors do not provide detailed discharge criteria.
Jul 2023, Int. J. Clinical Practice, https://www.hindawi.com/journals/ijclp/2023/5734675/, https://c19p.org/ahmadi4
Retrospective 159 COVID-19+ pregnant women in Turkey and 332 healthy pregnant controls, showing significantly lower vitamin D levels in COVID-19+ patients. 23% of COVID-19 patients where on vitamin D supplementation, while none of the 7 severe cases were on supplementation.
Aug 2021, The J. Steroid Biochemistry and Molecular Biology, https://www.sciencedirect.com/science/article/pii/S0960076021001576, https://c19p.org/sinaci
Retrospective 16,504 COVID-19 type 2 diabetes patients, showing lower risk of ICU admission with existing metformin use.
Sep 2021, BMJ Open Diabetes Research & Care, https://drc.bmj.com/content/9/1/e002299.abstract, https://c19p.org/wang5
Small trial of low dose HCQ for healthcare workers with mild SARS-CoV-2 showing 68% lower progression to pneumonia, p = 0.21, and faster, but not statistically significant viral clearance. There were no ICU admissions or deaths. Prospective non-randomized study. The figures and supplementary data are not currently available in the pre-proof edition.
Dec 2020, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/abs/pii/S0213005X20304134, https://c19p.org/agusti
Prospective analysis of 52 peritoneal dialysis patients, 31 on calcitriol (vitamin D) therapy. All patients tested positive for COVID-19 during followup (median 26 months). Mortality was significantly lower for patients on calcitriol therapy in univariate Cox regression analysis and in Kaplan-Meier analysis. Multivariate Cox regression analysis showed only diabetes mellitus with statistical significance.
Apr 2023, Nutrients, https://www.mdpi.com/2072-6643/15/9/2050, https://c19p.org/baralic
Retrospective survey of 41,529 participants, including 571 on antiandrogen therapy, showing no significant association between antiandrogen use and COVID-19 incidence, hospitalization, or ICU admission/mechanical ventilation.
Sep 2020, Dermatologic Therapy, https://onlinelibrary.wiley.com/doi/10.1111/dth.14166, https://c19p.org/ianhez
RCT 250 hospitalized COVID-19 patients showing reduced mortality rate and inflammatory markers with N-acetylcysteine (NAC) 400μg inhaled spray twice daily for 7 days as adjunctive treatment. There was no significant difference in hospital length of stay or ICU admission. The NAC group was older on average, while the control group had significantly lower SpO2 at baseline. 400 μg/day NAC inhaler spray for 7 days.
Dec 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.28393, https://c19p.org/panahi
RCT including 51 spironolactone patients and 87 control patients in Iran, showing improved recovery with spironolactone, sitagliptin, and the combination of both.
Feb 2022, J. the Endocrine Society, https://academic.oup.com/jes/article/6/4/bvac017/6523815, https://c19p.org/abbasi
RCT including 51 spironolactone patients and 87 control patients in Iran, showing improved recovery with spironolactone, sitagliptin, and the combination of both.
Feb 2022, J. the Endocrine Society, https://academic.oup.com/jes/article/6/4/bvac017/6523815, https://c19p.org/abbasisp
Retrospective study finding that regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly. For those receiving regular supplementation: Adjusted mortality hazard ratio with supplementation HR 0.07, p = 0.017. Risk of severe COVID-19 with supplementation OR 0.08, p = 0.033. For supplementation started after COVID-19 diagnosis: Adjusted mortality hazard ratio HR 0.37, p = 0.28. Risk of severe COVID-19 with supplementation OR 0.46, p = 0.4.
Nov 2020, Nutrients, https://www.mdpi.com/2072-6643/12/11/3377, https://c19p.org/annweiler2
RCT 138 COVID-19 outpatients in Japan showing lower progression to fever and hypoxemia with curcuRouge, a highly bioavailable oral curcumin formulation, compared to placebo. The curcuRouge group also had a greater reduction in body temperature and took fewer antipyretic medications. The event rate was lower than expected and the difference in progression was not statistically significant.
Jun 2024, J. Health, Population and Nutrition, https://jhpn.biomedcentral.com/articles/10.1186/s41043-024-00584-6, https://c19p.org/kishimoto
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehriziazaz
RCT 208 moderate COVID-19 patients in India, 103 treated with a combination of turmeric, ashwagandha, boswellia, and ginger, showing improved recovery with treatment. The dose of curcumin is unknown and bioavailability may be poor.
Nov 2022, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7683, https://c19p.org/chitre
Retrospective 11,993 hospitalized COVID-19 patients with diabetes mellitus but without chronic kidney disease or need for hemodialysis, showing lower mortality with metformin use.
Sep 2024, J. General Internal Medicine, https://link.springer.com/article/10.1007/s11606-024-08864-x, https://c19p.org/harmon
Late treatment RCT with 156 colchicine patients in the UK, showing no significant differences. ISRCTN86534580.
Sep 2021, British J. General Practice, https://bjgp.org/content/early/2022/03/23/BJGP.2022.0083.short, https://c19p.org/dorward
Retrospective 131 type II diabetes patients with COVID pneumonia, showing lower mortality with existing metformin use. Acarbose (commonly used in China as an initial therapy for diabetes) did not have a similar association with mortality, suggesting that the result may not be explained by metformin being used early in type II diabetes.
Sep 2020, Endocrine Practice, https://www.endocrinepractice.org/article/S1530-891X(20)48222-9/fulltext, https://c19p.org/li12
RCT 98 outpatients in Brazil, showing faster recovery from cough with inhaled hypertonic saline. Authors note that the effect on coughing may hypothetically be related to a hyperosmotic response influencing the function of different membrane channels and preventing virus entry into the cells; and that the hypertonic solution may increase mucociliary clearance and reduce the destructive inflammatory process in the airways with a decrease in respiratory symptoms.
Sep 2023, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/18/6075, https://c19p.org/tanni
Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with dutasteride.
Jul 2021, Epidemiology and Global Health Microbiology and Infectious Disease, https://elifesciences.org/articles/68165, https://c19p.org/israel2aa
79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. Retrospective 518 patients (141 treated, 377 control).
Jul 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304258, https://c19p.org/derwandz
Prospective analysis of 32,249 women from the Nurses’ Health Study II in the USA, showing lower risk of PASC with a healthy lifestyle, and in a dose-dependent manner. Participants with 5 or 6 healthy lifestyle factors had significantly lower COVID-19 hospitalization and PASC. BMI and sleep were independently associated with risk of PASC.
Feb 2023, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2800885, https://c19p.org/wang10dt
580 patient vitamin D prophylaxis study: 34% fewer symptomatic cases (p=0.01).
Prospective study of 580 ChAdOx1 recipients, 262 treated with calcifediol (patient choice), showing lower cases with treatment. Supplementation did not significantly affect antibody levels following ChAdOx1 receipt. Calcifediol patients were older (31 vs. 26 in the exposed subgroup containing most patients). 50μg/day calcifediol.
Mar 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323001317, https://c19p.org/bhat
Tiny RCT with 12 bromhexine and 6 control patients showing non-statistically significant improvements in chest CT, need for oxygen therapy, and discharge rate within 20 days. Authors recommend a larger scale trial.
Sep 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.12881, https://c19p.org/li5
Retrospective 9531 COVID+ diabetes patients in the USA, showing lower risk of hospitalization with existing biguanides treatment (defined as mainly metformin in the abstract and entirely metformin in the text).
Jul 2021, Diabetes Therapy, https://link.springer.com/article/10.1007/s13300-021-01110-1/fulltext.html, https://c19p.org/boye
Retrospective case control study of 3,100 healthcare workers in India showing lower cases with HCQ prophylaxis, and an inverse association between the number of HCQ doses taken and the risk of COVID-19 cases. Low risk population with no mortality and no severe cases.
Mar 2021, Transactions of The Royal Society of Tropical Medicine and Hygiene, https://academic.oup.com/trstmh/advance-article/doi/10.1093/trstmh/trab047/6186057, https://c19p.org/dev
106 patient vitamin D late treatment RCT: 40% lower ICU admission (p=0.42) and 17% shorter hospitalization (p=0.1).
RCT 106 hospitalized patients with vitamin D levels <30ng/ml in Iran, 53 treated with calcifediol, showing that treatment was able to correct vitamin D deficiency/insufficiency, resulting in improved immune system function. Hospitalization, ICU duration, ventilation, and mortality was lower with treatment, without reaching statistical significance with the small sample size. The dosage used in this trial was much lower than other trials.
Oct 2021, Endocrine Practice, https://www.sciencedirect.com/science/article/abs/pii/S1530891X21012593, https://c19p.org/maghbooli2
RCT 90 mild to moderate COVID-19 patients showing no significant differences with montelukast treatment.
Nov 2021, Int. J. Basic & Clinical Pharmacology, https://www.ijbcp.com/index.php/ijbcp/article/view/4867, https://c19p.org/kumar9
197 patients. CQ effective. Day 10 viral RNA negative 91.4% HCQ versus 57.4% control. Median time to negative test 3 days versus 9 days for control.
Mar 2020, Zhong Nanshan, https://twitter.com/JamesTodaroMD/status/1243260720944480265, https://c19p.org/zhong2
RCT 200 moderate/severe patients in Thailand, showing significantly lower progression with favipiravir vs. oseltamivir. NCT04303299.
Oct 2021, SSRN Electronic J., https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3936499, https://c19p.org/atipornwanicha
Case control study in China with 105 cases and 210 matched controls, showing COVID-19 cases associated with lack of sleep.
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241540, https://c19p.org/gao5sl
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with antihistamine H1RAs, without statistical significance. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3h1
RCT with 35 single dose 24mg, 38 single dose 12mg, and 39 SOC hospitalized patients with hematological illnesses in India, showing no significant differences. Results were better for 24mg vs. 12mg for all symptomatic outcomes. Viral clearance results do not follow the randomization with less than 50% of patients tested at day 7, and no adjusted results are provided. Results were obtained for only 43.8% of ivermectin patients and 56.4% of control patients at day 7 and may not be comparable due to the large difference in the percentage of patients tested. Lower test coverage in the ivermectin group is likely related to faster recovery. Ct 40 for E or S was used for viral clearance which may also have low relevance to infectious disease.
May 2022, Indian J. Hematology and Blood Transfusion, https://link.springer.com/10.1007/s12288-022-01546-w, https://c19p.org/george
RCT for mouthwash containing hydrogen peroxide 2% and chlorhexidine gluconate, showing higher discharge, shorter hospital stay, less intubation, and lower mortality with treatment.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.27.20234997v2, https://c19p.org/mukhtar
Retrospective 1,033 critical condition patients, showing lower in-hospital mortality with aspirin in PSM analysis. Patients receiving aspirin also had a higher risk of significant bleeding, although not reaching statistical significance. Authors note that the use of aspirin during an ICU stay should be tailored to each patient.
Sep 2021, J. Intensive Care Medicine, https://journals.sagepub.com/doi/pdf/10.1177/08850666221093229, https://c19p.org/alharthi
Retrospective 60 patients in Romania taking probiotics and 60 matched controls, showing faster symptom resolution with the use of probiotics. Spore-based probiotic containing five strains of Bacillus.
Jan 2023, Nutrients, https://www.mdpi.com/2072-6643/15/3/488, https://c19p.org/catinean
8,864 patient ursodeoxycholic acid prophylaxis study: 13% fewer cases (p=0.03).
Retrospective 8,964 primary care patients prescribed ursodeoxycholic acid (UDCA) in the UK. Higher categorized UDCA adherence (≥80%) was associated with lower COVID-19 incidence (OR 0.86), whereas adherence as a continuous variable was not significant. However, adherence was measured indirectly via prescription records which may not reflect actual usage. Additionally, more adherent patients may differ systematically on unmeasured confounders (e.g., health behaviors) that influence COVID-19 risk.
Nov 2023, Microbiology and Infectious Diseases The American Medical J., https://www.emjreviews.com/microbiology-infectious-diseases/article/a-retrospective-study-in-patients-with-varying-prescription-coverage-with-ursodeoxycholic-acid-and-association-with-incidence-of-covid-19-diagnosis-in-primary-care/, https://c19p.org/ming
201 patient vitamin D prophylaxis study: 22% lower mortality (p=0.61) and 31% lower progression (p=0.26).
Prospective study of 201 COVID+ hospitalized adults in Brazil, mean age 73, showing a lower risk of mortality and respiratory failure with vitamin D supplementation in unadjusted results, without statistical significance, and a higher risk of progression to mechanical ventilation with vitamin D levels <40ng/dl.
Feb 2022, BMC Geriatrics, https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-022-02776-3, https://c19p.org/junior
Small RCT with 72 low-risk patients in Thailand, showing improved recovery with ivermectin, without statistical significance. All patients recovered and there was no escalation of care in either group. There were no adverse events.
Feb 2022, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06649-3, https://c19p.org/manomaipiboon
RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The retrospective study included 660 outpatients showing fewer days with general COVID-19 symptoms, cough, anosmia, and ageusia compared to standard of care alone. The RCT results are listed separately [Valerio-Pascua].
Oct 2022, Research Square, https://www.researchsquare.com/article/rs-2167465/v1, https://c19p.org/valeriopascua3b
RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The retrospective study included 660 outpatients showing fewer days with general COVID-19 symptoms, cough, anosmia, and ageusia compared to standard of care alone. The RCT results are listed separately [Valerio-Pascua].
Oct 2022, Research Square, https://www.researchsquare.com/article/rs-2167465/v1, https://c19p.org/valeriopascua3bcpm
Retrospective 137 hospitalized mild to moderate COVID-19 patients with type 2 diabetes in Indonesia, showing a significantly lower mortality with metformin treatment.
Sep 2023, Folia Medica Indonesiana, https://e-journal.unair.ac.id/FMI/article/view/46944, https://c19p.org/zihono
RCT 320 patients in Thailand, showing significantly lower progression with HCQ for moderate/severe patients, and faster viral clearance with mild patients (statistically significant for 800mg). There are two sets of results - for moderate/severe patients, and for mild patients. There was no mortality for mild patients. NCT04303299.
Oct 2021, SSRN Electronic J., https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3936499, https://c19p.org/atipornwanich
Early terminated low-risk population (no hospitalization) very late treatment (mean 8 days) RCT with 44 patients treated with vitamin C, D, K, and zinc, and 46 control patients, showing no significant differences. Authors acknowledge that the very late treatment is a major limitation, noting that in an ideal setting, "patients would begin taking therapeutic interventions immediately after noticing symptoms". Authors note that patients already had a low symptom burden at baseline and that "it is likely that the majority of the participants had almost fully recovered before starting treatment." Authors note that most participants were young, had few comorbidities and had excellent self-rated health at baseline, leaving less room for improvement. There was low compliance with completing surveys. Data from only 64% of patients was in the main analysis. Authors claim "high internal validity", but the loss of data was statistically significantly..
Sep 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2023-073761, https://c19p.org/seelyd
Early terminated low-risk population (no hospitalization) very late treatment (mean 8 days) RCT with 44 patients treated with vitamin C, D, K, and zinc, and 46 control patients, showing no significant differences. Authors acknowledge that the very late treatment is a major limitation, noting that in an ideal setting, "patients would begin taking therapeutic interventions immediately after noticing symptoms". Authors note that patients already had a low symptom burden at baseline and that "it is likely that the majority of the participants had almost fully recovered before starting treatment." Authors note that most participants were young, had few comorbidities and had excellent self-rated health at baseline, leaving less room for improvement. There was low compliance with completing surveys. Data from only 64% of patients was in the main analysis. Authors claim "high internal validity", but the loss of data was statistically significantly..
Sep 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2023-073761, https://c19p.org/seely
Early terminated low-risk population (no hospitalization) very late treatment (mean 8 days) RCT with 44 patients treated with vitamin C, D, K, and zinc, and 46 control patients, showing no significant differences. Authors acknowledge that the very late treatment is a major limitation, noting that in an ideal setting, "patients would begin taking therapeutic interventions immediately after noticing symptoms". Authors note that patients already had a low symptom burden at baseline and that "it is likely that the majority of the participants had almost fully recovered before starting treatment." Authors note that most participants were young, had few comorbidities and had excellent self-rated health at baseline, leaving less room for improvement. There was low compliance with completing surveys. Data from only 64% of patients was in the main analysis. Authors claim "high internal validity", but the loss of data was statistically significantly..
Sep 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2023-073761, https://c19p.org/seelyz
Retrospective 849 COVID-19+ patients in skilled nursing homes, showing lower risk of combined hospitalization/death with vitamin D prophylaxis, very close to statistical significance.
Jan 2022, Gerontology, https://www.karger.com/Article/FullText/521412, https://c19p.org/levy
Prospective study of 206 outpatients in Iran, 103 treated with spironolactone and sitagliptin, showing lower hospitalization and faster recovery with treatment. spironolactone 100mg and sitagliptin 100mg daily.
Jan 2022, J. Endocrinological Investigation, https://link.springer.com/10.1007/s40618-023-02141-0, https://c19p.org/davarpanah
Prospective study of 206 outpatients in Iran, 103 treated with spironolactone and sitagliptin, showing lower hospitalization and faster recovery with treatment. spironolactone 100mg and sitagliptin 100mg daily.
Jan 2022, J. Endocrinological Investigation, https://link.springer.com/10.1007/s40618-023-02141-0, https://c19p.org/davarpanahsp
Prospective PSM study of 51 COVID-19 ICU patients in Croatia and 51 matched controls, showing significantly lower mortality with treatment.
Oct 2021, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15126, https://c19p.org/calusic
Retrospective 70 hospitalized patients in Italy, 28 treated with probiotic Sivomixx, showing lower risk of respiratory failure and faster recovery with treatment.
Jul 2020, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2020.00389/full, https://c19p.org/dettorre
RCT 42 hospitalized patients in the USA, showing improved recovery and lower progression with progesterone treatment.
Jul 2021, Chest, https://www.sciencedirect.com/science/article/pii/S0012369221002890, https://c19p.org/ghandehari
Retrospective 100 patients in India with 50 treated with ivermectin, and SOC for all patients including HCQ+AZ, showing much higher viral clearance with ivermectin. Baseline clinical status was worse in the control group. Time of testing after treatment initiation was longer in the control group (mean 7.24 days versus 5.22 days).
Mar 2021, Int. J. Health and Clinical Research, https://ijhcr.com/index.php/ijhcr/article/view/1263, https://c19p.org/mourya
Retrospective 450 late stage (median oxygen saturation 86%) COVID+ hospitalized patients in Peru, showing lower mortality with colchicine treatment.
Jun 2021, Revista Peruana de Medicina Experimental y Salud Pública, https://rpmesp.ins.gob.pe/rpmesp/article/view/7158, https://c19p.org/huedazavaleta
Observational study 1,064 hospitalized patients in the Netherlands, 53% reduced risk of transfer to the ICU for mechanical ventilation with HCQ treatment starting on the first day of admission. Weighted propensity score adjusted hazard ratio for transfer to the ICU with HCQ treatment, HR = 0.47, p = 0.008. For CQ, HR = 0.8, p = 0.207. Mortality results in this study are only for mortality before transfer to the ICU. The combined ICU/death HR was 0.68, p = 0.024 for HCQ, and 0.85, p = 0.224 for CQ. Observational, multicenter, cohort study of hospitalized COVID-19 patients. 189 HCQ patients, 377 CQ, 498 control.
Sep 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220321755, https://c19p.org/lammers
Retrospective 4035 hospitalized patients in Spain showing reduced mortality with HCQ (data is in the supplementary appendix).
Aug 2020, Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30431-6/fulltext, https://c19p.org/berenguer
Retrospective 1,687 nursing home residents in the USA, showing significantly lower risk of mortality with chronic low-dose aspirin use. Low dose 81mg aspirin users had treatment ≥10 of 14 days prior to the positive COVID date, control patients had no aspirin use in the prior 14 days.
Aug 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.03.22278392, https://c19p.org/abul
Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HCQ+AZ) or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched patients.
May 2020, Asian J. Medicine and Health, https://www.journalajmah.com/index.php/AJMAH/article/view/30224, https://c19p.org/guerin
Retrospective PSM analysis of 232 hospitalized patients, 28 treated with aspirin, showing lower mortality with treatment. There was no significant difference in viral clearance.
Feb 2021, Medicine, https://journals.lww.com/md-journal/Fulltext/2021/02120/Effect_of_low_dose_aspirin_on_mortality_and_viral.41.aspx, https://c19p.org/liu2
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3azaz
Small RCT with 60 severe hospitalized patients in Iran, 30 treated with quercetin, showing shorter time until discharge. All patients received remdesivir or favipiravir, and vitamin C, vitamin D, famotidine, zinc, dexamethasone, and magnesium (depending on serum levels). Quercetin 1000mg daily for 7 days. IRCT20200419047128N2.
Dec 2021, European J. Pharmacology, https://www.sciencedirect.com/science/article/pii/S0014299921007718, https://c19p.org/shohan
Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with vitamin D (defined as being picked up within 35 days prior to PCR+). Other patients may have acquired vitamin D supplements outside of the healthcare system.
Jul 2021, Epidemiology and Global Health Microbiology and Infectious Disease, https://elifesciences.org/articles/68165, https://c19p.org/israel2
Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with vitamin D supplementation. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2
Retrospective 140 diabetic patients in France, showing lower mortality for patients where metformin use was continued after hospitalization.
Nov 2021, Diabetes & Metabolism, https://www.sciencedirect.com/science/article/pii/S126236362100080X, https://c19p.org/alsalameh
RCT 4,862 community-dwelling adults in Denmark, showig no significant difference in COVID-19 cases with recommending the use of surgical masks outside the home. The prespecified mortality outcomes are not reported and the only severity information provided is symptom counts.
Nov 2020, Annals of Internal Medicine , https://www.acpjournals.org/doi/10.7326/M20-6817, https://c19p.org/bundgaard
Retrospective 775 nursing home residents in the USA, showing lower mortality with existing metformin use.
Jan 2021, J. the American Medical Directors Association, https://www.sciencedirect.com/science/article/pii/S1525861020309245, https://c19p.org/lally
64% lower hospitalization with HCQ. Retrospective 717 patients in Brazil with early treatment, adjusted OR 0.32, p=0.00081, for HCQ versus no medication, and OR 0.45, p=0.0065, for HCQ vs. anything else.
Oct 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/abs/pii/S1477893920304026, https://c19p.org/fonseca
70% lower mortality with vitamin D supplementation. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, vitamin D supplementation RR 0.30, p = 0.04. The paper provides the p value for regression but not the effect size. Treatment was 2x per month 25000IU.
Dec 2020, Aging, https://www.aging-us.com/article/202307/text, https://c19p.org/cangianod
Retrospective study from two registries of 1,096 COVID-19 patients with chronic liver disease, including 31 treated with ursodeoxycholic acid (UDCA). Propensity score matching was used to compare outcomes between UDCA-treated and untreated patients. The analysis found that UDCA treatment was associated with reduced hospitalization, ICU admission, ventilation, and death from COVID-19. The authors suggest that UDCA may decrease susceptibility to SARS-CoV-2 infection by downregulating the host receptor ACE2 through inhibition of the farnesoid X receptor. Authors also show that UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ; and that UDCA reduces the expression of ACE2 in the nasal epithelium in humans.
Dec 2022, Nature, https://www.nature.com/articles/s41586-022-05594-0, https://c19p.org/brevini
RCT 194 mild/asymptomatic low-risk patients in Cameroon, 97 treated with HCQ+AZ and 97 treated with doxycycline, showing 2.1% symptomatic patients at day 10 with HCQ+AZ, versus 4.3% with doxycycline, without statistical significance. There were only 6 patients with symptoms at day 10. There was no mortality or hospitalization, and no major adverse events.
Jul 2021, Cureus, https://www.cureus.com/articles/179159-doxycycline-vs-hydroxychloroquine--azithromycin-in-the-management-of-covid-19-patients-an-open-label-randomized-clinical-trial-in-sub-saharan-africa-doxycov, https://c19p.org/sobngwi
Prospective study of 260 hospitalized patients in Taiwan, 117 treated with herbal formula Jing Si Herbal Tea which includes antiandrogen glycyrrhiza glabra, showing improved recovery with treatment, with statistical significance for SpO2, Ct score, CRP, and Brixia score.
Mar 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.832321/full, https://c19p.org/hsieh
Retrospective 2,746 individuals in China showing significantly lower incidence of COVID-19 symptoms and fever with higher vitamin C intake, with a dose response relationship.
May 2024, The American J. the Medical Sciences, https://www.sciencedirect.com/science/article/pii/S0002962924012229, https://c19p.org/guan2
Retrospective 2,862 hospitalized COVID-19 patients in China showing lower mortality with azvudine treatment.
Mar 2024, Research Square, https://www.researchsquare.com/article/rs-4157424/v1, https://c19p.org/zhong6
Retrospective 319 hospitalized patients in Belgium showing significantly lower mortality with HCQ.
Nov 2020, BMC Infectious Diseases, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691970/, https://c19p.org/vanhalem
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3e
RCT with 66 very late stage (8 days from symptom onset) hospitalized patients, 44 treated with vitamin C and 22 control patients, showing no significant differences with treatment.
Mar 2022, Life, https://www.mdpi.com/2075-1729/12/3/453, https://c19p.org/coppock
Study of SARS-CoV-2-IgG antibodies in 1122 health care workers in India finding 87% lower positives for adequate HCQ prophylaxis, 1.3% HCQ versus 12.3% for no HCQ prophylaxis. Adequate prophylaxis is defined as 400mg 1/wk for >6 weeks.
Oct 2020, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3689618, https://c19p.org/goenka
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizi
840 patient HCQ late treatment study: 78% lower mortality (p<0.0001).
Retrospective 750 COVID-19 patients in Saudi Arabia, showing lower mortality with HCQ treatment in unadjusted results. Authors note that the poor results in some other trials may be related to increased dosages and later treatment.
Apr 2023, J. Multidisciplinary Healthcare, https://www.dovepress.com/profiles-of-independent-comorbidity-groups-in-senior-covid-19-patients-peer-reviewed-fulltext-article-JMDH, https://c19p.org/said2
Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm) - as per protocol mid-recovery results have priority. There was no mortality and only one hospitalization on day 0 before treatment. There were no severe adverse events.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.22.21252228v1, https://c19p.org/amaravadi
PSM retrospective 72 indomethacin and 72 paracetamol patients in India, showing lower progression and improved recovery with indomethacin.
Jul 2021, J. the Indian Medical Association, https://sapiensfoundation.org/wp-content/uploads/2021/08/Use-of-Indomethacin-in-Covid-19-patients-JIMA-2021.pdf, https://c19p.org/ravichandran2
Retrospective 113 outpatients, 53 (patient choice) treated with zinc, quercetin, vitamin C/D/E, l-lysine, and quina, showing lower cases with treatment. Results are subject to selection bias and limited information on the groups is provided. See [journals.sagepub.com].
Jul 2021, J. Evidence-Based Integrative Medicine, https://journals.sagepub.com/doi/full/10.1177/2515690X211026193, https://c19p.org/margolinq
PSM retrospective 9,638 patients in the USA, showing significantly lower mortality with HCQ in early 2020 (1,157 HCQ patients), and no significant difference in late 2020 (82 HCQ patients). The few patients treated in the later period may be in more serious condition due to the effort required to overcome the politicization and censorship in the study country. Authors refer to their result as "no relevant benefit in mortality between the two surges".
Feb 2023, Research Square, https://www.researchsquare.com/article/rs-2596201/v1, https://c19p.org/delgado
RCT very late treatment (>10 days from onset) comparing hydrogen peroxide + mint essence with water + mint essence, showing no significant differences.
Apr 2021, Epidemiology and Health, http://e-epih.org/journal/view.php?doi=10.4178/epih.e2021032, https://c19p.org/didomenico
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizisp
Very small late stage RCT with 10 control patients and 29 enzalutamide patients, showing mixed results. Discharge and hospitalization time favored the control group, while viral load reduction was better with treatment on days 4&6 (day 4 ΔCt −5.6 p = 0.084), and the only death occurred in the control group. 27% of enzalutamide patients had diabetes compared to 0% of the control group. This paper also includes a retrospective study which is listed separately, and an In Vitro HBEC study showing no significant differences (p = 0.084). The supplementary data is not currently available. NCT04475601. For discussion of issues with this study see [sciencedirect.com, sciencedirect.com, sciencedirect.com, sciencedirect.com].
Dec 2021, European Urology, https://www.europeanurology.com/article/S0302-2838(21)02224-7/fulltext, https://c19p.org/welen
RCT 23 patients in Colombia, showing improved viral clearance with cetylpyridinium chloride plus chlorhexidine mouthwash.
May 2023, Revista Estomatologia, https://estomatologia.univalle.edu.co/index.php/revista_estomatologia/article/download/12669/15872, https://c19p.org/rengifo
Open label RCT with 100 hospitalized patients in Iran, 50 treated with colchicine, showing shorter hospitalization time with treatment. There were no deaths.
Sep 2020, Mediterranean J. Rheumatology, http://www.mjrheum.org/assets/files/792/file382_1566.pdf, https://c19p.org/salehzadeh
Retrospective 9,748 COVID-19 patients in the USA showing lower risk with vitamin B12 use, without statistical significance.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejan
PSM retrospective 312 hospitalized patients in Japan, showing lower progression with vitamin D (alfacalcidol) treatment, statistically significant via KM log-rank.
Aug 2023, Clinical Nutrition, https://www.sciencedirect.com/science/article/pii/S0261561423002790, https://c19p.org/ogasawara
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhemz
Retrospective 34,936 hypertensive outpatients in Spain showing no significant difference in COVID-19 cases with PPIs and antihistamine H1RAs.
Jul 2020, The J. Clinical Hypertension, https://onlinelibrary.wiley.com/doi/10.1111/jch.13948, https://c19p.org/vilacorcoles2h1
36 patient HCQ late treatment study: 88% lower ICU admission (p=0.008).
Retrospective analysis of 36 hospitalized patients showing HCQ/AZ associated with lower ICU admission, p=0.008. Median age 66, no mortality. Confounding by indication, however it was patients with hypoxemic pneumonia that were treated with HCQ/AZ, patients were not treated with HCQ/AZ if they didn't need oxygen therapy.
Aug 2020, J. Global Antimicrobial Resistance, https://www.sciencedirect.com/science/article/pii/S221371652030206X, https://c19p.org/dubernet
Prospective study of 1,124 COVID-19 ICU patients, showing lower mortality with aspirin treatment.
Nov 2022, Research Square, https://www.researchsquare.com/article/rs-2313880/v1, https://c19p.org/aidouni
Retrospective 4,201 hospitalized COVID-19 patients in China, showing lower mortality with azvudine.
Jan 2024, Research Square, https://www.researchsquare.com/article/rs-3707560/v1, https://c19p.org/li28
Retrospective 40 hospitalized patients in Italy treated with melatonin and 40 control patients, showing improved sleep, reduced delirium, shorter hospitalization and oxygen times, and reduced ICU admission and mortality (not statistically significant).
Dec 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/24/5857, https://c19p.org/bologna
Retrospective 977 hospitalized patients in Saudi Arabia, showing significantly shorter hospitalization with zinc treatment.
Jun 2022, Healthcare, https://www.mdpi.com/2227-9032/10/7/1201, https://c19p.org/alahmari
Retrospective 1,190 ICU patients in Egypt, showing lower mortality with aspirin treatment. 150mg daily.
Oct 2022, Egyptian J. Anaesthesia, https://www.tandfonline.com/doi/full/10.1080/11101849.2022.2139104, https://c19p.org/ali6
Prospective study of 410 hospitalized patients in India showing lower mortality and ICU admission with cholecalciferol treatment, although not statistically significant with the small number of cases. The median total dose was 60,000IU. No significant difference was found for outcomes based on baseline vitamin D deficiency, however this analysis does not appear to account for the deficient patients that were treated with vitamin D.
Dec 2020, Scientific Reports, https://www.nature.com/articles/s41598-021-85809-y, https://c19p.org/jevalikar
Retrospective 103 hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir in unadjusted results, and greater efficacy for treatment within 3 days of admission.
Jun 2022, Advances in Virology, https://www.hindawi.com/journals/av/2022/9240941/, https://c19p.org/tawfik
Retrospective 1,787 hospitalized COVID-19 patients in the United Arab Emirates, identifying hydroxychloroquine as reducing the risk of ICU admission in a machine learning model. Only unadjusted quantitative results are provided, which also show a benefit.
Jan 2024, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291373, https://c19p.org/alshehhi
RCT with 55 patients (36 favipiravir, 19 control) who were PCR+ after recovery, showing improved viral clearance with treatment.
Apr 2021, Int. Immunopharmacology, https://www.sciencedirect.com/science/article/pii/S1567576921003386, https://c19p.org/zhao2
Rheumatic disease patients on HCQ had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for age, sex, smoking, systemic lupus erythematosus, infection in other family members, and comorbidities. 43 patients with rheumatic disease and COVID-19 exposure.
Jul 2020, Lancent Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30227-7/fulltext, https://c19p.org/zhong
Small 116 patient RCT with low-risk patients comparing ivermectin+doxycycline and HCQ+AZ, showing lower hospitalization, higher viral clearance, and faster symptom resolution and viral clearance with ivermectin+doxycycline. Mid-recovery resolution of symptoms is statistically significantly better with treatment, while other measures do not reach statistical significance. Instructions were to take ivermectin on an empty stomach, reducing lung tissue concentration.
Jul 2020, Eurasian J. Medicine and Oncology, https://ejmo.org/10.14744/ejmo.2021.16263/, https://c19p.org/chowdhury
RCT 7,763 hospitalized COVID-19 patients showing no significant differences with very late (75% on oxygen at baseline) azithromycin treatment. Only 91% of treatment patients received azithromycin and 17% of control patients received azithromycin or other macrolides.
Feb 2021, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673621001495, https://c19p.org/abalekeaz
This paper has conflicting values, table S2 shows 12 control hospitalizations, while table 2 shows 11. The original report for this paper had more conflicting values, with values reported in Table 2 and the abstract corresponding to 12 control hospitalizations, while others corresponded to 11 control hospitalizations. The counts in table S2 also do not match - n=290 is given for secondary endpoints but the three groups add up to n=238. The sum of the secondary endpoint counts for the control group in table 2 do not match the group size. One missing patient may be the 12th control hospitalization but there are 2 more missing. There was a 16% reduction in hospitalization and 34% reduction in the risk of no symptom resolution, without statistical significance due to small samples. Treatment delay is unknown at this time. They report a delay of up to 120 hours after symptoms plus an additional unspecified delay where medication was provided to patients at the first home visit. Authors..
Jul 2020, Clinical Infectious Diseases, ciaa1009, https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa1009/5872589, https://c19p.org/mitja
Retrospective COVID-19 patients requiring CPAP, 21 treated with SLAB51 probiotics and 15 control patients, showing improved outcomes with treatment, despite significantly lower blood oxygenation at baseline in the treatment group.
Jul 2022, Biomedicines, https://www.mdpi.com/2227-9059/10/8/1851, https://c19p.org/trinchieri
Small prospective study in Italy with 32 lactoferrin patients, 32 SOC, and 28 patients with no treatment, showing significantly faster viral clearance and improved recovery with treatment. Oral and intranasal lactoferrin.
Oct 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/20/10985, https://c19p.org/campione
HCQ reduced cases from 38% to 7%. 106 people. No serious adverse effects.
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.09.20116806v1, https://c19p.org/bhattacharya
Small prophylaxis RCT with 113 patients showing fewer cases with quercetin + vitamin C + bromelain prophylaxis. Note that this paper disappeared from SSRN without explanation.
Nov 2020, SSRN, https://europepmc.org/article/ppr/ppr239932, https://c19p.org/arslan
Small RCT with 56 eldery diabetes patients hospitalized in Egypt, 40 treated with cholecalciferol, not showing significant differences.
Aug 2021, Proceedings of Singapore Healthcare, https://journals.sagepub.com/doi/full/10.1177/20101058211041405, https://c19p.org/soliman
RCT 31 hospitalized COVID-19 patients with mild hypoxemia showing no significant difference in mechanical ventilation, ICU admission, or mortality with addition of losartan to standard care.
May 2021, Infectious Diseases and Therapy, https://link.springer.com/10.1007/s40121-021-00453-3, https://c19p.org/geriak
Retrospective 9,748 COVID-19 patients in the USA showing lower risk of mortality, ventilation, and ICU admission with vitamin C prophylaxis, without statistical significance.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanc
PSM retrospective 41,608 patients in the USA, 1,072 treated with ivermectin and 40,536 treated with remdesivir, showing lower mortality with ivermectin treatment. This study was presented at a conference (IMED 2021). Submissions were peer-reviewed. The treatment/control group sizes align with the estimated percentage of hospitals that used ivermectin vs. remdesivir. Hospitals in the USA receive financial incentives to use remdesivir. Authors have self-censored the conference report of this result, not due to any error in the analysis, but because they believe ivermectin "has proven to be ineffective in clinical trials". This is incorrect, while some studies show no statistically significant effect, studies show statistically significant positive results for one or more outcomes ( prospective and retrospective studies, including RCTs). The self-censorship and decision not to submit to a journal provide further evidence of a negative publication bias for ivermectin research. This study was self-censored by the authors.
Feb 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221009887, https://c19p.org/efimenko
Analysis of 3,947 participants in Vietnam, showing significantly lower risk of COVID-19-like symptoms with physical activity and with a healthy diet. The combination of being physically active and eating healthy reduced risk further compared to either alone. The analyzed period was Feb 14 to Mar 2, 2020, which may have been before testing was widely available.
Sep 2021, Nutrients, https://www.mdpi.com/2072-6643/13/9/3258, https://c19p.org/nguyen2dt
RCT 70 ivermectin+doxycycline patients and 70 control patients showing reduced time to recovery and reduced mortality with treatment. Earlier treatment was more successful. For ethical reasons, critical patients were all in the treatment group. NCT04591600.
Oct 2020, Iraqi J. Medical Science, http://www.iraqijms.net/upload/pdf/iraqijms60db8b76d3b1e.pdf, https://c19p.org/hashim
Authors have not responded to a request for the data. Outpatient RCT with 687 HCQ and 682 control patients in Brazil, showing lower hospitalization with treatment, not reaching statistical significance. Higher efficacy was seen with treatment <4 days from onset, RR 0.61. The associated meta analysis includes mostly late treatment studies, for example in [Schwartz] the median delay from onset was 7 days. [Omrani] is missing. The values for [Johnston] are incorrect - the study shows 4 hospitalizations in the control arm - RR for this study should be 0.58 instead of 0.78.
Mar 2022, The Lancet Regional Health - Americas, https://www.sciencedirect.com/science/article/pii/S2667193X22000606, https://c19p.org/avezum
Very late stage (APACHE II 8 and 12 for non-critical and critical) RCT with publication delayed over a year showing higher ventilation and no significant difference in mortality with vitamin C. Authors have combined what was to be two separate trials into one trial, however there are very large differences between the trials. The results for each source trial are shown separately here [Adhikari, Adhikari]. eTable 15 shows that results in LOVIT-COVID were substantially better than those in REMAP-CAP. eTable 13 shows improved survival for LOVIT-COVID and worse survival for REMAP-CAP (authors provide mortality breakdown only for hospital survival): LOVIT-COVID shows 85% and 82% probability of superiority of vitamin C (critical and non-critical). REMAP-CAP shows 12% and 7% probability of superiority of vitamin C. Notably, LOVIT-COVID patients were blinded, while REMAP-CAP was open-label, introducing additional opportunity for bias on this highly politicized treatment. REMAP-CAP had more..
Oct 2023, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2811212, https://c19p.org/adhikari2b
Retrospective 30 COVID-19 ARDS ICU patients and 30 control patients, showing lower mortality with treatment.
Oct 2021, Aydin Sağlik Dergi̇si̇, https://dergipark.org.tr/en/pub/asder/issue/65413/959218, https://c19p.org/ersoy
Retrospective 30 COVID-19 ARDS ICU patients and 30 control patients, showing lower mortality with treatment.
Oct 2021, Aydin Sağlik Dergi̇si̇, https://dergipark.org.tr/en/pub/asder/issue/65413/959218, https://c19p.org/ersoysp
Retrospective 246 hospitalized patients in Indonesia, 136 treated with curcumin, showing shorter hospitalization time with treatment. All patients received vitamin C, D, and zinc.
Jan 2022, ICE on IMERI, 2021, http://web.archive.org/web/20220209083251/http://writingcenter.fk.ui.ac.id/index.php/p/article/view/40, https://c19p.org/kartika
Retrospective 209 hospitalized patients in Colombia, showing lower mortality with antibiotics + LMWH + corticosteroids + colchicine in multivariable analysis.
Mar 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121000575?via%3Dihub, https://c19p.org/garciaposada
RCT 200 patients in Ukraine, 99 treated with IV quercetin/polyvinylirolidone followed by oral quercetin/pectin, showing improved recovery with treatment.
Aug 2021, Zaporozhye Med. J., http://zmj.zsmu.edu.ua/article/view/231714, https://c19p.org/zupanets
Retrospective 7,345 hospitalized COVID-19 patients in France showing lower mortality with hydroxyzine use, with a significant dose-response relationship. Hydroxyzine was also associated with a faster decrease in inflammatory markers.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.23.20154302, https://c19p.org/hoertel6
Early terminated late stage (8 days from onset, 59% on oxygen) RCT not showing statistically significant differences. NNF20SA0062834.
Jun 2021, European Respiratory J., https://erj.ersjournals.com/content/early/2021/05/28/13993003.00752-2021.article-info, https://c19p.org/sivapalan
Retrospective 11,468 vaccinated rheumatic disease patients in the USA, showing lower risk of COVID-19 with HCQ/CQ use compared with all other treatments. Adjusted results are only provided with respect to specific other treatments.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.13.22277606, https://c19p.org/patel4
Retrospective 99 COVID-19 patients in Argentina showing significantly lower mortality with inhaled alkaline hypertonic ibuprofen (AHI) treatment. The treatment has a pH of 8.5. 3 times daily for 7-10 days.
Dec 2022, European J. Respiratory Medicine, https://europeanjournalofrespiratorymedicine.com/safety-and-efficacy-of-nebulised-anti-inflammatory-solution-of-alkaline-hypertonic-ibuprofen-ahi-for-treatment-of-sars-cov-2-infection-a-compassionate-study-with-a-comparator-arms, https://c19p.org/kalayanph
Retrospective 3,712 hospitalized patients in Egypt, showing lower mortality with HCQ treatment in unadjusted results. According to the official treatment protocol, HCQ was recommended with higher risk and/or more serious cases.
Jan 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262348, https://c19p.org/abdelghaffar
148 patient diet study: 45% lower severe cases (p=0.06) and 32% improved viral clearance (p=0.03).
Retrospective 148 hospitalized COVID-19 patients in China, showing lower severity and faster viral clearance with improved nutrition.
Jul 2023, Infection and Drug Resistance, https://www.dovepress.com/improving-nutritional-status-was-associated-with-decreasing-disease-se-peer-reviewed-fulltext-article-IDR, https://c19p.org/wang18
Retrospective 510 patients in Iran, showing lower risk of severity with vitamin D (statistically significant) and zinc (not statistically significant) supplementation. IR.TUMS.VCR.REC.1398.1063.
Aug 2021, J. Family & Reproductive Health, https://europepmc.org/article/PMC/PMC7868648, https://c19p.org/bagheri
Retrospective 10,074 hospitalized veterans with COVID-19 in the USA, showing lower mortality with existing famotidine use.
Oct 2021, Nicotine & Tobacco Research, https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntab223/6409756?login=false, https://c19p.org/razjouyan
Retrospective 848 ICU patients in Saudi Arabia, showing lower mortality with HCQ in unadjusted results.
May 2023, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170223000122, https://c19p.org/alqadheeb
PSM retrospective 6,218 hospitalized COVID-19 patients in China showing lower 28-day all-cause mortality with azvudine treatment compared to controls (HR 0.63, 95% CI 0.40-1.00). Subgroup analysis found significantly faster clinical improvement when azvudine was initiated within 5 days of symptom onset compared to controls.
Jul 2023, Research Square, https://www.researchsquare.com/article/rs-3145554/v1, https://c19p.org/han
Prospective study of 24 hospitalized COVID-19 patients in Russia treated with NAC, and 22 matched controls, showing significantly improved SpO2/FiO2, and significantly shorter hospitalization with treatment.
Jul 2021, J. Infection, https://www.journalofinfection.com/article/S0163-4453(21)00329-7/fulltext, https://c19p.org/avdeev
Retrospective 58 prostate cancer patients in the USA, showing lower risk of hospitalization with ADT.
Jul 2020, Annals of Oncology, https://www.annalsofoncology.org/article/S0923-7534(20)39933-6/fulltext, https://c19p.org/patel3
Very late stage RCT with 56 colchicine and 60 control patients in Mexico, showing no significant differences.
Nov 2021, J. General Internal Medicine, https://link.springer.com/article/10.1007/s11606-021-07203-8, https://c19p.org/absalonaguilar
166 patients hospitalised with COVID-19, HCQ increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients were in relatively serious condition.
May 2020, Preprints, https://www.preprints.org/manuscript/202005.0057, https://c19p.org/membrillo
Retrospective 356 Hashimoto's thyroiditis outpatients, 270 taking vitamin D, zinc, and selenium, showing significantly lower hospitalization with treatment. Authors adjust for age, gender, BMI, and smoking status, reporting statistically significant associations with p<0.001 for hospitalization and mechanical ventilation, however they do not report the adjusted risks.
May 2021, Endocrine Abstracts, https://www.endocrine-abstracts.org/ea/0073/ea0073pep14.2, https://c19p.org/asimi
Retrospective 356 Hashimoto's thyroiditis outpatients, 270 taking vitamin D, zinc, and selenium, showing significantly lower hospitalization with treatment. Authors adjust for age, gender, BMI, and smoking status, reporting statistically significant associations with p<0.001 for hospitalization and mechanical ventilation, however they do not report the adjusted risks.
May 2021, Endocrine Abstracts, https://www.endocrine-abstracts.org/ea/0073/ea0073pep14.2, https://c19p.org/asimiz
Retrospective 403 hospitalized patients in Spain, showing lower mortality with treatment, however authors do not adjust for the differences between the groups. Confounding by indication is likely.
May 2021, Archivos de Medicina Universitaria, https://digibug.ugr.es/handle/10481/69170, https://c19p.org/ramirezgarcia
Small RCT with 27 famotidine and 28 placebo patients, showing improved recovery with treatment. Recovery was faster with treatment for 14 of 16 symptoms. There was no mortality or hospitalization. NCT04724720.
Feb 2022, Gut, https://gut.bmj.com/content/early/2022/02/09/gutjnl-2022-326952, https://c19p.org/brennan
PSM retrospective 2,785 hospitalized patients in the USA, showing lower mortality and higher ventilation and ICU admission with aspirin treatment.
Nov 2020, Blood, https://ashpublications.org/blood/article/136/Supplement%201/23/470342/Admission-Rothman-Index-Aspirin-and-Intermediate, https://c19p.org/goshua
Small RCT 60 ICU patients in Iran, 30 treated with vitamins A, B, C, D, and E, showing significant improvement in SOFA score and several inflammatory markers at day 7 with treatment. 5,000 IU vitamin A daily, 600,000 IU vitamin D once, 300 IU of vitamin E twice a day, 500 mg vitamin C four times a day, and one ampule daily of B vitamins [thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg].
Nov 2021, Trials, https://link.springer.com/article/10.1186/s13063-021-05795-4/fulltext.html, https://c19p.org/beigmohammadi2a
RCT with 50 hospitalized COVID+ patients in Egypt, 25 treated with glycyrrhizin and boswellic acid, showing improved recovery with treatment. Glycyrrhizin 60mg and boswellic acid 200mg bid for 2 weeks. NCT04487964.
Feb 2022, Inflammopharmacology, https://link.springer.com/article/10.1007/s10787-022-00939-7, https://c19p.org/gomaa
97 patient HCQ late treatment study: 51% shorter hospitalization (p=0.01) and 56% faster viral clearance (p=0.005).
Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HCQ+antibiotic. Preprint withdrawn pending peer review.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.13.20094193v1?versioned=true, https://c19p.org/kim
Retrospective 1,276 hospitalized patients showing significantly faster viral clearance with HCQ. Authors also perform a meta-analysis of 9 studies, with 1,461 HCQ-treated patients and 958 controls, showing significantly faster viral clearance with HCQ on day 7.
Jul 2024, Acta Scientific Microbiology, https://actascientific.com/ASMI/pdf/ASMI-07-1413.pdf, https://c19p.org/brouqui4
Retrospective 235 hospitalized diabetes patients in South Korea, showing lower mortality and lower progression to severe disease with metformin.
Aug 2020, Diabetes & Metabolism J., https://www.e-dmj.org/journal/view.php?doi=10.4093/dmj.2020.0146, https://c19p.org/kim3
Phase 2 RCT of sabizabulin showing lower mortality with treatment. For more discussion see [twitter.com].
Apr 2022, European Congress of Clinical Microbiology & Infectious Diseases, https://verupharma.com/news/veru-announces-oral-late-breaking-presentation-of-phase-2-data-of-sabizabulin-for-the-treatment-of-hospitalized-severe-covid-19-patients-at-high-risk-for-acute-respiratory-distress-syndrome-at-the-32n/, https://c19p.org/gordon2
RCT 546 patients showing significantly faster recovery and lower mortality with sodium bicarbonate (inhaled and nasal drops). The reduction in mortality is only statistically significant when excluding baseline critical cases. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Nov 2022, Research Square, https://www.researchsquare.com/article/rs-2214180/v1, https://c19p.org/elbadrawy
RCT 546 patients showing significantly faster recovery and lower mortality with sodium bicarbonate (inhaled and nasal drops). The reduction in mortality is only statistically significant when excluding baseline critical cases. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Nov 2022, Research Square, https://www.researchsquare.com/article/rs-2214180/v1, https://c19p.org/elbadrawysb
Observational study of 43 patients >= 50 years old, with 17 patients receiving vitamin D, magnesium, and vitamin B12 (DMB); and 26 control patients, showing a significantly lower need for oxygen therapy and ICU admission with treatment. DMB OR 0.20 [0.04–0.93] for oxygen therapy and/or intensive care support with multivariate analysis.
Jun 2020, Nutrition, https://www.sciencedirect.com/science/article/pii/S0899900720303002, https://c19p.org/tan
3,885 patient HCQ late treatment study: 36% lower mortality (p=0.005).
Retrospective 352 hospitalized COVID-19 patients in Belgium and 3,533 control patients from the contemporaneous Belgian Collaborative Group, showing significantly lower mortality with HCQ treatment. The survival benefit was consistent in all age groups. No torsade de pointes or ventricular arrhythmias were observed. Mean time from onset is not provided, but 43% of patients with known onset were admitted within 5 days, making the efficacy consistent with expectations based on the treatment delay [c19hcq.org]. HCQ 800mg day one, 200mg bid for five days, according to national guidelines. Authors note that the poor results in SOLIDARITY/RECOVERY may be related to the excessively high doses used. Most patients also received AZ. Adjusted results are only provided for all HCQ patients. Publication was delayed over 3 years. Authors reported in 2021 that the paper had been rejected by the editors of four different journals, without peer review [twitter.com].
Sep 2023, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297523000914, https://c19p.org/meeus
Prospective study of 9,212 autoimmune rheumatic disease patients showing lower mortality with HCQ, without reaching statistical significance. Authors incorrectly state "HCQ use did not influence occurrence of COVID-19 (RR = 0.909, CI (0.715,1.154), p = 0.432) or mortality (p = 0.097)" [nature.com]. CFR for the autoimmune rheumatic disease patients was 4.6 times higher than in the general population from the same area.
Aug 2021, Research Square, https://www.researchsquare.com/article/rs-805748/v1, https://c19p.org/patil
Small retrospective study of 29 hip fracture patients in the UK, 14 with COVID-19. All COVID-19 patients were treated with vitamin D except for 2 where testing and supplementation was missed due to a clerical error. The two COVID-19 patients that died were the two that did not receive vitamin D supplementation.
Feb 2021, SICOT-J, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7888253/#!po=1.28205, https://c19p.org/burahee
RCT of PCR+ patients with Ct<=20 with 12 treatment and 12 control patients, concluding that nasopharyngeal decolonization may reduce the carriage of infectious SARS-CoV-2 in adults with mild to moderate COVID-19. All patients but 1 had negative viral titer by day 3 (group not specified). There was no significant difference in viral RNA quantification over time. The mean relative difference in viral titers between baseline and day 1 was 75% [43%-95%] in the intervention group and 32% [10%-65%] in the control group. Thyroid dysfunction occurred in 42% of treated patients, with spontaneous resolution after the end of treatment. Patients in the treatment group were younger.
Feb 2021, JAMA Otolaryngol Head Neck Surg., https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2775984, https://c19p.org/guenezan
RCT 50 preschool children, 25 treated with bovine lactoferrin (bLf) prophylaxis, showing significantly lower frequency and duration of respiratory infections during the active phase with treatment. The only COVID-19 specific results reported are the number as patients with COVID, 1 vs. 2 for treatment vs. control. bLf 400mg bid for 4 months.
Feb 2024, Children, https://www.mdpi.com/2227-9067/11/2/249, https://c19p.org/pasinato
RCT of relatively low risk hospitalized patients with 50 ivermectin and 50 control patients showing significantly faster viral clearance with treatment. 9 patients in the treatment arm were lost to followup compared with 5 in the control arm, which could be in part due to faster recovery with treatment. There were no safety concerns. No mortality was reported. The numbers in Table 3 are the number of patients that became negative on that day, i.e., non-cumulative. SOC included vitamin C and vitamin D. NCT04392713.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.02.21250840v1, https://c19p.org/bukhari
Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.03.20239863v1, https://c19p.org/modrak
Prophylaxis study with 376 mostly high-risk patients, 188 treated with nigella sativa, showing significantly lower cases with treatment. Black seeds 40mg/kg orally once daily.
Jan 2021, Pakistan J. Medical and Health Sciences, https://pjmhsonline.com/2021/jan/384.pdf, https://c19p.org/alhaidari2
RCT very late treatment (>9 days from onset) comparing hydrogen peroxide + mint essence with water + mint essence, showing no significant differences.
Aug 2021, Epidemiology and Health, http://e-epih.org/journal/view.php?doi=10.4178/epih.e2021051, https://c19p.org/didomenico2
Retrospective 352 prostate cancer patients in Finland, showing no significant differences in COVID-19 with ADT.
Jun 2020, Annals of Oncology, https://www.sciencedirect.com/science/article/pii/S0923753420399257, https://c19p.org/koskinen
Small RCT comparing ivermectin 6mg & 12mg q84hr with lopinavir/ritonavir, showing a statistically significant and dose dependent effect of ivermectin on reducing the time to PCR-. The study does not report mortality, hospitalization, progression, recovery, etc. The paper does report change in SpO2 (Figure 3, ∆Spo2), where a similar improvement with a smaller p value is seen with ivermectin, however this result is unadjusted and there are large differences between groups. Specifically, baseline SpO2 is lower in the control group, giving the control group more room to improve, therefore the actual benefit of ivermectin is likely to be even larger than the benefit in ∆SpO2 shown. See also [doyourownresearch.substack.com].
Jan 2021, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcab035/6143037, https://c19p.org/babalola
49 patient potassium canrenoate antiandrogen late treatment RCT: 17% lower mortality (p=1), 11% lower ICU admission (p=1), and 30% improved recovery (p=0.51).
RCT with 24 patients treated with potassium canrenoate and 25 placebo patients in Poland, showing no significant differences.
Feb 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/2/200, https://c19p.org/kotfis
150 patient very late stage RCT showing no significant difference. Treatment was very late, an average of 16.6 days after symptom onset. Data favorable to HCQ was deleted in the second version, see analysis [mediterranee-infection.com]. "[HCQ] accelerate[s] the alleviation of clinical symptoms"; "More rapid alleviation of clinical symptoms with SOC plus HCQ than with SOC alone was observed during the second week since randomization"; "The efficacy of HCQ on the alleviation of symptoms, HR 8.83 [1.09-71.3], was more evident when the confounding effects of other anti-viral agents were removed".
Apr 2020, BMJ 2020, 369, https://www.bmj.com/content/369/bmj.m1849, https://c19p.org/tang
RCT with 30 patients treated with curcumin and virgin coconut oil (VCO), and 30 SOC patients in Indonesia, showing faster viral clearance with treatment. Treatment also reduced IL-1β, IL-2, IL-6, IL-18, and IFN-β levels. VCO improves the bioavailability of curcumin. There were large unadjusted differences in baseline severity and age, for example 20% vs. 47% of patients >50. VCO 30ml and curcumin 1g tid for 21 days. 066/UN27.06.6.1/KEPK/EC/2020.
Feb 2022, Pharmacognosy J., https://phcogj.com/article/1755, https://c19p.org/hartono
120 patient RCT comparing vitamin D, nigella sativa, and combined vitamin D+nigella sativa, showing improved symptom recovery and viral clearance with both vitamin D and nigella sativa, and further improvements with the combination of both. All patients received vitamin C, zinc, and lactoferrin.
Nov 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.1011522/full, https://c19p.org/saidns
Retrospective 69 consecutive hospitalized COVID-19 patients in Italy, 30 patients receiving canrenone, and 39 treated with vasodilator agents or renin–angiotensin–aldosterone system (RAAS) inhibitors, showing lower mortality with canrenone.
Sep 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/9/2943, https://c19p.org/vicenzi
Prospective study with 221 healthcare workers, showing lower risk of COVID-19 with HCQ prophylaxis.
Aug 2021, NCT04333225, https://clinicaltrials.gov/study/NCT04333225, https://c19p.org/mccullough4
Retrospective 79,083 adults aged ≥50 years in Spain showing lower with of PCR-confirmed COVID-19 with antihistamine use, close to statistical significance.
Dec 2020, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2020-041577, https://c19p.org/vilacorcoles
RCT 100 outpatients in Pakistan, 50 treated with quercetin phytosome, showing faster viral clearance and improved recovery with treatment. Patients in the treatment group were significantly younger (41 vs. 54).
Jan 2023, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.1096853/full, https://c19p.org/dipierro5
Small RCT 60 healthcare workers in Iran, showing lower cases with treatment but without statistical significance. Once daily oral synbiotic capsule (Lactocare®) containing 1 billion CFU L. (Lactobacillus) casei, L. rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, L. acidophilus, Bifidobacterium infantis, L. bulgaricus, and Fructooligosacharide.
May 2021, Open J. Nursing, https://www.scirp.org/journal/paperinformation.aspx?paperid=108986, https://c19p.org/ahanchian
Prospective study of 131 hospitalized patients in Poland, showing lower mortality and improved recovery with a history of higher physical activity.
Jun 2023, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/12/4046, https://c19p.org/sutkowska
Retrospective 1,387 hospitalized PCR confirmed COVID-19 patients in Tanzania, showing lower mortality with ivermectin treatment and with steroid treatment in multivariable analysis.
Jul 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.07.13.23292643, https://c19p.org/osati
Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir.
Dec 2020, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034120307735, https://c19p.org/guner
Observational study in France with 28 hospitalized patients treated with prednisone/furosemide/colchicine/salicylate/direct anti-Xa inhibitor, and 40 control patients, showing lower combined mortality, ventilation, or high-flow oxygen therapy with treatment.
Jun 2021, J. Infection, https://www.journalofinfection.com/article/S0163-4453(21)00058-X/fulltext, https://c19p.org/kevorkian
PSM retrospective with 1,493 patients, showing significantly improved viral clearance with favipiravir. There were no significant differences in clinical improvement or mortality. Mortality was lower (2.1% vs 3.1%), without statistical significance with the small number of events.
Nov 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S187603412200212X, https://c19p.org/alattar
Analysis of 237 COVID-19 patients in Brazil, showing lower risk of long COVID with physical activity.
Jun 2023, Public Health, https://www.sciencedirect.com/science/article/pii/S0033350623001592, https://c19p.org/feter
RCT 173 family members of COVID-19 patients, showing lower incidence of COVID-19 symptoms with nasal drops containing nigella sativa oil and olea europaea oil. One drop in each nostril twice daily for 7 days.
Jul 2023, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/epdf/10.1002/ptr.7915, https://c19p.org/daneshfard
Retrospective 115 hospitalized COVID-19 patients in China showing faster time to body temperature recovery with ursodeoxycholic acid (UDCA) treatment. Results were better for higher dose treatment (300mg vs. 150mg). Authors also perform a meta analysis showing lower risk of severe/critical COVID-19 with UDCA, which is listed separately [Yu].
Jul 2024, Expert Review of Anti-infective Therapy, https://www.tandfonline.com/doi/full/10.1080/14787210.2024.2376153, https://c19p.org/yu10
PSM retrospective 84 hospitalized COVID-19 patients with pre-existing cancer in China, showing faster viral clearance with azvudine. There was no significant difference in length of hospital stay or ICU admission.
Mar 2024, J. Cancer, https://www.jcancer.org/v15p2442, https://c19p.org/li29
Prospective study of 100 COVID-19 patients in South Africa, 50 with COVID-19 pneumonia and 50 asymptomatic, showing higher risk of symptomatic COVID-19 with lower exposure to sunlight, and with vitamin D deficiency. Sunlight exposure may be correlated with physical activity and may have additional benefits independent of vitamin D [sciencedirect.com].
Apr 2022, Southern African J. Infectious Diseases, https://sajid.co.za/index.php/sajid/article/view/359, https://c19p.org/kalichuransun
Small RCT 49 severe condition hospitalized patients in Syria, showing lower mortality with colchicine and shorter hospitalization time with both colchicine and budesonide (all of these were not statistically significant).
Dec 2021, Interdisciplinary Perspectives on Infectious Diseases, https://www.hindawi.com/journals/ipid/2021/2129006/, https://c19p.org/alsultano
Retrospective 948 intubated patients, 33 treated with budesonide, showing lower mortality with treatment.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.15.20213546v1, https://c19p.org/ramlallu
Retrospective 307 hospital patients in Ghana showing 33% reduction in hospitalization time with HCQ, 29% reduction with HCQ+AZ, and 37% reduction with CQ+AZ.
Sep 2020, Pan African Medical J., https://www.panafrican-med-journal.com/content/series/37/1/9/full/, https://c19p.org/ashinyo
Retrospective 416 non-hospitalized and 184 hospitalized COVID-19 patients in Bangladesh, showing higher acetaminophen and lower vitamin C usage for hospitalized patients. Confounding may be significant and baseline details per treatment group are not provided, however fever and symptomatic patients were more common in the non-hospitalized group. Note there is an alignment mismatch in Table 1.
Nov 2023, Molecular Mechanism Research, https://ojs.as-pub.com/index.php/MMR/article/view/133, https://c19p.org/rahman5
Retrospective 3,136 patients with prediabetes and 282 with PCOS, showing metformin associated with reduced COVID-19 severity.
Aug 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.29.22279355, https://c19p.org/chan
PSM retrospective 490 hospitalized COVID-19 patients with pre-existing conditions in China showing that azvudine was associated with a significantly lower risk of the composite outcome of disease progression, driven largely by lower rates of non-invasive respiratory support. However, there was no significant difference in all-cause mortality or other individual outcomes like ICU admission or invasive mechanical ventilation between the azvudine and control groups.
May 2023, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S258953702300158X, https://c19p.org/sun4
Small prospective nonrandomized trial with 41 patients, 21 treated with curcumin, showing lower disease progression and faster recovery with treatment. IRCT20200408046990N1.
Jan 2021, Phytotherapy Research, doi:10.1002/ptr.7004 , https://onlinelibrary.wiley.com/doi/10.1002/ptr.7004, https://c19p.org/sabermoghaddam
RCT with 89 famotidine and 89 control patients in Pakistan, showing faster recovery but no significant difference in mortality. 40mg oral famotidine daily.
Feb 2022, Cureus, https://www.cureus.com/articles/78980-efficacy-of-oral-famotidine-in-patients-hospitalized-with-severe-acute-respiratory-syndrome-coronavirus-2, https://c19p.org/pahwani
Early terminated RCT with only 20 patients.
Jul 2020, Novartis, NCT04358081, https://clinicaltrials.gov/study/NCT04358081, https://c19p.org/novartis
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizifm
Retrospective 500 COVID-19 patients, showing dietary inflammatory index (DII) and energy-adjusted dietary inflammatory index (E-DII) associated with COVID-19 severity.
Mar 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1075061/full, https://c19p.org/baraniaadabi
Retrospective 478 moderate to severe hospitalized patients in Iran, showing lower mortality with vitamin D treatment.
Oct 2022, J. Pharmaceutical Care, https://publish.kne-publishing.com/index.php/JPC/article/view/10790, https://c19p.org/karimpourrazkenari2
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizie
RCT 251 high-risk individuals in India, mostly with direct contact with COVID-19 positive patients, testing polyherbal formulations Infuza, which includes nigella sativa, and Kulzam. Both formulations showed lower risk, without statisical significance, while the best results were from the combination of both.
Jul 2022, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7531, https://c19p.org/chandra
Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing lower mortality with vitamin C treatment in unadjusted results.
Jan 2022, Infectious Diseases & Immunity, https://journals.lww.com/10.1097/ID9.0000000000000037, https://c19p.org/tuc
Retrospective 2,830 people in the USA, showing lower risk of COVID-19 with a history of moderate/vigorous exercise.
Mar 2022, American J. Infection Control, https://www.sciencedirect.com/science/article/pii/S0196655322001018, https://c19p.org/beydoun
Analysis of 120 COVID-19 and 120 control patients in Iraq, showing lower risk of cases with regular sunlight exposure (3 times/week).
Dec 2021, Natural Volatiles & Essential Oils, https://www.nveo.org/index.php/journal/article/view/1046, https://c19p.org/jabbarsun
Prospective study of 102 patients in India, showing improved recovery of cough with budesonide+formoterol. Authors note better results with earlier treatment. Budesonide 800mcg + formoterol 12mcg bid for 7 days.
Mar 2023, Lung India, https://journals.lww.com/10.4103/lungindia.lungindia_268_22, https://c19p.org/samajdar2
Retrospective 161 hospitalized patients in Saudi Arabia showing lower ventilation and ICU admission with HCQ, but not statistically significant with the small sample sizes.
Sep 2020, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016420302334, https://c19p.org/almazrou
Retrospective 180 hospitalized pediatric COVID-19 patients in the Philippines showing lower mortality with vitamin D and zinc, and higher mortality with remdesivir, all without statistical significance. Remdesivir was given to few patients and authors do not provide information on the timing of treatment - confounding by indication may be significant.
Apr 2024, Acta Medica Philippina, https://actamedicaphilippina.upm.edu.ph/index.php/acta/article/view/8392, https://c19p.org/miland
Small RCT of nasopharyngeal viral load not showing significant differences. The rate of reduction for HCQ was 0.24 [0.03-0.46] RNA copies/mL/24h, and 0.14 [-0.10-0.37] for the control group (71% faster with HCQ but not statistically significant with the small sample size of 27 HCQ and 26 control patients). Analysis only over 96 hours. NCT04316377.
Jul 2020, Nature Communications, https://www.nature.com/articles/s41467-020-19056-6, https://c19p.org/lyngbakken
RCT 52 acute COVID-19 inpatients in Italy showing a multistrain synbiotic formula prevented a decrease in gut microbiota diversity and prevented decreases in lymphocyte count and hemoglobin levels compared to placebo. The probiotic group also had enrichment of beneficial bacteria and fewer neurological/neurocognitive symptoms at 6 months, although not statistically significant. Authors suggest modulating gut microbiota in acute COVID-19 through probiotics could be a useful supportive strategy.
Jul 2024, Microorganisms, https://www.mdpi.com/2076-2607/12/7/1443, https://c19p.org/giancola
Retrospective 976 hospitalized patients with 834 treated with HCQ+AZ showing HCQ mortality relative risk RR 0.35, p < 0.0001. Note that in this case HCQ was recommended for mild/moderate cases, so more severe cases may not have received HCQ (which may also be why they became severe cases). We note that this is opposite to a common bias in HCQ studies - in many cases HCQ was more likely to be given to more severe cases.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.16.20232223v1, https://c19p.org/budhiraja
67% lower mortality with HCQ. Retrospective 416 elderly patients in Spain showing adjusted HCQ mortality hazard ratio HR 0.33, p = 0.1.
Nov 2020, Revista Española de Geriatría y Gerontología, https://www.sciencedirect.com/science/article/pii/S0211139X20301748, https://c19p.org/aguilagordo
Retrospective 179 elderly patients in France, showing higher risk of COVID-19 cases with acetaminophen use, without statistical significance.
May 2020, Preprints, https://www.preprints.org/manuscript/202005.0016/v1, https://c19p.org/blanc2ppi
Retrospective 766 hospitalized patients in DRC showing mortality reduced from 29% to 11%, and improvement at 30 days increased from 65% to 84%. Mortality cox regression adjusted hazard ratio aHR 0.26, p < 0.001 Risk of no improvement adjusted odds ratio aOR 0.28, p < 0.001 Using marginal structural model analysis these risks became: Mortality MSM adjusted odds ratio aOR 0.65, p = 0.166 Risk of no improvement MSM adjusted odds ratio aOR = 0.65, p = 0.132 Median age 46, 630 treated with CQ+AZ.
Oct 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/content/journals/10.4269/ajtmh.20-1240, https://c19p.org/nachega
Prospective study of 187 telemedicine patients in Brazil. 74 presenting with moderate symptoms were offered treatment with HCQ+AZ, 12 did not accept HCQ (taking AZ only), forming a control group. There was lower hospitalization and improved recovery with treatment.
Nov 2021, Heliyon, https://www.sciencedirect.com/science/article/pii/S2405844023025446, https://c19p.org/chechter
Retrospective 69 COVID-19 patients in Turkey, showing improved fever recovery with the addition of favipiravir to HCQ, but no significant difference in discharge, ICU admission, or hospitalization time.
Dec 2022, Acta Clinica Croatica, https://hrcak.srce.hr/clanak/428402, https://c19p.org/delen
Retrospective 3,974,272 COVID-19 patients in the USA, showing 3% lower risk of hospitalization with pre-existing metformin use.
Mar 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0282961, https://c19p.org/sandhu2
Retrospective survey based study in Italy with 82 patients treated with lactoferrin, and 39 control patients, showing significantly faster viral clearance with treatment. There was no significant difference in recovery time overall, however the treatment group had significantly more moderate condition patients (39% versus 8%), and improved recovery was seen with treatment as age increased. Median dose for asymptomatic patients was 400mg/day, for paucisymptomatic patients 600mg/day, and for moderate condition patients 1000mg three times a day.
Sep 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/18/4276, https://c19p.org/rosa
Retrospective 17 hospitalized lung cancer patients showing lower mortality with HCQ+AZ treatment.
May 2020, Lung Cancer, https://www.lungcancerjournal.info/article/S0169-5002(20)30468-2/fulltext, https://c19p.org/rogado
Retrospective 652 transplant recipient patients in Spain showing 46% lower mortality for patients treated with HCQ, unadjusted relative risk RR 0.54, p<0.0001.
Oct 2020, American J. Transplantation, https://onlinelibrary.wiley.com/doi/abs/10.1111/ajt.16369, https://c19p.org/coll
Case control study of 295 COVID-19 patients in Iran, showing lower risk of severe cases with higher dietary antioxidant quality scores, and with higher intake of vitamin D.
Jul 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1174113/full, https://c19p.org/aghajani2
Retrospective 39 hospitalized COVID-19 survivors >60 years old, showing shorter hospitalization for patients with active lifestyles before COVID-19 symptoms.
Jun 2022, Sport Sciences for Health, https://link.springer.com/10.1007/s11332-022-00948-7, https://c19p.org/antunes
Retrospective 19,208 COVID+ hospitalized patients in Spain, 2,071 treated with high dose NAC, showing lower mortality with treatment. In multivariable analysis, authors adjust for corticosteroids, but do not adjust for HCQ use which was also significantly more common in the NAC group. NAC 600mg every 8 hours.
Jan 2022, Science Progress, https://journals.sagepub.com/doi/10.1177/00368504221074574, https://c19p.org/izquierdo
Small RCT with 100 patients, 48 with bromhexine added to SOC, showing slower viral- conversion but lower mortality and greater clinical improvement with bromhexine (not statistically significant with few deaths and very high recovery). The very large difference between unadjusted and adjusted results is due to much higher risk for patients with renal disease and the much higher prevalence of renal disease in the bromhexine group. The study also shows 90% of patients in the control group had BMI>=30 compared to 0% in the treatment group, suggesting a possible problem with randomization. Due to the imbalance between groups, results were adjusted for BMI>30, smoking, and renal disease. 11 patients were lost to followup in the treatment group compared to zero in the control group, perhaps in part due to faster recovery in the treatment group. 9 patients were excluded from the treatment group because they did not want to take bromhexine after discharge. Therefore up to 29% of treatment..
Mar 2021, J. Investig. Med., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970656/, https://c19p.org/tolouian
Survey analysis of dietary supplements showing vitamin D usage associated with lower incidence of COVID-19. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/louca
RCT mechanically ventilated patients in Croatia, 42 treated with sodium bicarbonate inhalation, and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delicph
RCT mechanically ventilated patients in Croatia, 42 treated with sodium bicarbonate inhalation, and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delicphsb
RCT mechanically ventilated patients in Croatia, showing no significant difference in mortality with saline inhalation. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delicnacl
RCT 633 hospitalized patients in Colombia, 153 treated with colchicine + rosuvastatin, not showing statistically significant differences in outcomes. Improved results were seen with the combination of emtricitabine/tenofovir disoproxil + rosuvastatin + colchicine. NCT04359095.
Jul 2021, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00523-X/fulltext, https://c19p.org/gaitanduarte
Prospective study of 51 mild COVID-19 cases in Nigeria, showing faster recovery and improved viral clearance with nigella sativa oil (NSO) treatment. NSO patients received 5mL twice daily in addition to usual care (zinc, vitamin C and a multivitamin).
Jan 2024, The Nigerian Health J., https://tnhjph.com/index.php/tnhj/article/view/712, https://c19p.org/idris
Retrospective 2,533 SLE patients in Denmark showing no significant difference in hospitalization risk for COVID-19 cases with HCQ treatment.
Aug 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/17/3842, https://c19p.org/cordtz2
Retrospective 2,449 hospitalized COVID-19 diabetes patients in France, 1,496 with existing metformin use, showing lower mortality with treatment. Statistical significance was reached in model 1 but not in models 2-4 which also adjust for HbA1c, eGFR, and diabetes duration, but have a lower number of patients. CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes).
Dec 2020, Diabetes & Metabolism, https://www.sciencedirect.com/science/article/pii/S1262363620302731, https://c19p.org/lalau
Comparison of two similar communities in Brazil, with one using a phthalocyanine derivative mouthwash, suggesting efficacy of the treatment in lowering COVID-19 cases. There was 54% lower risk of confirmed cases during the intervention in the treatment community, compared with 15% higher and 8% lower risk before and after the intervention. Gargle/rinse with 5mL of mouthwash containing phthalocyanine derivative for 1 minute, 3 to 5 times per day.
Nov 2021, German Medical Science GMS Publishing House, https://www.egms.de/en/journals/dgkh/2022-17/dgkh000426.shtml, https://c19p.org/britoreia
Small prospective PSM study in the USA, showing 75% lower mortality with ivermectin treatment, without reaching statistical significance, significantly shorter ventilation and ICU time, and longer hospitalization time. Authors leave the statistically significant improvements in ventilation and ICU time out of the abtract and conclusions, and incorrectly state that there were no differences in other outcomes (there were no statistically significant differences) [nature.com]. Authors are ambiguous on the primary outcome, referring to the primary mortality outcome in one case, and "clinical outcomes, measured by the rate of intubation, length of hospital stay, and mechanical ventilation duration" in another case. The longer hospitalization time may be partially due to the greater mortality in the control group.
Nov 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27469, https://c19p.org/ozer
Retrospective 250 COVID-19 patients in Iran, showing lower risk of severe disease with greater adherence to a Mediterranean diet.
Jul 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.911273/full, https://c19p.org/zargarzadeh
Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a median of 5.9 days after onset (6.2 and 6.3 in the treatment arms). The median time to viral clearance for vitamin C + folic acid was 8 days in the preprint but changed to 7 days in the published paper without explanation. Both vitamin C [c19early.org] and folic acid [Deschasaux-Tanguy, Farag] show efficacy in other trials, so the true effectiveness of HCQ(+AZ) may be higher than observed. Low risk patients, median age 37, no deaths (not matching the title which claims "high risk"). There was a post hoc addition of a new cycle threshold that obscures the statistically significant faster clearance. There was no analysis for time from symptom onset. Authors identify (relatively) low and high risk cohorts, but do not provide either viral..
Dec 2020, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00053-5/fulltext, https://c19p.org/johnston
Retrospective COVID+ hospitalized patients in Uganda, 23 patients receiving vitamin D treatment, showing significantly lower mortality with treatment.
Dec 2021, Research Square, https://www.researchsquare.com/article/rs-1193578/v1, https://c19p.org/bagumad
Retrospective diabetes patients in the UK, showing lower mortality for metformin treatment (administered within 21 days after a positive PCR test).
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.20.20174169, https://c19p.org/abujamous
RCT 60 outpatients in Iran, 30 treated with nano-curcumin showing lower hospitalization and faster recovery with treatment.
Jun 2021, Food Science and Nutrition, https://onlinelibrary.wiley.com/doi/full/10.1002/fsn3.2226, https://c19p.org/ahmadi
1,150 patient HCQ late treatment study: 44% lower mortality (p=0.14).
Retrospective 1210 hospitalized patients in Turkey focused on chronic kidney disease, haemodialysis and renal transplant patients, but also showing lower mortality with HCQ. Subject to confounding by indication.
Dec 2020, Nephrology Dialysis Transplantation, https://academic.oup.com/ndt/article/35/12/2083/6020341, https://c19p.org/ozturk
Retrospective 2,118 hospitalized COVID-19 patients in China, showing improved results with azvudine vs. paxlovid.
Aug 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323002906, https://c19p.org/dian
Retrospective 654 hospitalized patients focused on low-density lipoprotein cholesterol levels, also showing results for HCQ with 605 HCQ patients, unadjusted 30 day mortality relative risk RR 0.37, p = 0.008.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20207092v1, https://c19p.org/aparisi
Prospective analysis of 69 severe COVID-19 patients requiring non-invasive oxygen therapy, 40 treated with probiotic formulation SLAB51, showing lower oxygen requirements and higher blood levels of pO2, O2Hb and SaO2 with treatment. Authors suggest that enzymes in SLAB51 could reduce oxygen requirements in intestinal cells, resulting in more oxygen available for other organs.
Aug 2021, Nutrients, https://www.mdpi.com/2072-6643/13/8/2898, https://c19p.org/ceccarelli2
Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of the medications >24hrs. Analyzing these patients rather than excluding them may have revealed effectiveness with early use as shown in other studies. The..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2019014, https://c19p.org/cavalcantiazaz
Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone, showing lower PCR+ at day 10 or hospitalization >10 days with treatment. Bromhexine 8mg 4 times daily, spironolactone 25-50 mg/day for 10 days.
Dec 2020, Кардиология, https://lib.ossn.ru/jour/article/view/1440, https://c19p.org/mareev
Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone, showing lower PCR+ at day 10 or hospitalization >10 days with treatment. Bromhexine 8mg 4 times daily, spironolactone 25-50 mg/day for 10 days.
Dec 2020, Кардиология, https://lib.ossn.ru/jour/article/view/1440, https://c19p.org/mareevaa
Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone, showing lower PCR+ at day 10 or hospitalization >10 days with treatment. Bromhexine 8mg 4 times daily, spironolactone 25-50 mg/day for 10 days.
Dec 2020, Кардиология, https://lib.ossn.ru/jour/article/view/1440, https://c19p.org/mareevaasp
Retrospective 250 hospitalized patients in Iran, showing higher consumption of fruits, vegetables, and fiber associated with lower COVID-19 severity.
Sep 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.934568/full, https://c19p.org/tadbirvajargah
Prospective prophylaxis trial with 255 healthcare workers taking vitamin D and 2,827 controls, showing significantly lower influenza-like illness with treatment, and lower COVID-19 cases, without statistical significance. While the intervention and control groups were initially randomized, exclusions were only processed in the treatment arm.
Sep 2022, Nutrients, https://www.mdpi.com/2072-6643/15/1/180, https://c19p.org/vanhelmond
Retrospective 180 hospitalized pediatric COVID-19 patients in the Philippines showing lower mortality with vitamin D and zinc, and higher mortality with remdesivir, all without statistical significance. Remdesivir was given to few patients and authors do not provide information on the timing of treatment - confounding by indication may be significant.
Apr 2024, Acta Medica Philippina, https://actamedicaphilippina.upm.edu.ph/index.php/acta/article/view/8392, https://c19p.org/milan
RCT 60 hospitalized patients in Iran, 30 treated with nano-curcumin, showing significant improvements in inflammatory cytokines, and improvements in clinical outcomes without statistical significance. 240 mg/day nano-curcumin for 7 days.
Jan 2022, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7375, https://c19p.org/asadirad
RCT 294 low-risk subjects with mild COVID-19 showing significantly greater reduction in viral load with azelastine 0.1% nasal spray vs. placebo. There was no COVID-19 related hospitalization in either group. The reduction in viral load was significantly higher in the azelastine group at day 3, 6 and 11. Authors report that treatment was associated with significant improvement in fever (p=0.0046), weakness (p=0.0012) and hypoxia (p<0.0001) compared to placebo, however detailed results are not provided for these and other symptoms. Treatment delay from symptom onset is not specified, however the baseline viral load, lack of progression, and recovery profile are consistent with relatively late treatment among low-risk patients. Time to recovery results are not clear, with an inconsistent HR and 95% CI reported 0.32 [0.83-2.32].
Oct 2024, MDPI AG, https://www.preprints.org/manuscript/202410.2532/v1, https://c19p.org/meiser
RCT 294 low-risk subjects with mild COVID-19 showing significantly greater reduction in viral load with azelastine 0.1% nasal spray vs. placebo. There was no COVID-19 related hospitalization in either group. The reduction in viral load was significantly higher in the azelastine group at day 3, 6 and 11. Authors report that treatment was associated with significant improvement in fever (p=0.0046), weakness (p=0.0012) and hypoxia (p<0.0001) compared to placebo, however detailed results are not provided for these and other symptoms. Treatment delay from symptom onset is not specified, however the baseline viral load, lack of progression, and recovery profile are consistent with relatively late treatment among low-risk patients. Time to recovery results are not clear, with an inconsistent HR and 95% CI reported 0.32 [0.83-2.32].
Oct 2024, MDPI AG, https://www.preprints.org/manuscript/202410.2532/v1, https://c19p.org/meiserazl
Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative risk: RR 0.35, p = 0.2, propensity score matched RR 0.75, p = 0.36, multivariate Cox regression RR 0.43, p < 0.001, univariate Cox regression
Nov 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa563/5992463, https://c19p.org/falcone
RCT 96 hospitalized patients in Iran, 48 treated with melatonin, showing improved sleep quality and SpO2 with treatment. 3mg oral melatonin daily. Authors recommend studies with a higher dose. IRCT20200411047030N1.
Aug 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.27312, https://c19p.org/mousavi
Retrospective 3,473 hospitalized patients showing lower mortality with HCQ+zinc.
Oct 2020, Research Square, https://www.researchsquare.com/article/rs-94509/v1, https://c19p.org/frontera
Retrospective 3,473 hospitalized patients showing 37% lower mortality with HCQ+zinc. PSM aHR 0.63, p=0.015 regression aHR 0.76, p = 0.023
Oct 2020, Research Square, https://www.researchsquare.com/article/rs-94509/v1, https://c19p.org/frontera2
PSM retrospective 29 hospitals in Saudi Arabia, finding lower mortality with HCQ, without reaching statistical significance (described by authors as "no impact").
Feb 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000348, https://c19p.org/alshamrani
RCT 80 hospitalized patients with severe COVID-19, 40 treated with methylene blue + vitamin C + N-acetylcysteine, showing lower mortality, shorter hospitalization, and significantly improved SpO2 and respiratory distress with treatment.
Mar 2021, Clinical and Translational Investigation, https://www.clinicalandtranslationalinvestigation.com/frame_esp.php?id=375, https://c19p.org/hamidialamdari
Retrospective 1,816 COVID-19 patients with atrial fibrillation in Spain, showing lower mortality with HCQ treatment.
Mar 2022, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775322000549, https://c19p.org/azanagomez
Retrospective 2,463 hospitalized patients in Spain, 265 treated with melatonin, showing lower mortality with treatment in PSM analysis, however these results are subject to immortal time bias. Authors excluded from the sample patients that died during the first 72 hours of admission without taking melatonin, and patients that started on melatonin in the last 7 days of their admittance, having completed 75% of their stay.
Jul 2021, Sánchez-González, https://jcsm.aasm.org/doi/10.5664/jcsm.9554, https://c19p.org/sanchezgonzalez
Retrospective 75 diabetes patients, 34 on metformin, showing improved clinical outcomes with treatment, without statistical significance.
Jan 2022, J. Thrombosis and Thrombolysis, https://link.springer.com/article/10.1007%2Fs11239-022-02631-7, https://c19p.org/usman
Early terminated prophylaxis RCT for healthcare workers in Canada, showing 0/19 cases with vitamin D prophylaxis vs. 2/15 for control. 100,000IU cholecalciferol at baseline, 10,000IU weekly for 16 weeks.
Jul 2022, Research Square, https://www.researchsquare.com/article/rs-1588325/v1, https://c19p.org/hosseini4
Retrospective 258 hospitalized patients in Italy showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.455, p<0.001. Data is in the supplementary appendix.
Nov 2020, Bioscience Reports, https://portlandpress.com/bioscirep/article/doi/10.1042/BSR20203455/226985, https://c19p.org/boari
Analysis of nutrient intake and COVID-19 outcomes for 3,996 people in Iran, showing lower risk of COVID-19 hospitalization with sufficient vitamin A, vitamin C, and selenium intake, with statistical significance for vitamin A and selenium.
May 2023, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13632, https://c19p.org/vaisi
Prospective study of 60 patients in China with three arms: SOC, SOC+TCM, and SOC+TCM+high dose vitamin C, showing successively faster recovery with the addition of TCM and the addition of high dose vitamin C. TCM included inhaled vitamin C 10g, 3-7 times per day. IV vitamin C 10g/60kg twice a day, and oral vitamin C 3g three times a day. Group C vs. group A includes combined treatment with TCM, while group C vs. group B both include vitamin C (high vs. low dose).
Jan 2022, American J. Translational Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8829592/, https://c19p.org/yang2
Retrospective 80 consecutive pregnant patients with autoimmune rheumatic diseases in Qatar, showing lower risk of COVID-19 cases with HCQ prophylaxis.
Apr 2022, Cureus, https://www.cureus.com/articles/91696-characteristics-and-obstetric-outcomes-in-women-with-autoimmune-rheumatic-disease-during-the-covid-19-pandemic-in-qatar, https://c19p.org/satti
120 patient RCT comparing vitamin D, nigella sativa, and combined vitamin D+nigella sativa, showing improved symptom recovery and viral clearance with both vitamin D and nigella sativa, and further improvements with the combination of both. All patients received vitamin C, zinc, and lactoferrin.
Nov 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.1011522/full, https://c19p.org/said
Retrospective 19 COVID-19 ECMO patients in South Korea, showing a higher rate of weaning from ECMO with vitamin B12 treatment, without statistical significance. Authors perform multivariate analysis but do not provide full results, only reporting p > 0.05.
Dec 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S0147956320304027, https://c19p.org/jang2b12
RCT 192 critically ill COVID-19 ICU patients showing reduced SOFA score, hospital stay and ICU stay with spirulina supplementation (5g/day), but no significant difference in mortality, NEWS2 score, APACHE score, NUTRIC score, or respiratory support at discharge.
Sep 2024, J. Cellular and Molecular Anesthesia, https://brieflands.com/articles/jcma-149015, https://c19p.org/shadnoushspi
Retrospective 75 patients in Turkey showing lower ICU admission with vitamin D treatment in unadjusted results subject to confounding by time and indication (treatment was given to patients with low levels and only during a certain period). There was no significant difference in outcomes based on vitamin D levels.
May 2022, J. Health Sciences and Medicine, https://dergipark.org.tr/en/doi/10.32322/jhsm.1063405, https://c19p.org/baykal
RCT 80 hospitalized COVID-19 patients in Iran, 40 treated with finasteride, showing no significant differences other than improved oxygen saturation on the 5th day with treatment. There was significantly more patients with diabetes in the control group. 5mg finasteride for 7 days. IRCT20200505047318N1.
Apr 2021, Medical J. The Islamic Republic of Iran, https://mjiri.iums.ac.ir/article-1-7160-en.html, https://c19p.org/zarehoseinzade
RCT 116 healthcare workers comparing 0.2% chlorhexidine mouthwash (n=36), 7.5% sodium bicarbonate mouthwash (n=40), and placebo (n=40) twice daily for 2 weeks, with symptoms followed for 4 weeks. There were lower symtoms and cases in both treatment groups, with statistical significance for chlorhexidine only. The treatments were stopped after two weeks, results may be better with continued use, more frequent use, and with the addition of nasal use.
Jan 2024, Iranian J. Nursing and Midwifery Research, https://journals.lww.com/jnmr/fulltext/2024/29010/a_comparison_of_the_effects_of_chlorhexidine_and.8.aspx, https://c19p.org/karamiph
Case control study with 2,431 hospitalized COVID-19 patients in India, showing lower mortality with HCQ treatment, without statistical significance.
Apr 2023, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/view/journals/tpmd/108/4/article-p727.xml, https://c19p.org/krishnan2
HCQ HR 0.83 [0.77-0.89] based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88], 14 other medications showed either no signicant benefit or a negative effect.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.17.20155960v1, https://c19p.org/bernaola
Retrospective 100 severe condition hospitalized patients in the USA, 25 treated with high dose IV vitamin C, showing lower mechanical ventilation and cardiac arrest, and increased length of survival with treatment. 3g IV vitamin C every 6h for 7 days.
Mar 2022, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-022-02954-6/fulltext.html, https://c19p.org/hess
Retrospective 393 hospitalized patients with hematologic disorders in China, showing lower risk of COVID-19 with UDCA use.
Nov 2023, Blood, https://ashpublications.org/blood/article/142/Supplement%201/7308/500982/Effect-of-Ursodeoxycholic-Acid-for-Sars-Cov-2, https://c19p.org/gao6
Long COVID trial comparing L-arginine + vitamin C with multivitamin treatment (vitamin B1, B2, B6, B12, nicotinamide, folic acid, pantothenic acid), showing significant improvement in symptoms with L-arginine + vitamin C treatment.
Jul 2022, Pharmacological Research, https://www.sciencedirect.com/science/article/pii/S104366182200305X, https://c19p.org/izzo
RCT 91 vitamin A and 91 control patients in Iran, showing improved recovery with treatment. All patients received HCQ. 25,000IU/day oral vitamin A for 10 days.
Aug 2022, Eastern Mediterranean Health J., http://www.emro.who.int/in-press/research/evaluation-and-comparison-of-the-effect-of-vitamin-a-supplementation-with-standard-therapies-in-the-treatment-of-patients-with-covid-19.html, https://c19p.org/rohani
RCT 78 patients in Iran, showing improved recovery with favipiravir treatment.
Jun 2022, Mediterranean J. Infection Microbes and Antimicrobials, https://mjima.org/pdf.php?&id=340, https://c19p.org/tehrani4
122 patient selenium late treatment RCT: 35% lower mortality (p=0.68), 81% lower need for oxygen therapy, and 22% improved recovery.
Randomized, double-blind, placebo-controlled trial of 122 moderate hospitalized COVID-19 patients in Iran, evaluating the addition of BCc1 iron chelator and Hep-S selenium nanomedicines to standard treatment. The nanomedicine group showed a significant 77% reduction in IL-6 levels by day 28 compared to an 18% increase in the placebo group, along with improvements in TNF-alpha and clinical scores for cough, fatigue, and oxygen need, without statistical significance.
Nov 2023, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07624-2, https://c19p.org/hafizi
Retrospective 26,508 COVID+ veterans in USA, showing lower mortality with vitamin D use after testing positive (defined as being administered ≥7 days or half of the survival time within 2 weeks after testing), with statistical significance for hospitalized patients.
Dec 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/19/1/447/html, https://c19p.org/efird
Small trial with 21 colchicine patients and 22 control patients in Russia, showing improved recovery with treatment. The trial was originally an RCT, however randomization to the control arm was stopped after 5 patients, and 17 retrospective patients were added for comparison.
Feb 2021, Kardiologiia, https://lib.ossn.ru/jour/article/view/1560/0?locale=en_US, https://c19p.org/mareev2
RCT 92 hospitalized patients, 47 treated with NAC, showing non-significant improvements in outcomes. IRCT20120215009014N355. NAC 40mg/kg/day intravenous for 3 days.
Jun 2021, Pharmacological Reports, https://link.springer.com/article/10.1007%2Fs43440-021-00296-2, https://c19p.org/taher
456 patient favipiravir late treatment study: 56% higher mortality (p=0.26), 90% lower ventilation (p<0.0001), and 49% higher hospital discharge (p<0.0001).
Retrospective 234 favipiravir and 223 control patients in Saudi Arabia, showing shorter time to discharge and lower progression to ventilation, but no significant difference in mortality.
May 2021, Current Medical Research and Opinion, https://www.tandfonline.com/doi/full/10.1080/03007995.2021.1920900, https://c19p.org/alamer
Small PrEP RCT showing that PrEP with HCQ is safe at the dosage used. There were no deaths, hospitalizations, or serious adverse events. The paper states: "Among all trial participants at the end of the first month (n=253), only one participant from the placebo arm (1/116, 0.8%), tested positive for SARS-CoV-2 PCR and for a SARS-CoV-2 serology test". The abstract states: "only one participant in each group was diagnosed with COVID-19".
Sep 2020, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05758-9, https://c19p.org/graupujol
UK Biobank retrospective showing a higher risk of COVID-19 cases and mortality for patients with gout. Among patients with gout, mortality risk was lower for those on colchicine, OR 1.06 [0.60-1.89], compared to those without colchicine, OR 1.38 [1.08-1.76].
Jan 2022, The Lancet Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00401-X/fulltext, https://c19p.org/topless
Survey analysis of dietary supplements showing probiotic usage associated with lower incidence of COVID-19. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucak
50 patient curcumin early treatment RCT: 33% improved recovery (p=0.15) and 50% improved viral clearance (p=0.009).
RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.
Apr 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.898062/full, https://c19p.org/khan4t
50 patient quercetin early treatment RCT: 33% improved recovery (p=0.15) and 50% improved viral clearance (p=0.009).
RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.
Apr 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.898062/full, https://c19p.org/khan4q
Pilot study of probiotic SIM01 with 25 consecutive COVID-19 patients in Hong Kong and 30 control patients treated by a different team during the same time period, showing improved antibody formation, reduced viral load and pro-inflammatory responses, and improvements for gut dysbiosis. SIM01 contains bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (derived from metagenomic databases of COVID-19 patients and healthy patients).
Mar 2022, J. Gastroenterology and Hepatology, https://onlinelibrary.wiley.com/doi/10.1111/jgh.15796, https://c19p.org/zhang5
Retrospective 752 patients in Thailand showing mixed results with 50mg fluvoxamine bid. Authors note that trials showing benefit mostly used 100mg bid.
Oct 2023, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034123003374, https://c19p.org/siripongboonsitti5
Retrospective 1,478 hospitalized Hispanic patients in the USA with 705 receiving vitamin D treatment, showing lower mortality with treatment in unadjusted results. Very minimal information is currently available.
Jun 2022, Abstracts from the 2022 Annual Meeting of the Society of General Internal Medicine, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07653-8, https://c19p.org/shahid
Retrospective 108 T2D patients hospitalized with COVID-19, showing lower risk of unfavorable outcomes with metformin use vs. other diabetic medications.
Jan 2022, Int. J. Endocrinology, https://www.hindawi.com/journals/ije/2022/9322332/, https://c19p.org/fu
RCT with 24 probiotics and 15 control patients in Spain, showing lower overall symptoms and lower digestive symptoms with treatment. Kluyveromyces marxianus B0399 plus lactobacillus rhamnosus CECT 30579.
Aug 2022, Medicine in Microecology, https://www.sciencedirect.com/science/article/pii/S2590097822000118, https://c19p.org/navarrolopez
Retrospective cohort of 6,145 SLE patients showing lower incidence of COVID-19 for patients receiving HCQ/CQ (antimalarials), without statistical significance. Groups were not matched and results may be influenced by factors such as disease severity. HCQ/antimalarials were used more in moderate/severe SLE patients, suggesting that the estimated protective effect will underestimate the real effect.
Nov 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-071072, https://c19p.org/rabe
Very late stage RCT (O2 88%, 84% on oxygen) with 1,279 hospitalized patients in Argentina, showing lower mortality and lower combined mortality/ventilation, statistically significant only for the combined outcome and per-protocol analysis. NCT04328480. COLCOVID.
Dec 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787585, https://c19p.org/diaz2
Retrospective 4,694 COVID-19 patients in Iran, showing lower risk of hospitalization and mortality with regular sports participation.
Nov 2020, J. Physical Activity and Health, https://journals.humankinetics.com/view/journals/jpah/18/1/article-p8.xml, https://c19p.org/halabchi
Small RCT with 23 nitazoxanide and 13 control patients showing significantly more patients achieved over 35% reduction in viral load from baseline. NCT04463264.
Mar 2021, Medical Research Archives, https://esmed.org/MRA/mra/article/view/3364, https://c19p.org/silva
Retrospective 7,158 hospitalized COVID-19 patients in the USA, showing higher risk or mortality with in-hospital famotidine use, but lower risk when there was pre-existing at-home use, without statistical significance in both cases.
Feb 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)35249-5/fulltext, https://c19p.org/yeramaneni
Very small early terminated RCT in India, showing lower mortality but without statistical significance with the very small sample size. Time since symptom onset is not provided. The recovery percentage for non-severe group B (86.7%) does not match any number of recoveries, we have used the closest number (15/17).
Jun 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.06.06.21258091v1, https://c19p.org/singh2
Retrospective 80 ICU patients, and in vitro study with human airway epithelial cells, showing that vitamin D enhances host IFN-a/β signaling. Significantly lower mortality was seen with vitamin D treatment.
Oct 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-22307-9, https://c19p.org/hafezi
RCT with 60 patients treated with colchicine and phenolic monoterpenes and 60 control patients in Iran, showing lower mortality with treatment. NCT04392141.
Apr 2021, NCT04392141, https://clinicaltrials.gov/ct2/show/NCT04392141, https://c19p.org/mostafaie
Retrospective 66 hospitalized COVID-19 patients in Greece, showing significantly improved recovery with a history of exercise in unadjusted results. Exercise after hospitalization was also associated with lower levels of dyspnea one month post hospitalization.
Apr 2022, J. Personalized Medicine, https://www.mdpi.com/2075-4426/12/4/645, https://c19p.org/kontopoulou
33 patient HCQ late treatment RCT: 24% improved viral clearance (p=0.71).
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76, p = 0.71. Small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR 1.29, p = 0.7. The RCT and retrospective study are listed separately [Chen, Chen].
Jul 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242763, https://c19p.org/chen25
Case control study with 53 inpatients and 88 outpatients in Iran, showing lower risk of hospitalization with increased adherence to the DASH (Dietary Approach to Stop Hypertension) diet. Increased intake of fruits, vegetables and low-fat dairy products, and lower intake of sodium and processed/red meat were significantly associated with reduced risk of hospitalization due to COVID-19.
Mar 2023, Clinical Nutrition Open Science, https://www.sciencedirect.com/science/article/pii/S2667268523000050, https://c19p.org/zamanian
Retrospective 512 rheumatic disease patients in Iran, showing lower risk of COVID-19 with HCQ use.
Sep 2022, Reumatologia/Rheumatology, https://www.termedia.pl/doi/10.5114/reum.2022.119039, https://c19p.org/sahebari
RCT 40 hospitalized, 40 ICU, and 40 control patients in Iran, showing lower mortality and improved regulatory T cell responses with nanocurcumin treatment (SinaCurcumin).
Mar 2021, Life Sciences, https://www.sciencedirect.com/science/article/abs/pii/S0024320521004227, https://c19p.org/tahmasebi
PSM retrospective 110 patients, 55 treated with high-dose IV vitamin C, showing lower progression to severe disease with treatment. Patients in each group were in different time periods, time based confounding is likely due to SOC improving over time. ChiCTR2000033050.
Apr 2021, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2021.638556/full, https://c19p.org/zhao4
Survey 2,148 COVID-19 recovered patients in Jordan, showing lower hospitalization with turmeric prophylaxis, not reaching statistical significance.
Jun 2022, F1000Research, https://f1000research.com/articles/11-639/v1, https://c19p.org/nimer2
RCT 111 patients in India in 5 groups: severe patients: a) standard treatment, b) hydroxychloroquine + ribavirin + standard treatment, or c) lopinavir + ritonavir + ribavirin + standard treatment, and non-severe: a) standard treatment or b) hydroxychloroquine + ribavirin. Non-severe patients were transferred to the severe group on progression.
Sep 2021, Clinical Pharmacology: Advances and Applications, https://www.dovepress.com/antiviral-combination-clinically-better-than-standard-therapy-in-sever-peer-reviewed-fulltext-article-CPAA, https://c19p.org/panda2
Retrospective 71 hospitalized patients in Israel, 20 treated with inhaled nitric oxide, showing no significant differences.
Jul 2022, Obstetrics & Gynecology, https://journals.lww.com/10.1097/AOG.0000000000004847, https://c19p.org/valsecchi
Early terminated NIAID RCT for HCQ. Patients >60 were only in the HCQ arm. 57% of patients were high risk in the HCQ arm vs. 22% for control. Treatment started up to 20 days after symptoms.
Jul 2020, NCT04358068, https://clinicaltrials.gov/study/NCT04358068, https://c19p.org/smith2
Retrospective 192 hospitalized patients in Indonesia, 96 patients treated with favipiravir, showing improved recovery with treatment. Only the abstract is currently available.
Oct 2021, Kesmas: National Public Health J., https://journal.fkm.ui.ac.id/kesmas/article/view/5433, https://c19p.org/damayanti
Small early terminated RCT showing better recovery with camostat treatment, without statistical significance.
Nov 2023, BJGP Open, http://bjgpopen.org/lookup/doi/10.3399/BJGPO.2023.0109, https://c19p.org/tarecm
Retrospective 458 healthcare workers in Ghana, showing lower COVID-19 cases with hydrogen peroxide prophylaxis (oral and nasal rinse), without statistical significance.
Aug 2022, J. Hospital Infection, https://www.sciencedirect.com/science/article/pii/S0195670122001499, https://c19p.org/amoah
Prospective study of 30 patients treated with vitamin D, magnesium, and vitamin B12, and 25 control patients, showing shorter hospitalization and lower oxygen and ICU requirements with treatment. Cholecalciferol 1000IU, magnesium oxide 150mg, vitamin B12 500μg.
Apr 2022, Int. J. Pharmaceutical and Clinical Research, http://impactfactor.org/PDF/IJPCR/14/IJPCR,Vol14,Issue5,Article113.pdf, https://c19p.org/valecha
208 patient HCQ late treatment study: 44% lower mortality (p=0.14) and 3% improved recovery (p=0.91).
Retrospective 208 hospitalized COVID-19 patients in Burkina Faso showing lower mortality with HCQ/CQ+AZ treatment, without statistical significance. There was no difference for recovery.
Feb 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-192.php?jid=jide, https://c19p.org/baguiya
RCT 54 late stage patients, 18 treated with IV vitamin C (2g every 6h for 5 days), showing significant relative improvements in oxygen saturation and respiratory rate.
Nov 2021, Urology J., https://journals.sbmu.ac.ir/urolj/index.php/uj/article/view/6863, https://c19p.org/tehrani3
Retrospective 944 5ARI users in the USA and 944 matched controls, showing lower risk of COVID-19 cases with treatment.
Jan 2022, J. Urology, https://www.auajournals.org/doi/10.1097/JU.0000000000002180, https://c19p.org/lyon
Study of hospital health care workers showing HCQ prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis was important in this study which used a low dose of 400mg/week HCQ (800mg for week 1), so it may take longer to reach therapeutic levels. Actual benefit of HCQ may be larger because severity of symptoms are not considered here but HCQ may also reduce severity.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.21.20159301v1, https://c19p.org/khurana
Retrospective 615 hospitalized COVID-19 patients in Morocco, showing lower mortality with HCQ in unadjusted results.
Dec 2022, Cureus, https://www.cureus.com/articles/122896-predictive-factors-of-death-and-the-clinical-profile-of-hospitalized-covid-19-patients-in-morocco-a-one-year-mixed-cohort-study, https://c19p.org/charif
Retrospective 546 COVID+ patients in the USA, showing lower risk of hospitalization with higher frequency of strength training, without statistical significance.
Oct 2022, American J. Lifestyle Medicine, http://journals.sagepub.com/doi/10.1177/15598276221135541, https://c19p.org/reis6ex
Retrospective 101 hospitalized pediatric patients in Saudi Arabia, showing zinc treatment associated with lower respiratory failure and shorter hospitalization in unadjusted results. Patients receiving zinc were older. Authors note elevated serum creatinine and the possibility of kidney injury.
Mar 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000415, https://c19p.org/ibrahimalhajjaji
Retrospective 4,476 participants in Brazil, showing lower risk of COVID-19 cases with a history of physical activity, statistically significant only for those following specific practices to protect against COVID-19.
Oct 2022, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/19/21/14155, https://c19p.org/pitanga
Retrospective 991 hospitalized patients in Iran, showing lower mortality with aspirin treatment.
Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27053, https://c19p.org/hajiaghajanie
Prospective study of 217 patients treated with NAC and 245 matched controls, showing improved recovery with treatment. 1500mg intravenous NAC daily.
May 2023, Caspian J Intern Med, https://caspjim.com/article-1-3389-fa.html, https://c19p.org/afaghi2
60 patient N-acetylcysteine late treatment RCT: 67% lower mortality (p=0.61).
RCT 60 hospitalized COVID-19 patients evaluating the efficacy and safety of adding oral N-acetylcysteine (NAC) at 600mg three times daily to standard antiviral treatment regimens. The NAC group showed significantly greater reduction in C-reactive protein levels, indicating reduced inflammation. Authors conclude that oral NAC may provide benefits through reducing inflammation, increasing oxygen saturation, and potentially reducing mortality when combined with certain antiviral medications in hospitalized COVID-19 patients.
Nov 2023, Immunity, Inflammation and Disease, https://onlinelibrary.wiley.com/doi/10.1002/iid3.1083, https://c19p.org/atefi
RCT 278 COVID-19 ICU patients in Pakistan, showing lower mortality and ventilation, and shorter length of stay with high dose vitamin C treatment, without statistical significance. 30 grams IV vitamin C for four days.
Jun 2023, Biological and Clinical Sciences Research J., http://bcsrj.com/ojs/index.php/bcsrj/article/view/343, https://c19p.org/rana2
RCT 609 inpatients in Iran. Reported outcomes are very different from the pre-specified outcomes [irct.ir]. The outpatient trial is listed separately. From the pre-specified outcomes, all are either positive or not reported. Pre-specified outcomes: - Reduction in persistent cough - RR 0.36 p = 0.06 - Negative RT-PCR - not reported - Main complaints recovery time - not reported - Mortality - RR 0.69 p = 0.36 - Side effects - reported as none (anomalous) - Reduction in tachypnea - RR 0.24 p = 0.38 - Oxygen saturation >94% - not reported All negative outcomes are protocol violations and are not listed in the protocol, including the novel "relative recovery" outcome. Authors include a researcher caught on video admitting that conclusions on ivermectin research were influenced by a funder [c19ivm.org]. Severe cases were more frequent in the ivermectin group, 49% vs. 43%. Dose was limited at a maximum of 30mg for 75+kg, resulting in underdosing for patients at higher risk. Almost..
Jun 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.919708/full, https://c19p.org/rezai2
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin B12 prophylaxis, without statistical significance.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerb12
RCT 140 ICU patients in Spain, 72 treated with N-acetylcysteine (NAC). NAC patients showed improved PaO2/FiO2, CRP, D-dimer, and LDH, and there were associations between glutathione and clinical outcomes and severity biomarkers in NAC-treated patients. There was no significant difference in mortality.
May 2023, Nutrients, https://www.mdpi.com/2072-6643/15/9/2235, https://c19p.org/gamarramorales
PSM retrospective 207 hospitalized patients in China, 46 treated with diammonium glycyrrhizinate and vitamin C, showing lower risk of ARDS with treatment.
Jul 2021, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcab184/6329274, https://c19p.org/tan3
RCT 75 very late stage patients in Colombia, showing no significant difference in outcomes with a single dose of 400μg/kg ivermectin.
Oct 2022, Revista Infectio, http://revistainfectio.org/P_OJS/index.php/infectio/article/view/1105, https://c19p.org/ochoajaramillo
Retrospective 539 patients in the USA, showing lower mortality, ICU admission, and ARDS with aspirin treatment, without statistical significance.
Jul 2022, Health Science Reports, https://onlinelibrary.wiley.com/doi/10.1002/hsr2.699, https://c19p.org/malik
N3C/PCORnet retrospective adults with type 2 diabetes in the USA showing lower incidence of mortality or long COVID with metformin use.
Sep 2024, Diabetes Care, https://diabetesjournals.org/care/article/doi/10.2337/DCa24-0032/157171/Prevalent-Metformin-Use-in-Adults-With-Diabetes, https://c19p.org/johnson
Small early terminated RCT with 33 hospitalized patients in Australia, 15 treated with zinc, showing no significant difference in clinical outcomes. Treatment increased zinc levels above the deficiency cutoff. Intravenous zinc 0.5mg/kg/day (elemental zinc concentration 0.24mg/kg/day) for up to 7 days. ACTRN12620000454976.
Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26895, https://c19p.org/patel2
Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304696, https://c19p.org/rodriguezgonzalez
Retrospective 293 COVID+ patients in Russia, showing lower risk of severe COVID-19 for individuals who regularly practice aerobic training in unadjusted results.
Oct 2020, Pulmonologiya, https://journal.pulmonology.ru/pulm/article/view/1376, https://c19p.org/tretyakov
144 patient vitamin C late treatment study: 63% lower mortality (p=0.22).
Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing lower mortality with vitamin C treatment.
Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocy
Retrospective 42 patients in Bangladesh, 11 treated with aspirin, showing fewer complications with treatment.
Oct 2020, ResearchGate, https://www.researchgate.net/publication/344567523_Beneficial_effect_of_low_dose_aspirin_Acetyl_salicylic_acid_in_adult_Covid-19_patients_a_retrospective_observational_study_in_Bangladesh, https://c19p.org/husain
Retrospective 103 SLE and 524 RA patients in Italy, showing significantly lower mortality/ventilation with HCQ use for SLE patients, and no significant difference for RA patients in unadjusted results. Authors did not include HCQ in multivariable analysis, only including four variables "chosen among the most clinically relevant". Multivariable analysis may significantly improve results for RA patients because HCQ use may correlate with more severe disease due to use for patients that failed or do not tolerate first-line therapies. It is not clear how the patients were selected - the very high ~25% ventilation/mortality suggests that most were hospitalized COVID-19 patients, in which case any benefit of HCQ in reducing hospitalizations will not be reflected in the results. Authors falsely state that "subsequent studies have definitely proved that [HCQ] is not linked to COVID-19 prognosis", suggesting significant bias, and possibily indicating why HCQ..
Oct 2023, Lupus Science & Medicine, https://lupus.bmj.com/lookup/doi/10.1136/lupus-2023-000945, https://c19p.org/scirocco
Retrospective 47 rheumatic disease patients not finding significant differences with HCQ.
Apr 2021, Rheumatology Int. , https://link.springer.com/article/10.1007/s00296-021-04857-9, https://c19p.org/alzahrani
Retrospective 92 hospitalized patients showing lower clinical deterioration with montelukast treatment, without statistical significance in multivariable analysis. The treatment group was older.
Mar 2021, J. Asthma, https://www.tandfonline.com/doi/full/10.1080/02770903.2021.1881967, https://c19p.org/khan7
Retrospective 393 hospitalized COVID-19 patients in Turkey, showing lower ICU admission and shorter hospitalization time with HCQ. There was no significant difference for mortality. Severity was higher in the HCQ group with greater baseline ventilation, high flow oxygen, fever, and dyspnea.
Jan 2022, The J. Infection in Developing Countries, https://jidc.org/index.php/journal/article/view/14933, https://c19p.org/omma
100 patient probiotics early treatment RCT: 80% lower hospitalization (p=0.2) and 18% improved recovery (p=0.42).
RCT 150 patients in Egypt showing no significant difference in outcomes with probiotic lactobacillus acidophilus, although hospitalization was 2% versus 10% for control. SOC included vitamin C, D, and zinc.
Jun 2023, Research Square, https://www.researchsquare.com/article/rs-3049708/v1, https://c19p.org/hassan
RCT 100 patients showing no significant difference with camostat. Results are currently unclear—different mortality numbers were provided for all-cause mortality and mortality rate (2/50 vs. 3/46 for the treatment group at 28 days, with the 28 day all-cause mortality result removed in an updated submission). The main outcome measures appear to be different due to only including patients that submitted day 28 outcome data.
Mar 2024, NCT04470544, https://clinicaltrials.gov/study/NCT04470544, https://c19p.org/bryce
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin C prophylaxis, without statistical significance.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerc
Small RCT comparing mouthwashing with PVP-I, chlorhexidine, and water, showing significant efficacy for both PVP-I and chlorhexidine, with PVP-I increasing Ct by a mean of 4.45 (p < 0.0001) and chlorhexidine by a mean of 5.69 (p < 0.0001), compared to no significant difference for water.
Mar 2021, J. Evidence Based Dental Practice, https://www.sciencedirect.com/science/article/abs/pii/S1532338221000592, https://c19p.org/elzein
Retrospective 139 hospitalized patients in Turkey, 58 treated with high dose vitamin C, showing improved kidney functioning with treatment. Mortality was lower with treatment, but not reaching statistical significance with the small sample size.
Sep 2021, Annals of Medical Research, https://www.annalsmedres.org/index.php/aomr/article/view/3910, https://c19p.org/simsekc
Retrospective 89 COVID-19 patients in Spain, showing lower mortality with adherence to the Mediterranean diet.
Dec 2021, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457721009293, https://c19p.org/magana
421 patient metformin early treatment RCT: 27% lower mortality (p=0.53), 6% lower hospitalization (p=0.88), 14% more combined hospitalization/ER visits (p=0.58), and 31% lower progression (p=0.48).
Data for the primary outcome in this trial appears to be impossible [doyourownresearch.substack.com]. For example, considering the metformin arm and the ITT population: 24 were hospitalized and 8 had an ER visit (tables S2/S3), therefore the number for combined ER or hospitalization must be between 24 and 32. However, authors report 34 events for ER/hospitalization. RCT with 215 patients treated with metformin and 203 controls, showing no significant difference with treatment. For multiple major issues with this trial see [doyourownresearch.substack.com, doyourownresearch.substack.com]. An expression of concern was posted in 2024 [thelancet.com]. The hospitalization risk for off-protocol patients was several times higher in both arms, resulting in Simpson's paradox when combining per-protocol and off-protocol patients [web.archive.org]. 750mg twice daily for 10 days.
Aug 2021, The Lancet Regional Health - Americas, https://www.sciencedirect.com/science/article/pii/S2667193X21001381, https://c19p.org/reis3
Retrospective 1,267 hospitalized patients in Spain, 189 on vitamin D supplementation before admission, showing lower ICU admission with supplementation, and no statistically significant difference for mortality or ventilation.
Sep 2021, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2021.758347/full, https://c19p.org/arroyodiaz
55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showing adjusted OR 0.24 [0.03-2.2].
Dec 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244272, https://c19p.org/matangila
Retrospective 333 hospitalized patients in Israel, showing no significant difference in outcomes with low folate levels or with folic acid supplementation.
Mar 2021, Nutrients, https://www.mdpi.com/2072-6643/13/3/812, https://c19p.org/meisel
Analysis of 1,317 hospitalized COVID-19 patients with diabetes showing lower mortality with metformin use, without statistical significance.
May 2020, Diabetologia, https://link.springer.com/10.1007/s00125-020-05180-x, https://c19p.org/cariou
Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment.
Feb 2021, Viruses 2021, https://www.mdpi.com/1999-4915/13/2/329, https://c19p.org/bae
Survey of 307 patients in the USA, showing no significant difference in COVID-19 cases with famotidine use.
Jan 2021, J. Voice, https://www.sciencedirect.com/science/article/pii/S0892199721000321, https://c19p.org/balouch
Retrospective 864 hospitalized late stage COVID-19 patients in the USA, 138 receiving NAC treatment for acute hepatitis, showing lower mortality with treatment. Results are adjusted for confounders, however details are not provided.
May 2021, Gastroenterology, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8108159/, https://c19p.org/pellegrini
Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.
Nov 2021, PAMJ - Clinical Medicine, https://www.clinical-medicine.panafrican-med-journal.com/content/article/7/15/full/, https://c19p.org/calderon2
38 patient colchicine early treatment RCT: 67% lower hospitalization (p=0.55) and 24% improved recovery (p=0.72).
RCT 38 low risk outpatients in Japan, showing no significant differences for colchicine and low-dose aspirin compared to loxoprofen. Hospitalization was lower, without statistical significance (4.3% vs. 13.3%, p=0.34). There were no critical cases, deaths, or severe adverse events in either group. Colchicine: 1.0mg loading dose, followed approximately half a day later by 0.5mg twice daily for 10 doses, and then 0.5 mg once daily for four doses. Aspirin: 100mg daily for 10 days. Both groups received probiotics and acetaminophen.
Mar 2024, The Kurume Medical J., https://www.jstage.jst.go.jp/article/kurumemedj/advpub/0/advpub_MS7012003/_article, https://c19p.org/inokuchi
Case control study with 39 COVID+ and 172 COVID- Parkinson's disease patients in Spain, showing positive and severe cases being less likely to use vitamin D supplementation compared to negative or mild/negative cases respectively. These differences were not statistically significant.
Oct 2020, J. Neurology, https://link.springer.com/article/10.1007/s00415-020-10272-0, https://c19p.org/sainzamo
85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, p = 0.006.
Dec 2020, BioScience Trends, https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.03340/_article/-char/ja/, https://c19p.org/su
RCT 60 ICU patients in India, showing no significant difference in outcomes with vitamin C. Mortality was lower in the vitamin C arm despite having more severe cases at baseline (87% vs. 67%). 1 gram intravenous vitamin C 8 hourly for four days.
Aug 2022, J. Family Medicine and Primary Care, https://journals.lww.com/10.4103/jfmpc.jfmpc_2437_21, https://c19p.org/kumar5
Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.
Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26880, https://c19p.org/elalfyn
Small RCT 60 patients in India, 30 treated with ImmunoSEB and ProbioSEB CSC3, showing faster recovery with treatment. CTRI/2020/09/027685, CTRI/2020/08/027168.
Feb 2021, Advances in Clinical Toxicology, https://advancedenzymesdirect.com/wp-content/uploads/2021/05/Covid-Published-paper.pdf, https://c19p.org/shah
Retrospective 376 hospitalized COVID-19 patients in the United States showing no significant differences with aspirin. Mortality, mechanical ventilation, and hypoxia were lower with treatment, without statistical significance.
Jun 2024, Cardiology Research, http://www.cardiologyres.org/index.php/Cardiologyres/article/view/1645, https://c19p.org/vinod
Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information on severity is provided. 33% of the control group used HCQ within the last year. Remaining confounding by differences in the nature and severity of rheumatic disease is likely.
Dec 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20307527, https://c19p.org/jung
Retrospective 477 COVID+ public transportation workers in Turkey, showing lower risk of hospitalization with vitamin C use in unadjusted results.
Nov 2022, Work, https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-220292, https://c19p.org/guldemir
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin B9 prophylaxis, without statistical significance.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerb9
Retrospective 84 flight attendants, 52 reporting COVID-19 status and diet quality, showing higher risk of COVID-19 with lower self-reported diet quality.
Dec 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-04350-0, https://c19p.org/yamamoto
PSM retrospective 144 alopecia patients in the USA, showing lower risk of COVID-19 with HCQ prophylaxis. The supplemental appendix is not available.
Jun 2021, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961621P0914X, https://c19p.org/shaw
Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases are not provided, and the results are subject to survey bias. Authors also report on community prophylaxis but present only combined ivermectin/HCQ results.
Nov 2021, J. the Association of Physicians India, https://www.researchgate.net/publication/356294136_Ivermectin_and_Hydroxychloroquine_for_Chemo-Prophylaxis_of_COVID-19_A_Questionnaire_Survey_of_Perception_and_Prescribing_Practice_of_Physicians_vis-a-vis_Outcomes, https://c19p.org/samajdar
Small study with 28 patients treated with ivermectin + AZ + cholecalciferol and 7 control patients. All treated patients were PCR- at day 10 while all control patients remained PCR+. The mean duration of symptoms was 3 days in the treatment group and 10 days in the control group.
Aug 2020, Biomedical Research, https://www.biomedres.info/biomedical-research/effects-of-ivermectinazithromycincholecalciferol-combined-therapy-on-covid19-infected-patients-a-proof-of-concept-study-14435.html, https://c19p.org/espitiahernandez
Retrospective 197 hospitalized COVID-19 patients in Spain, showing lower progression to pneumonia with HCQ in unadjusted results.
Mar 2021, Advances in Laboratory Medicine / Avances en Medicina de Laboratorio, https://www.degruyter.com/document/doi/10.1515/almed-2021-0017/html, https://c19p.org/rubiosanchez
Retrospective 1,213 rheumatic disease patients in France, showing lower risk of mortality and severe cases with HCQ use in univariate analysis, without statistical significance.
Mar 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1152587/full, https://c19p.org/chevalier
Retrospective 509 COVID-19 patients in Taiwan, showing higher risk of critical COVID-19 cases with non-vegetarian diets.
Apr 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.837458/full, https://c19p.org/hou
Retrospective study focused on eosinophil recovery with 9,644 hospitalized patients in Spain, showing lower mortality for HCQ (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model including potential confounding factors, HCQ and AZ are associated with lower mortality, HCQ OR 0.662, p=0.057.
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.18.20172874v1, https://c19p.org/gonzalez2
607 patient HCQ late treatment study: 20% lower mortality (p=0.36).
Retrospective 607 patients reporting results for early outpatient HCQ use with mortality odds ratio OR 0.092 [0.022-0.381], p = 0.001 (65 patients), and for hospital use, mortality odds ratio OR 0.737 [0.38-1.41], p = 0.36 (558 patients). Median age 69.
Oct 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303357, https://c19p.org/guisadovasco
RCT 100 mild/moderate COVID-19 outpatients in Iran, showing lower post COVID symptoms 12 weeks after infection, statistically significant only for fatigue with the small sample size. All symptoms may occur for non-COVID-19 reasons, smell/taste disorder may be the most likely to be related to COVID-19 infection. Fluvoxamine 100mg daily for 10 days.
Mar 2023, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08172-5, https://c19p.org/farahani
Small prophylaxis study with 130 healthcare workers in the USA, showing lower symptomatic cases with HCQ prophylaxis, without statistical significance. HCQ participants were significantly older. The only symptomatic HCQ patient reported headache only as a potential COVID-19 symptom.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277058, https://c19p.org/raabe
Retrospective 1,847 COVID+ patients in Poland, showing no significant difference in moderate/severe cases with physical activity. Hospitalized patients were excluded.
Oct 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.1036556/full, https://c19p.org/plywaczewska
RCT mechanically ventilated patients in Croatia, 39 treated with N-acetylcysteine and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delic
Retrospective 1,645 hospitalized patients in the USA, showing lower mortality with aspirin use, without statistical significance.
Nov 2022, Chest, https://www.sciencedirect.com/science/article/pii/S0012369222041617, https://c19p.org/ali7
Retrospective 600 hospitalized patients in Italy, showing lower mortality with HCQ treatment, without reaching statistical significance (p = 0.1).
Oct 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-00243-4/, https://c19p.org/guglielmetti2
Retrospective 162 hospitalized COVID-19 patients in Indonesia, showing lower incidence of delayed viral clearance with favipiravir treatment in unadjusted results.
May 2023, Pathophysiology, https://www.mdpi.com/1873-149X/30/2/16, https://c19p.org/arfijanto
Retrospective 65 ICU patients in the USA and Honduras, showing shorter ICU stay with combined treatment including colchicine, LMWH, tocilizumab, dexamethasone, and methylprednisolone.
Jan 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245025, https://c19p.org/valeriopascua
33% lower mortality with HCQ+AZ, p=0.28. Retrospective 122 French dialysis patients. 69% lower combined mortality/ICU, p=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment).
Oct 2020, Clinical Kidney J., October 2020, 878–888, https://academic.oup.com/ckj/article/13/5/878/5934808, https://c19p.org/lano
Retrospective 12,331 diabetes patients in Hong Kong, showing no significant difference in outcomes with metformin use.
Sep 2022, SSRN Electronic J., https://www.ssrn.com/abstract=4225660, https://c19p.org/yip2
Two RCTs with a total of 247 recently diagnosed COVID-19 patients showing a significant reduction in salivary SARS-CoV-2 viral load 30 minutes after rinsing with a cetylpyridinium chloride (CPC) mouthwash compared to rinsing with saline or water. No significant difference was seen 60 minutes post-rinse or with other mouthwashes. Supplementary tables 9 and 10 show that viral load was lower for all treatments at 60 minutes (including saline and water), without statistical significance. Authors only report short-term viral load, no clinical or longer term results are reported. Patients were late stage, 6-7 days post symptoms, when there has likely been significant viral spread to other tissues.
Dec 2024, JDR Clinical & Translational Research, https://journals.sagepub.com/doi/10.1177/23800844241296840, https://c19p.org/gravesp
Prospective study of 60 hospitalized type 2 diabetes patients with COVID-19 on metformin monotherapy compared to 40 patients on other diabetes treatments, showing significantly lower inflammatory biomarkers, oxidative stress, and mortality, and improvements in radiological and clinical outcomes with metformin. Confounding due to differences in baseline characteristics may be significant.
Nov 2023, European Review for Medical and Pharmacological Sciences, https://doi.org/10.26355/eurrev_202312_34583, https://c19p.org/alkuraishy3
Retrospective 1,106 prostate cancer patients, showing no significant differences in COVID-19 outcomes with ADT.
Nov 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786026, https://c19p.org/schmidt
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with vitamin A prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimera
Viral load comparison for 34 HCQ and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for beneficial effects. While not achieving statistical significance, results show faster recovery with HCQ. The greatest benefit is seen mid-recovery as expected for an effective treatment: Δt7-12: 81% improvement with HCQ Δt<7: 24% improvement with HCQ For Δt>12, everyone has recovered so there is no room for improvement. Since the HCQ group started slightly higher the improvement is slightly less. Most participants have also dropped out by this test, with only 6 HCQ and 9 control remaining (also suggesting HCQ patients recovered faster).
Jun 2020, Braz J Microbiol, https://link.springer.com/article/10.1007/s42770-020-00395-x, https://c19p.org/faicofilho
Retrospective 109 hospitalized COVID-19 patients in Syria, 68 with diabetes, showing significantly lower mortality with metformin vs. sulfonylureas, and significantly higher mortality with discontinuation of metformin.
Nov 2023, Research J. Pharmacy and Technology, https://www.rjptonline.org/HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmacy%20and%20Technology;PID=2023-16-11-25, https://c19p.org/mamari
Analysis of 8,157 adults showing significantly higher risk of COVID-19 with higher adherence to an unhealthy diet, characterized by higher intake of less healthy foods such as fruit juices, refined grains, potatoes, and sugar-sweetened beverages. The association was independent of socio-demographic status and BMI.
Nov 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10115-7, https://c19p.org/darand2
Retrospective 1,847 COVID+ patients in Poland, showing lower moderate/severe cases with improved sleep, without statistical significance. Hospitalized patients were excluded.
Oct 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.1036556/full, https://c19p.org/plywaczewskasl
Retrospective 9,748 COVID-19 patients in the USA showing lower ventilation and ICU admission with zinc prophylaxis, without statistical significance.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanz
Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatment to make improvements. Time since symptom onset is not specified, but the distribution of symptoms at baseline suggests that the enrollment is relatively late within a cohort of low risk patients.
Jun 2021, Research Square, https://www.researchsquare.com/article/rs-506195/v1, https://c19p.org/byakikakibwika
Retrospective 17 COVID+ patients treated with favipiravir and 17 matched controls in Japan, showing faster viral clearance with treatment. Favipiravir 3600mg day one, 1600mg per day for up to 14 days.
Mar 2022, Viruses, https://www.mdpi.com/1999-4915/14/4/670, https://c19p.org/shinada
RCT comparing favipiravir and lopinavir/ritonavir, showing no significant differences. All patients received interferon-beta. Favipiravir 1600mg bid for the first day and 600mg bid for the following 4 days.
Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27724, https://c19p.org/hassaniazad2
Early terminated low-risk patient RCT with 32 low-dose vitamin C, 32 melatonin, and 34 placebo patients, showing faster resolution of symptoms with melatonin in spline regression analysis, and no significant difference for vitamin C. All patients recovered with no serious outcomes reported. Baseline symptoms scores were higher in the melatonin and vitamin C arms (median 27 and 24 vs. 18 for placebo).
Jul 2022, The J. the American Board of Family Medicine, http://www.jabfm.org/lookup/doi/10.3122/jabfm.2022.04.210529, https://c19p.org/fogleman
Dietary analysis of 95 adults in Poland, showing lower risk of COVID-19 with higher intake of polyphenols, lignans, and phytosterols. Results were statistically significant for total phytosterols, secoisolariciresinol, β-sitosterol, matairesinol, and stigmasterol. Authors suggest that beneficial effects on gut microbiota and immune function may contribute to the lower risk.
Aug 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1241016/full, https://c19p.org/micek
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihins
RCT 1,250 outpatients with mild to moderate COVID-19 showing no significant difference in time to sustained recovery with montelukast treatment. There were no deaths and only 2 hospitalizations in each group. Notably, results were better with patients that had mild COVID-19 at baseline compared to moderate/severe cases, and overall efficacy is reduced by poor results with extremely late treatment 9 days after onset, and with patients that had no symptoms at baseline. Authors note the treatment drug was voluntarily recalled and replaced from another source but do not report why the drug was recalled. Authors describe previous research testing 10mg and 20mg doses, noting that only 20mg showed improved pulmonary function testing, however authors do not indicate why they chose to test the lower dose for COVID-19. It is unclear why authors only report all-cause hospitalization and urgent care and do not report COVID-19 specific outcomes. Given the low rate of urgent care visits and..
May 2024, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825081, https://c19p.org/rothman
Prospective study of 182 COVID-19 pneumonia patients, 127 treated with sodium bicarbonate inhalation and nasal drops, showing significantly faster recovery and improved CT scores with treatment. Authors note that contacts of index cases also received sodium bicarbonate treatment, with none reporting COVID-19. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Jun 2022, Indian J. Respiratory Care, https://www.ijrc.in/abstractArticleContentBrowse/IJRC/98/10/3/30725/abstractArticle/Article, https://c19p.org/elbadrawy2
Prospective study of 182 COVID-19 pneumonia patients, 127 treated with sodium bicarbonate inhalation and nasal drops, showing significantly faster recovery and improved CT scores with treatment. Authors note that contacts of index cases also received sodium bicarbonate treatment, with none reporting COVID-19. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Jun 2022, Indian J. Respiratory Care, https://www.ijrc.in/abstractArticleContentBrowse/IJRC/98/10/3/30725/abstractArticle/Article, https://c19p.org/elbadrawy2sb
Very small RCT with 20 patients in Iran, showing shorter hospitalization time with famotidine treatment. There was no mortality or ICU admission. Famotidine 160mg four times a day. IRCT20200509047364N2.
Apr 2021, Research Square, https://www.researchsquare.com/article/rs-462937/v1, https://c19p.org/samimagham
PSM retrospective 322 rheumatological patients on HCQ and 645 matched controls, showing lower risk of COVID-19 with treatment, without statistical significance. Authors mention lower mortality with HCQ but do not provide details. Only an abstract is available.
May 2023, J. Clinical Rheumatology, https://journals.lww.com/10.1097/RHU.0000000000001986, https://c19p.org/dulcey
Small RCT 31 mild/moderate COVID-19 outpatients in Iran, 14 treated with melatonin, showing improved recovery with treatment.
May 2021, Iranian J. Allergy, Asthma and Immunology, https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3086, https://c19p.org/alizadeh
Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ.
Dec 2020, Virus Research, https://www.sciencedirect.com/science/article/abs/pii/S0168170220311692, https://c19p.org/tan2
Retrospective 700 patients with autoimmune rheumatic disease in Qatar, showing lower risk of COVID-19 with HCQ use, without statistical significance. For patients having close contact with COVID-19 cases, there was a statistically significant association with HCQ use and lower risk of COVID-19 in unadjusted results.
Aug 2022, Qatar Medical J., https://www.qscience.com/content/journals/10.5339/qmj.2022.37, https://c19p.org/becetti
Retrospective 7,047 outpatients with type 2 diabetes showing a lower risk of PASC (long COVID) with metformin compared to sulfonylurea or DPP-4 inhibitor use, without statistical significance.
May 2024, Clinical Epidemiology, https://www.dovepress.com/risk-of-post-acute-sequelae-of-sars-cov-2-infection-pasc-among-patient-peer-reviewed-fulltext-article-CLEP, https://c19p.org/olawore
Analysis of 94 hemodialysis COVID-19 positive patients, showing lower mortality with HCQ treatment, not reaching statistical significance.
May 2020, Kidney Int., 20-26, July 1, 2020, https://www.kidney-international.org/article/S0085-2538(20)30508-1/fulltext, https://c19p.org/alberici
Prospective study of HCQ prophylaxis in the USA, with 56 HCQ patients and 24 control patients, showing no significant differences. NCT04354870
Oct 2021, ClinicalTrials.gov, NCT04354870, https://clinicaltrials.gov/ct2/show/results/NCT04354870, https://c19p.org/belmont
Open label RCT of colchicine showing improved recovery with treatment. Only the abstract is currently available. Colchicine 0.5mg bid for 14 days.
May 2022, Indian J. Rheumatology, http://www.indianjrheumatol.com/preprintarticle.asp?id=344591;type=0, https://c19p.org/jalal
90 patient metformin prophylaxis study: 45% lower mortality (p=0.1).
Retrospective 90 hospitalized COVID-19 patients with diabetes in Italy, showing lower mortality with metformin use, without statistical significance.
Oct 2020, Diabetes Care, https://diabetesjournals.org/care/article/43/12/3042/30894/Impact-of-Comorbidities-and-Glycemia-at-Admission, https://c19p.org/mirani
Retrospective 249 elderly patients with severe COVID-19, 128 treated with azvudine, 66 treated with paxlovid, and 55 receiving neither treatment, showing no significant differences for Ct value changes, progression, or survival for either treatment. Early viral decline was faster with paxlovid, without statistical significance.
Feb 2024, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537024000476, https://c19p.org/wang25
Tiny RCT with 5 PVP-I patients, gargling 30 seconds, 3x per day, and 5 control patients (essential oils and tap water were also tested), showing improved viral clearance with PVP-I.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.07.20180448v1, https://c19p.org/mohamed
Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.
Jan 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full, https://c19p.org/dinujjant
Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.
Jan 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full, https://c19p.org/dinujjanq
Retrospective 81 cases and 396 controls among rheumatic disease patients in the Netherlands, showing lower risk of hospitalization with HCQ prophylaxis, without statistical significance.
Feb 2022, Clinical Pharmacology & Therapeutics, https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2551, https://c19p.org/opdam
Small RCT for high dose vitamin C for ICU patients showing reduced (but not statistically significant) mortality. Dosage was 12g of vitamin C/50ml every 12 hours for 7 days at a rate of 12ml/hour.
Aug 2020, Annals of Intensive Care, https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00792-3, https://c19p.org/zhang
Small mouthwash RCT with 4 PVP-I patients and 2 water patients concluding that PVP-I may have a sustained effect on reducing the salivary SARS-CoV-2 level in COVID-19 patients. ISRCTN95933274.
Dec 2020, Infection, https://link.springer.com/article/10.1007/s15010-020-01563-9, https://c19p.org/seneviratne
Small RCT 60 ICU patients in Iran, 30 treated with vitamins A, B, C, D, and E, showing significant improvement in SOFA score and several inflammatory markers at day 7 with treatment. 5,000 IU vitamin A daily, 600,000 IU vitamin D once, 300 IU of vitamin E twice a day, 500 mg vitamin C four times a day, and one ampule daily of B vitamins [thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg].
Nov 2021, Trials, https://link.springer.com/article/10.1186/s13063-021-05795-4/fulltext.html, https://c19p.org/beigmohammadi2
Retrospecttive 220 COVID-19 patients with rheumatic disease in Japan, showing lower mortality and hospitalization with HCQ prophylaxis, without statistical significance.
Sep 2022, Modern Rheumatology, https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roac104/6692611, https://c19p.org/oku
Multicenter double-blind RCT with 100 hospitalized patients in Bulgaria showing faster viral clearance, greater clinical improvement, and improved biomarkers with treatment. Limited data has been reported currently. No serious adverse events were observed.
Mar 2021, Huvemek, Press Release, https://huvemec.bg/covid-19-huvemec-klinichno-izpitanie/za-isledvaneto/, https://c19p.org/petkov
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnanc
Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no significant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43 [0.09-2.03]. Table 4 shows different results to the abstract - table 4 adjusted HR 0.80 [0.51-1.23], abstract HR 0.88 [0.51-1.53]. There was no significant difference in severe adverse events.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.01.21250371v1, https://c19p.org/hernandezcardenas
Retrospective 1,500 COVID+ patients in Bangladesh, showing lower risk of severe cases with regular exercise in unadjusted results.
Sep 2021, Infection and Drug Resistance, https://www.dovepress.com/lifestyle-and-comorbidity-related-risk-factors-of-severe-and-critical--peer-reviewed-fulltext-article-IDR, https://c19p.org/mohsinex
Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, p=0.005.
Nov 2020, Internal and Emergency Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649104/, https://c19p.org/nunezgil
Analysis of interactions between viral and human proteins for SARS-CoV-2, SARS-CoV-1, and MERS-CoV and genetic screening to identify host factors that enhance or inhibit viral infection. Authors predict indomethacin will have antiviral activity for SARS-CoV-2 and perform a retrospective study of patients in the USA that started treatment within 21 days after COVID-19 infection - 103 with indomethacin, and 103 using a celecoxib, a clinically similar drug without predicted antiviral activity. There were fewer hospital visits and hospitalizations with indomethacin, without statistical significance.
Dec 2020, Science, https://www.science.org/doi/10.1126/science.abe9403, https://c19p.org/gordon3
Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox regression. The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but does not specify the adjusted risk values.
Nov 2020, Critical Care Explorations, https://journals.lww.com/ccejournal/Fulltext/2020/12000/Predictors_of_Mortality_and_Effect_of_Drug.10.aspx, https://c19p.org/lambermont
Retrospective 524 hospitalized COVID-19 patients with diabetes in Italy, showing lower risk of mortality with metformin use, without statistical significance. The results adjusted only for COVID-19 MRS differ between the text and Figure 2.
Mar 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/7/1874, https://c19p.org/silverii
Retrospective 3,074 patients with antimalarial prescriptions and 58,955 matched controls, showing no significant differences with antimalarial prophylaxis for PCR+ cases (99% HCQ). Authors provide only PCR+ and mortality outcomes, and do not provide intermediate clinical outcomes that may show a statistically significant benefit. Authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri] (for symptomatic disease).
Jun 2023, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961623P0840X, https://c19p.org/klebanov
Retrospective 96 late stage patients receiving a single dose of 200 μg/kg ivermectin for strongyloides and 96 matched controls, showing no significant difference in outcomes. Authors note that this may be due to the low dose used.
May 2023, Viruses, https://www.mdpi.com/1999-4915/15/5/1138, https://c19p.org/llenasgarcia
RCT 447 moderate-to-severe hospitalized patients in Turkey, 52 treated with quercetin, bromelain, and vitamin C, showing no statistically significant difference in clinical outcomes.
Jan 2021, Turk. J. Biol.-529, https://journals.tubitak.gov.tr/biology/vol45/iss7/13/, https://c19p.org/onal
Analysis of 2,586 participants of a running injury prevention RCT in the Netherlands, showing higher risk of COVID-19 symptoms with sleep disturbance.
Oct 2020, J. Science and Medicine in Sport, https://www.sciencedirect.com/science/article/pii/S144024402030788X, https://c19p.org/cloostermansl
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihiz
Very small RCT with 22 indomethacin and 23 control patients, showing no significant difference in outcomes. All patients were treated with HCQ.
Jan 2022, Immunopathologia Persa, https://immunopathol.com/Inpress/ipp-29284.pdf, https://c19p.org/salmasi
Small 62 patient late stage RCT in Iran comparing favipiravir and lopinavir/ritonavir, showing significant improvement in fever, cough, and dyspnea with favipiravir on day 5. There was no significant difference in mortality, ICU admission, or chest CT improvement. IRCT20151227025726N14.
Sep 2021, Iranian J. Pharmaceutical Research, http://ijpr.sbmu.ac.ir/article_1101552.html, https://c19p.org/tabarsi
Retrospective 539 COVID-19 hospitalized patients in Milan, with treatment a median of 1 day after admission, showing lower mortality with HCQ and with HCQ+AZ, with statistical significance only for HCQ+AZ.
Jul 2020, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(20)30600-7/fulltext, https://c19p.org/darminiomonforte
242 patient zinc late treatment study: 34% lower mortality (p=0.09).
Retrospective 242 hospitalized patients in the USA showing adjusted hazard ratio for zinc treatment, aHR 0.66 [0.41-1.07]. [ncbi.nlm.nih.gov] notes that the study would be more informative if baseline serum zinc levels were known.
Jul 2020, Chest, https://journal.chestnet.org/article/S0012-3692(20)31961-9/fulltext, https://c19p.org/yao2
Retrospective 545 hospitalized COVID-19 patients with diabetes showing high mortality (33%). Metformin, SGLT inhibitors, and DPP4 inhibitors were associated with lower mortality compared with insulin.
Jun 2024, The Review of Diabetic Studies, https://diabeticstudies.org/menuscript/index.php/RDS/article/view/393, https://c19p.org/hussein3
70 patient camostat early treatment RCT: 37% improved recovery (p=0.15).
RCT 70 outpatients showing significantly lower symptom scores at day 6, faster recovery, and improved taste/smell, and fatigue with camostat treatment. There was no significant difference for viral load. The recovery result is from [bmcinfectdis.biomedcentral.com].
Jan 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.01.28.22270035, https://c19p.org/chupp
Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard ratio aHR 0.65 [0.33–1.30].
Dec 2020, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034120307516, https://c19p.org/guglielmetti
Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.
Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26880, https://c19p.org/elalfy
7,019 patient budesonide prophylaxis study: 33% fewer cases (p=0.1).
Retrospective 44,968 patients in South Korea, 7,019 on inhaled corticosteroids, showing no statistically significant differences in COVID-19 cases.
Sep 2021, Research Square, https://www.researchsquare.com/article/rs-72221/v1, https://c19p.org/lee2
RCT with 38 patients treated with vitamin C and vitamin E, and 34 control patients, showing lower ICU admission with treatment, but not statistically significant.
Apr 2021, Immunopathologia Persa, https://immunopathol.com/Article/ipp-22230, https://c19p.org/hakamifard
Prospective study of 64 rheumatic disease patients with COVID-19, showing no significant difference in outcomes with HCQ use.
Feb 2023, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkad025/7059537, https://c19p.org/mathew
Retrospective 6,256 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment, statistically significant only for women.
Dec 2020, The Lancet Healthy Longevity, https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(20)30033-7/fulltext, https://c19p.org/bramante
Retrospective 76,764 diabetes patients in Italy, showing that patients on metformin had lower rates of COVID-19 hospitalization compared to those on insulin/insulin secretagogues, GLP-1 receptor agonists, and DPP-4 inhibitors. Metformin vs. no metformin results are not provided. The most relevant result for COVID-19 and metformin may be the DPP-4i comparison, based on the DPP-4i group being the most similar to the metformin group in terms of baseline COVID-19 risk and confounders. Patients on insulin/secretagogues may have more severe or advanced diabetes.
Aug 2023, Biomedicines, https://www.mdpi.com/2227-9059/11/8/2292, https://c19p.org/greco
Small RCT with 40 nano-curcumin patients and 40 control patients showing lower mortality with treatment. Authors conclude that nano-curcumin may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may improve clinical outcomes.
Oct 2020, Int. Immunopharmacol., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574843/, https://c19p.org/valizadeh
40 hospitalized patients in Iran, 20 treated with melatonin, showing faster recovery and attenuated inflammatory cytokines with treatment.
May 2021, European J. Pharmacology, https://www.sciencedirect.com/science/article/abs/pii/S0014299921003460#, https://c19p.org/hosseini
Prospective 56 patients in Uganda, 29 HCQ and 27 control, showing 25.6% faster recovery with HCQ, 6.4 vs. 8.6 days (p = 0.20). There was no ICU admission, mechanical ventilation, or death. Treatment delay is not specified but at least a portion of patients appear to have been treated early.
Sep 2020, BMJ Open Respiratory Research, https://bmjopenrespres.bmj.com/content/7/1/e000646, https://c19p.org/kirenga
Very late stage RCT 155 ICU patients in Croatia with low vitamin D levels, showing no significant differences with 10,000IU cholecalciferol daily. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage. The baseline mean age and median WHO scores for the treatment and control groups are both higher than the respective values reported for all patients combined, which is not possible. The trial was registered after completion in May 2022.
Feb 2023, Nutrients, https://www.mdpi.com/2072-6643/15/5/1234, https://c19p.org/domazetbugarin
Prospective observational study of 199 hospitalized COVID-19 patients in Belgium showing a high prevalence of persistent symptoms including dyspnea and fatigue at 6 months after discharge. Pulmonary function tests revealed reduced diffusion capacity, and CT scans showed a high prevalence of persistent lung abnormalities at 3 months, mainly ground glass opacities. Logistic regression shows lower risk of persistent symptoms with HCQ treatment, without statistical significance.
Aug 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221005725, https://c19p.org/darcis
Retrospective 849 COVID-19+ patients in skilled nursing homes, showing lower risk of combined hospitalization/death with aspirin prophylaxis, not reaching statistical significance.
Jan 2022, Gerontology, https://www.karger.com/Article/FullText/521412, https://c19p.org/levye
Retrospective 27,493 type II diabetes patients in the USA, 7,204 on metformin, showing significantly lower COVID-19 cases, but no significant difference in mortality.
Feb 2021, Acta Diabetologica, https://link.springer.com/article/10.1007%2Fs00592-020-01666-7, https://c19p.org/oh
Retrospective 459 patients in Iran with 93% treated with HCQ, showing HCQ mortality RR 0.45, p = 0.028. HCQ was the only antiviral that showed a significant difference. There was relatively few control patients and the result is subject to confounding by indication. Average admission delay 5.72 days.
Sep 2020, The Tohoku J. Experimental Medicine, https://www.jstage.jst.go.jp/article/tjem/252/1/252_73/_article/-char/ja/, https://c19p.org/alamdari
Prospective study of 1,063 health workers in Colombia showing lower COVID-19 infection rates with adherence to a vitamin D and C supplementation plan, however very limited baseline information is provided for the adherent vs. non-adherent groups, and no adjusted results are provided. Higher risk patients had a much higher adherence rate, suggesting that the efficacy of treatment may be significantly higher than observed.
Mar 2024, Behavioural Public Policy, https://www.cambridge.org/core/product/identifier/S2398063X24000113/type/journal_article, https://c19p.org/arboleda
Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic aspirin use vs. sporadic NSAID use. Since aspirin is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2
Remote post-exposure prophylaxis RCT reporting that "[HCQ] did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure". However, this statement is incorrect - cases were reduced, just without statistical significance - it's not possible to conclude there was no efficacy. Additionally, treatment was not within 4 days - there was up to 68 hours shipping delay as below. Further, 6 independent analyses of the data in this study indicate efficacy: [arxiv.org, blog.philbirnbaum.com, drive.google.com, longdom.org, medrxiv.org, osf.io, researchgate.net]. COVID-19 cases were reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. For more detailed analysis, see [c19hcq.org]. See also: [nejm.org]. Authors compare with treatment with folic acid. [Kaur] et al. note that folic..
Jun 2020, NEJM, June 3 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2016638, https://c19p.org/boulwarepep
Survey of Indian doctors not finding a significant effect of HCQ prophylaxis.
Nov 2020, J. Vaccines & Vaccination, S6:1000002, https://www.longdom.org/open-access/no-role-of-hcq-in-covid19-prophylaxis-a-survey-amongst-indian-doctors.pdf, https://c19p.org/datta
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihit
Retrospective database analysis focused on famotidine but also showing results for HCQ users, with unadjusted mortality RR 0.85, p<0.001 (13.6% vs. 16.1%).
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.23.20199463v1, https://c19p.org/shoaibi
Retrospective 432 autoimmune disease patients in China showing lower hospitalization with HCQ without statistical significance (OR 0.566, p=0.085) in unadjusted results, slightly higher COVID-19 cases without statistical significance, and increased cough compared with CNI.
Dec 2023, J. Translational Autoimmunity, https://www.sciencedirect.com/science/article/pii/S2589909023000400, https://c19p.org/huang7
Small RCT 34 hospitalized patients in Iran showing improved imflammatory markers and lower ICU admission with vitamin B12 treatment, without statistical significance. There was no mortality.
Sep 2023, Health Science Reports, https://onlinelibrary.wiley.com/doi/10.1002/hsr2.1509, https://c19p.org/erfani
Small RCT 41 patients treated with nigella sativa, glycyrrhiza glabra, punica granatum, and rheum palmatum, and 41 control patients, showing shorter hospitalization with treatment.
Jun 2022, Integrative Medicine Research, https://www.sciencedirect.com/science/article/pii/S2213422022000373, https://c19p.org/setayesh
Retrospective 427 hospitalized COVID-19 patients in the United Kingdom, showing lower mortality with vitamin D supplementation (p=0.12), and higher mortality with both low and high vitamin D levels compared to a reference range of 50-74 nmol/L.
Jan 2022, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqac027/6518440, https://c19p.org/subramanian
83 patient N-acetylcysteine late treatment RCT: 2% lower mortality (p=1), 27% lower ventilation (p=0.57), 6% greater improvement (p=0.82), and 5% higher hospital discharge (p=0.8).
RCT 83 severe COVID-19 pnuemonia patients in Iran, 42 treated with acetylcysteine, showing no significant difference in clinical outcomes. All patients received remdesivir, famotidine, and vitamin C. More patients were at baseline category 4+ in the treatment group - 18 vs. 12. The trial focused on preventing liver injury in patients treated with remdesivir, showing improved AST/ALT levels with acetylcysteine.
Jun 2022, Gastroenterology and Hepatology from Bed to Bench, https://journals.sbmu.ac.ir/ghfbb/index.php/ghfbb/article/view/2565, https://c19p.org/mousapour
Retrospective 572 fully vaccinated hospitalized patients in China, showing lower risk with azvudine treatment, without statistical significance. The composite outcome included intubation, non-invasive respiratory support, ICU admission, and all-cause death. Azvudine was not included in the multivariable analysis (only combined antiviral therapy was used without explanation).
Oct 2023, Heliyon, https://www.sciencedirect.com/science/article/pii/S240584402308595X, https://c19p.org/liu13azv
Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Randomization resulted in 64.3% male patients (HCQ) vs. 54.2% (control) which may significantly affect results due to the much higher risk for male patients. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2019014, https://c19p.org/cavalcanti
RCT 99 ivermectin and 103 control low risk patients in China, up to 7 days from symptom onset, showing statistically significant improvement in recovery with treatment, and non-statistically significant improvements in recovery time and deterioration. Authors selectively omitted the p-value for recovery which shows statistical significance. Very little information on the patients is provided (only age, gender, and insurance status). The table, text, and abstract show three different versions of recovery numbers. The table and abstract show two different versions of recovery time. The abstract contains a hazard ratio that is not in the text, and no statistical methods are reported. Given the selective omission of the statistically significant recovery p-value, three different sets of numbers for that outcome, and other inconsistencies, the data in this study does not appear to be very reliable. Patients >50 were excluded.
Dec 2021, Indian J. Pharmaceutical Sciences, https://www.ijpsonline.com/abstract/the-effect-of-ivermectin-on-reducing-viral-symptoms-in-patients-with-mild-covid19-4455.html, https://c19p.org/abbas2
Analysis of 1255 COVID-19 patients in Wuhan Tongji Hospital finding 0.61% with systemic autoimmune diseases, much lower than authors expected (3%-10%). Authors hypothesise that protective factors, such as CQ/HCQ use, reduce hospitalization.
Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/79/9/1163, https://c19p.org/huangard
Prospective study of 146 hospitalized COVID-19 patients showing shorter hospitalization with high-dose intravenous vitamin C. 104 patients received 10g of vitamin C intravenously daily for 3 days and 42 patients received only standard care. Mortality was lower with treatment (8.7% vs 14.3%) without statistical significance. Treatment was associated with significantly shorter hospitalization in multivariable analysis (−4.95, p=0.041). No adverse events were reported in the vitamin C group.
Jul 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/13/3987, https://c19p.org/corrao
Retrospective 1,831 hospitalized COVID-19 patients in the USA, showing lower mechanical ventilation and ICU admission, but no significant difference in mortality.
Aug 2022, J. Cannabis Research, https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00152-x, https://c19p.org/shover
Prospective study of 2,646 ICU patients ≥70 years old, showing no significant difference in mortality with acetaminophen use in the 10 days prior to ICU admission.
Dec 2022, BMC Geriatrics, https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-022-03709-w, https://c19p.org/baldia
Retrospective 61 COVID+ kidney transplant patients and 122 matched controls, showing significantly lower vitamin D levels in COVID+ patients, and lower cases with vitamin D supplementation, without statistical significance.
Jan 2022, Nutrients, https://www.mdpi.com/2072-6643/14/2/317/htm, https://c19p.org/regalia
Small prophylaxis trial with 29 low dose HCQ and 455 control healthcare workers in India, showing no statistically significant differences.
Sep 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.09.13.21262971v1, https://c19p.org/agarwal2
Small quasi-randomized (patient choice) study with 25 PCR+ patients in a nursing home offered ivermectin, of which 10 chose to be treated. The mean age was 83.5 in the treatment group and 81.8 in the control group. There was lower mortality and fewer serious cases with treatment.
Apr 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-202.php?jid=jide, https://c19p.org/loue
Retrospective 430 hospitalized COVID-19 patients with type 2 diabetes in Poland showing lower mortality with metformin and higher mortality with remdesivir, convalescent plasma, and aspirin in univariable analysis. These results were not statistically significant except for aspirin, and no baseline information per treatment is provided to assess confounding.
Mar 2024, Biomedicines, https://www.mdpi.com/2227-9059/12/3/605, https://c19p.org/lewandowski
Analysis of nutrient intake and COVID-19 outcomes for 3,996 people in Iran, showing lower risk of COVID-19 hospitalization with sufficient vitamin A, vitamin C, and selenium intake, with statistical significance for vitamin A and selenium.
May 2023, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13632, https://c19p.org/vaisic
Late treatment (6.6 days after onset/PCR+) RCT with 221 low risk (no deaths) COVID-19 patients in Japan, showing no significant difference in viral clearance with a single dose of ivermectin under fasting. Authors note that a single 200 μg/kg dose under fasting was used as approved in Japan, and that the low dose, single day dosing, and fasting administration (~2.5 times lower plasma concentration according to [Guzzo]) limit applicability, and that studies with more favorable outcomes generally used a higher dose or multiday dosing. Details of PCR testing are not provided but the very slow clearance within the low risk population suggests a very high Ct value that may not accurately represent any reduction in replication-competent viral load. An erratum notes a conflict of interest for a reviewer that was a Merck employee: [frontiersin.org]
May 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1139046/full, https://c19p.org/wada
Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lower with CQ. HCQ+AZ vs. neither HCQ or CQ relative risk RR 0.68, p = 0.03 CQ vs. neither HCQ or CQ relative risk RR 0.63, p = 0.02 HCQ+AZ or CQ vs. neither relative risk RR 0.65, p = 0.006
Oct 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S014795632030412X, https://c19p.org/namendyssilva
Retrospective 176 hospitalized patients, 96 treated with oral vitamin C (from 500mg to 1500mg daily), showing lower mortality with treatment.
Sep 2020, Chest Infections, https://journal.chestnet.org/article/S0012-3692(20)32508-3/fulltext, https://c19p.org/patel
RCT 54 hospitalized patients in Egypt, showing no significant differences in recovery with lactoferrin treatment. 200mg lactoferrin orally once daily (group 1) or 200mg lactoferrin orally twice daily (group 2).
Aug 2021, Medicina, https://www.mdpi.com/1648-9144/57/8/842, https://c19p.org/algahtani
Retrospective 508 hospitalized COVID-19 patients in Iran showing lower mortality with vitamin D supplementation (not reaching statistical significance), and an association between lower vitamin D levels and disease severity, ICU admission, and increased mortality. Details of supplementation are not provided. The multivariate result for vitamin D deficiency is in the preprint, the journal version only contains the multivariate result for serum level.
Jan 2021, Scientific Reports, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413335/, https://c19p.org/vasheghani
Retrospective type 1 diabetes patients in Saudi Arabia showing reduced risk of cases with HCQ prophylaxis.
Nov 2021, BioMed Research Int., https://www.hindawi.com/journals/bmri/2021/1676914/, https://c19p.org/ahmed2
RCT 40 ICU patients in Iran, showing lower mortality with NAC treatment, without statistical significance. Single dose intravenous NAC 300 mg/kg.
Oct 2022, Jundishapur J. Natural Pharmaceutical Products, https://brieflands.com/articles/jjnpp-129817.html, https://c19p.org/rahimi
PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with H1RAs+H2RAs versus famotidine alone, without statistical significance.
Mar 2021, Signal Transduction and Targeted Therapy, https://www.nature.com/articles/s41392-021-00689-y, https://c19p.org/murah1
Retrospective 117 COVID-19 positive doctors in India showing lower mortality and severity with HCQ prophylaxis, without statistical significance in unadjusted results without group details. Results do not include the risk of positive cases.
Jun 2024, J. College of Medical Sciences-Nepal, https://www.nepjol.info/index.php/JCMSN/article/view/43302, https://c19p.org/dey2
Retrospective 2,365 patients prescribed acetaminophen and 398 prescribed NSAIDs in South Korea, showing no significant differences.
Mar 2021, Scientific Reports, http://www.nature.com/articles/s41598-021-84539-5, https://c19p.org/park2
Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, p = 0.15.
Jun 2020, Aging, 11306-11313, https://www.aging-us.com/article/103583/text, https://c19p.org/bousquet
Retrospective 5,211 prostate cancer patients, 799 on ADT, showing no significant differences in COVID-19 outcomes with treatment.
Jan 2021, Annals of Oncology, https://www.annalsofoncology.org/article/S0923-7534(21)00095-8/fulltext, https://c19p.org/kwon
Retrospective 1,544 participants in Slovakia, showing a lower risk of more severe COVID-19 for physically active participants, without statistical significance.
Jul 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/13/7158, https://c19p.org/bielik
32,085 patient fluvoxamine prophylaxis PSM study: 27% lower mortality (p=0.41) and 37% higher hospitalization (p=0.5).
Retrospective COVID+ patients in Croatia, showing no significant difference in outcomes with fluvoxamine prophylaxis.
Nov 2022, European J. Clinical Pharmacology, https://link.springer.com/10.1007/s00228-023-03479-3, https://c19p.org/trkulja2
Very high conflict of interest RCT with design optimized for a null result: very low risk patients, high existing immunity, post-hoc change to exclude patients more likely to benefit. There was no significant difference in viral clearance among low risk patients with high viral load at baseline. All 3 progression events occured in the control arm - one hospitalization and two cases of COVID-19 related rhabdomyolysis. Patients in both arms cleared the virus quickly with a viral clearance half-life of 21.1 hours vs. 19.2 hours, which may be in part due to prior immunity. With rapid viral clearance and very low risk patients, infection is less likely to spread to other tissues. Systemic treatment is less applicable, and has less time to reach therapeutic concentrations before self-recovery. Treatment administered directly to the respiratory tract, e.g. as in [ Albariqi , Albariqi (B) , Aref , Chaccour , Elkholy , Errecalde , Francés-Monerris , Mansour ] , may be more effective for COVID..
Jul 2022, eLife, https://elifesciences.org/articles/83201, https://c19p.org/schilling
Retrospective 247 hospitalized COVID-19 diabetes patients, showing lower mortality with metformin use in unadjusted results.
Dec 2020, Diabetes, Obesity and Metabolism, https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.14256, https://c19p.org/sourij
Prospective 320 hospitalized moderate COVID-19+ patients in Egypt, 160 treated with ivermectin, showing lower mortality, improved recovery, and decreased cytokine expression with treatment. All patients were treated with HCQ. 7890/26-8-2020.
Oct 2021, Zagazig University Medical J., https://journals.ekb.eg/article_202150_0.html, https://c19p.org/rezk
Prospective study of 270 female COVID-19 patients in Brazil, 75 with hyperandrogenism, of which 8 were on spironolactone. Results suggest that HA patients may be at increased risk, and that spironolactone use may reduce the risk compared to both other HA patients and non-HA patients. SOC included other treatments and there was no mortality or hospitalization.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.05.20206870v1, https://c19p.org/cadegiani9
Prospective study of 270 female COVID-19 patients in Brazil, 75 with hyperandrogenism, of which 8 were on spironolactone. Results suggest that HA patients may be at increased risk, and that spironolactone use may reduce the risk compared to both other HA patients and non-HA patients. SOC included other treatments and there was no mortality or hospitalization.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.05.20206870v1, https://c19p.org/cadegiani9sp
Retrospective 31,006 diabetic COVID-19 patients in Spain, showing lower mortality with metformin treatment, without statistical significance. Authors provide results for metformin compared with untreated patients rather than all non-metformin patients, which may increase confounding due to higher prevalence for treatment of patients with more severe disease.
Oct 2022, Primary Care Diabetes, https://www.sciencedirect.com/science/article/pii/S175199182200167X, https://c19p.org/ouchi
Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with vitamin C supplementation, without statistical significance. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2c
60 patient melatonin early treatment study: 91% lower hospitalization (p=0.05).
Small study with 30 patients treated with melatonin, cannabidiol, and for 14 patients angiotensin 1-7, compared with an age/sex matched control group during the same period, showing lower hospitalization with treatment.
Dec 2020, J. Infectiology, https://www.infectiologyjournal.com/articles/covid-19-disease-as-an-acute-angiotensin-1-7-deficiency-a-preliminary-phase-2-study-with-angiotensin-1-7-in-association-with-melatonin-and-cannabidiol-in-symptomatic-covid19-infected-subjects, https://c19p.org/lissoni
RCT 90 outpatients with post-COVID-19 anosmia showing significant improvements in smell alterations with olfactory training after 3 and 12 months. Adding oral vitamin A to olfactory training resulted in higher rates of improvement, but the difference was not statistically significant.
Jun 2024, Brazilian J. Otorhinolaryngology, https://www.sciencedirect.com/science/article/pii/S1808869424000661, https://c19p.org/taheri2
Retrospective study of 77 outpatients with rheumatic diseases diagnosed with COVID-19, showing lower risk of severe COVID-19 with HCQ use in unadjusted results.
Dec 2023, Immunopathologia Persa, https://immunopathol.com/Article/ipp-40568, https://c19p.org/salesi
215 patient HCQ ICU study: 29% lower mortality (p=0.07).
Retrospective 215 mechanically ventilated COVID-19 patients in Brazil, 71 treated with HCQ, showing lower mortality with treatment in unadjusted results, without statistical significance. Authors note HCQ was used more toward the start of the pandemic, which may introduce confounding due to overall protocols improving over time, suggesting that the actual benefit may be greater.
Jun 2022, The J. Critical Care Medicine, https://www.sciendo.com/article/10.2478/jccm-2022-0015, https://c19p.org/osawa
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtse
Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ, and 418 control. Authors report PCR and IgG results, with no baseline results for either. Authors note they "identified 69 HCWs receiving HCQ" while providing no information as to why or when they started HCQ. No conclusions can be drawn from this study because many workers may have been positive before starting HCQ. Only 14% of workers chose to use HCQ and they may have been motivated to do so because they had an infection. Authors perform several different adjustments, finding very different results. No information on death, hospitalization, symptoms, or severity is provided. Details on timing of serology and baseline serology status is not provided. Potential bias due to self-selection for risk. 25% of infections were detected before 7 days, indicating that they actually happened earlier (PCR false positive is very high initially). It is likely that many infections were before HCQ could reach therapeutic..
Nov 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa477/5997449, https://c19p.org/revollo
Retrospective 9,748 COVID-19 patients in the USA showing no significant differences with vitamin B9 use, without statistical significance.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanb9
323 patient camostat early treatment RCT: 8% faster recovery (p=0.54).
Double-blind RCT with 342 mild to moderate COVID-19 outpatients in South Korea, showing no significant difference in time to clinical improvement with camostat mesylate. In a post-hoc subgroup analysis of high-risk patients, there were non-statistically significant trends towards faster improvement in ordinal scale scores and subjective symptom scores at day 7 with treatment. Viral cultures suggested faster viral clearance with treatment, without statistical significance.
Jan 2023, Antimicrobial Agents and Chemotherapy, https://journals.asm.org/doi/10.1128/aac.00452-22, https://c19p.org/kim19
Retrospective 129 hospitalized patients with vitamin D levels measured within 90 days prior to admission, showing lower, but not statistically significant, risk of severe cases with vitamin D supplementation among patients with levels <20ng/mL or <12ng/mL. For <30ng/mL, lower (but not statistically significant) risk was seen overall but not for ≥50,000IU (the sample size is not given, it may be extremely small for this case). Only minimal details for <30ng/mL are provided, and no details for <20ng/mL or <12ng/mL are provided. The potential effect of supplementation on the risk of a case severe enough for hospitalization is not included.
May 2021, J. the Endocrine Society, https://academic.oup.com/jes/article/5/Supplement_1/A279/6240740, https://c19p.org/levitus
Combined retrospective (Mar-Jun 2020) and prospective (until Mar 2021) study of 954 COVID+ ICU patients in Saudi Arabia, 68 treated with ICS (80% budesonide or budesonide/formoterol, 20% fluticasone/salmeterol), showing lower mortality with treatment, statistically significant for 30-day but not in-hospital mortality.
Nov 2021, J. Intensive Care Medicine, https://journals.sagepub.com/doi/full/10.1177/08850666211053548, https://c19p.org/alsulaiman3
Mouse models showing reduced lung and kidney injury with metformin. Metformin minimized lung damage and fibrosis in a mouse model of LPS-induced ARDS, and reduced UUO and FAN-induced kidney fibrosis. In Vitro study showing that metformin increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis, and inflammation markers in lung epithelial cells. Authors also include a retrospective study showing lower ICU admission with metformin without statistical significance.
Nov 2023, Redox Biology, https://www.sciencedirect.com/science/article/pii/S2213231723003580, https://c19p.org/miguel
Retrospective 976 hospitalized patients with 34 treated with ivermectin showing lower mortality with ivermectin in unadjusted results.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.16.20232223v1, https://c19p.org/budhirajai
PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with aspirin (not reaching statistical significance) and famotidine, and improved results from the combination of both.
Mar 2021, Signal Transduction and Targeted Therapy, https://www.nature.com/articles/s41392-021-00689-y, https://c19p.org/mura
Open-label RCT with 52 severe COVID-19 pneumonia patients showing no significant differences in mortality with colchicine. All patients received infliximab and remdesivir.
Feb 2024, Coronaviruses, https://www.eurekaselect.com/223567/article, https://c19p.org/yadollahzadeh
Retrospective 510 patients in Iran, showing lower risk of severity with vitamin D (statistically significant) and zinc (not statistically significant) supplementation. IR.TUMS.VCR.REC.1398.1063.
Aug 2021, J. Family & Reproductive Health, https://europepmc.org/article/PMC/PMC7868648, https://c19p.org/bagheriz
Retrospective 468,569 adults in the UK, showing no significant difference in COVID-19 mortality based on sleep quality.
Aug 2021, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912100180X, https://c19p.org/ahmadi2sl
Retrospective 34 rheumatological disease patients with COVID-19 in Saudi Arabia, showing lower risk of severe cases with HCQ use in unadjusted results, without statistical significance.
May 2023, J. Medicine and Life, https://europepmc.org/article/PMC/PMC10478665, https://c19p.org/alqatari
50 patient vitamin D early treatment RCT: 33% improved recovery (p=0.15) and 50% improved viral clearance (p=0.009).
RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.
Apr 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.898062/full, https://c19p.org/khan4
Retrospective 315 COPD patients in China showing significantly lower COVID-19 cases with budesonide/formoterol or budesonide/glycopyrronium/formoterol use. Note that Table 4 includes only infected patients, we show the COVID-19 hospitalization risk among all patients with known medication status. Minimal details are provided for the groups on these medications.
May 2024, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13790, https://c19p.org/bai
Retrospective 64 patients with intellectual and developmental disability in the UK, showing no significant difference in COVID-19 status with vitamin D supplementation. Only 6 patients were not on vitamin D supplementation.
May 2021, BJPsych Bulletin, https://www.cambridge.org/core/journals/bjpsych-bulletin/article/revisiting-vitamin-d-status-and-supplementation-for-inpatients-with-intellectual-and-developmental-disability-in-the-north-of-england-uk/9ABB85B839DD2343107CCD98B10A81EA, https://c19p.org/dudley
Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with HCQ.
Dec 2020, Nephrology Dialysis Transplantation, https://academic.oup.com/ndt/article/35/12/2095/6020340, https://c19p.org/peng
RCT 74 patients in Iran, showing no significant differences in outcomes with high dose vitamin C treatment. Tables 1b and 2a show conflicting baseline SOFA scores. The percentages of patients receiving antiviral treatments and corticosteroids are switched between the text and Table 1b. Authors indicate ICU admission was an outcome, but the result is not provided. AKI was lower with treatment, though not reaching statistical significance.
Dec 2022, J. Research in Pharmacy Practice, http://www.jrpp.net/text.asp?2022/11/2/64/363550, https://c19p.org/labbanimotlagh
Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases are not provided, and the results are subject to survey bias. Authors also report on community prophylaxis but present only combined ivermectin/HCQ results.
Nov 2021, J. the Association of Physicians India, https://www.researchgate.net/publication/356294136_Ivermectin_and_Hydroxychloroquine_for_Chemo-Prophylaxis_of_COVID-19_A_Questionnaire_Survey_of_Perception_and_Prescribing_Practice_of_Physicians_vis-a-vis_Outcomes, https://c19p.org/samajdarh
Retrospective 111 patients with moderate COVID-19 pneumonia, 56 treated with NAC, showing shorter hospitalization time with treatment. NAC 1200mg daily intravenous, divided into two doses.
Nov 2021, Russian Medical Inquiry, https://www.rusmedreview.com/upload/iblock/b14/473-478.pdf, https://c19p.org/ignatova
Prophylaxis RCT with 127 probiotics and 128 control healthcare workers in Spain, showing no significant difference in cases. There were only 4 cases. Severity information by arm is not provided. L. coryniformis K8 CECT 5711. Treatment may help sustain the immune response to vaccination - in the subgroup of subjects for whom more than 81 days had passed since they received the first dose, IgG levels were significantly higher in the treatment group. Patients that started probiotic consumption before the first vaccine dose also reported significantly fewer side effects.
Aug 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.962566/full, https://c19p.org/rodriguezblanque
Retrospective 301 consecutive SLE patients with COVID-19, showing lower risk of severe outcomes with HCQ use, with statistical significance in multivariable adjusted model 1 but not model 2.
Feb 2024, Lupus, http://journals.sagepub.com/doi/10.1177/09612033241230736, https://c19p.org/liu18
100 patient prospective trial of ivermectin + doxycycline showing reduced time to symptom resolution and shorter hospital stay with treatment.
Nov 2020, IAIM, 2020, 177-182, http://iaimjournal.com/wp-content/uploads/2020/10/iaim_2020_0710_23.pdf, https://c19p.org/spoorthi
108 patient prospective study showing improved viral clearance with Panthexyl nasal spray (a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid).
Nov 2022, Pharmaceutics, https://www.mdpi.com/1999-4923/14/11/2502, https://c19p.org/cegolon
725 patient azvudine late treatment study: no change in mortality (p=1), 28% lower ventilation (p=0.04), 55% lower ICU admission (p=0.05), and 22% lower progression (p=0.07).
PSM retrospective 725 hospitalized COVID-19 patients in China compared the effectiveness and safety of the oral antivirals azvudine and paxlovid. There was no significant difference in the risk of disease progression between groups, but azvudine was associated with lower ICU admission and invasive ventilation use.
Oct 2023, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2023.1274294/full, https://c19p.org/wei2
PSM retrospective 87 patients in Nigeria, 61 treated with ivermectin, showing lower mortality, faster recovery, and faster viral clearance with ivermectin treatment. All patients received zinc and vitamin C. A synergistic effect was seen for viral clearance when ivermectin and remdesivir were combined, as predicted by In Vitro research [Jeffreys]. Subject to confounding by time, with ivermectin patients from April-June 2021, and non-ivermectin patients from September-November 2021.
Feb 2022, J. Pharmaceutical Research Int., https://journaljpri.com/index.php/JPRI/article/view/36328, https://c19p.org/thairu
Retrospective 84 elderly nursing home residents in Spain showing no mortality, hospitalization, or ICU admission with early treatment with antihistamines alone or in combination with azithromycin.
Apr 2021, Pulmonary Pharmacology & Therapeutics, https://www.sciencedirect.com/science/article/pii/S1094553921000018, https://c19p.org/moranblancoppi
Prospective convenience sampling study of 210 hospitalized age-matched COVID-19 patients, showing faster viral clearance with ivermectin. Baseline information per group is not provided.
Aug 2022, Pakistan J. Medical and Health Sciences, https://pjmhsonline.com/index.php/pjmhs/article/view/2153, https://c19p.org/qadeer
Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with calcium + zinc supplements (defined as being picked up within 35 days prior to PCR+), however only 10 patients took the supplements. Other patients may have acquired supplements outside of the healthcare system.
Jul 2021, Epidemiology and Global Health Microbiology and Infectious Disease, https://elifesciences.org/articles/68165, https://c19p.org/israel2z
Retrospective 20 ICU patients treated with vitamin D in the UAE, and 25 matched controls, showing significantly shorter ICU stay with treatment. Lower proinflammatory cytokines were associated with lower severity markers. Authors also perform a PBMC In Vitro study, with both the clinical and in vitro studies showing vitamin D attenuated major proinflammatory signaling pathways.
Aug 2022, Life Sciences, https://www.sciencedirect.com/science/article/pii/S0024320522006099, https://c19p.org/sahebsharifaskari
Retrospective 477 hospitalized patients in Indonesia, showing lower mortality with favipiravir in unadjusted results, not reaching statistical significance.
Feb 2022, J. Clinical Virology Plus, https://www.sciencedirect.com/science/article/pii/S2667038022000084, https://c19p.org/kurniyanto
Retrospective 179 patients in France exposed to COVID-19 showing, without statistical significance, a higher risk of cases, and a lower risk of mortality among cases with existing metformin treatment.
Jul 2021, GeroScience, https://link.springer.com/article/10.1007/s11357-021-00397-z, https://c19p.org/blanc
RCT 60 hospitalized patients showing that oral N-acetylcysteine (NAC) at 1800mg daily significantly decreased plasma TNF-α levels and increased glutathione peroxidase levels. The NAC group had a shorter duration of oxygen support, while there were no significant difference for length of hospital stay, need for oxygen support, or mortality. Overall, the addition of high-dose NAC reduced inflammatory markers and oxidative stress in moderate COVID-19. Limitations include the small sample size, late treatment, lack of blinding, potential overlap of treatment effect with SOC, clinical significance of biomarker results, and limited adverse event reporting.
May 2023, Archives of Pharmaceutical Sciences Ain Shams University, https://aps.journals.ekb.eg/article_306468.html, https://c19p.org/sherkawy
Small limited trial with 100 patients concluding that HCQ improved clinical outcome, OR 0.016 [0.002-0.11] in regression analysis.
Apr 2020, medRxiv doi:10.1101/2020.04.20.20072421, https://www.researchgate.net/publication/341197843_COVID-19_in_Iran_a_comprehensive_investigation_from_exposure_to_treatment_outcomes, https://c19p.org/ashraf
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More..
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v1, https://c19p.org/sotobecerra
Retrospective 2,174 hospitalized patients showing significantly shorter length of stay with favipiravir treatment.
Sep 2022, Iranian J. Science and Technology, Transactions A: Science, https://link.springer.com/10.1007/s40995-022-01351-0, https://c19p.org/behboodikhah
Retrospective 120 COVID-19 diabetes patients, showing non-statistically significantly lower mortality with existing metformin treatment.
Jul 2020, Diabetes Care, https://care.diabetesjournals.org/content/43/7/1399, https://c19p.org/chen3
RCT 50 hospitalized patients in Pakistan, 25 treated with S. salivarius K12, showing lower mortality with treatment, without statistical significance. There were more patients with higher oxygen requirements at baseline in the control group - 18 vs. 6 with O2 ≥ 8 L/min.
Sep 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/10/1926, https://c19p.org/dipierro6
Retrospective database analysis in France with 272 patients treated with melatonin, showing 19% lower mortality after adjustments, without statistical significance. Risk was lower for higher dosage (not statistically significant). Age was only in three age ranges and severe COVID was binary, likely leading to substantial residual confounding. Unadjusted differences were extreme with 60% >80 years old for melatonin compared to 15% for control. Mean daily dose 2.61mg. The title of the paper is incorrect, the most adjusted results show melatonin did reduce mortality (without reaching statistical significance).
Feb 2022, J. Travel Medicine, https://academic.oup.com/jtm/advance-article/doi/10.1093/jtm/taab195/6523003, https://c19p.org/sanchezrico
Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note that HCQ may have more promising efficacy in immune system modulation, indicated by ferritin reduction in the moderate cases and improvement of CT scores and lymphocyte counts in the severe cases. HCQ and CQ were well tolerated. Authors also compare RCT patients to a matched sample of non-RCT patients in the same hospital, showing shorter time to discharge with CQ/HCQ, but not statistically significant due to the small size.
Jan 2021, Science China Life Sciences, https://link.springer.com/article/10.1007/s11427-020-1871-4, https://c19p.org/li3
Small retrospective study of 22 lung cancer patients, 14 treated with HCQ+AZ, showing HCQ+AZ mortality relative risk RR 0.57, p = 0.145.
Sep 2020, Ann. Oncol., 2020, Sep, 31, S1026, https://www.annalsofoncology.org/article/S0923-7534(20)41826-5/fulltext, https://c19p.org/serrano
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with zinc prophylaxis.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtoz
Retrospective 140 mechanically ventilated patients in Spain, showing lower mortality with acetylcysteine treatment in unadjusted results, not reaching statistical significance.
May 2022, J. Intensive Care Medicine, http://journals.sagepub.com/doi/10.1177/08850666221105423, https://c19p.org/farinagonzalez
PSM retrospective 1,994 PCR+ patients in the USA, not showing a significant difference in mortality with aspirin treatment.
May 2021, Vascular Medicine, https://journals.sagepub.com/doi/10.1177/1358863X211012754, https://c19p.org/sahai
Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subject to significant confounding by indication and confounding by time.
Sep 2021, Int. J. General Medicine, https://www.dovepress.com/getfile.php?fileID=73585, https://c19p.org/alotaibia
RCT 100 ICU patients in Iran, 31 treated with vitamin C, showing lower mortality with treatment.
Dec 2021, Frontiers in Immunology, https://www.frontiersin.org/articles/10.3389/fimmu.2021.717816/full, https://c19p.org/majidi
Retrospective 91 hospitalized patients, 36 treated with high-dose cholecalciferol, showing lower combined death/ICU admission with treatment. Authors also analyze the relationship with comorbidity burden, finding that the positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden.
Jan 2021, Nutrients , https://www.mdpi.com/2072-6643/13/1/219/htm, https://c19p.org/giannini
Phone survey based RCT with low risk patients, 200 ivermectin and 198 control, showing lower mortality, lower disease progression, lower treatment escalation, and faster resolution of symptoms with treatment, without reaching statistical significance. Authors find the results of this trial alone do not support the use of ivermectin. However the effects are all positive, especially for serious outcomes which are unable to reach statistical significance with the very small number of events in the low risk population. An open letter, signed by >100 physicians, concluding this study is fatally flawed can be found at [ jamaletter.com ] . With the low risk patient population, there is little room for improvement with an effective treatment - 59/57% (IVM/control) recovered within the first 2 days to either "no symptoms" or "not hospitalized and no limitation of activities"; 73/69% within 5 days. Less than 3% of all patients ever deteriorated. The primary outcome was changed mid-trial, it..
Mar 2021, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2777389, https://c19p.org/lopezmedina
Retrospective 346 hospitalized patients in Iraq, showing lower mortality with HCQ in unadjusted results. HCQ results are only provided within the 93% of patients treated with enoxaparin.
Oct 2022, Current Issues in Pharmacy and Medical Sciences, https://www.sciendo.com/article/10.2478/cipms-2022-0020, https://c19p.org/assad
Retrospective 238 hospitalized patients in Spain showing lower mortality with HCQ, adjusted hazard ratio aHR 0.81 [0.24-2.76].
Jul 2020, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775320304486, https://c19p.org/riveraizquierdo
Survey analysis of dietary supplements showing no significant difference in PCR+ cases with vitamin C usage in the UK, however significant reductions were found in the US and Sweden. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucac
Retrospective 807 hospitalized patients, no statistically significant reduction in mortality or the need for mechanical ventilation with HCQ or HCQ+AZ, or for death with HCQ+AZ, HR 1.83, p=0.009 for HCQ mortality. The preprint notes that HCQ was more likely to be prescribed to patients with more severe disease, however this was deleted in the published version. 425 patients had dispositions of death or discharge by the end of the study period and thus did not encounter the issue of length-biased sampling and differential rates of right-censored observations among the groups. Also see: [mediterranee-infection.com]
Apr 2020, Med, https://www.sciencedirect.com/science/article/pii/S2666634020300064, https://c19p.org/magagnoli
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3fm
Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, p = 0.53.
Jun 2020, Clinical Kidney J., 334–339, https://academic.oup.com/ckj/article/13/3/334/5860798, https://c19p.org/fontana
Prospective study of 77 men hospitalized with COVID-19, 12 taking antiandrogens (9 dutasteride, 2 finasteride, 1 spironolactone), showing lower ICU admission with treatment (statistically significant with age-matched controls only when excluding the spironolactone patient). NCT04368897.
Sep 2020, J. the European Academy of Dermatology and Venereology, https://onlinelibrary.wiley.com/doi/10.1111/jdv.16953, https://c19p.org/goren
Retrospective 78 ICU patients in Turkey, showing lower mortality with high-dose vitamin C treatment, without statistical significance. The SOFA score was significantly better with treatment at day 4. Authors incorrectly state that "HDVC treatment did not reduce the short-term mortality...". Mortality was lower with treatment, although not statistically significant given the sample size. 6g of vitamin C daily in 4 equal doses every 6h, for a total of 96h.
Mar 2023, SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital, https://sislietfaltip.org/jvi.aspx?un=SETB-66742&volume=, https://c19p.org/coskun
Retrospective 126 patients in Turkey, showing no significant difference in PCR+ at day 14 with vitamin C treatment.
Jun 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7706&category_id=179&option=com_virtuemart, https://c19p.org/usanmakobanc
Retrospective 348 hospitalized patients in Italy showing vitamin D deficiency associated with acute hypoxemic respiratory failure. Vitamin D supplementation during hospitalization was not significantly associated with mortality or ventilation.
Mar 2021, J. Endocrinological Investigation, https://link.springer.com/article/10.1007/s40618-021-01535-2, https://c19p.org/mazziotti
Retrospective 301 pneumonia patients in Colombia showing lower mortality with colchicine treatment.
Oct 2020, Research Square, https://www.researchsquare.com/article/rs-94922/v1, https://c19p.org/pinzon
Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 [0.25 - 3.64]. There was no hospitalization or death, no significant difference in QTc, no severe adverse events, no cardiac events (e.g., syncope and arrhythmias) observed. Medication adherence was 81%. Therapeutic levels of HCQ may not have been reached by the time of the infection in the first week. 2 infections were reported to be after discontinuation of the medication, but the authors do not specify which arm these were in. Hypothetically, if these were both in the HCQ arm, the resulting RR for treatment would be much lower.
Sep 2020, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771265, https://c19p.org/abella
Retrospective 206 patients in Iran, showing COVID-19 disease severity associated with lower physical activity.
Feb 2021, J. Public Health, http://link.springer.com/article/10.1007/s10389-020-01468-9/fulltext.html, https://c19p.org/tavakol
Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ.
Nov 2020, Research Square, https://www.researchsquare.com/article/rs-113418/v1, https://c19p.org/capsoni
Retrospective database analysis of 7,654 hospitalized patients in Japan, showing no significant differences with favipiravir treatment. NCGM-G-003494-0.
Mar 2022, Infectious Diseases and Therapy, https://link.springer.com/article/10.1007/s40121-022-00617-9/fulltext.html, https://c19p.org/tsuzuki2
605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ).
Mar 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221002769, https://c19p.org/barry
Retrospective 59 ICU patients in Turkey, showing no significant difference in 30-day mortality or invasive mechanical ventilation with 160mg/day famotidine treatment. However, the famotidine group had lower fibrinogen and procalcitonin, suggesting possible benefits for coagulation, inflammation, and secondary infections. Limitations include the small sample size, lack of randomization, and other confounding treatments.
Feb 2023, Boğazi̇çi̇ Tip Dergi̇si̇, https://jag.journalagent.com/bmj/pdfs/BMJ-77044-ORIGINAL_RESEARCH-OZDEN.pdf, https://c19p.org/ozden
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtk
Small RCT 46 outpatients in Iran, 23 treated with curcimin-piperine, showing no significant difference in recovery. 1000mg curcumin and 10mg piperine/day for 14 days.
Jun 2022, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06375-w, https://c19p.org/askari
Retrospective 199 prostate cancer patients hospitalized with COVID-19 in Brazil, showing no significant difference in mortality with active ADT.
Nov 2021, Infectious Agents and Cancer, https://link.springer.com/article/10.1186/s13027-021-00406-y/fulltext.html, https://c19p.org/duarte
Retrospective 179 hospitalized patients in Turkey, 85 treated with famotidine and 94 treated with pantoprazole, showing faster recovery with famotidine in unadjusted results.
Jul 2021, Konuralp Tıp Dergisi, https://dergipark.org.tr/en/pub/ktd/article/935888, https://c19p.org/tasdemir
Mendelian randomization study showing lower risk of severe COVID-19 with physical activity.
Feb 2021, BMC Medical Genomics, https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-021-00887-1, https://c19p.org/li17
Retrospective 4,462 COVID+ diabetes patients in the USA, showing no significant difference in outcomes with metformin use.
Nov 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.1002834/full, https://c19p.org/miao
Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, p = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, p = 0.58, which may be due to survey bias, treatment self-selection, and inconsistent regimens. Improvement on severity may be related to the higher HCQ concentration in lung tissue, and also reflect that binary PCR does not distinguish replication-competence. Details of the pneumonia numbers for treatment/control are from the author, it's unclear why the lower progression to pneumonia was not reported in the paper.
Dec 2020, Infectious Diseases and Clinical Microbiology, https://www.idcmjournal.org/hqn-use-among-physicians-during-the-pandemic, https://c19p.org/gonenli
Survey analysis of dietary supplements showing no significant difference in PCR+ cases with zinc usage. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucaz
Retrospective 125 pregnant women hospitalized with COVID-19 in Turkey, showing no significant difference in hospitalization length with HCQ, and longer hospitalization with lopinavir/ritonavir use.
Jul 2024, J. Controversies in Obstetrics & Gynecology and Pediatrics, http://journal-jcogp.com/Publication/DisplayArticle/27358, https://c19p.org/degirmencih
Very late stage (9 days from symptom onset) RCT with 116 favipiravir patients and 120 arbidol patients in China, showing no significant difference in clinical recovery (relief of fever and cough, respiratory frequency ≤24 times/min, and oxygen saturation ≥98%), however the time to resolution of fever and cough was significantly lower with favipiravir. ChiCTR2000030254.
Sep 2021, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2021.683296/full, https://c19p.org/chen4
Case control study of healthcare workers in India, showing lower risk of cases with HCQ prophylaxis, without statistical significance. While authors comment negatively, as may be required for publication, and this study alone is not statistically significant, the result is consistent with the positive results in all studies to date.
Nov 2022, F1000Research, https://f1000research.com/articles/11-1298/v1, https://c19p.org/sukumar
Retrospective 68 COVID-19 patients showing physical activity and healthier nutrition associated with lower COVID-19 severity.
Oct 2023, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-023-00727-8, https://c19p.org/hegazy
Retrospective 63,369 hospitalized COVID-19 survivors aged 60 years or older in Korea, showing lower 1-year mortality with macrolides (including azithromycin), higher 1-year mortality with corticosteroids (including dexamethasone and methylprednisolone), and no significant difference with HCQ (only used for 0.2% of patients).
Oct 2024, Scientific Reports, https://www.nature.com/articles/s41598-024-76871-3, https://c19p.org/kim21h
RCT with 21 PVP-I and 20 saline patients gargling for 30 seconds and testing PCR Ct after 30 minutes, showing greater improvement with PVP-I, without statistical significance. Ct values differ across testing platforms, however the reported Ct value difference can represent a large difference in viral load. For example, using the calibration included with the ct2vl converter, the reported difference in mean Ct values corresponds to a reduction in viral load of over 3x for PVP-I.
Jul 2022, Dental and Medical Problems, https://dmp.umw.edu.pl/en/ahead-of-print/150831/, https://c19p.org/sevincgul
Retrospective 300 participants in Palestine, showing lower risk of hospitalization with physical activity, without statistical significance.
Dec 2021, J. Int. Medical Research, http://journals.sagepub.com/doi/10.1177/03000605211064405, https://c19p.org/hamdan
PSM retrospective 144 alopecia patients in the USA, showing no significant difference in COVID-19 cases with anti-androgen use. The supplemental appendix is not available.
Jun 2021, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961621P0914X, https://c19p.org/shawaa
Retrospective 94 outpatients attending a university hospital gastroenterology clinic in Japan showing no significant difference in SARS-CoV-2 infection rates between ursodeoxycholic acid (UDCA)-treated patients and control groups without UDCA treatment. However, UDCA-treated patients tended to have higher rates of subclinical infection based on serology, suggesting UDCA may reduce COVID-19 severity.
Jul 2023, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13704, https://c19p.org/okushin
Early terminated RCT with 34 patients showing no significant differences with camostat treatment.
Mar 2022, NCT04455815, https://clinicaltrials.gov/study/NCT04455815, https://c19p.org/dhaliwal
Retrospective 984 COVID-19 patients, 253 taking aspirin prior to admission, showing lower risk of respiratory support upgrade with treatment.
Oct 2021, Int. J. Cardiology, https://www.sciencedirect.com/science/article/abs/pii/S0167527321014996, https://c19p.org/sisinni
Retrospective 117 patients showing lower mortality for HCQ patients, without statistical significance. Version 1 of this paper stated: "HCQ, AZ, [and ...] were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores <3". FACTCLINYCoD scores predict mortality risk based on severity markers and comorbidities.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.05.20184655v2, https://c19p.org/synolaki
Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level. Although authors mention immortal time bias, full details on the timing of HCQ administration is not provided and this is not fully addressed. Survival curves indicate immortal time bias will significantly change results, although the observed benefit appears to exceed the potential bias.
May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.05.28.21258012v1, https://c19p.org/smith
Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with HCQ in unadjusted results.
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimerh
Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing no significant difference with aspirin treatment.
Jul 2020, J. Hematology & Oncology, https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00934-x, https://c19p.org/wang3e
Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing non-statistically significant lower mortality with metformin treatment.
Jul 2020, J. Hematology & Oncology, https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00934-x, https://c19p.org/wang3
Retrospective 4,944 COVID-19 patients with type 2 diabetes in the USA, showing lower risk of hospitalization and combined ICU/intubation/death with metformin use.
Jun 2022, BMJ Open Diabetes Research & Care, https://drc.bmj.com/content/10/3/e002774.long, https://c19p.org/yeh2
46,535 patient sleep study: 43% lower mortality (p=0.02) and 36% lower hospitalization (p=0.008).
UK Biobank retrospective, 46,535 participants with sleep behavior assessed between 2006 and 2010, showing higher risk of hospitalization and mortality with poor sleep.
Jun 2021, Sleep, https://academic.oup.com/sleep/article/doi/10.1093/sleep/zsab138/6304657, https://c19p.org/li13
Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences found for treatment escalation, ventilator-free days, viral load, or mortality. Authors consider treatment escalation more important than mortality, for unknown reasons.
Jul 2020, Critical Care, 2020, https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03117-9, https://c19p.org/lecronier
Retrospective 616 COVID-19 patients with asthma in Qatar showing no significant difference in hospitalization risk with montelukast use.
Sep 2023, Qatar Medical J., https://www.qscience.com/content/journals/10.5339/qmj.2023.15, https://c19p.org/alhmoud
Prophylaxis study using ivermectin and iota-carrageenan showing 0 of 788 cases from treated healthcare workers, compared to 237 of 407 control. See [doyourownresearch.substack.com] for discussion of issues with this trial.
Nov 2020, J. Biomedical Research and Clinical Investigation, https://medicalpressopenaccess.com/upload/1605709669_1007.pdf, https://c19p.org/carvalloprep
RCT 164 hospitalized patients in Egypt showing lower mortality and shorter hospitalization, but without statistical significance. There were no serious adverse effects. Authors suggest the low dosage may have resulted in lower efficacy than other trials, and recommend increased dosage in future trials. Time from symptom onset is not specified. The trial was retrospectively registered and the recruitment start date in the trial registration (June 2020) differs from the paper (March 2020) [osf.io]. For other concerns see [onlinelibrary.wiley.com].
Jun 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27122, https://c19p.org/abdelsalam3
RCT 60 low-risk outpatients, median age 31, with mild to moderate COVID-19 showing no significant differences with combined favipiravir/ivermectin/niclosamide treatment compared to favipiravir alone. There was limited room for improvement with almost no progression and no hospitalization, ICU admission, supplemental oxygen, or mortality. The combined group showed significantly improved visual analog scale (VAS) scores for cough, runny nose, and diarrhea from day 3. Authors note that "the WHO-CPS were significantly decreased among FPV/IVM/NCL vs FPV alone on day 10", however the degree of improvement cannot be determined based on the values reported. Authors state that "All data generated or analyzed during this study are included in this published article", which is incorrect - only summary statistics are published. The trial registration states that data will not be made available. This raises concerns, especially given many inconsistencies in the published data:..
Mar 2024, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034124001060, https://c19p.org/siripongboonsitti6
Retrospective 95 outpatients in Pakistan with strong clinical suspicion of COVID-19 (testing was not widely available), with 40 patients treated with ivermectin, showing significantly shorter duration of febrile illness with treatment. Most patients also received HCQ, AZ, zinc, and aspirin. Authors note that there was a treatment delay-response relationship.
Dec 2020, Int. J. Clinical Studies & Medical Case Reports, https://ijclinmedcasereports.com/pdf/IJCMCR-RA-00320.pdf, https://c19p.org/ghauri
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/behera
Retrospective 283 COVID-19+ diabetes patients in China, showing non-statistically significant lower mortality with HCQ/CQ treatment.
May 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/configurable/content/journals$002ftpmd$002f103$002f1$002farticle-p69.xml?t:ac=journals%24002ftpmd%24002f103%24002f1%24002farticle-p69.xml, https://c19p.org/luo3h
Retrospective 1,000 hospitalized COVID-19 patients in Pakistan, showing lower mortality with ivermectin without statistical significance.
Apr 2023, Healthcare, https://www.mdpi.com/2227-9032/11/8/1192, https://c19p.org/munir
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holta
Retrospective 8,634 hospitalized patients in India, showing lower mortality with high-dose vitamin C in unadjusted results. No group details are provided, the text and table appear to show different results, and some numbers do not match.
Jun 2021, Indian J. Basic and Applied Medical Research, https://www.ijbamr.com/assets/images/issues/pdf/FuXsaN_e2u6D7_ZY1348_LzacYt_766641.pdf, https://c19p.org/vishnuram
Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehab
Treatment and prophylaxis studies of vitamin A in Iraq. The prophylaxis study contained 209 contacts of COVID-19 patients, 97 treated with vitamin A, showing significantly lower cases with treatment, and shorter duration of symptoms. The treatment study is listed separately [Al-Sumiadai].
Jan 2021, Systematic Reviews in Pharmacy, https://www.researchgate.net/publication/351637178_THERAPEUTIC_EFFECT_OF_VITAMIN_A_ON_COVID-19_PATIENTS_AND_ITS_PROPHYLACTIC_EFFECT_ON_CONTACTS, https://c19p.org/alsumiadaip
Small very late (>50% 7+ days from symptom onset, 9 PVP-I patients) RCT testing mouthwashing with cetylpyridinium chloride, chlorhexidine, povidone-iodine, hydrogen peroxide, and distilled water, showing no significant differences. Over 30% of patients show >90% decrease in viral load @2 hrs with all 5. Authors note that a trend was observed for viral load decrease with PVP-I @2h for patients <6 days from onset (p=0.06, Wilcox test).
Dec 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-03461-y, https://c19p.org/ferrer2
Retrospective 133 COVID+ hemodialysis patients in Poland, showing lower mortality with existing vitamin D use, without statistical significance.
Jan 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/2/285, https://c19p.org/tylicki
Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically significant due to the small number of events. The actual benefit for HCQ could be much larger. The study does not address the risk of being sick enough to visit the hospital. HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Jan 2021, J. the American Academy of Dermatology, https://www.sciencedirect.com/science/article/pii/S0190962221001109, https://c19p.org/rangel
Analysis of 200 mild and moderate COVID-19 outpatients showing an association between higher ESSAP scores (measuring exercise, sugar and prebiotic consumption, sleep, and antibiotic use) and milder COVID-19 disease. Authors find increased risk with daily yogurt containing probiotics. Probiotic intake based on yogurt only may be inaccurate. Authors hypothesize that commercial yogurt products may not contain sufficient beneficial bacteria or may be contaminated. Other research shows that probiotic food labels are often misleading—of 26 probiotic foods tested, only 5 contained Bifidobacterium in sufficient concentration for exhibiting a therapeutic effect [Hazan]. For sleep, authors compare <8 hours and ≥8 hours, while sleep for less than or longer than a recommended range may indicate increased risk.
Jun 2021, British J. Nutrition, https://www.cambridge.org/core/product/identifier/S0007114521001926/type/journal_article, https://c19p.org/hegazy2
Retrospective 1,084 residents from 6 long-term care facilities in Spain showing no signficant difference in cases and mortality with PPI use in unadjusted results.
Oct 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241030, https://c19p.org/masromero
Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ.
Jul 2020, Research Square, https://www.researchsquare.com/article/rs-39421/v1, https://c19p.org/trullas
191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. No information on baseline zinc values was recorded. Egypt has a low rate of zinc deficiency so supplementation may be less likely to be helpful [ncbi.nlm.nih.gov, ncbi.nlm.nih.gov]. For several issues with this trial, see [osf.io]. See also [link.springer.com]. The primary outcome was changed from viral clearance to "improvement or mortality" in the last month of the trial. The pre-specified outcome was not reported.
Nov 2020, Biological Trace Element Research, https://link.springer.com/article/10.1007/s12011-020-02512-1, https://c19p.org/abdelsalam2z
Early terminated low-risk patient RCT with 32 low-dose vitamin C, 32 melatonin, and 34 placebo patients, showing faster resolution of symptoms with melatonin in spline regression analysis, and no significant difference for vitamin C. All patients recovered with no serious outcomes reported. Baseline symptoms scores were higher in the melatonin and vitamin C arms (median 27 and 24 vs. 18 for placebo).
Jul 2022, The J. the American Board of Family Medicine, http://www.jabfm.org/lookup/doi/10.3122/jabfm.2022.04.210529, https://c19p.org/foglemanc
Retrospective 600 COVID-19 patients in Iran with moderate/severe CT scans, showing lower prevalence of dyspnea, fever, taste/smell abnormalities, and cough with high adherence to the Mediterranean diet in unadjusted results.
Jan 2023, Medicina, https://www.mdpi.com/1648-9144/59/2/227, https://c19p.org/mohajeri2
107 patient ursodeoxycholic acid prophylaxis study: 38% improved recovery (p=0.05).
Retrospective 115 COVID-19 patients hospitalized during an Omicron outbreak in China, of which 65 received ursodeoxycholic acid (UDCA) treatment and 50 received standard care. It found that UDCA was associated with faster body temperature recovery, with a hazard ratio of 1.62 (95% CI 0.99-2.60, p=0.053) compared to standard care after adjusting for covariates. Patients receiving higher UDCA doses (≥300mg daily) had significantly faster recovery than the standard care group, with a hazard ratio of 1.82 (95% CI 1.07-3.10, p=0.028). To further analyze the exposure-response relationship, the authors developed an AI model called VirtualBody that accurately predicted individualized UDCA pharmacokinetic profiles. Additional analysis using VirtualBody-generated data found UDCA AUC, indicating total exposure over time, had a stronger correlation with clinical outcome than cumulative dose. Overall, the study suggests UDCA may shorten recovery time from COVID-19, especially at higher doses,..
May 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.05.02.23289410, https://c19p.org/yu5
Retrospective 689 hospitalized patients in Indonesia, showing lower mortality with favipiravir treatment.
Feb 2023, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368223000276, https://c19p.org/hartantri
Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided.
Sep 2021, Southeast Asian J. Tropical Medicine and Public Health, https://journal.seameotropmednetwork.org/index.php/jtropmed/article/view/490, https://c19p.org/sawanpanyalerta
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoroo
PSM retrospective 2,664 COVID-19 hospitalized patients receiving steroids/antiviral therapy in Hong Kong, showing lower risk of combined death/intubation with aspirin use.
Jun 2023, Heart, https://heart.bmj.com/content/109/Suppl_3/A244.2, https://c19p.org/tse
Retrospective 53,030 COVID-19 patients from 138 hospitals in Hubei, China showing lower mortality with metformin.
Nov 2024, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906724002409, https://c19p.org/he2
Retrospective 234 COVID-19 cases in the United Arab Emirates, showing lower risk of mortality with increased physical activity.
Aug 2021, J. Epidemiology and Global Health, https://link.springer.com/article/10.1007/s44197-021-00006-4/fulltext.html, https://c19p.org/baynounaalketbi
Retrospective 246 COVID-19 patients in the USA, showing the risk of hospitalization inversely associated with maximal exercise capacity. Adjusted results are only provided for MET as a continuous variable.
Oct 2020, Mayo Clinic Proceedings, https://www.mayoclinicproceedings.org/article/S0025-6196(20)31130-7/fulltext, https://c19p.org/brawner
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of loratadine.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoroh1
70 patient HCQ prophylaxis study: 50% lower mortality (p=0.67).
Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.26.20219154v1, https://c19p.org/arleo
Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.
Jan 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full, https://c19p.org/dinujjan
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/beherac
Retrospective 10,074 hospitalized veterans with COVID-19 in the USA, showing higher risk of mortality for former smokers and no significant difference for current smokers.
Oct 2021, Nicotine & Tobacco Research, https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntab223/6409756?login=false, https://c19p.org/razjouyansm
Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabz
FinnGen Mendelian randomization study showing higher risk of COVID-19 mortality, hospitalization, and infection with insomnia.
Jul 2022, Sleep Medicine, https://www.sciencedirect.com/science/article/pii/S1389945722005536, https://c19p.org/jones
Retrospective 14 patients with long-COVID symptoms attributed to mast cell activation treated with H1 and H2 antihistamines compared to 13 control patients, showing significant improvements in several symptoms in the treatment group compared to controls after 20 days. 29% of treated patients had complete resolution of long-COVID symptoms, compared with none in the control group.
Jul 2023, Frontiers in Cardiovascular Medicine, https://www.frontiersin.org/articles/10.3389/fcvm.2023.1202696/full, https://c19p.org/salvucci
Retrospective 7,158 hospitalized COVID-19 patients in the USA analyzing famotidine treatment, showing no significant difference in mortality with associated azithromycin treatment.
Feb 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)35249-5/fulltext, https://c19p.org/yeramaneniazaz
24 patient povidone-iodine early treatment RCT: 74% improved viral load (p=0.27).
60 patient RCT comparing chlorhexidine, PVP-I, and saline in Saudi Arabia with a single mouth rinse treatment and PCR testing 5 minutes later, showing statistically significant improvement in Ct value for PVP-I. PVP-I showed greater improvement than saline, without statistical significance.
Jul 2022, Medicine, https://journals.lww.com/md-journal/Fulltext/2022/07290/The_short_term_effect_of_different_chlorhexidine.78.aspx, https://c19p.org/natto
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.
Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darbanz
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.
Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darban
Retrospective 75 diabetes patients, 34 on metformin, showing lower mortality with treatment in unadjusted results with minimal group details.
Nov 2021, Circulation, 144:A12228, https://www.ahajournals.org/doi/abs/10.1161/circ.144.suppl_1.12228, https://c19p.org/bliden
Retrospective 11 critically ill COVID-19 ICU patients with organ failure treated with camostat mesylate (6 patients) or HCQ (5 patients). Over an 8 day period, the severity of COVID-19 decreased in the camostat group as measured by a decline in the SOFA score, inflammatory markers, and improvement in oxygenation. A similar effect was not seen in the HCQ group.
Nov 2020, Critical Care Explorations, https://journals.lww.com/10.1097/CCE.0000000000000284, https://c19p.org/hofmannwinkler
Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with increased leisure time physical activity, without statistical significance. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2ex
Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, p = 1.0.
Dec 2020, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://www.sciencedirect.com/science/article/pii/S1871402120305154, https://c19p.org/orioli
Retrospective 689 healthcare workers in India, showing non-statistically significant lower risk of IgG positivity with a vegetarian diet in unadjusted results.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtodt
Very late treatment (10 days from onset) RCT 110 patients in Iran, showing no significant difference in outcomes with colchicine. Colchicine 2mg loading dose followed by 0.5mg bid for 7 days.
Jan 2023, J. Investigative Medicine, http://journals.sagepub.com/doi/10.1177/10815589221141815, https://c19p.org/kasiri
Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication.
Sep 2021, PharmAdvances, http://www.pharmadvances.com/a-retrospective-analysis-on-pharmacological-approaches-to-covid-19-patients-in-an-italian-hub-hospital-during-the-early-phase-of-the-pandemic-2/, https://c19p.org/menardi
Together Trial Ivermectin: impossible data, critical issues, blinding broken, randomization failure, data pledge violation, protocol violations.
Aug 2021, New England J. Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2115869, https://c19p.org/togetherivm
Mouthrinse RCT in Italy comparing short-term viral load after a single 60 second treatment with povidone-iodine, hydrogen peroxide, chlorhexidine, and saline. The greatest efficacy was seen with povidone-iodine, especially for patients with low viral load at baseline.
Jul 2022, American J. Otolaryngology, https://www.sciencedirect.com/science/article/pii/S0196070922001764, https://c19p.org/fantozzi
Retrospective 32 ICU patients showing lower mortality with aspirin treatment, without statistical significance.
Aug 2021, Microbial Drug Resistance, https://www.liebertpub.com/doi/full-xml/10.1089/mdr.2020.0489, https://c19p.org/karruli
Prospective study of 40 acute coronary syndrome patients in Pakistan, 20 given a single dose of 200,000IU vitamin D, showing lower incidence of COVID-19 in the following 2 months.
May 2022, Pakistan J. Medical and Health Sciences, https://pjmhsonline.com/index.php/pjmhs/article/view/773, https://c19p.org/jabeen
Retrospective COVID+ hospitalized patients in Uganda, showing no statistically significant difference in mortality with ivermectin, however there were only 7 patients receiving ivermectin.
Dec 2021, Research Square, https://www.researchsquare.com/article/rs-1193578/v1, https://c19p.org/baguma
Retrospective 43 diabetes patients hospitalized for COVID-19 in Italy, showing lower risk of severe cases with metformin vs. insulin.
Jan 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/1/145, https://c19p.org/pinchera
Retrospective 829 hospitalized COVID-19 patients in Spain focused on gastrointestinal symptoms, showing lower risk of severe COVID-19 with HCQ treatment in bivariate analysis, without statistical significance.
Jun 2023, Gastroenterología y Hepatología, https://www.sciencedirect.com/science/article/pii/S2444382423001104, https://c19p.org/cardenasjaen
Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), HCQ alone (HR, 1.02 [95% CI, 0.83-1.27]), or HCQ+AZ (HR, 0.98 [95% CI, 0.75-1.28]). Misclassification is possible due to manual abstraction of EHR data. They observed a change in the prescribing patterns of HCQ during the study timeframe. Confounding by indication.
May 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237693, https://c19p.org/ip2
Retrospective 9,748 COVID-19 patients in the USA showing no signficant difference with aspirin use.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejane
Retrospective 167 multiple myeloma patients in Spain, showing no significant difference in mortality with HCQ treatment in unadjusted results without group details.
Jun 2020, Blood Cancer J., https://www.nature.com/articles/s41408-020-00372-5, https://c19p.org/martinezlopez
Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic ibuprofen use vs. sporadic NSAID use. Since ibuprofen is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2ib
Very late stage (mean 10 days from symptom onset, 90% on oxygen at baseline) vitamin D supplementation RCT not showing significant differences. Ethnicity was poorly matched between arms, and diabetes was 41% in the treatment arm vs. 29% in the control arm. Baseline ventilation was 15% in the treatment arm vs. 12% control. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage. Treatment was dissolved in 10mL of peanut oil.
Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2776738, https://c19p.org/murai
60 patient azithromycin late treatment study: 85% lower mortality (p=0.31).
RCT 60 hospitalized COVID-19 patients evaluating the efficacy and safety of adding oral N-acetylcysteine (NAC) at 600mg three times daily to standard antiviral treatment regimens. There was lower mortality for patients that received azithromycin, without statistical significance.
Nov 2023, Immunity, Inflammation and Disease, https://onlinelibrary.wiley.com/doi/10.1002/iid3.1083, https://c19p.org/atefiazaz
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnan
Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir.
Apr 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/4/498, https://c19p.org/hafez
Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, p=0.23.
Nov 2020, Medicina Intensiva, https://www.sciencedirect.com/science/article/pii/S2173572720301739, https://c19p.org/rodriguez
Retrospective 296 hospitalized patients in France, showing no significant difference with HCQ treatment.
Feb 2022, Infectious Diseases Now, https://www.sciencedirect.com/science/article/pii/S266699192200032X, https://c19p.org/beaumont
Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered.
Jun 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa791/5859555, https://c19p.org/paccoud
PSM retrospective 9,565 COVID-19 hospitalized patients in the USA, 1,593 receiving famotidine, showing no significant difference in mortality.
Oct 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.27375, https://c19p.org/kuno2
Retrospective 322 hospitalized patients ≥65 in China, showing lower mortality with azvudine treatment, without statistical significance.
Oct 2023, Frontiers in Microbiology, https://www.frontiersin.org/articles/10.3389/fmicb.2023.1280026/full, https://c19p.org/zhou13azv
Retrospective 230 severe COVID-19 patients in India, showing lower mortality with resveratrol + copper, without statistical significance. This study followed preclinical data showing that sepsis-related cytokine storm and fatality in mice could be prevented with oral administration of resveratrol and copper.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.21.20151423, https://c19p.org/mittra
Survey analysis of 1,858 RA patients in Iran, showing no significant difference in cases with HCQ prophylaxis.
Jan 2021, Postgraduate Medical J., https://pmj.bmj.com/content/early/2021/01/13/postgradmedj-2020-139561, https://c19p.org/khoubnasabjafari
Retrospective 2,102 rheumatology patients in Spain showing no significant difference in cases with vitamin D supplementation. Details of vitamin D supplementation are not providied - other patients may have also independently taken vitamin D.
Oct 2020, Aging, https://www.aging-us.com/article/104117/text, https://c19p.org/blanchrubio
Retrospective 175 ICU patients, 113 treated with a single dose of 300,000IU intramuscular cholecalciferol, showing lower mortality with treatment, but not reaching statistical significance. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage.
Jul 2021, European J. Clinical Nutrition, https://www.nature.com/articles/s41430-021-00984-5, https://c19p.org/guven
30 patient povidone-iodine early treatment RCT: 6% improved viral clearance (p=0.74).
Small mouth rinsing and gargling RCT with 15 1% PVP-I, 12 0.5% PVP-I, 15 3% hydrogen peroxide, 12 1.5% hydrogen peroxide, and 15 water patients, showing rapid improvement in Ct value in all groups, and no significant differences between groups.
Mar 2022, F1000Research, https://f1000research.com/articles/11-1238/v1, https://c19p.org/sulistyani
Study focused on remdesivir but with results for HCQ in the supplementary appendix, showing 9% death with HCQ versus 12% control, unadjusted relative risk uRR 0.78, p = 0.46.
May 2020, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2015301, https://c19p.org/goldmanh
Small RCT with 32 ivermectin patients and 30 control patients. The mean recovery time after enrolment in the intervention arm was 5.31 ± 2.48 days vs. 6.33 ± 4.23 days in the control arm, p > 0.05. Negative PCR results were not significantly different between control and intervention arms, p>0.05. We are not sure what the results were because the abstract and Table 5 have switched the results.
Sep 2020, IMC J. Med. Science, http://imcjms.com/registration/journal_abstract/353, https://c19p.org/podder
Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabt
Retrospective 31 ICU patients, 12 treated with melatonin, showing lower mortality with treatment, without statistical significance. Melatonin 15mg daily.
Mar 2022, Annals of Medicine and Surgery, https://www.sciencedirect.com/science/article/pii/S2049080122002527, https://c19p.org/karimpourrazkenari
Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with HCQ treatment in unadjusted results.
Dec 2020, Indian J. Critical Care Medicine, https://www.ijccm.org/doi/pdf/10.5005/jp-journals-10071-23599, https://c19p.org/mahaleh
Retrospective 158 critically ill patients receiving vitamin C and propensity matched controls, showing mortality OR 0.77 [0.48-1.23], and statistically significantly lower thrombosis, OR 0.42 [0.18-0.94]. 1000mg of vitamin C was given daily.
Apr 2021, Research Square, https://www.researchsquare.com/article/rs-354711/v1, https://c19p.org/alsulaiman2
Retrospective 53,030 COVID-19 patients from 138 hospitals in Hubei, China showing lower mortality with metformin.
Nov 2024, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906724002409, https://c19p.org/he2h
Retrospective 672 COVID-19 patients in Zimbabwe, showing lower mortality with vitamin C treatment.
Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombe
Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharifc
Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharifz
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoro
Retrospective 375 hospitalized diabetes patients in Belgium, showing lower risk of COVID-19 mortality with metformin use.
Dec 2022, Annals of Endocrinology, https://pubmed.ncbi.nlm.nih.gov/37574109/, https://c19p.org/servais
Retrospective 29,875 university staff and students in Spain, 3,662 with data, showing lower risk of COVID-19 symptoms for people that exercise. Exercise more than 5 days/week was the most protective, and intense exercise was more effective than moderate exercise.
Apr 2023, Fisioterapia, https://www.sciencedirect.com/science/article/pii/S0211563823002006, https://c19p.org/sanchez
Retrospective 857 severe COVID-19 cases and matched controls in Sweden, showing lower risk of severe COVID-19 with higher cardiorespiratory fitness.
Oct 2021, Int. J. Behavioral Nutrition and Physical Activity, https://link.springer.com/article/10.1186/s12966-021-01198-5/fulltext.html, https://c19p.org/ekblombak
Retrospective 3,139 adults >50 in Europe, with 66 COVID-19 hospitalizations, showing lower risk of hospitalization with higher physical activity and with higher muscle strength. Note that model 2 includes muscle strength which is correlated with physical activity [eurapa.biomedcentral.com].
Aug 2021, J. Sports Sciences, https://www.tandfonline.com/doi/pdf/10.1080/02640414.2021.1964721, https://c19p.org/maltagliati
Retrospective 10,427 volunteers in India, 1,058 anti-nucleocapsid antibody positive, showing lower risk of seropositivity with a vegetarian diet.
Apr 2021, eLife, https://elifesciences.org/articles/66537, https://c19p.org/naushin
Retrospective 219,000 patients showing lower risk of COVID-19 with antihistamine H1RA use. In Vitro study showing these drugs exhibit direct antiviral activity against SARS-CoV-2. Molecular docking suggests hydroxyzine and azelastine may exert antiviral effects by binding ACE2 and the sigma-1 receptor.
Jan 2021, Biochemical and Biophysical Research Communications, https://www.sciencedirect.com/science/article/pii/S0006291X20321409, https://c19p.org/reznikovazl
Retrospective 672 COVID-19 patients in Zimbabwe, showing lower mortality with azithromycin treatment.
Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombeazaz
Retrospective study of 367 hematology patients with COVID-19 in Spain. Among 216 patients with very severe COVID-19, there was significantly lower mortality with azithromycin treatment. Mortality was also lower with HCQ, but without statistical significance.
Aug 2020, Experimental Hematology & Oncology, https://ehoonline.biomedcentral.com/articles/10.1186/s40164-020-00177-z, https://c19p.org/pinanaazaz
Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing lower mortality with zinc treatment, without statistical significance.
Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocyz
Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, p = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Median age 87.
Dec 2020, J. the American Medical Directors Association, https://www.sciencedirect.com/science/article/pii/S1525861020310525, https://c19p.org/bielza
Early terminated REMAP-CAP results delayed >600 days, showing no significant differences with very low dose, poor administration, very late treatment of ICU patients. Results trend towards benefit for non-critical patients, with 32% lower mortality in unadjusted results, despite higher baseline severity in the treatment group. Results are currently only available in a CCR24 presentation. There are many critical issues as below. Authors appear to have post-hoc removed adjustment for severity to favor the control group. Preliminary analysis, please report errors or other issues. Severity Issue CRITICAL 1. Severity adjustment deleted in second post-hoc SAP CRITICAL 2. Baseline severity favors control CRITICAL 3. 32% lower mortality for non-critical patients CRITICAL 4. Expected failure based on design CRITICAL 5. Inclusion change to ICU only CRITICAL 6. >600 days delay in reporting CRITICAL 7. Adjustment direction different from expected CRITICAL 8. Remdesivir use CRITICAL 9. Bias in..
Jun 2024, Critical Care Reviews, CCR24, https://criticalcarereviews.com/meetings/ccr24#1, https://c19p.org/hashmi
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with HCQ prophylaxis in unadjusted results.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahto
Retrospective 246 severe COVID-19 patients in Uganda, showing lower mortality with zinc treatment in unadjusted results, without statistical significance.
May 2023, Infection and Drug Resistance, https://www.dovepress.com/thirty-day-outcomes-of-young-and-middle-aged-adults-admitted-with-seve-peer-reviewed-fulltext-article-IDR, https://c19p.org/kyagambiddwaz
Retrospective 118 prostate cancer patients, 4 on androgren deprivation therapy, not showing significant differences (as expected with only 4 patients in the treatment group).
Aug 2020, Annals of Oncology, https://www.annalsofoncology.org/article/S0923-7534(20)42103-9/fulltext, https://c19p.org/bennani
RCT 67 extremely late stage intubated patients in Iran, showing lower CRP with melatonin treatment, but no significant difference in outcomes.
May 2022, J. Taibah University Medical Sciences, https://www.sciencedirect.com/science/article/pii/S1658361222000877, https://c19p.org/alizadeh2
RCT ICU patients in Russia, showing significantly increased lymphocyte counts with treatment. Mortality was lower but without statistical significance. 40% of patients were on mechanical ventilation at baseline in the treatment group, compared to 30% in the placebo group. Authors state that there has been 6 RCTs for COVID-19 and vitamin D, however there was at least 23 at the time of publication: [c19early.org].
Nov 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-22045-y, https://c19p.org/bychinin2
PSM retrospective 86 ICU patients on mechanical ventilation in Turkey, showing lower mortality with high dose vitamin C treatment (≥200mg/kg for 4 days).
Sep 2020, Intensive Care Medicine Experimental, 9:S1, 001458, https://icm-experimental.springeropen.com/track/pdf/10.1186/s40635-021-00413-8.pdf, https://c19p.org/yuksel
Retrospective 25 hospitalized patients treated with cephalosporin, azithromycin, and HCQ, and 217 SOC patients in South Korea, reporting no significant differences. 5 patients receiving lopinavir/ritonavir and HCQ >5 days were excluded for unknown reasons. HCQ was typically initiated based on progression or side effects from another treatment. Conflicting results are reported. Table 2 indicates 15 CA/HCQ patients after matching, while Table S2 shows 25, and the Table 3 count is blank. S2 appears to incorrectly show before matching results, and the after matching results are missing in Table 3. 200mg HCQ bid.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267645, https://c19p.org/hong2
Retrospective 12 hospitalized patients in India treated with CQ and 17 controls, showing faster recovery with treatment. There was no significant difference in viral clearance. The CQ group mean age was 41.3 vs. 47.6 for controls.
Oct 2020, Advances in Respiratory Medicine, https://journals.viamedica.pl/advances_in_respiratory_medicine/article/view/69692, https://c19p.org/niwas
Retrospective 49 severe COVID-19 patients treated with tocilizumab, showing lower mortality with vitamin D treatment and a dose-dependent response.
Aug 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/8/1078, https://c19p.org/hafez2
Small RCT with 25 ivermectin and 25 control patients, not finding a significant difference in recovery at day 7.
Sep 2020, Int. J. Sciences-35, https://www.ijsciences.com/pub/article/2378, https://c19p.org/chachar
Case control study of 105 COVID-19 patients in India, 55 with mucormycosis and 50 without, showing zinc prophylaxis and diabetes both associated with mucormycosis in unadjusted results. This is likely confounded because zinc supplementation is commonly used with diabetes [academic.oup.com], and Arora et al. show lower risk of mucormycosis with zinc prophylaxis, aOR 0.05 [0.01–0.19] [Arora]. There was no significant difference in mortality based on zinc prophylaxis in unadjusted results.
Feb 2022, Cureus, https://www.cureus.com/articles/87998-role-of-zinc-and-clinicopathological-factors-for-covid-19-associated-mucormycosis-cam-in-a-rural-hospital-of-central-india-a-case-control-study, https://c19p.org/kumar4
Retrospective 448 pregnant women with COVID-19. Patients with calcium, zinc, and magnesium supplementation, or magnesium only, had a significantly higher titer of SARS-CoV-2 anti-RBD antibodies. There was no statistically significant difference in severe cases based on supplementation.
Mar 2022, Nutrients, https://www.mdpi.com/2072-6643/14/7/1445, https://c19p.org/citu
Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases and shorter recovery and hospitalization times with a healthy diet. Notably, all individual symptoms show lower incidence with a healthy diet with the exception of fever and chills. Fever and chills help the immune system fight infections (shivering helps to raise the body temperature).
Aug 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.929384/full, https://c19p.org/ebrahimzadeh
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing no significant difference in mortality with existing use of folic acid. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3b9
Prospective analysis of 1,047 Behçet’s syndrome patients in Turkey, showing no significant difference in cases with colchicine use.
Nov 2021, Rheumatology Int., https://link.springer.com/10.1007/s00296-021-05056-2, https://c19p.org/ozcifci
Very small retrospective of 12 dialysis patients showing 1/11 deaths with HCQ and 1/1 without HCQ.
Nov 2020, Nefrología, https://www.sciencedirect.com/science/article/pii/S0211699520301661, https://c19p.org/maldonado
Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21253121v1, https://c19p.org/martinvicente
Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.
Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27053, https://c19p.org/hajiaghajani
Retrospective 723 hospitalized COVID-19 patients in Italy showing no significant difference with azithromycin treatment.
Jan 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09034-4, https://c19p.org/donidaazaz
Retrospective 207 COVID-19 patients in China, showing azvudine associated with faster viral clearance, with azvudine-treated patients obtaining a negative PCR test result 1.7 days faster on average compared to supportive care alone after adjusting for age and sex.
Jan 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.01.05.23284180, https://c19p.org/chen13
Retrospective 71 hospitalized haematologic patients in Spain, showing lower mortality with HCQ treatment in unadjusted results and without statistical significance.
Jan 2022, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S259017022200005X, https://c19p.org/fernandezcruz
Tiny RCT for early treatment of mild COVID-19 in low risk patients, with 12 400mcg/kg single dose ivermectin patients and 12 control patients, showing significantly faster viral load reduction and symptom improvement with ivermectin. Average median viral load for gene E and gene N mid-viral recovery at day 7: Ivermectin: 1637, control: 30175 (supplementary appendix).
Dec 2020, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30464-8/fulltext, https://c19p.org/chaccour
Retrospective 2,594 COVID-19 patients in the United States showing no significant association between proton pump inhibitor (PPI) use and COVID-19 severity, including need for hospitalization or 30-day mortality. There was increasing mortality with increasing PPI use with 14%, 20%, and 27% mortality for low, standard, and high use, without statistical significance.
May 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-11680-0, https://c19p.org/shupp
Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with good sleep quality in the month before infection.
Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paul
Retrospective 1,846 hospitalized COVID-19 patients in North America showing no significant association between preadmission proton pump inhibitor (PPI) use and mechanical ventilation or mortality. Results do not account for the risk of hospitalization based on PPI use.
Mar 2021, Gastroenterology, https://www.sciencedirect.com/science/article/pii/S0016508520353956, https://c19p.org/elmunzer
Retrospective 1,035 hospitalized patients in India. Of 366 diabetic patients, there was lower mortality for the 53 that were on metformin.
May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.20.21255792v2, https://c19p.org/ravindra
Prospective analysis of 802 COVID-19 pediatric patients in Thailand, showing no significant difference in long COVID with favipiravir treatment in unadjusted results.
May 2023, Frontiers in Pediatrics, https://www.frontiersin.org/articles/10.3389/fped.2023.1127582/full, https://c19p.org/lokanuwatsatien
Retrospective 763 COVID-19 patients with type 2 diabetes in Uzbekistan, showing lower hospitalization with metformin use in unadjusted results, without statistical significance.
Jun 2023, Obesity and metabolism, https://www.omet-endojournals.ru/jour/article/view/12801, https://c19p.org/alieva
Retrospective 266 ICU patients showing lower mortality with zinc treatment, reaching statistical significance only for 30 day mortality, and lower odds of acute kidney injury, without statistical significance. NRC21R/287/07.
Jun 2021, Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-021-03785-1, https://c19p.org/alsulaiman
Retrospective 904 patients in Sweden, showing higher risk of COVID-19-like symptoms with poor muscle strength. Risk was slightly higher for physical inactivity, without statistical significance.
Oct 2021, Aging Clinical and Experimental Research, https://link.springer.com/article/10.1007/s40520-021-02006-7/fulltext.html, https://c19p.org/saadeh
Retrospective 54,009 diabetes patients in Italy, showing lower mortality with metformin use.
Oct 2022, Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, https://www.dovepress.com/infection-rates-and-impact-of-glucose-lowering-medications-on-the-clin-peer-reviewed-fulltext-article-DMSOhttps://www.dovepress.com/getfile.php?fileID=84551, https://c19p.org/mannucci
Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6 days from ARDS.
May 2020, Ann. Intensive Care, https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00678-4, https://c19p.org/hraiech
Single-blind, sham-controlled, crossover study of 17 COVID-19 outpatients showing significantly increased peripheral oxygen saturation (SpO2) levels correlated with hyperthermia (up to 44°C) produced by 30 minutes of low-field thoracic magnetic stimulation (LF-ThMS) applied to the dorsal thorax. The safety and lack of adverse events supports future research into mechanisms and potential therapeutic use of localized heat therapy for improving respiratory function in COVID-19 patients.
May 2021, Medicine, https://journals.lww.com/10.1097/MD.0000000000027444, https://c19p.org/domingueznicolas
Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, p = 0.11.
Dec 2020, F1000Research, https://f1000research.com/articles/9-1439, https://c19p.org/alqassieh
Retrospective 587 COVID+ hospitalized patients in Iran, showing no significant differences in outcomes with aspirin treatment.
Jul 2021, Identification of Biomarkers, New Treatments, and Vaccines for COVID-19, https://link.springer.com/chapter/10.1007%2F978-3-030-71697-4_17, https://c19p.org/vahedianazimi2
Study of SARS-CoV-2 burden in whole mouth fluid and respiratory droplets with povidone iodine, hydrogen peroxide, and chlorhexidine mouthwashes in 36 hospitalized COVID-19 patients using PCR and rapid antigen testing. There were significant reductions in SARS-CoV-2 burden with all treatments in both respiratory droplets and whole mouth fluid. . Authors perform antigen testing for 6 hydrogen peroxide patients, showing that 50% became negative after treatment.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.25.21252488v1, https://c19p.org/jayaramanhp
Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, p = 0.61.
Nov 2020, Thrombosis Research, https://www.sciencedirect.com/science/article/pii/S0049384820306277, https://c19p.org/qin
Retrospective 40 pediatric hospitalized patients, 15 treated with HCQ, showing 7.2 vs. 8.2 days until PCR-, not quite reaching statistical significance.
Sep 2021, Northern Clinics of Istanbul, https://northclinist.com/jvi.aspx?pdir=nci&plng=eng&un=NCI-65471&look4=, https://c19p.org/uygen
Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.01.06.20249091v1, https://c19p.org/yegerov
Retrospective 356 hospitalized COVID-19 patients, shorter hospitalization time with colchicine treatment. There were no statistically significant differences for mortality or ICU admission. Significantly lower mortality was seen with higher dosage (1mg/day vs 0.5mg/day). More control patients were on oxygen at baseline (65% vs. 54%).
Jan 2022, The J. Infection in Developing Countries, https://jidc.org/index.php/journal/article/view/14924, https://c19p.org/karakas
Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely.
Mar 2021, Cureus, https://www.cureus.com/articles/53247-clinical-features-and-prognostic-factors-of-245-portuguese-patients-hospitalized-with-covid-19, https://c19p.org/salvador
Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.
Apr 2021, J. Medical Virology, https://europepmc.org/article/med/33913549, https://c19p.org/hajiaghajania
Retrospective case-control study of 140 COVID-19 patients with autoimmune rheumatic diseases (AIRDs) and 140 matched controls showing higher rates of hospitalization, oxygen therapy, and mechanical ventilation with AIRDs. For the AIRD patients, there was no significant difference in outcomes based on HCQ use (only 10 patients).
Aug 2024, Medicina, https://www.mdpi.com/1648-9144/60/9/1377, https://c19p.org/rutskayamoroshan
Retrospective 4,002 COVID-19 patients in Denmark, 264 with ibuprofen prescriptions, showing no significant difference for COVID-19 severity.
Oct 2020, Clinical and Translational Science, https://onlinelibrary.wiley.com/doi/10.1111/cts.12904, https://c19p.org/kragholm
Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].
Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos
Retrospective 655 prostate cancer patients in Sweden, showing no significant difference in seropositivity with ADT.
Jan 2023, The Prostate, https://onlinelibrary.wiley.com/doi/10.1002/pros.24485, https://c19p.org/davidsson
Retrospective 444 hospitalized patients in Pakistan, showing lower mortality with ivermectin treatment in unadjusted results, not reaching statistical significance. Ivermectin was mostly used with patients in severe condition. Dose ranged from 12mg to 36mg for up to seven days.
Dec 2021, Exploratory Research in Clinical and Social Pharmacy, https://www.sciencedirect.com/science/article/pii/S2667276621001013, https://c19p.org/mustafa
Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, p = 0.65. The treatment group had significantly more severe illness and significantly more male patients.
May 2020, medRxix, https://www.medrxiv.org/content/10.1101/2020.05.08.20095679v1, https://c19p.org/shabrawishi
Retrospective 952 COVID-19 patients in Hong Kong, showing no significant difference in severe disease with famotidine use or PPI use.
Apr 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34940-4/fulltext, https://c19p.org/cheungppi
Retrospective 981 hospitalized patients in the UK, showing no significant difference with metformin use.
Oct 2020, Epidemiology and Infection, https://www.cambridge.org/core/journals/epidemiology-and-infection/article/risk-factors-for-severe-disease-in-patients-admitted-with-covid19-to-a-hospital-in-london-england-a-retrospective-cohort-study/9B704FF68359D8413E194D7123E49123, https://c19p.org/goodall
Retrospective 70 severe condition patients treated with vitamin A (200,000IU for two days), salbutamol, and budesonide, and 70 patients not treated with vitamin A, showing significantly lower mortality with the addition of vitamin A.
Dec 2020, EurAsian J. Biosciences-7350, http://ejobios.org/article/therapeutic-effect-of-vitamin-a-on-severe-covid-19-patients-8517, https://c19p.org/alsumiadai2
Retrospective 491 ICU patients in Spain showing lower mortality with HCQ without statistical significance in unadjusted results.
Jun 2023, Respiratory Research, https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02462-x, https://c19p.org/degonzalocalvo
Retrospective 19 COVID-19 ECMO patients in South Korea, showing a higher rate of weaning from ECMO with vitamin C treatment, without statistical significance. Authors perform multivariate analysis but do not provide full results, only reporting p > 0.05.
Dec 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S0147956320304027, https://c19p.org/jang2
Very small RCT with 4 control patients and 28 ivermectin patients split across 3 different dosage levels, showing lower (non-statistically significant) ICU admission with treatment. Authors suggest that ivermectin for SARS-CoV-2 is safe and reduces symptoms and viral load, and that the antiviral effect appears to be dose-dependent. NCT04431466. Retraction/censorship: this paper appears to have been censored at the request of the journal's founding editor [pubmed.ncbi.nlm.nih.gov]. An external review is mentioned but is not provided, and there is no reply from the authors, or indication that the authors were notified. Conclusions in this study are limited due to the small size, however we should consider all information in the context of the full body of research.
Mar 2021, Toxicology Reports, https://www.sciencedirect.com/science/article/pii/S2214750021000445, https://c19p.org/pottjunior
Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].
Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos2
Small prospective study with 31 patients gargling povidone-iodine, 17 hydrogen peroxide, and 40 control patients, showing lower viral load mid-recovery with povidone-iodine, without reaching statistical significance. Oropharyngeal only, and only every 8 hours for two days. Results may be better with the addition of nasopharyngeal use, more frequent use, and without the two day limit. Authors report only one of the 7 previous trials for PVP-I and COVID-19. Non-randomized study with no adjustments or group details. Some results in Figure 1 appear to be switched compared to the text and the labels in the figure. The viral clearance figures do not match the group sizes - for example authors report 62% PCR- for PVP-I at the 3rd test, however there is no number of 31 patients that rounds to 62%.
Oct 2021, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/pii/S0213005X21002950, https://c19p.org/pablomarcos
Prospective study of 9,058 COVID-19 ICU patients in Romania, showing lower mortality with HCQ treatment.
Nov 2022, European J. Anaesthesiology, https://journals.lww.com/10.1097/EJA.0000000000001776, https://c19p.org/bubenekturconi
Retrospective 759 hospitalized patients in the USA, showing lower mortality with combined HCQ+AZ+methylprednisolone treatment compared to methylprednisolone monotherapy.
Sep 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.935370/full, https://c19p.org/go2
Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharif
UK Biobank retrospective analysis of 387,109 people, showing lower risk of COVID-19 hospitalization with physical activity.
Jul 2020, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912030996X?via%3Dihub, https://c19p.org/hamer
Retrospective 2,884 high-risk healthcare workers in France, Germany, Italy, Spain, UK, and the USA, showing shorter sleep duration associated with increased risk of COVID-19 cases and severity.
Mar 2021, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/132.info, https://c19p.org/kim5
Analysis of UVA exposure and COVID-19 mortality in the USA, England, and Italy, showing increased UVA exposure associated with lower mortality.
Apr 2021, British J. Dermatology, https://onlinelibrary.wiley.com/doi/10.1111/bjd.20093, https://c19p.org/cherrie
Retrospective 219,000 patients showing lower risk of COVID-19 with antihistamine H1RA use. In Vitro study showing these drugs exhibit direct antiviral activity against SARS-CoV-2. Molecular docking suggests hydroxyzine and azelastine may exert antiviral effects by binding ACE2 and the sigma-1 receptor.
Jan 2021, Biochemical and Biophysical Research Communications, https://www.sciencedirect.com/science/article/pii/S0006291X20321409, https://c19p.org/reznikov
Independent analysis of the IHU-Mediterranean data [Brouqui] with 30,423 COVID-19 patients showing significantly lower risk of ICU admission or death with early treatment of hydroxychloroquine plus azithromycin (HCQ-AZ), and with azithromycin, both compared to no treatment.
Feb 2024, Archives of Microbiology & Immunology, https://www.fortunejournals.com/articles/an-independent-analysis-of-a-retrospective-cohort-of-30423-covid19-patients-treated-at-ihumediterranean-in-marseille-france-part-1.html, https://c19p.org/lounnas2azaz
Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, p = 0.17 (data is in the supplementary material).
Dec 2020, Blood, https://www.sciencedirect.com/science/article/pii/S0006497120839044, https://c19p.org/chari
Retrospective 205 patients in Italy, 160 treated with HCQ, showing lower mortality with treatment in multivariate analysis, but not reaching statistical significance.
Jun 2021, Vaccines, https://www.mdpi.com/2076-393X/9/6/640, https://c19p.org/turrini
Retrospective 323 hospitalized patients, 153 treated with vitamin C, showing no significant differences. Patients in each group were in different time periods, with the vitamin C group first. Time based confounding is possible due to improvements in SOC.
May 2021, Med. Clin., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112281/, https://c19p.org/suna
Retrospective 831 hospitalized COVID-19 patients showing lower mortality with HCQ in unadjusted results, without statistical significance.
Aug 2024, Cureus, https://www.cureus.com/articles/263779-anticoagulant-use-in-covid-19-patients-a-longitudinal-study-from-zanjan-iran, https://c19p.org/azimipirsaraeih
Retrospective 113 consecutive mechanically ventilated COVID+ ICU patients in Greece, 10 receiving high dose IV vitamin C, showing lower mortality with treatment, without statistical significance (p=0.11). The associated meta analysis includes only 11 studies, while there are currently studies, with mortality results. Authors only include critical patients, however not all studies with critical patients are included, for example [Hamidi-Alamdari, Majidi, Yüksel, Özgünay]. The meta analysis also uses unadjusted results, while PSM, Cox proportional hazards, or KM results are reported by [Al Sulaiman, Gao, Zhang, Zheng]. For [Zhang] authors use 28 day mortality, while the study reports longer term in-hospital mortality.
Feb 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.814587/full, https://c19p.org/gavrielatou
Retrospective 125 COVID+ hospitalized patients in the USA, showing no significant differences with aspirin prophylaxis.
Mar 2022, World J. Critical Care Medicine, https://www.wjgnet.com/2220-3141/full/v11/i2/92.htm, https://c19p.org/gogtay
Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ treatment, 52.1% (HCQ) versus 35.7% (control), p=0.001, but no statistically significant difference at day 14, or in progression. Patients were relatively young and there was no mortality. Only 3% of patients had any disease progression and all patients recovered, so there is little if any room for treatment benefit. Progression among higher-risk patients with comorbidities was lower with treatment (12.9% versus 28.6%, p=0.3, very few cases). Despite the title, this is not an RCT since patients self-selected the arm, or were chosen based on allergies/contraindications. The treatment group had about twice the number of patients with comorbidities. Treatment delay is unknown - it was recorded but not reported in the paper. Viral load was not measured...
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.30.20165365v1, https://c19p.org/kamran
Small 108 patient RCT comparing HCQ vs. remdesivir in very late stage treatment. All patients received tocilizumab. There were significant unadjusted baseline differences in ventilation and ICU admission. NCT04779047. REC-H-PhBSU-21011.
Nov 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121003452, https://c19p.org/sarhan
Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.
Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateef
Analysis of Mexico City's use of an ivermectin-based medical kit, showing significantly lower hospitalization with use. Authors use logistic-regression models with matched observations, including adjustments for age, sex, COVID severity, and comorbidities. This preprint was censored by the original preprint host. Censors claim that the government treatment program, which used approved medications and saved over 500 people from hospitalization, was unethical. In part they also indicate that studies of "the effects of a medication on a disease outcome" are outside the scope of their site, however retroactively censoring a paper for this reason is not appropriate. The author's response (not provided by the censors) can be found here: [twitter.com]. Author's provide the data and code for the study, and the results have been independently verified. See also: [doyourownresearch.substack.com]. This study was censored.
May 2021, Preprint, http://web.archive.org/web/20211218011849/https://files.osf.io/v1/resources/r93g4/providers/osfstorage/609085945533b4031ee1c789?action=download&direct&version=1, https://c19p.org/merino
Mendelian randomization study suggesting a causal association between retinol and related proteins (RBP4, RDH16, CRABP1) and COVID-19. The study found that genetically-predicted higher retinol levels were associated with lower COVID-19 susceptibility. There was a lower risk of hospitalization and severity without statistical significance. Authors conclude that the results support a potential protective effect of vitamin A treatment for COVID-19. Given the lack of clear evidence for pleiotropy, and the lower precision of the MR-Egger estimates, the IVW estimates are likely more reliable in this case when the IVW and MR-Egger estimates differ.
Apr 2024, BMC Pulmonary Medicine, https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-024-03013-w, https://c19p.org/wang31
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 36 low dose ivermectin and 37 control patients not finding significant differences. NCT04391127. Another study reports results on a larger group of patients in the same hospital, showing ivermectin mortality RR 0.81 [0.53-1.24] [ Guzman ] . Questions have been raised about this study and the early termination of the study and discontinuation of treatments, because the hospital statistics show a dramatically lower (~75%) case fatality rate during the period of the study [ web.archive.org ] (data from [ gob.mx ] ). Date Cases Deaths CFR 3/2020 2 1 50% 4/2020 4 1 25% 5/2020 13 1 8% 6/2020 37 2 5% 7/2020 65 5 8% 8/2020 79 23 29% 9/2020 54 12 22% 10/2020 62 21 34% 11/2020 80 26 33% 12/2020 41 13 32% Several other inconsistencies have been reported [ Chamie ] . Although the data from this study is reported to be available and has been shared with an anti-treatment group,..
Feb 2021, Infectious Disease Reports, https://www.mdpi.com/2036-7449/14/2/20, https://c19p.org/beltrangonzalez
Retrospective 547 hospitalized COVID+ patients in Egypt, showing lower mortality with lactoferrin treatment (without statistical significance).
Oct 2021, World J. Gastroenterology, https://www.wjgnet.com/1007-9327/full/v27/i40/6951.htm, https://c19p.org/shoushalf
Retrospective 46 idiopathic pulmonary fibrosis patients with COVID-19 in Turkey, showing lower mortality with favipiravir in unadjusted results, without statistical significance.
Mar 2022, Respiratory Medicine and Research, https://www.sciencedirect.com/science/article/pii/S2590041222000174?via%3Dihub, https://c19p.org/cilli
Prophylaxis study using ivermectin and carrageenan showing 0 of 131 cases from treated healthcare workers, compared to 11 of 98 control. The effect is likely to be primarily due to ivermectin - the author has later reported that carrageenan is not necessary [youtube.com]. See [doyourownresearch.substack.com] for discussion of issues with this trial.
Oct 2020, NCT04425850, https://clinicaltrials.gov/ct2/show/results/NCT04425850, https://c19p.org/carvalloprep2
EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indication is likely.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.12.20099028v1, https://c19p.org/singh
Small trial of hospitalized patients with 16 of 87 patients being treated with ivermectin, showing a significantly lower mean hospital stay with ivermectin: 7.62 vs. 13.22 days, p=0.00005. 0 of 16 ivermectin patients died vs. 2 of 71 control patients.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.07.20145979v1, https://c19p.org/gorial
Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, p=1.0.
Jul 2020, Research Square, https://www.researchsquare.com/article/rs-41653/v1, https://c19p.org/desbois
Tiny 26 patient retrospective study of very late treatment with ivermectin 200 μg/kg, median 12 days after symptoms, not showing significant differences. Authors suggest the dose is too low and recommend evaluation of higher doses. All patients received HCQ which may reduce the potential benefit for adding ivermectin.
Nov 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242184, https://c19p.org/camprubi
PSM retrospective 332 hospitalized moderate to critically ill COVID-19 patients with myocardial injury in China, showing improved 14 day mortality but no difference in overall in-hospital mortality with azvudine treatment.
Apr 2023, Cardiology Plus, https://journals.lww.com/10.1097/CP9.0000000000000049, https://c19p.org/chen16
Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR 0.67, p = 0.34.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.13.20247254v1, https://c19p.org/naseem
Retrospective 15 pediatric patients in Spain, showing faster viral clearance with HCQ+AZ, without statistical significance. Treatment time and details are not provided.
Apr 2022, Anales de Pediatría, https://www.sciencedirect.com/science/article/pii/S1695403321000126, https://c19p.org/bassetsbosch
Retrospective 679 healthcare workers post COVID-19 discharge, 76 using HCQ prophylaxis, showing no significant difference in PASC.
Dec 2022, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368222001469, https://c19p.org/shukla
Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases with higher vitamin C intake.
Mar 2023, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457723000803, https://c19p.org/asoudeh
Retrospective 133 COVID-19 patients and 322 controls, showing higher risk of COVID-19 for diets that have a higher inflammatory index (E-DII).
Mar 2022, Int. J. Clinical Practice, https://www.hindawi.com/journals/ijclp/2022/5452488/, https://c19p.org/firoozi
Retrospective 60 COVID-19 hospitalized patients and 60 controls in Iran, showing pro-inflammatory diets associated with COVID-19 cases and severity. IR.KUMS.REC.1399·444, IR.TBZMED.REC.1399·225.
Aug 2021, British J. Nutrition, https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0007114521003214, https://c19p.org/moludi
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtd
Retrospective 142 patients in Saudi Arabia, showing no significant difference in cases with physical activity.
Feb 2022, J. Multidisciplinary Healthcare, https://www.dovepress.com/the-influence-of-physical-activity-on-covid-19-prevention-among-quaran-peer-reviewed-fulltext-article-JMDH, https://c19p.org/almansour
Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.
Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadi
Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76.
Jan 2021, Revista Espanola de Quimioterapia, https://europepmc.org/article/med/33522213, https://c19p.org/roig
Retrospective 790 hospitalized type 2 diabetes patients ≥80 years old in Spain, showing no significant difference in mortality with existing metformin use.
Dec 2020, Research Square, https://www.researchsquare.com/article/rs-133358/v1, https://c19p.org/ramosrincon
Retrospective 444 hospitalized patients in Pakistan, showing lower mortality with aspirin treatment in unadjusted results, not reaching statistical significance.
Dec 2021, Exploratory Research in Clinical and Social Pharmacy, https://www.sciencedirect.com/science/article/pii/S2667276621001013, https://c19p.org/mustafae
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsifm
Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, p=0.63. Confounding by indication is likely.
Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322761, https://c19p.org/tehrani
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnanz
Retrospective 7,713 COVID-19 patients in Korea, showing no significant difference in mortality with paracetamol use.
Jun 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/13/6804, https://c19p.org/oh3
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.
Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darbanc
Retrospective 505 ECMO patients showing no significant difference in mortality in unadjusted results.
Feb 2022, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/abs/pii/S0003497522001989, https://c19p.org/hall
RCT 249 hospitalized patients with mild to moderate COVID-19 in Sri Lanka, showing statistically significant lower viral load. There was no significant difference in clinical outcomes. Only one patient had a serious outcome. Mid-recovery 11/15 symptoms showed lower scores with treatment on day 5 and on day 10. On day 10, 19% of treatment patients were asymptomatic vs. 13% of placebo patients. WHO score analysis is limited by the large percentage of missing data. Authors report that ivermectin blood levels taken before or with meals were not significantly different, however authors note that most patients consumed low fat meals. [Guzzo] show that absorption of ivermectin was significantly higher when administered following a high-fat meal.
Jul 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09563-y, https://c19p.org/wijewickrema
Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with NAC treatment. IR.MUQ.REC.1399.013.
May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholina
Retrospective 183 hospitalized patients in China, 52 taking low-dose aspirin prior to hospitalization, showing no significant difference with treatment.
Dec 2020, J. Cellular and Molecular Medicine, https://onlinelibrary.wiley.com/doi/10.1111/jcmm.16198, https://c19p.org/yuan
Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HCQ and 2 no-HCQ, confirmed+likely cases were 1 HCQ and 3 no-HCQ. 1 HCQ and 2 no-HCQ patients were admitted to hospital. We do not think a conclusion can be drawn based on these sample sizes. There are very significant differences between the groups, for example 30% of the HCQ group have SLE vs. 2.5% of the no-HCQ group. SLE patients have a 5.7 times relative risk of pneumonia according to [ncbi.nlm.nih.gov], whereas the relative risk with glucocorticoids and TNF-α inhibitors is significantly lower [academic.oup.com]. Two more recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.16.20104141v1, https://c19p.org/macias
Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with vitamin D prophylaxis in unadjusted results.
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimer
Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days. Other studies show faster resolution for HCQ, suggesting there will be a significant improvement when extending past 28 days. Hopefully authors will extend the analysis. Note that the median age is higher in the group not treated with HCQ or AZ. For other issues with the adjustments see [medrxiv.org]. Also see the analysis here [web.archive.org].
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.16.20132597v1, https://c19p.org/sbidian
Retrospective 93 hospitalized patients in Saudi Arabia, 45 treated with CQ/HCQ, showing no significant difference in viral clearance. More patients treated with CQ/HCQ had severe cases at baseline (20% vs. 2%).
Jan 2022, Cureus, https://www.cureus.com/articles/82181-negative-nasopharyngeal-sars-cov-2-pcr-conversion-in-response-to-different-therapeutic-interventions, https://c19p.org/alwafi
UK Biobank retrospective showing significantly lower COVID-19 cases with objectively measured physical activity.
Dec 2020, J. Global Health, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719276/, https://c19p.org/zhang4
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsi
Retrospective 103 mechanically ventilated patients, 41 treated with inhaled nitric oxide, and 62 with inhaled epoprostenol, showing no significant difference in outcomes.
Jun 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270646, https://c19p.org/poonam
Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with vitamin C treatment. IR.MUQ.REC.1399.013.
May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholi
Small study of 24 consecutive patients in serious condition (9 days post symptoms, mean SpO2 87.4) using combined treatment with ivermectin, doxycycline, zinc, vitamin D, and vitamin C, showing no mortality or hospitalization with treatment. Two patients declined treatment and both died. This study uses a synthetic control arm.
Jul 2021, Future Microbiology, https://www.futuremedicine.com/doi/full/10.2217/fmb-2022-0014, https://c19p.org/hazan
Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing no significant difference with HCQ treatment in unadjusted results, however HCQ was significantly more likely to be used for severe patients (33% vs. 12%).
Jan 2022, Infectious Diseases & Immunity, https://journals.lww.com/10.1097/ID9.0000000000000037, https://c19p.org/tu
Retrospective 80 hospitalized severe COVID-19 patients in Turkey, showing no significant difference with HCQ treatment in unadjusted results. All patients received favipiravir.
Jul 2023, Acta Clinica Croatica, https://www.researchgate.net/publication/372951875_FACTORS_AFFECTING_PROGNOSIS_AND_MORTALITY_IN_SEVERE_COVID-19_PNEUMONIA_PATIENTS, https://c19p.org/afsin
Treatment and prophylaxis studies of vitamin A in Iraq. The treatment study contained 100 patients, 50 treated with 200,000IU vitamin A for two days, showing lower progression to severe disease, and shorter duration of symptoms. The prophylaxis study is listed separately [Al-Sumiadai].
Jan 2021, Systematic Reviews in Pharmacy, https://www.researchgate.net/publication/351637178_THERAPEUTIC_EFFECT_OF_VITAMIN_A_ON_COVID-19_PATIENTS_AND_ITS_PROPHYLACTIC_EFFECT_ON_CONTACTS, https://c19p.org/alsumiadai
Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment.
Aug 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/article/75/11/3359/5896161, https://c19p.org/pasquini
30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HCQ but not statistically significant. One HCQ patient developed to a severe case. Treatment group 4 years older and with higher incidence of hypertension.
Mar 2020, J. Zhejiang University, https://pubmed.ncbi.nlm.nih.gov/32391667/, https://c19p.org/chenmedsci
Retrospective 165 hospitalized patients in Pakistan showing unadjusted lower mortality with combined ivermectin and doxycycline treatment. Details of the ivermectin group compared to other patients are not provided, however ivermectin was given to a similar percentage of patients in the mild, moderate, and severe/critical groups (34.5%, 29.1%, and 36.4%), suggesting that ivermectin treatment was not based on severity.
Apr 2021, Cureus, https://www.cureus.com/articles/56545-clinical-variants-characteristics-and-outcomes-among-covid-19-patients-a-case-series-analysis-at-a-tertiary-care-hospital-in-karachi-pakistan, https://c19p.org/ahsan
Small prospective study with 31 patients gargling povidone-iodine, 17 hydrogen peroxide, and 40 control patients, showing lower viral load mid-recovery with povidone-iodine, without reaching statistical significance. Oropharyngeal only, and only every 8 hours for two days. Results may be better with the addition of nasopharyngeal use, more frequent use, and without the two day limit. Authors report only one of the 7 previous trials for PVP-I and COVID-19. Non-randomized study with no adjustments or group details. Some results in Figure 1 appear to be switched compared to the text and the labels in the figure. The viral clearance figures do not match the group sizes - for example authors report 62% PCR- for PVP-I at the 3rd test, however there is no number of 31 patients that rounds to 62%.
Oct 2021, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/pii/S0213005X21002950, https://c19p.org/pablomarcoshp
PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ.
Mar 2022, Acta Medica, https://actamedica.org/index.php/actamedica/article/view/719, https://c19p.org/uyaroglua
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of HCQ.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfadden
Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases with higher zinc intake.
Mar 2023, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457723000803, https://c19p.org/asoudehz
Retrospective hospitalized patients in Indonesia, showing lower mortality and shorter hospitalization with favipiravir.
Mar 2022, Pathophysiology, https://www.mdpi.com/1873-149X/29/1/9, https://c19p.org/yulia
Retrospective 420 people in Spain, showing lower risk of COVID-19 hospitalization with a history of physical activity.
Jun 2021, Research in Sports Medicine, https://www.tandfonline.com/doi/full/10.1080/15438627.2021.1937166, https://c19p.org/latorreroman
Analysis of 42,935 participants showing lower risk of COVID-19 with healthier diets. Risk of severe cases was also lower with healthier diets, while not reaching statistical significance. Severity results are only provided with diet indices as a continuous variable.
Aug 2022, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqac219/6659183, https://c19p.org/yue
Prospective survey based study with 14,335 participants, showing risk of viral symptoms associated with shorter sleep duration.
Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253120, https://c19p.org/marcussl
Analysis of 7,766 adults in France, showing higher intakes of vitamin C, folate, vitamin K, dietary fibre, and fruit and vegetables associated with lower seropositivity.
Nov 2021, BMC Medicine, https://link.springer.com/article/10.1186/s12916-021-02168-1/fulltext.html, https://c19p.org/deschasauxtanguyb9
Retrospective 120 patients in Thailand, showing improved viral clearance with andrographis compared with favipiravir.
Dec 2022, OSIR, https://www.osirjournal.net/index.php/osir/article/download/311/251, https://c19p.org/prempree
Analysis of 7,766 adults in France, showing higher intakes of vitamin C, folate, vitamin K, dietary fibre, and fruit and vegetables associated with lower seropositivity.
Nov 2021, BMC Medicine, https://link.springer.com/article/10.1186/s12916-021-02168-1/fulltext.html, https://c19p.org/deschasauxtanguyvk
Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing no significant difference with vitamin A treatment in unadjusted results with only 8 patients receiving vitamin A.
Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocyva
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsie
Retrospective 200 hospitalized COVID-19 patients in Saudi Arabia, showing no significant difference in outcomes between HCQ and favipiravir.
Nov 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/12/1456, https://c19p.org/alosaimia
Retrospective 100 ICU patients in Turkey, showing improved survival with favipiravir vs. lopinavir/ritonavir.
Jun 2022, SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital, https://sislietfaltip.org/jvi.aspx?un=SETB-35902&volume=, https://c19p.org/acarsevinc
Prospective multicenter study of 354 hospitalized type 2 diabetes patients with COVID-19 in Greece showing increased risk with DPP4 inhibitor use as part of chronic diabetes treatment. There was no significant difference with metformin use in unadjusted results. Results do not account for differences in the risk of hospitalization.
May 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/6/1416, https://c19p.org/akinosoglou
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtz
Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64.
Jan 2021, Critical Care Research and Practice, https://www.hindawi.com/journals/ccrp/2021/7510306/, https://c19p.org/ubaldo
Late (5.4 days) outpatient RCT showing no significant difference in outcomes with aspirin treatment.
Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002995, https://c19p.org/eikelboom2e
UK Biobank retrospective 77,271 patients aged 50-86, showing no significant differences with aspirin use. Matching lead to different results for the gender vs. overall analysis, for example the overall result for cases was OR 1.07, however both gender results are lower OR 0.97 and 1.02.
Aug 2021, Drugs & Aging, https://link.springer.com/article/10.1007%2Fs40266-021-00886-y, https://c19p.org/ma3
Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided.
Sep 2021, Southeast Asian J. Tropical Medicine and Public Health, https://journal.seameotropmednetwork.org/index.php/jtropmed/article/view/490, https://c19p.org/sawanpanyalert
Retrospective 116,209 pediatric patients showing lower risk of COVID-19 with PPI use. There was no significant difference for hospitalization.
Jun 2024, The J. Pediatrics, https://www.sciencedirect.com/science/article/pii/S0022347624002828, https://c19p.org/hirsch2
Retrospective database analysis with PSM not including COVID-19 severity, finding mortality OR 0.95 [0.62-1.46] for HCQ, and 1.24 [0.70-2.22] for HCQ+AZ. Confounding by indication likely.
Oct 2020, Pharmacotherapy, https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2467, https://c19p.org/annie
Retrospective 4,363 COVID-19 patients and 67,125 controls in South Korea, showing higher risk of mortality and cases with insufficient physical activity.
Feb 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1072198/full, https://c19p.org/park3
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsid
Retrospective 517 hip fracture patients in the UK with vitamin D levels measured during COVID-19 admission, not showing significant differences in mortality for supplementation in unadjusted analysis with no group details and subject to confounding by indication. There was also no significant effect based on deficiency.
Dec 2021, European J. Medical and Health Sciences, https://ej-med.org/index.php/ejmed/article/view/1159, https://c19p.org/mahmood
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnand
200 patient probiotics late treatment RCT: 2% higher mortality (p=1), 18% lower ventilation (p=1), 27% lower ICU admission (p=0.77), and 5% faster recovery (p=0.47).
RCT 200 patients, 99 treated with a probiotic (Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301). There was no significant difference in mortality or recovery time, however benefits were seen for diarrhea. NCT04854941.
Oct 2021, Probiotics Antimicrob Proteins, https://pubmed.ncbi.nlm.nih.gov/34643888/, https://c19p.org/ivashkin
Prospective study of 966 ICU patients in France, 289 treated with HCQ, showing no significant difference with treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Jul 2021, Anaesthesia Critical Care & Pain Medicine, https://www.sciencedirect.com/science/article/pii/S2352556821001351, https://c19p.org/roger
RCT 47 ICU patients showing no significant differences with vitamin C treatment.
Apr 2024, NCT04344184, https://clinicaltrials.gov/study/NCT04344184, https://c19p.org/fowler
Retrospective 755 autoimmune rheumatic disease patients, showing lower risk of PASC (long COVID) with HCQ use, without statistical significance.
Apr 2023, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991323000668, https://c19p.org/sen2
Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mentions differences favoring HCQ but ignores those favoring control (large differences in ethnicity, rheumatic conditions, hypertension, coronary artery disease, solid organ transplant recipients, immunosuppresive drugs). 61% of control patients also received HCQ. Adherence for chronic HCQ patients was not examined. Despite the very large differences between the groups, no adjustments are made. The study claims that HCQ did not prevent severe cases, but the study is among hospitalized patients, i.e., they already have cases severe enough for hospitalization - this study can not identify a protective effect of HCQ that reduces the probability of disease severe enough for hospitalization.
Mar 2021, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkab014/6156645, https://c19p.org/pham
Retrospective 246 severe COVID-19 patients in Uganda, showing lower mortality with vitamin C treatment, without statistical significance (p = 0.06).
May 2023, Infection and Drug Resistance, https://www.dovepress.com/thirty-day-outcomes-of-young-and-middle-aged-adults-admitted-with-seve-peer-reviewed-fulltext-article-IDR, https://c19p.org/kyagambiddwa
Prospective survey analysis of 28,575 people in 99 countries, showing a lower risk of COVID-19 with a exercise, without statistical significance.
Sep 2021, BMJ Open, https://bmjopen.bmj.com/content/11/9/e052025, https://c19p.org/lin
Retrospective 148 hospitalized kidney transplant patients with COVID-19 in China showing lower risk of disease progression with azvudine treatment compared, and higher risk with paxlovid treatment.
Apr 2024, Infections in the immunosuppressed and immunocompromised host, https://www.atsjournals.org/doi/10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A2917, https://c19p.org/liu23
Small single-arm trial testing short-term viral load change after a single administration of three puffs of 0.4% PVP-I, showing lower viral titer at 3 minutes and 4 hours, not reaching statistical significance. Authors note that one reason for the lower change compared to in vitro results is that the spray administration may be less effective.
Aug 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.18.22278340, https://c19p.org/sirijatuphat3
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297521000792, https://c19p.org/cadegianii
Retrospective 1376 hospitalized patients in Italy, 211 treated with HCQ and 166 with HCQ+AZ.
Aug 2020, J, Clinical Medicine, https://www.mdpi.com/2077-0383/9/9/2800, https://c19p.org/albani
Retrospective 1,699 ICU patients in Saudi Arabia, 193 treated with favipiravir, showing no significant difference in mortality.
Jun 2022, J. Ayub Medical College Abbottabad, https://jamc.ayubmed.edu.pk/jamc/index.php/jamc/article/view/10305, https://c19p.org/abdulrahman2
Database analysis of 7,592 patients in NYC, showing adjusted HCQ mortality odds ratio OR 0.96, p = 0.82, and HCQ+AZ OR 0.94, p = 0.63
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.11.20128926v1, https://c19p.org/wangrx
Retrospective 603 patients in Iran, 192 taking vitamin D supplements, showing no significant difference in COVID-19 cases in unadjusted results. IR.SHOUSHTAR.REC.1399.015.
Aug 2021, Nutrition & Food Science, https://www.emerald.com/insight/content/doi/10.1108/NFS-11-2020-0421/full/html, https://c19p.org/mohseni
Retrospective 193 ICU patients in Iran, showing lower mortality with famotidine treatment.
May 2022, Obesity Medicine, https://www.sciencedirect.com/science/article/pii/S245184762200032Xhttps://www.sciencedirect.com/science/article/pii/S245184762200032X/pdf, https://c19p.org/zangeneh
Small study of SLE patients taking HCQ with a phone survey for COVID-19 suggestive symptoms. There was 2 hospitalizations (group not identified) and no ICU or death cases. A similar percentage of suspected infections were reported for HCQ users and non-HCQ users, RR 0.96, p = 0.93. There was no mortality and severity was not analyzed to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity of SLE. Only 5 cases were PCR confirmed.
Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/06/25/annrheumdis-2020-218244, https://c19p.org/gendebien
Retrospective survey-based analysis of 349 COVID-19 patients, showing no significant difference with vitamin C prophylaxis in unadjusted analysis. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabc
Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.
Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateefc
Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. "It is notable that HQ plus antibiotics group had worse baseline clinical profiles (i.e. higher percentage of moderate severity patients, more patients with fever >=37.5C, higher average body temperature) and prognostic indicators such as age, LDH, lymphocyte count, and CRP". We note that propensity score matching removed almost all of the male patients in the control group (40% -> 5%) but increased the percentage of male patients in the treatment group. This provides a large advantage to the control group because there is a very large difference in severity and mortality based on gender [ncbi.nlm.nih.gov]. In terms of viral RNA clearance we note that other research has found that "active viral replication drops quickly after the first week, and viable virus..
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.04.20146548v1, https://c19p.org/an
Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 [0.68-1.23]. Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity of autoimmune or inflammatory condition.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.03.21251069v1, https://c19p.org/fitzgerald
Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 [0.57-1.57], p=0.82 after adjustments.
May 2020, Annals of the Rheumatic Diseases, 859-866, https://europepmc.org/article/med/32471903, https://c19p.org/gianfrancesco
Retrospective database analysis of 328,374 adults in South Korea, showing lower risk of COVID-19 cases with aspirin use, but no difference in mortality for COVID-19 patients.
Jun 2021, Yonsei Medical J., https://eymj.org/DOIx.php?id=10.3349/ymj.2021.62.7.577, https://c19p.org/oh2
Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.
Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateefz
PSM retrospective case control study in South Korea, showing a trend towards lower mortality, but no significant differences with aspirin use.
Jul 2021, Medicine, https://journals.lww.com/10.1097/MD.0000000000026670, https://c19p.org/son
Retrospective 147 ICU patients in Turkey, showing no significant difference in outcomes based on HCQ treatment before ICU admission. This is not very informative, for example we do not know if HCQ treated patients were much less likely to be admitted to the ICU.
Apr 2021, South. Clin. Ist. Euras., https://jag.journalagent.com/scie/pdfs/SCIE-89847-RESEARCH_ARTICLE-CIYILTEPE.pdf, https://c19p.org/ciyiltep
Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity with a 16% higher mNEWS score for HCQ vs. SOC in the matched cohort. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse. Authors note: "overall, there was an indication bias, with the reason of prescription being associated with the outcome of interest. Indeed, patients with more severe COVID-19 were more likely to receive experimental therapies."
Dec 2020, Swiss Medical Weekly, https://smw.ch/article/doi/smw.2020.20446, https://c19p.org/vernaz
Retrospective 2017 hospitalized patients in India, showing lower mortality with ivermectin treatment in unadjusted results. No group details are provided and this result is subject to confounding by indication.
Aug 2021, Lung India, https://journals.lww.com/lungindia/Fulltext/2022/01000/Clinical_features,_demography,_and_predictors_of.5.aspx, https://c19p.org/elavarasi
Prospective PrEP study with low risk healthcare workers in India showing RR=0.89 [0.53-1.52]. There were no significant adverse effects. Only mean age and gender distribution are provided for baseline characteristics, no severity information is provided, and no adjustments were made. Authors analyze HCQ use for <8 vs. ≥8 weeks, noting a lack of statistical significance, but not providing the results.
Dec 2021, Expert Review of Anti-infective Therapy, https://www.tandfonline.com/doi/abs/10.1080/14787210.2022.2015326, https://c19p.org/rao
Retrospective 477 COVID+ public transportation workers in Turkey, showing no significant difference in hospitalization with vitamin D use in unadjusted results.
Nov 2022, Work, https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-220292, https://c19p.org/guldemird
Retrospective 406 COVID-19 patients in Iran, showing lower risk of severe cases with metformin use in unadjusted results, without statistical significance.
Oct 2023, Cureus, https://www.cureus.com/articles/194481-development-of-a-scoring-method-based-on-a-chest-ct-scan-to-determine-the-outcomes-of-covid-19-patients, https://c19p.org/bidari
Retrospective 668 hospitalized patients in Argentina, 18 treated with HCQ, not showing a significant difference in unadjusted results.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.30.21261220v1, https://c19p.org/barra
Retrospective study of 367 hematology patients with COVID-19 in Spain. Among 216 patients with very severe COVID-19, there was significantly lower mortality with azithromycin treatment. Mortality was also lower with HCQ, but without statistical significance.
Aug 2020, Experimental Hematology & Oncology, https://ehoonline.biomedcentral.com/articles/10.1186/s40164-020-00177-z, https://c19p.org/pinana
Prospective study of 382 hospitalized COVID-19 patients in New York City, showing significantly worse 6-month functional outcomes, activities of daily living, and return to work with neurological complications during initial hospitalization.
Jul 2021, J. the Neurological Sciences, https://www.sciencedirect.com/science/article/pii/S0022510X21001805, https://c19p.org/frontera3
RCT 298 mild-to-moderate COVID-19 outpatients in the UK showing no significant difference in hospitalization or death with late azithromycin treatment. Treatment was delayed an average of 6 days from onset. 7 vs. 3 hospitalizations occurred by day 1 in the treatment vs. control groups in this open label trial (Figure 2).
Oct 2021, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260021002630, https://c19p.org/hinksaz
Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.
Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadifm
Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support. Confounding by indication likely.
Nov 2020, Mayo Clinic Proceedings: Innovations, Quality & Outcomes, https://www.sciencedirect.com/science/article/pii/S2542454820302071, https://c19p.org/rodrigueznavao
Small PEP trial with 51 HCQ patients, not showing a significant difference in cases. IRCT20130917014693N10.
Aug 2021, Pulmonary Pharmacology & Therapeutics, https://www.sciencedirect.com/science/article/abs/pii/S109455392100081X, https://c19p.org/shabani
Prospective study of 200 ECMO patients showing no significant difference in unadjusted results for HCQ treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (as shown in figure 4), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Jul 2021, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/pii/S0003497521011772, https://c19p.org/jacobs
Analysis of 239 consecutive diabetic patients, 97 taking vitamin D supplements, showing significantly higher vitamin D levels in supplemented patients. There was no statistically significant difference in cases based on supplementation, with only 3 cases total.
Sep 2021, Endocrine Abstracts, https://www.endocrine-abstracts.org/ea/0070/ea0070ep552, https://c19p.org/lazaro
Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.
Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadie
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More..
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v1, https://c19p.org/sotobecerrai
Retrospective survey-based analysis of 349 COVID-19 patients, showing no significant difference with nigella sativa prophylaxis in unadjusted analysis. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabns
Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HCQ patient cases. Only considers people tested at a time when primarily symptomatic cases were tested. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. Adjusting for the difference in baseline risk using the result in Ferri et al. shows substantial benefit for HCQ, RR 0.211, but with only 3 HCQ cases the result is inconclusive. More recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.
May 2020, Autoimmunity Reviews, July 2020, https://www.sciencedirect.com/science/article/pii/S1568997220301282, https://c19p.org/gendelman
Retrospective 965 late stage (44% severe, 27% ICU) hospitalized patients in India, showing no significant difference with ivermectin treatment. Overall mortality was very high, suggesting very late treatment. The low non-weight-adjusted dose may not be very effective with such late stage patients. 210 patients were excluded due to early discharge, which may have been patients with earlier onset that are more likely to benefit with ivermectin. Age grouping is very unusual with no breakdown of ages for the 71% of patients >45. Numbers may be unreliable, e.g., cardiovascular disease counts and/or percentages for IVM appear incorrect. Details of adjustments are not provided, there may be extreme confounding by age within the >45 groups which contain the majority of the patients, in addition to confounding by indication.
Apr 2022, Research Square, https://www.researchsquare.com/article/rs-1522422/v1, https://c19p.org/ravikirti2
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of spironolactone.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenaa
UK Biobank retrospective showing lower cases with acetaminophen use.
Aug 2021, COVID, https://www.mdpi.com/2673-8112/1/1/18, https://c19p.org/leal
UK Biobank retrospective showing no significant difference in cases with ibuprofen use.
Aug 2021, COVID, https://www.mdpi.com/2673-8112/1/1/18, https://c19p.org/lealib
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of spironolactone.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenaasp
Analysis of 80 SLE patients diagnosed with COVID-19, showing the frequency of hospitalisation did not differ between individuals using an antimalarial versus non-users (55% (16/29) vs 57% (29/51), p=ns. Authors suggest that the dosage used may be too low to reach therapeutic levels.
May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/20/annrheumdis-2020-217690, https://c19p.org/konig
Retrospective 32 ICU patients, showing no significant difference with HCQ treatment in unadjusted results.
Aug 2021, Microbial Drug Resistance, https://www.liebertpub.com/doi/full-xml/10.1089/mdr.2020.0489, https://c19p.org/karrulih
Small case control analysis with 15 probiotics patients and 15 contol patients, showing no significant differences. PCR tests were only done weekly. Dosage is unknown. 115/LOE/301.4.2/IX/2020.
Jun 2021, Indian J. Forensic Medicine & Toxicology, http://medicopublication.com/index.php/ijfmt/article/view/15003/13584, https://c19p.org/veterini
Retrospective 1,349 prostate cancer patients in Spain, 156 on ADT, showing no significant differences in COVID-19 outcomes with treatment.
Sep 2021, The Prostate, https://onlinelibrary.wiley.com/doi/full/10.1002/pros.24232, https://c19p.org/jimenezalcaide
Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became more controversial in Brazil over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients (those refusing HCQ) likely come later in the period when treatment protocols were greatly improved. The paper does not mention the word "confounding" or make any adjustments.
Feb 2021, The Brazilian J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S141386702100012X, https://c19p.org/lamback
Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with 3+ hours of exercise per week in the month before infection, without statistical significance (p=0.16).
Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paulex
Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with no smoking in the month before infection, not reaching statistical significance (p=0.14).
Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paulsm
Retrospective 4,017 coronary artery disease patients hospitalized for COVID-19 in the USA, showing no significant difference in outcomes with low dose aspirin use.
Dec 2022, Innovation in Aging, https://academic.oup.com/innovateage/article/6/Supplement_1/850/6939246, https://c19p.org/zadeh
Prospective survey-based study with 15,227 people in the UK, showing reduced risk of COVID-19 cases with lower impact physical activity. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtex
Prospective survey-based study with 15,227 people in the UK, showing reduced risk of COVID-19 cases with 8 hours sleep, with statistical significance when compared with ≥9 hours. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtsl
Prospective study of 78,674 COVID-19 patients, showing no significant difference in mortality with ibuprofen use.
Jul 2021, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991321001041, https://c19p.org/drake
Prospective trial of ivermectin, dexamethasone, enoxaparin, and aspirin, showing no hospitalization for mild cases, and lower mortality for moderate/severe patients.
Sep 2020, J. Clinical Trials, https://www.longdom.org/open-access/safety-and-efficacy-of-the-combined-use-of-ivermectin-dexamethasone-enoxaparin-and-aspirina-against-covid19-the-idea-protocol-70290.html, https://c19p.org/carvallo
Retrospective 280 hospitalized patients in the Philippines, 25 treated with HCQ, not showing any significant differences in unadjusted results.
Nov 2021, Western Pacific Surveillance and Response J., https://ojs.wpro.who.int/ojs/index.php/wpsar/article/view/852, https://c19p.org/cortez
Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with vitamin C treatment in unadjusted results.
Mar 2022, Research Square, https://www.researchsquare.com/article/rs-1362678/v1, https://c19p.org/salehic
Analysis of 1,957 older adults showing lower risk of COVID-19 hospitalization with higher dietary zinc intake. Each unit increase in zinc intake was associated with a 31% reduction in the risk of COVID-19 hospitalization after adjustments. A dynamical system model showed that consumption of zinc < 9.7mg per day was associated with a 1.5 times greater risk of COVID-19 infection.
Mar 2024, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-024-00821-5, https://c19p.org/seifi
Retrospective 131 COVID-19 patients with aspirin use and 131 matched controls in Iran, showing no significant difference in outcomes, however age matching used only two categories, 40-60 and 60+, therefore matching may be very poor given the relationship between age and COVID-19 risk. The percentages given for the control group death/recovery outcomes do not match the reported counts.
Feb 2023, J. Nephropharmacology, https://www.jnephropharmacology.com/Inpress/npj-10506.pdf, https://c19p.org/azizi
Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri]. Authors compare with patients that never used HCQ and with patients that previously used HCQ. The comparison with patients previously using HCQ is more relevant because the matching of patients with systemic autoimmune disease is likely to be better.
Sep 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266922, https://c19p.org/fung
Retrospective causal inference analysis of 4,091 COVID+ long-term care high risk patients in the USA, showing lower mortality with vitamin D, without statistical significance.
Nov 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.11.18.21266489, https://c19p.org/ahmed3
Retrospective 2,736,091 individuals in the U.S., U.K., and Sweden, showing lower risk of hospital/clinic visits with aspirin use.
May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.28.21256261, https://c19p.org/drew
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of metformin.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenmf
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of famotidine.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenfm
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of vitamin B9.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenb9
Small 89 patient RCT comparing favipiravir and inhaled interferon with HCQ for moderate to severe COVID-19 pneumonia, not finding significant differences. There was no control group.
Nov 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220323195, https://c19p.org/khamisf
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21252883v1, https://c19p.org/royh
Retrospective database analysis of 374,229 patients in the USA, showing higher cases, lower hospitalizations, and no change in mortality with famotidine use.
Sep 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266922, https://c19p.org/fungfm
Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ significantly from previous studies, for example showing mortality OR 0.94 [0.83-1.06] for patients with rheumatic disease and mortality OR 0.88 [0.74-1.05] for patients with RA/SLE. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall.
Apr 2021, Rheumatology, https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab348/6226505?searchresult=1, https://c19p.org/alegiani
Comparison of CQ/HCQ users with the general population in a region of Italy, showing no significant difference in the probability of COVID-19. CQ/HCQ users were mostly systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Aug 2020, Arthritis & Rheumatology, https://onlinelibrary.wiley.com/doi/10.1002/art.41475, https://c19p.org/salvarani
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups. Subject to the usual limitation of a database study, very small size, and limited evaluation of patients.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21252883v1, https://c19p.org/roy
Retrospective 193 ICU patients in Iran, showing no significant difference with vitamin C treatment.
May 2022, Obesity Medicine, https://www.sciencedirect.com/science/article/pii/S245184762200032Xhttps://www.sciencedirect.com/science/article/pii/S245184762200032X/pdf, https://c19p.org/zangenehc
Report on ivermectin prophylaxis in a hospital in Argentina showing lower cases for healthcare workers taking ivermectin. Results have been published in the press [lanacion.com.ar] (interim results), and a presentation posted online: [web.archive.org], however there is no formal publication to date. These results would be expected to receive priority publication due to the predicted impact on the pandemic and confirmation of previous prophylaxis studies. The lack of formal publication suggests a negative publication bias that may be due to politicization in the authors' location. Note that this prophylaxis study is different to the Vallejos early treatment trial.
Dec 2020, IVERCOR PREP, Preliminary Results, https://web.archive.org/web/20210226215453/https://twitter.com/Covid19Crusher/status/1365420061859717124, https://c19p.org/vallejos
Retrospective 600 PCR+ outpatients in Australia treated with ivermectin, zinc, and doxycycline, showing significantly lower mortality and hospitalization with treatment. This trial uses a synthetic control group, and the preliminary report provides minimal details. For discussion of the use of a synthetic control group, see [doyourownresearch.substack.com]. Notably, advantages include less-biased recruitment (patients do not opt-out if they feel they need treatment and don't want to risk placebo), trials are cheaper, there is less delay in treatment, and trials can be run where it is not ethical to give patients placebo.
Oct 2021, TrialSite News, https://www.trialsitenews.com/a/combination-therapy-for-covid-19-based-on-ivermectin-in-an-australian-population, https://c19p.org/borody
25 patient HCQ late treatment study: 38% improved viral clearance (p=0.17).
Early results from a very small trial, reported within the application for a later trial. Very minimal details are provided, but we include this as the earliest published results. For COVID-19 patients with pneumonia the viral negative conversion rate was 50% (5/10) with CQ versus 20% (3/15) with lopinavir/ritonavir.
Feb 2020, ChiCTR2000029741, http://www.chictr.org.cn/showproj.aspx?proj=49263, https://c19p.org/xia
Retrospective 160 ICU patients, 32 with raised neutrophil/lymphocyte ratio treated with vitamin C, showing no significant differences.
Jul 2021, The European Research J., https://dergipark.org.tr/en/download/article-file/1774154, https://c19p.org/ozgunay
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with aspirin prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimere
Retrospective 433,609 COVID-19 patients in Croatia showing no significant difference in mortality or hospitalization risk with proton-pump inhibitor (PPI) use before COVID-19 diagnosis compared to matched controls with PPI-requiring morbidities but no PPI prescriptions. There was significantly higher hospitalization for users with 1-3 prescriptions which authors do not comment on. The classification of users and possible users may introduce confounding. Users required a PPI prescription, while possible users includes those with ≥3 NSAID prescriptions. Possible users may be OTC PPI users, and may differ significantly in NSAID use. NSAID use per group is not reported, and was not used in adjustments.
Oct 2022, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15525, https://c19p.org/kodvanj
Retrospective 1,000 hospitalized COVID-19 patients in New York City showing high rates of acute kidney injury, inpatient dialysis, prolonged intubation times, and length of stay compared to previous cohorts.
May 2020, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj.m1996, https://c19p.org/argenziano
RCT with 20 saline and 20 control low risk patients in India, showing faster recovery with saline gargling, but no significant difference in viral clearance.
Jul 2022, Indian J. Community Medicine, https://journals.lww.com/ijcm/Fulltext/2022/47020/Impact_of_Steam_Inhalation,_Saline_Gargling,_and.12.aspx, https://c19p.org/chalagerisa
Retrospective hospitalized patients in Saudi Arabia showing higher mortality with most treatments although not reaching statistical significance. Confounding by indication, time, or other factors is likely (a 19x higher risk with lopinavir/ritonavir and 3.5x higher risk with azithromycin is not supported by other studies for example). The number of patients treated with HCQ is not provided.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.13.21260428v1, https://c19p.org/alhamlan
Retrospective 75 hospitalized COVID-19 patients over 60 in Turkey showing no significant differences with montelukast treatment.
Aug 2024, Genel Tıp Dergisi, http://dergipark.org.tr/en/doi/10.54005/geneltip.1352153, https://c19p.org/zengin2
Retrospective 17 rheumatoid arthritis COVID-19+ patients, 7 on HCQ treatment, showing no significant differences. They study reports only including hospitalized patients, but the results include non-hospitalized patients. Results do not reflect potential difference in the probability that a case is serious enough to have been tested and identified. Few group details are provided (even the age of patients in each group is not specified).
Jul 2021, Research Square, https://www.researchsquare.com/article/rs-43812/v1, https://c19p.org/kucukakkas
Retrospective 193 ICU patients in Iran, showing no significant difference with vitamin D treatment.
May 2022, Obesity Medicine, https://www.sciencedirect.com/science/article/pii/S245184762200032Xhttps://www.sciencedirect.com/science/article/pii/S245184762200032X/pdf, https://c19p.org/zangenehd
Population-based case-control study of 86,602 people in Spain, shower lower risk of COVID-19 cases with low-dose aspirin, but no significant difference for severity, hospitalization, or mortality.
Jan 2024, Revista Española de Cardiología, https://www.sciencedirect.com/science/article/pii/S1885585724000148, https://c19p.org/prietocampo
Retrospective database analysis of 64,781 hospitalized patients in the USA, showing lower mortality with vitamin C or vitamin D (authors do not distinguish between the two), and higher mortality with zinc and HCQ, statistically significant for zinc. Authors excluded hospital-based outpatient visits, without explanation. Confounding by indication is likely, adjustments do not appear to include any information on COVID-19 severity at baseline.
Dec 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2773971, https://c19p.org/rosenthal
Retrospective 193 ICU patients in Iran, showing no significant difference with zinc treatment.
May 2022, Obesity Medicine, https://www.sciencedirect.com/science/article/pii/S245184762200032Xhttps://www.sciencedirect.com/science/article/pii/S245184762200032X/pdf, https://c19p.org/zangenehz
Retrospective database analysis of 64,781 hospitalized patients in the USA, showing lower mortality with vitamin C or vitamin D (authors do not distinguish between the two), and higher mortality with zinc and HCQ, statistically significant for zinc. Authors excluded hospital-based outpatient visits, without explanation. Confounding by indication is likely, adjustments do not appear to include any information on COVID-19 severity at baseline.
Dec 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2773971, https://c19p.org/rosenthalz
Retrospective 1,824 hospitalized COVID-19 patients in South Korea, showing higher progression to combined death, ICU, ventilation, or sepsis (4% versus 0%, group sizes not provided) with paracetamol vs. NSAIDs. Treatment time may vary - exposure was defined as 7 days before and including cohort entry in hospitalized COVID-19 patients.
Jul 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/73/11/e4179/5876905, https://c19p.org/jeong
Retrospective case-control study in Italy with 943 male COVID-19 patients, 45 on chronic 5ARI treatment (finasteride/dutasteride). There was significantly fewer COVID-19 patients >55 on 5ARI treatment compared to age-matched controls (5.57 vs. 8.14%, p=0.0083). The difference was greater for men aged >65 (7.14 vs. 12.31%, p=0.0001). There was no significant difference for ICU admission or death.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.04.20.20068056v2, https://c19p.org/lazzeri
Retrospective 1,811 COVID-19 patients in the UK, showing no significant difference in self-reported long COVID based on having ≤14 vs. >14 alcoholic drinks per week in the month before infection.
Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paulac
RCT 401 hospitalized COVID-19 patients showing no significant differences with low-dose oral vitamin C (1000mg daily for 5 days).
Jul 2023, Disease and Diagnosis, https://ddj.hums.ac.ir/Article/ddj-500, https://c19p.org/mousaviasl
Retrospective 717 patients in Brazil showing OR 1.17 [0.72-1.90] for ivermectin. This paper focuses on HCQ, event counts for ivermectin are not provided. With significant correlation between the variables used, including overlap in the prescription of multiple treatments that show efficacy alone, and limited data for the model size, the model used here may be inaccurate due to multicollinearity [statisticsbyjim.com].
Oct 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/abs/pii/S1477893920304026, https://c19p.org/fonsecai
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoroe
UK Biobank retrospective showing a higher risk of COVID-19 cases with a history of cannabis use.
Jun 2022, Chronic Diseases and Translational Medicine, https://onlinelibrary.wiley.com/doi/10.1002/cdt3.38, https://c19p.org/lehrer2
Retrospective paracetamol use with a primary care database in Italy, showing no significant difference in hospitalization/death for use 0-3 and 4-7 days from diagnosis, and significantly higher risk for use >7 days from diagnosis. Confounding by indication may have a greater effect on late usage.
Jul 2022, Internal and Emergency Medicine, https://link.springer.com/10.1007/s11739-022-03054-1, https://c19p.org/lapi
Retrospective 5,783 hospitalized patients in France, showing higher mortality with paracetamol use, without statistical significance.
Mar 2022, JMIR Medical Informatics, https://medinform.jmir.org/2022/3/e35190, https://c19p.org/lerner
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing higher cases with chronic use of acetaminophen.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenace
397,064 patient UK Biobank retrospective showing higher risk of COVID-19 with acetaminophen use.
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241264, https://c19p.org/kolin
Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with HCQ treatment in unadjusted results.
Mar 2022, Research Square, https://www.researchsquare.com/article/rs-1362678/v1, https://c19p.org/salehih
Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, p = 0.07. Confounding by indication is likely.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.28.20248920v1, https://c19p.org/sarfaraz
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsih
Retrospective 269 favipiravir ICU patients in Saudi Arabia and 269 matched controls receiving different treatments, showing no significant difference.
Feb 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034122000259, https://c19p.org/almutair
Early terminated RCT with 62 very late stage (79% on oxygen) degarelix patients and 34 placebo patients, showing no significant differences with treatment. For discussion of many issues with this study see [twitter.com].
Apr 2022, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791293, https://c19p.org/nickols
UK Biobank retrospective with 13,099 cannabis users, showing a lower risk of COVID-19 infection, however regular users had a significantly higher risk of mortality.
Mar 2022, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2022.829715/abstract, https://c19p.org/huang2
Retrospective 154 hospitalized moderate COVID-19 patients in China showing no significant difference in viral clearance time or hospital stay duration with proton pump inhibitor (PPI) use. There was no association between PPI use and viral clearance or hospital stay duration in univariate or multivariate analysis. The same results were obtained after propensity score matching.
Feb 2021, J. Inflammation Research, https://www.dovepress.com/analysis-of-the-effect-of-proton-pump-inhibitors-on-the-course-of-covi-peer-reviewed-article-JIR, https://c19p.org/zhang30
Retrospective analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity. 17.5% of HCQ patients required oxygen while only 12.6% of control patients did.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.25.20234914v1, https://c19p.org/abdulrahman
Retrospective 603 patients in Iran, 34 taking vitamin C supplements, showing increased risk of COVID-19 cases in unadjusted results. IR.SHOUSHTAR.REC.1399.015.
Aug 2021, Nutrition & Food Science, https://www.emerald.com/insight/content/doi/10.1108/NFS-11-2020-0421/full/html, https://c19p.org/mohsenic
Analysis of 103 elderly hospitalized COVID-19 patients in Spain, showing higher mortality with acetaminophen, without statistical significance.
Apr 2021, Gerontology, https://www.karger.com/Article/FullText/515159, https://c19p.org/galvezbarron
Retrospective 459 patients in Iran, 53 treated with aspirin, showing no significant difference with treatment.
Sep 2020, The Tohoku J. Experimental Medicine, https://www.jstage.jst.go.jp/article/tjem/252/1/252_73/_article/-char/ja/, https://c19p.org/alamdarie
Small late stage RCT for the addition of vitamin C to HCQ and lopinavir/ritonavir, with 30 treatment and 30 control patients, finding a significant reduction in temperature and a significant improvement in oxygenation after 3 days in the vitamin C group. However, hospitalization time was longer and there was no significant difference in mortality.
Jan 2021, Research Square, https://www.researchsquare.com/article/rs-139942/v1, https://c19p.org/jamalimoghadamsiahkali
PSM retrospective 9,469 UK Biobank participants tested for COVID-19, showing no significant association between proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H2RA) use and risk of SARS-CoV-2 infection or COVID-19 mortality. Omeprazole was associated with higher risk of cases in patients with upper gastrointestinal diseases. The results for patients with upper gastrointestinal diseases should be more accurate due to reduced confounding and more accurate ascertainment of current use.
Jan 2021, Gastroenterology, https://www.sciencedirect.com/science/article/pii/S0016508520352094, https://c19p.org/fan4
299 patient HCQ late treatment RCT: 15% higher mortality (p=0.7) and 24% improved viral clearance (p=0.68).
Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial. 4% more patients were on ventilation at baseline in the HCQ group. This preprint presents more recent results than the earlier journal article.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2022.02.16.22271064, https://c19p.org/discovery
Small RCT of hospitalized patients in India with 19 ivermectin patients and 13 control patients, with all receiving SOC including HCQ, showing no significant differences. The patient population is biased because the study recruited patients that did not respond to standard treatment. Authors do not specify the treatment delay but it is likely relatively late because the patients had already undergone standard treatment. Criteria for discharge are not provided. The time of discharge status is not specified and may not have been an equal time since treatment initiation for all patients. Authors indicate 19 treatment and 16 control patients, but the results only show 13 control patients. Authors do not indicate why the other 3 are missing. Randomization in this small sample resulted in very large differences in the groups, with over twice as many in the ivermectin group with age >40, and the only 2 patients with age >60 both in the ivermectin group. Authors did not adjust for these..
Aug 2020, Paripex - Indian J. Research, https://www.worldwidejournals.com/paripex/recent_issues_pdf/2020/August/ivermectin-as-adjuvant-to-hydroxycholoroquine-in-patients-resistant-to-standard-treatment-for-sarscov2-results-of-an-openlabel-randomized-clinical-study_August_2020_1597492974_4801859.pdf, https://c19p.org/kishoria
32 patient vitamin C ICU PSM study: 11% higher mortality (p=1).
PSM retrospective 8 ICU patients treated with vitamin C and 24 matched controls, showing no significant difference. Authors note that "it is possible for the delayed timing of IV vitamin C to have blunted the beneficial effects as these patients may have already progressed to the late fibroproliferative phase or ARDS". IV vitamin C 1.5 grams every 6 hours.
Jun 2021, J. Pharmacy Practice, https://journals.sagepub.com/doi/10.1177/08971900211015052, https://c19p.org/li7
Retrospective 263 COVID+ patients, showing lower hospitalization with higher self-reported cardiorespiratory fitness, but no significant differences for physical activity. Participants in the study were healthier and more fit than the general population.
Jun 2021, J. Physical Activity and Health, https://journals.humankinetics.com/view/journals/jpah/18/7/article-p782.xml, https://c19p.org/brandenburg
Retrospective 9 COVID-19 patients with antiphospholipid syndrome in Turkey, showing no significant differences based on existing HCQ treatment.
Jan 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7533&category_id=179&option=com_virtuemart&vmcchk=1&Itemid=1, https://c19p.org/erden
Retrospective 8,570 individuals in Spain and Italy, showing higher mortality with combined vitamin B9 and B12 supplementation. Adjustments only considered age.
Nov 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/22/11786, https://c19p.org/bliekbuenob9
Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidities and symptoms in the HCQ+AZ group.
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.05.20151027v1, https://c19p.org/saleemi
Retrospective 9,379 patients attending a rheumatology outpatient clinic in Spain, showing higher mortality and hospitalization with colchicine use, without statistical significance.
Jan 2021, Therapeutic Advances in Musculoskeletal Disease, http://journals.sagepub.com/doi/10.1177/1759720X211002684, https://c19p.org/madridgarcia
Retrospective 43 ICU patients in Turkey, 21 treated with vitamin C, showing no significant difference in mortality and increased renal failure. Treatment included stage 1 AKI patients. Vitamin C 45-50 g/day for 5 days.
Sep 2022, Kastamonu Medical J., https://www.kastamonumedicaljournal.com/index.php/kmj/article/view/59, https://c19p.org/ozgultekin
Significantly improved recovery and significantly lower risk of long COVID with ivermectin, despite very late treatment, low-risk patients, and poor administration. 36% lower ongoing persistent COVID-19 specific symptoms, p 0.999), missing from the abstract (details below). The p values for sustained recovery, early sustained recovery, alleviation of all symptoms, and sustained alleviation are all The efficacy seen for ivermectin here is despite the trial being the most clearly designed to fail trial, with major bias in design, operation, analysis, and reporting. This trial is a great example of bias in clinical trials which will be covered in detail in the future. c19 early .org Molnupiravir PANORAMIC [ Gbinigie , isrctn.com ] Ivermectin PRINCIPLE [ isrctn.com (B) ] Investigator Prof. Chris Butler Prof. Chris Butler Delay ≤5 days from onset median 2 days ≤14 days from onset median unknown Population 50+ or 18+ w/comorbidities 18+ (mid-trial change) Treatment 5 days, 2x per day 3..
Feb 2024, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445324000641, https://c19p.org/principleivm
Prospective observational study of 598 hospitalized patients in Saudi Arabia, showing higher risk of mortality and longer hospitalization time with favipiravir.
Mar 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.826247/full, https://c19p.org/almuhsen
Retrospective 188 hospitalized patients in Pakistan, 90 treated with ivermectin, showing no significant differences with treatment. The ivermectin group had more severe disease (66% vs 58%, with 6x higher risk for severe disease patients), and more male patients (70% vs. 65%). Higher use of remdesivir and steroids in the ivermectin group also suggests that ivermectin was more likely to be given to patients in more severe condition. There were no side effects seen with ivermectin. Authors note that significantly improved ferritin levels were seen with treatment. Authors state that ivermectin patients received 2 12mg doses, 24 hours apart, but later state that the dosage was not standardized.
Jan 2022, Monaldi Archives for Chest Disease, https://monaldi-archives.org/index.php/macd/article/download/2062/1397, https://c19p.org/zubair
Retrospective 514 patients in Thailand, showing higher risk of progression with favipiravir treatment.
Sep 2022, Tropical Medicine and Infectious Disease, https://www.mdpi.com/2414-6366/7/9/238, https://c19p.org/bruminhent
Small RCT 49 severe condition hospitalized patients in Syria, showing lower mortality with colchicine and shorter hospitalization time with both colchicine and budesonide (all of these are not statistically significant).
Dec 2021, Interdisciplinary Perspectives on Infectious Diseases, https://www.hindawi.com/journals/ipid/2021/2129006/, https://c19p.org/alsultan
Retrospective 430 hospitalized COVID-19 patients with type 2 diabetes in Poland showing lower mortality with metformin and higher mortality with remdesivir, convalescent plasma, and aspirin in univariable analysis. These results were not statistically significant except for aspirin, and no baseline information per treatment is provided to assess confounding.
Mar 2024, Biomedicines, https://www.mdpi.com/2227-9059/12/3/605, https://c19p.org/lewandowski2e
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatorob9
In Vitro study showing lower pH increased ACE2 expression and viral load on SARS-CoV-2 infection, and retrospective study showing proton pump inhibitor use, which is correlated with low gastric pH-related diseases, was associated with higher mortality.
Aug 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.637885/full, https://c19p.org/jimenez2ppi
Retrospective 225 hospitalized patients in Egypt, showing significantly lower thromboembolic events with aspirin treatment, but no significant difference in the need for mechanical ventilation.
Jul 2021, Clinical Drug Investigation, https://link.springer.com/article/10.1007/s40261-021-01061-2, https://c19p.org/abdelwahab
Analysis of hospitalized lung cancer patients with 35 of 48 taking HCQ, mortality OR 1.03, p = 0.99.
Jun 2020, Annals of Oncology, 1386-1396, https://www.annalsofoncology.org/article/S0923-7534(20)39894-X/fulltext, https://c19p.org/luo
Retrospective 200 hospitalized COVID-19 patients in Saudi Arabia, showing no significant difference in outcomes between HCQ and favipiravir.
Nov 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/12/1456, https://c19p.org/alosaimi
Small retrospective study of 56 ICU patients in Mexico showing HCQ RR 1.1, p = 1.0.
Jun 2020, Cir Cir. 2020, 569-575, https://cirugiaycirujanos.com/frame_esp.php?id=358, https://c19p.org/sosagarcia
Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with colchicine treatment in unadjusted results.
Dec 2020, Indian J. Critical Care Medicine, https://www.ijccm.org/doi/pdf/10.5005/jp-journals-10071-23599, https://c19p.org/mahale
Retrospective 166 hospitalized NSCLC patients with COVID-19 showing no significant difference in mortality with paxlovid or azvudine in univariate analysis.
Jan 2024, Technology in Cancer Research & Treatment, https://journals.sagepub.com/doi/10.1177/15330338241248573, https://c19p.org/peng4azv
RCT 274 very late stage (>80% pulmonary involvement at baseline) hospitalized COVID-19 patients treated with a single dose of cholecalciferol, and 269 control patients, showing no significant differences. High serum calcidiol levels at admission were associated with lower pulmonary involvement, shorter hospitalization, and lower ICU admission. Serum levels increased in the treatment group, however average levels were still insufficient at discharge. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage. 100,000IU cholecalciferol.
Feb 2022, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02290-8, https://c19p.org/cannataandia
Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with aspirin prophylaxis in unadjusted results.
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimere
Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients analyzing progression to ARDS and 30-day mortality from ARDS. Confounding by indication is likely. Chronological bias is likely, with HCQ more likely to be used earlier on, before significant improvements in overall treatment. No results are provided for HCQ for progression to ARDS.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.16.20214130v1, https://c19p.org/solh
Retrospective 7,894 COVID+ prostate cancer patients, analyzing patients on antiandrogen treatment, ADT, and ADT + abiraterone acetate or enzalutamide, showing mixed results and higher mortality for ADT + abiraterone acetate or enzalutamide. This paper also includes a small RCT which is listed separately, and an In Vitro HBEC study showing no significant differences (p = 0.084). The supplementary data is not currently available. NCT04475601. For discussion of issues with this study see [sciencedirect.com, sciencedirect.com, sciencedirect.com, sciencedirect.com].
Dec 2021, European Urology, https://www.europeanurology.com/article/S0302-2838(21)02224-7/fulltext, https://c19p.org/welen2
Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing higher mortality with aspirin treatment. IR.MUQ.REC.1399.013.
May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholie
106 patient vitamin D prophylaxis study: 25% more cases (p=0.56).
Analysis of vitamin D and zinc levels in 53 PCR+ outpatients and 53 matched controls, showing lower zinc levels in COVID-19 patients, and increased risk of cases and symptoms with vitamin D deficiency. There was no significant difference in the use of supplements between cases and controls. IR.ABADANUMS.REC.1399.073.
Aug 2021, Nutrients, https://www.mdpi.com/2072-6643/13/10/3368, https://c19p.org/golabi2
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiyaz
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (March 1 to May 31, 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiya
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiyac
PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ.
Mar 2022, Acta Medica, https://actamedica.org/index.php/actamedica/article/view/719, https://c19p.org/uyaroglu
Retrospective 616 patients in China showing increased risk of disease progression with vitamin C treatment.
Dec 2020, BioScience Trends, https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.03340/_article/-char/ja/, https://c19p.org/suc
Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death however the group is not specified. Confounding by indication is likely.
Jan 2021, Research Square, https://www.researchsquare.com/article/rs-119202/v1, https://c19p.org/li2
Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, p = 0.77. Confounding by indication likely.
Nov 2020, Mayo Clinic Proceedings: Innovations, Quality & Outcomes, https://www.sciencedirect.com/science/article/pii/S2542454820302071, https://c19p.org/rodrigueznava
Retrospective 190 critical COVID-19 patients in Turkey, showing no significant differences with N-acetylcysteine treatment in unadjusted results with no baseline details. NAC 2400mg/day.
Oct 2022, Aksaray Üniversitesi Tıp Bilimleri Dergisi, https://dergipark.org.tr/en/pub/asujms/issue/73171/1062868, https://c19p.org/cavus
Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for example saying that "currently, no obvious connection exists between a known rheumatological disorder and the risk of contracting SARS-CoV-2". Many papers show that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, e.g., Ferri et al. show OR 4.42, p<0.001 [Ferri]. Supplementary data is not currently available.
May 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221004781, https://c19p.org/kamstrup
Retrospective 27 severe COVID-19 patients and 23 non-COVID-19 patients, showing significantly lower vitamin A levels in COVID-19 patients (0.37mg/L vs. 0.52 mg/L, p<0.001). 10 of 27 COVID-19 patients received vitamin A, with higher mortality. Group details are not provided but authors note that 8 of 10 had comorbidities.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.01.30.21250844v1, https://c19p.org/sarohan
Retrospective 175 hospitalized COVID-19 patients in the USA, showing no significant difference in mortality with HCQ. Authors note that "patients treated with HCQ in our cohort were more likely to be sicker at baseline".
Nov 2020, HCA Healthcare J. Medicine, https://scholarlycommons.hcahealthcare.com/hcahealthcarejournal/vol1/iss0/20, https://c19p.org/aboulenain
Retrospective 1,215 hospitalized patients in the Phillipines, showing no significant difference in outcomes with remdesivir or HCQ use in unadjusted results subject to confounding by indication.
Jul 2022, IJID Regions, https://www.sciencedirect.com/science/article/pii/S2772707622000935, https://c19p.org/malundo
903 patient HCQ late treatment study: 37% higher mortality (p=0.28).
Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, p = 0.28. Confounding by indication is likely.
Nov 2020, The American J. Pathology, https://www.sciencedirect.com/science/article/pii/S0002944020304892, https://c19p.org/salazar
Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, with significant differences seen between hospitalized and non-hospitalized patients. 9 of 10 hospitalized patients were in the HCQ group and only one in the control group. 2 additional control patients were added between the first and second version of this preprint (including the only hospitalized control patient).
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.30.20143289v1, https://c19p.org/komissarov
Small early-terminated RCT with 40 inhaled budesonide and 49 control patients, showing no significant differences. 400µg/12h via Pulmicort Turbuhaler.
Feb 2022, European Respiratory J., https://erj.ersjournals.com/content/early/2022/01/13/13993003.03036-2021, https://c19p.org/agusti2
Retrospective 689 hospitalized COVID-19 patients in Denmark, showing higher risk of ICU/death with aspirin use in unadjusted results subject to confounding by indication.
May 2020, J. Hypertension, https://journals.lww.com/10.1097/HJH.0000000000002515, https://c19p.org/holt2e
RCT 49 outpatients in the USA, showing no significant differences with camostat treatment.
May 2021, NCT04524663, https://clinicaltrials.gov/study/NCT04524663, https://c19p.org/parsonnet
Retrospective 185 hospitalized COVID-19 patients in China, showing no significant difference in mortality with budesonide use in unadjusted results.
Aug 2022, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2022-0569/html, https://c19p.org/yang3
Survey of 165 SLE patients, 127 on HCQ. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for concomitant medications or severity of SLE. Confounding by indication.
May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/23/annrheumdis-2020-217717.info, https://c19p.org/cassione
Retrospective 171 ICU patients in Saudi Arabia showing no significant difference for HCQ treatment in unadjusted results.
Aug 2021, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016421001559, https://c19p.org/alghamdi2
Retrospective 176 hospitalized patients (144 HCQ, 32 control) showing no significant differences with HCQ or TCZ. Confounding by indication.
Aug 2020, J. Medical Internet Research, https://www.jmir.org/2020/9/e21758/, https://c19p.org/roomi
Very late treatment (7 days from onset) RCT comparing 11 & 13 PVP-I (0.5% and 2%), and 11 saline spray patients in the USA, showing no significant differences. There was no control group (saline is likely not a placebo, showing efficacy in other trials). There are large unadjusted differences between groups, e.g. 7.1 days from onset for PVP-I versus 4.8 for saline. Baseline Ct was higher for PVP-I, providing less room for improvement. Authors note that they cannot determine if earlier use is more beneficial.
Oct 2021, Laryngoscope, https://onlinelibrary.wiley.com/doi/abs/10.1002/lary.29935, https://c19p.org/zarabanda
324 patient azvudine late treatment study: 42% higher mortality (p=0.64).
Retrospective 324 hospitalized kidney transplant recipients with COVID-19 showing no significant benefit with molnupiravir, paxlovid, or azvudine. The study was conducted during the omicron wave in China between December 2022 and January 2023. Adjusted results are only provided for all antivirals combined, however the results are similar before and after adjustment. Multivariable Cox regression analysis for all antivirals combined showed an adjusted hazard ratio for mortality of 6.06, p=0.099. While adjustment includes factors related to baseline severity, there may be residual confounding by indication.
Jun 2024, J. Zhejiang University - SCIENCE B (Biomedicine & Biotechnology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199089/, https://c19p.org/lv3azv
Retrospective 397 severe COVID-19 patients in China, showing worse outcomes with vitamin C treatment, without statistical significance. IV vitamin C 2-4g/day. Subject to confounding by indication and immortal time bias. Exclusion criteria were (a) the duration of hospitalization was less than 3 days; (b) vitamin C treatment started before admission; and (c) the length of vitamin C use was less than 3 days. Includes vitamin C use started at any time during hospitalization, for many patients this was >15 days later (Figure A2). Duration of treatment varied widely (Figure A1). Treatment was determined by clinicians according to the condition of each patient.
Sep 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0361/html, https://c19p.org/zheng
Small retrospective study with 63 patients (32 treated with HCQ), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been published several months later.
Apr 2020, Preprint, https://www.sefq.es/_pdfs/NEJM_Hydroxychlorquine.pdf, https://c19p.org/barbosa
100 patient colchicine early treatment RCT: 40% higher hospitalization (p=0.76) and 4% improved recovery (p=1).
RCT 150 patients in Egypt showing no significant difference in outcomes with colchicine. SOC included vitamin C, D, and zinc. Colchicine 0.5mg tid days 1-3, bid days 4-7.
Jun 2023, Research Square, https://www.researchsquare.com/article/rs-3049708/v1, https://c19p.org/hassano
Retrospective 31 hospitalized patients ≤19 with pre-existing inborn errors of immunity, showing no significant difference in mortality with acetaminophen. Only 6 patients were treated with acetaminophen.
Sep 2022, J. Allergy and Clinical Immunology, https://www.sciencedirect.com/science/article/pii/S009167492201185X, https://c19p.org/abolhassani
Retrospective 928 cancer patients, showing higher mortality with HCQ+AZ. The relative risks of different treatments suggest significant confounding by indication. Authors note that HCQ+AZ might not be the cause of increased mortality, but instead was given to patients with more severe COVID-19.
May 2020, Lancet, June 20, 2020, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext, https://c19p.org/kuderer
Retrospective 928 cancer patients, showing higher mortality with HCQ+AZ. The relative risks of different treatments suggest significant confounding by indication. Authors note that HCQ+AZ might not be the cause of increased mortality, but instead was given to patients with more severe COVID-19.
May 2020, Lancet, June 20, 2020, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext, https://c19p.org/kudererazaz
Retrospective 416 non-hospitalized and 184 hospitalized COVID-19 patients in Bangladesh, showing higher acetaminophen and lower vitamin C usage for hospitalized patients. Confounding may be significant and baseline details per treatment group are not provided, however fever and symptomatic patients were more common in the non-hospitalized group. Note there is an alignment mismatch in Table 1.
Nov 2023, Molecular Mechanism Research, https://ojs.as-pub.com/index.php/MMR/article/view/133, https://c19p.org/rahman5ace
Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.
Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadic
Retrospective database analysis of 22,660 patients tested for COVID-19 in South Korea. There was no significant difference in cases according to aspirin use. Aspirin use before COVID-19 was related to an increased death rate and aspirin use after COVID-19 was related to a higher risk of oxygen therapy. Results for prophylaxis are listed separately [Kim].
Sep 2021, Medicina, https://www.mdpi.com/1648-9144/57/9/931, https://c19p.org/kim2b
Retrospective 478 moderate to severe hospitalized patients in Iran, showing higher mortality with aspirin treatment. Authors note confounding by indication for aspirin treatment.
Oct 2022, J. Pharmaceutical Care, https://publish.kne-publishing.com/index.php/JPC/article/view/10790, https://c19p.org/karimpourrazkenari2e
RCT 168 patients, 112 receiving favipiravir and 56 SOC, showing shorter time to clinical improvement and faster viral clearance with favipiravir.
Oct 2020, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3696907, https://c19p.org/ruzhentsova
Retrospective 311 severe condition hospitalized patients in China, 123 treated with probiotics, showing slower viral clearance and recovery with treatment. Authors note that probiotics were able to moderate immunity and decrease the incidence of secondary infections.
Mar 2021, Int. Immunopharmacology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934664/, https://c19p.org/li10
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtmf
Retrospective 811 hospitalized COVID+ patients in Saudi Arabia, showing higher mortality with HCQ treatment in unadjusted results subject to confounding by indication.
Feb 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S187603412200034X, https://c19p.org/albanghali
Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir.
Apr 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/4/498, https://c19p.org/hafeza
Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing higher mortality with ivermectin. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22% for SpO2 >95%. The more extreme Cox result compared to the event counts also supports this. There may also be significant confounding by time with SOC changing substantially over the first few months of the pandemic. Patients may overlap with those in [Soto-Becerra]. The results in the table and text do not match.
Mar 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264789, https://c19p.org/soto
HCQ+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HCQ patients survived and 92% of HCQ+AZ patients. Patients not receiving either had 93% survival but were not considered comparable because the treated groups were significantly more ill (100% hypoxic at admission vs. 59%) and this study does not adjust for the differences. Transition from an early intubation strategy to aggressive utilization of high flow nasal cannula and noninvasive ventilation (i.e, BiPAP) was successful in freeing up ICU resources.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.17.20156521v1, https://c19p.org/mcgrail
Retrospective 395 hospitalized patients in Brazil, showing higher mortality with HCQ treatment, without statistical significance.
May 2022, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2022.899702/full, https://c19p.org/silva3
Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indication is likely.
Mar 2021, Antibiotics, https://www.mdpi.com/2079-6382/10/4/365, https://c19p.org/alghamdi
Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing no significant difference with HCQ. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22% for SpO2 >95%. There may also be significant confounding by time with SOC changing substantially over the first few months of the pandemic.
Mar 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264789, https://c19p.org/sotoh
Retrospective 952 COVID-19 patients in Hong Kong, showing no significant difference in severe disease with famotidine use or PPI use.
Apr 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34940-4/fulltext, https://c19p.org/cheung
Retrospective 80 mild COVID-19 patients in Italy, showing no significant difference in long COVID with acetaminophen use during infection.
Apr 2023, Int. J. Molecular Sciences, https://www.mdpi.com/1422-0067/24/8/7445, https://c19p.org/stufano
Retrospective 831 hospitalized COVID-19 patients showing higher mortality with aspirin treatment in unadjusted results.
Aug 2024, Cureus, https://www.cureus.com/articles/263779-anticoagulant-use-in-covid-19-patients-a-longitudinal-study-from-zanjan-iran, https://c19p.org/azimipirsaraei
Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for LPV/r and HCQ. There are large differences in severity across groups. Authors did PSM but chose not to prioritize severity, resulting in incomparable groups, e.g., baseline pneumonia of 44% in the HCQ group and 15% in the control group (after PSM). Authors note this but offer no explanation for not correcting for severity: "However, the disease severity and proportion of accompanying pneumonia were still significantly higher in the LPV/r and HCQ-group".
Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322669, https://c19p.org/choi
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhemc
Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). Even if all propensity matched control patients had hypertension, the control prevalence would only be 14% compared to 49% for treatment. Since patients with hypertension are at much greater risk of mortality (HR 2.12, see [academic.oup.com]), this appears to invalidate the results. Observational study of 1,446 hospitalized patients showing no significant effect on a combined intubation/death outcome for late treatment. However, secondary analysis shows the success of HCQ was hidden by combining intubation and death - death / (combined death/intubation) for HCQ was 60% vs. control 89%, for details see: [twitter.com]. RCT recommended. No AZ or Zinc. HCQ group much sicker - patients already in mild/moderate ARDS, most of the control group not in ARDS. Control cases received other therapeutics.
May 2020, NEJM, May 7, 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2012410, https://c19p.org/geleris
Retrospective 1,039 diabetes patients in Jordan, showing no significant difference in COVID-19 cases with metformin use in unadjusted results. Severity outcomes are not provided for metformin.
Sep 2023, J. Int. Medical Research, http://journals.sagepub.com/doi/10.1177/03000605231198413, https://c19p.org/farah
Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. One notable result is that even within this extremely late stage population, results suggest increased efficacy with the addition of AZ for patients with earlier use of AZ/HCQ, OR 0.71 [0.25-2.03] (Figure S4). Patients received 8g of HCQ over 10 days, approaching the high levels used in the RECOVERY trial (9.2g over 10 days), showing significantly more adverse events than typical trials. 50% of patients were on mechanical ventilation at baseline. More than the increase in mortality at day 29 occurred on day 0, and more than 3x the increase occurred by day 2.
Sep 2020, The Lancet, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31862-6/fulltext, https://c19p.org/furtadoazaz
37 patient HCQ late treatment study: 29% worse viral clearance (p=0.7).
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76, p = 0.71. Small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR 1.29, p = 0.7. The RCT and retrospective study are listed separately [Chen, Chen].
Jul 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242763, https://c19p.org/chen26
Analysis of autoimmune disease patients on HCQ, compared to a control group from the general population (matched on age and sex, but not adjusted for autoimmune disease), showing non-significant differences between groups. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the mortality result becomes RR 0.35, p=0.23, suggesting a substantial benefit for HCQ treatment (as shown in other studies).
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.31.20185314v1, https://c19p.org/delaiglesia
Small RCT in Nigeria with 31 nitazoxanide and atazanavir/ritonavir patients, and 26 control patients, showing no significant differences with treatment. 4 treatment group patients discontinued treatment due to the size of the tablets. Time from onset is not provided, only time from diagnosis. NACOVID. 14-day course of nitazoxanide (1000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od). NCT04459286.
Feb 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.02.03.22270152, https://c19p.org/fowotade
Retrospective database analysis showing no significant differences with camostat use.
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2cm
Retrospective 230 hospitalized patients in Brazil showing no significant difference with ivermectin treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors note that they do not know if treatment was started before or after ICU admission and intubation. Baseline total chest CT opacities were higher for ivermectin (20% vs. 15%). 25% of control patients were admitted within 3 days, compared to 5 days for ivermectin. Only 38% of patients in the ivermectin arm were treated within 7 days, compared to 61% for HCQ. These are consistent with ivermectin being used for more severe patients. Dosage is unknown.
Nov 2021, Revista da Associação Médica Brasileira, https://www.scielo.br/j/ramb/a/kzbmDvJqjJdQR9GfqK65CZs/, https://c19p.org/ferreira2
Retrospective 465 prostate cancer patients, showing no significant difference in COVID-19 outcomes with ADT.
May 2022, JNCI Cancer Spectrum, https://academic.oup.com/jncics/article/6/3/pkac035/6584832, https://c19p.org/shah3
Retrospective 481 low-risk COVID-19 patients in China showing no significant difference in recovery or symptomatic severity with azvudine, but slightly lower total viral load.
Feb 2024, J. Clinical Pharmacology and Therapeutics, https://www.medtextpublications.com/open-access/effects-of-azvudine-on-the-low-risk-patients-infected-with-covid-19-1584.pdf, https://c19p.org/jin
Retrospective 1,213 rheumatic disease patients in France, showing no significant difference with colchicine use in univariate analysis.
Mar 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1152587/full, https://c19p.org/chevaliero
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulheme
Retrospective very late stage hospitalized patients in New York during the first wave, showing no significant relationship between HCQ levels and outcomes. Authors note that the patients with data were the sickest patients.
Aug 2022, British J. Clinical Pharmacology, https://onlinelibrary.wiley.com/doi/10.1111/bcp.15489, https://c19p.org/lyashchenko
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtc
Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals started treatment only after further deterioration. Short cutoff (21 days) - other studies have shown treated patient cases resolved faster and more control patients remaining in hospital at this time. In the preprint, 58 of 341 control patients died. In the journal version, 53 of 353 control patients died. Significant differences between hospitals - HCQ hospitals had significantly older patients with significantly more comorbidities. Non-HCQ hospitals were "tertiary academic centres" whereas HCQ hospitals were "secondary care hospitals". Residual confounding likely. This study compares overcrowded regular hospitals with undercrowded academic hospitals. A subset of patients were excluded due to transfer to other hospitals. This introduces bias..
Aug 2020, Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30615-7/fulltext, https://c19p.org/peters
Analysis of 2,215 intensive care unit patients showing no significant differences with this very late stage use of HCQ.
Jul 2020, JAMA Intern. Med., https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2768602, https://c19p.org/gupta
RCT 30 hospitalized patients in Iran, showing no significant difference with vitamin A treatment. All patients received HCQ. 50,000 IU/day intramuscular vitamin A for up to 2 weeks.
Oct 2022, Nutrition and Health, http://journals.sagepub.com/doi/10.1177/02601060221129144, https://c19p.org/somi
Small RCT with 40 low risk patients in Iran, 20 treated with nano-curcumin, showing no significant difference in outcomes with treatment. Authors note that treatment can improve peripheral blood inflammatory indices and modulate immune response by decreasing Th1 and Th17 responses, increasing T regulatory responses, further reducing IL-17 and IFN-γ, and increasing suppressive cytokines TGF-β and IL-4.
Sep 2021, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/full/10.1002/ptr.7294, https://c19p.org/hassaniazad
Retrospective 459 SLE, RA, SjS, or PsA patients in France, showing no significant difference with HCQ treatment. However, the statistical analysis shows significant mismatches with prior research, which may be due to overfitting with the limited data and very small number of events. For example, the analysis estimates lower risk OR 0.72 for age, and shows very different relative risks of SLE, RA, SjS, or PsA compared to other research. We note the very different distribution of diseases in the groups, for example there is a much higher prevalence of PsA in the no HCQ group. The inaccurate estimations of risk for the different diseases and for age likely makes the adjusted analysis very inaccurate.
Sep 2021, Rheumatology and Therapy, https://link.springer.com/10.1007/s40744-021-00373-1, https://c19p.org/guillaume
Retrospective 790 hospitalized type 2 diabetes patients ≥80 years old in Spain, showing higher mortality with existing aspirin use.
Dec 2020, Research Square, https://www.researchsquare.com/article/rs-133358/v1, https://c19p.org/ramosrincone
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhem
PSM retrospective 1,218 COVID-19 ICU patients in Saudi Arabia, showing no significant difference in mortality, and longer ICU/MV time with favipiravir treatment.
Jun 2023, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034123002162, https://c19p.org/sulaiman2
Retrospective 200 patients with ARDS due to COVID-19 on invasive mechanical ventilation, showing no significant difference in mortality with colchicine treatment. The Cox proportional hazards result is from [journals.plos.org].
Dec 2022, PeerJ, https://peerj.com/articles/14290, https://c19p.org/huedazavaleta2
Retrospective 815 COVID-19 ICU patients in Saudi Arabia, showing significant improvement in oxygenation. There was no significant difference in mortality, and ICU and hospitalization time was longer.
Oct 2022, Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-022-04158-y, https://c19p.org/alsulaiman4
Retrospective 188 hospitalized patients in Brazil, showing higher risk of mortality with HCQ. Relatively few patients received HCQ. The results are likely subject to confounding by indication with treatment more likely for severe cases, and severity was not used in adjustments. Confounding by time is likely, with declining use of HCQ and improving SOC over the study period.
Jul 2021, Diabetology & Metabolic Syndrome, https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-021-00695-8, https://c19p.org/tamurah
Low-risk (1% hospitalization) outpatient RCT with 738 fluvoxamine + budesonide patients and 738 placebo patients, showing significantly lower hospitalization/ER visits with treatment.
Apr 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/epdf/10.7326/M22-3305, https://c19p.org/reis10
Low-risk (1% hospitalization) outpatient RCT with 738 fluvoxamine + budesonide patients and 738 placebo patients, showing significantly lower hospitalization/ER visits with treatment.
Apr 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/epdf/10.7326/M22-3305, https://c19p.org/reis10u
Retrospective COVID+ hospitalized patients in Uganda, 385 patients receiving vitamin C treatment, showing higher mortality with treatment, without statistical significance.
Dec 2021, Research Square, https://www.researchsquare.com/article/rs-1193578/v1, https://c19p.org/bagumac
Database analysis of 11,721 hospitalized patients, 4,232 on HCQ. Strong evidence for confounding by indication and compassionate use of HCQ. 24.9% of HCQ patients were on mechanical ventilation versus 12.2% control. Ventilation mortality was 70.5% versus 11.6%. This study does not adjust for the differences in comorbid conditions and disease severity, and therefore does not make a conclusion. Unadjusted HCQ mortality was 24.8% versus control 19.6%. Adjusting for ventilation only gives us 17.7% HCQ versus 19.6% control (adjusting the HCQ group to have the same proportion of ventilation patients), RR 0.90. Hopefully authors can do a full adjustment analysis. Comorbidities may favor control, while patients remaining in the hospital (5.3%) may favor HCQ (other studies show faster resolution for HCQ patients). Data inconsistencies have been found in this study, for example 99.4% of patients treated with HCQ were treated in urban hospitals, compared to 65% of untreated patients ..
Aug 2020, Clinical Infectious Disease, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1268/5898276, https://c19p.org/fried
Retrospective 89 febrile COVID-19 patients in Israel taking paracetamol and 49 taking ibuprofen, showing higher need for respiratory support with paracetamol. Although not statistically significant, patients in the paracetamol group were older.
Sep 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20303438, https://c19p.org/rinottace
Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confounding is also likely as HCQ became controversial during the period studied, therefore HCQ use was likely more frequent toward the beginning of the period, a time when overall treatment protocols were significantly worse.
Dec 2020, Turk. Thorac. J., https://turkthoracj.org/en/use-of-hydroxychloroquine-in-patients-with-covid-19-a-retrospective-observational-study-131729, https://c19p.org/lotfy
RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of enrolled patients is not provided.
Apr 2021, Infect. Dis. Ther., https://link.springer.com/epdf/10.1007/s40121-021-00496-6, https://c19p.org/bosaeed
Retrospective 1,435 ICU patients in Saudi Arabia, showing no significant difference in mortality, and longer mechanical ventilation with treatment. Vitamin D patients had higher Q1, median, and Q3 SOFA scores after propensity score matching. 98% of patients were treated with cholecalciferol.
Aug 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1237903/full, https://c19p.org/alsulaiman5
Retrospective 150 patients in the Dominican Republic, 132 treated with HCQ, showing higher mortality with treatment in unadjusted results. Confounding by indication is likely.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.11.20247437v1, https://c19p.org/deluna
Retrospective 365 prostate cancer patients in Turkey, 138 treated with ADT, showing no significant differences with treatment.
Oct 2021, Türk Üroloji Dergisi/Turkish J. Urology, https://turkishjournalofurology.com/en/the-clinical-impact-of-androgen-deprivation-therapy-on-sars-cov-2-infection-rates-and-disease-severity-133775, https://c19p.org/kazan
Retrospective 13,585 COVID+ patients in the USA, showing higher hospitalization with aspirin use, and no significant difference for mortality, ventilation, and ICU admission.
Oct 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0275787, https://c19p.org/morrisone
Retrospective 689 hospitalized COVID-19 patients in Denmark, showing higher risk of ICU/death with spironolactone use in unadjusted results subject to confounding by indication.
May 2020, J. Hypertension, https://journals.lww.com/10.1097/HJH.0000000000002515, https://c19p.org/holt2
Retrospective 689 hospitalized COVID-19 patients in Denmark, showing higher risk of ICU/death with spironolactone use in unadjusted results subject to confounding by indication.
May 2020, J. Hypertension, https://journals.lww.com/10.1097/HJH.0000000000002515, https://c19p.org/holt2sp
Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HCQ. Power of study appears too low to support conclusions [bmj.com]. None of the 15 patients receiving HCQ+AZ were transferred to intensive care or died compared to 23% overall.
May 2020, BMJ 2020, https://www.bmj.com/content/369/bmj.m1844, https://c19p.org/mahevas
PSM retrospective 1,620 hospitalized patients in the USA, showing higher risk of combined death/intubation with PPI treatment.
May 2020, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34706-5/fulltext, https://c19p.org/freedbergppi
Retrospective 11 critically ill COVID-19 ICU patients with organ failure treated with camostat mesylate (6 patients) or HCQ (5 patients). Over an 8 day period, the severity of COVID-19 decreased in the camostat group as measured by a decline in the SOFA score, inflammatory markers, and improvement in oxygenation. A similar effect was not seen in the HCQ group.
Nov 2020, Critical Care Explorations, https://journals.lww.com/10.1097/CCE.0000000000000284, https://c19p.org/hofmannwinklerh
Retrospective 670 COVID-19 patients in Iran showing significantly higher COVID-19 severity scores and more symptomatic presentation in patients with a history of proton pump inhibitor (PPI) use. Adjusted results are only provided for severity. Several values in Table 4 are likely misreported raising concern for the reliability of the main result.
Mar 2023, Annales Pharmaceutiques Françaises, https://www.sciencedirect.com/science/article/pii/S0003450922001122, https://c19p.org/shokri
Retrospective 340 patients with hematological malignancy in Turkey, showing higher mortality with HCQ treatment. Confounding by time is likely because more HCQ patients were earlier in time when overall treatment protocols were significantly worse.
Sep 2021, Turk. J. Haematol., https://pubmed.ncbi.nlm.nih.gov/34521187/, https://c19p.org/civrizbozdag
N3C retrospective 250,533 patients showing higher COVID-19 severity with ibuprofen use. Note that results for individual treatments are not included in the journal version or v2 of this preprint.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reeseib
Retrospective 388 hospitalized COVID-19 patients in Italy showing higher use of aspirin in ICU patients, without statistical significance.
Jul 2020, Thrombosis Research, https://www.sciencedirect.com/science/article/pii/S0049384820301407, https://c19p.org/lodigiani
Observational study of 927 low-risk healthcare workers in India, 731 volunteering for weekly HCQ prophylaxis, showing higher cases with treatment in unadjusted results. Clinical outcome was in the protocol, however no information on which patients were symptomatic is provided. There were no adverse events and no hospitalizations or deaths. Adherence was very low, decreasing weekly, with almost all participants discontinuing by week 11. The majority of infections occurred in later weeks when adherence was very low, and there was no per protocol analysis. #ECR/206/Inst/GJ/2013/RR-20.
Aug 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.08.02.21260750v1, https://c19p.org/bhatt
Analysis of 103 elderly hospitalized COVID-19 patients in Spain, showing higher mortality with metformin, without statistical significance.
Apr 2021, Gerontology, https://www.karger.com/Article/FullText/515159, https://c19p.org/galvezbarronmf
Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortality of severity information is provided to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity.
Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/08/19/annrheumdis-2020-218500, https://c19p.org/singer
Retrospective 132 hospitalized COVID-19 patients over age 65 in Japan during the Alpha variant surge, showing higher mortality with favipiravir in unadjusted results, without statistical significance.
Jan 2024, Infection Prevention in Practice, https://www.sciencedirect.com/science/article/pii/S2590088924000052, https://c19p.org/saito2
PSM retrospective 629 hospitalized COVID-19 patients showing no significant difference in survival between 108 patients taking UDCA prior to infection compared to 521 matched controls not taking the drug. The lack of observed benefit in this retrospective inpatient cohort does not preclude potential protective effects of UDCA against infection or illness severe enough to require hospitalization.
Sep 2023, Liver Int., https://onlinelibrary.wiley.com/doi/10.1111/liv.15736, https://c19p.org/marrone
Retrospective 217 critically ill patients, 114 receiving HCQ, showing no significant difference in mortality.
Apr 2020, Critical Care Medicine, https://journals.lww.com/ccmjournal/Fulltext/2020/09000/ICU_and_Ventilator_Mortality_Among_Critically_Ill.35.aspx, https://c19p.org/auld
Retrospective 559 COVID-19 ICU patients in Indonesia, showing no difference in mortality with HCQ in unadjusted results.
Sep 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0290964, https://c19p.org/burhan
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with selenium prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerse
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with vitamin C prophylaxis.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtoc
Retrospective 390 hospitalized patients in Israel, showing higher risk of mortality with prior aspirin use. Details of the analysis are not provided.
Oct 2021, Metabolites, https://www.mdpi.com/2218-1989/11/10/679, https://c19p.org/basheer
203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding.
Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252388, https://c19p.org/saib
Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended during the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S330/6057008, https://c19p.org/psevdos
Retrospective 280 Chinese families with children previously seen in a liver clinic assessing whether ursodeoxycholic acid (UDCA) reduced SARS-CoV-2 infection risk. Among infected families, the study found no significant difference in confirmed or suspected SARS-CoV-2 infections between children taking UDCA (80.9%) and those not taking it (77.6%) (p=0.843).
Jun 2023, Liver Int., https://onlinelibrary.wiley.com/doi/10.1111/liv.15660, https://c19p.org/liu12
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizio
Early terminated RCT with 14 colchicine, 13 edoxaban, 16 colchicine+edoxaban, and 16 control patients, showing no significant difference in outcomes with treatment up to 7 days after PCR diagnosis.
May 2024, J. Cardiovascular Medicine, https://journals.lww.com/10.2459/JCM.0000000000001639, https://c19p.org/landi
Retrospective 770 COVID-19 patients with cancer, showing increased mortality with aspirin use in unadjusted results.
Oct 2021, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S238702062100485X, https://c19p.org/perezsegura
Retrospective 12,457 patients prescribed paracetamol with codeine/dihydrocodeine and 13,202 prescribed NSAIDs, showing no significant differences in cases and mortality. Patients prescribed codeine/dihydrocodeine may have different susceptibility to COVID-19.
Apr 2021, Arthritis & Rheumatology, https://onlinelibrary.wiley.com/doi/10.1002/art.41593, https://c19p.org/chandan
Retrospective 14,958 US veterans who tested positive for SARS-CoV-2, showing no significant difference in severe COVID-19 outcomes (mechanical ventilation, death, ICU admission, or hospitalization) with proton pump inhibitor (PPI) use compared to non-use in a propensity score weighted analysis.
Oct 2021, Gut, https://gut.bmj.com/lookup/doi/10.1136/gutjnl-2021-325701, https://c19p.org/shah8
108 patient zinc early treatment RCT: 44% higher hospitalization (p=0.72) and 12% faster recovery (p=0.38).
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. Study performed in the USA where zinc deficiency is relatively uncommon. The zinc dosage is relatively low, 50mg zinc gluconate (7mg elemental zinc), one tenth of that shown to reduce the duration of colds in other studies [patrickholford.com].
Feb 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305, https://c19p.org/thomas
1,370,600 patient acetaminophen prophylaxis study: 5% higher hospitalization (p=0.83) and 3% fewer cases (p=0.82).
PSM retrospective 1,370,600 osteoarthritis or back pain patients in the US, showing no significant differences in COVID-19 cases and hospitalization for paracetamol vs. ibuprofen.
Jul 2022, Drugs, https://link.springer.com/article/10.1007/s40265-022-01822-z, https://c19p.org/xie
Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.
Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiriz
Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 [0.80-1.33] (HR 0.78 before adjustments). 70 patients with HCQ prescriptions died. One major problem is that there is no knowlege of medication adherence for these 70 - for example, it is possible that they were part of the expected percentage of patients that did not take the medication as prescribed, invalidating the result. Other limitations include confounding by use of bDMARDs and confounding by severity of rheumatological disease.
Sep 2020, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991320303787, https://c19p.org/rentsch
Retrospective cancer patients, showing adjusted OR 1.03 [0.62-1.73] for HCQ. The study reports the number of HCQ+AZ patients but they do not provide results for HCQ+AZ (only HCQ + any other treatment). Significant confounding by indication and compassionate use is likely.
Jul 2020, Cancer Discovery, https://cancerdiscovery.aacrjournals.org/content/early/2020/09/12/2159-8290.CD-20-0941, https://c19p.org/rivera
Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S251/6058327, https://c19p.org/teixeira
Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.
Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiria
Retrospective database analysis with 17 cases for existing HCQ users and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2
Prospective study with 75 NAC patients and 16 control patients, showing no significant difference in mortality.
Dec 2021, Indonesian J. Tropical and Infectious Disease, https://www.e-journal.unair.ac.id/IJTID/article/view/30874, https://c19p.org/ramadhan
Prospective study of 494 COVID-19 patients showing higher risk of PASC with acetaminophen use in unadjusted results, without reaching statistical significance (p=0.07). Higher risk is also seen for dexamethasone and remdesivir (statistically significant for dexamethasone), however confounding by indication may be significant for these treatments, with increased use for more severe patients. While details of treatment timing and dose are not available, the result for acetaminophen can be compared with ibuprofen, with comparable indication for use. Notably there is no increased risk with ibuprofen, suggesting higher risk with acetaminophen, consistent with the higher risk seen in meta analysis.
Oct 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1227883/full, https://c19p.org/chen12
Retrospective 2,666 type 2 diabetes COVID-19 patients in Spain, showing higher mortality with existing metformin use (not statistically significant).
Nov 2020, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01832-2, https://c19p.org/perezbelmonte
Retrospective 82 hospitalized patients HCQ/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication - authors note that the HCQ/AZ patients were more severely ill, and do not attempt to adjust for confounders.
Jul 2020, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14482, https://c19p.org/kelly
262 patient HCQ prophylaxis study: 17% higher mortality (p=0.8), 78% higher combined mortality/ICU admission (p=0.21), and 45% higher hospitalization (p=0.12).
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extreme confounding - 77.5% of HCQ patients with systemic autoimmune diseases vs. 21.5% of control patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Jan 2021, Revue du Rhumatisme, https://www.sciencedirect.com/science/article/abs/pii/S1169833021002489, https://c19p.org/trefond
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihid
Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.
Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiri
Retrospective database analysis showing no significant differences with pre-existing metformin use.
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2mf
325 patient HCQ late treatment study: 890% higher progression (p=0.03).
Retrospective 325 hospitalized COVID-19 patients in Malaysia, showing higher progression with HCQ, however the groups are not comparable. 17 HCQ vs. 3 control patients had severity category ≥3 at baseline (7 vs. 0 for severity ≥4).
Mar 2023, Malaysian J. Medicine and Health Sciences, https://medic.upm.edu.my/upload/dokumen/2023032211275502_MJMHS_0551.pdf, https://c19p.org/ho2
Retrospective 293 patients in South Korea, showing higher risk of progression with ibuprofen use, without statistical significance.
Jun 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/6/1959, https://c19p.org/choi2
Retrospective 10,000 adults in Qatar, showing higher risk of COVID-19 cases with vitamin B9 supplementation, without statistical significance. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2b9
Analysis of 144 hospitalized kidney transplant patients showing HCQ mortality HR 1.53, p = 0.17. Subject to confounding by indication.
Jul 2020, American J. Transplantation, https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.16185, https://c19p.org/cravedi
Retrospective 506 outpatients in Oman showing no significant association between proton pump inhibitor (PPI) use and COVID-19 hospitalization in unadjusted results.
Oct 2024, Cureus, https://www.cureus.com/articles/310267-association-between-the-use-of-proton-pump-inhibitors-and-severe-clinical-outcomes-in-covid-19-patients-a-retrospective-observational-study, https://c19p.org/pinto2
Retrospective 605 hospitalized patients in Thailand, showing higher progression with andrographis, without statistical significance.
Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.947373/full, https://c19p.org/tanwettiyanont
Retrospective 293 patients in South Korea, showing higher risk of progression with metformin use, without statistical significance.
Jun 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/6/1959, https://c19p.org/choi2mf
Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing no significant difference in mortality with famotidine use. The study provides results for use before, after, and before+after. Before+after should more accurately represent prophylaxis up to COVID-19 infection (and continued use). Before included use up to 2 years before, and after included use up to 60 days later.
Dec 2021, BMJ Open, https://bmjopen.bmj.com/content/11/12/e050051.info, https://c19p.org/wallacefm
Early terminated 89 patient RCT with 29 high dose and 32 very high dose ivermectin patients, showing dose dependent viral load reduction, although not reaching statistical significance due to early termination. Since most patients have low viral load at day 7, there is little room for improvement with a treatment at day 7. Intermediate results may show significantly greater improvement, but are not provided. Authors note that ivermectin remained safe even at the very high dose used, although tolerability was reduced. Adherence was very low in the very high dose arm (~60%). The paper reports 4 SAEs, all resolved, with 3 patients hospitalized in the very high dose ivermectin arm, 1 in the high dose arm, and 0 in the control arm. However, the supplementary data is contradictory, showing 2 grade 3 events in both ivermectin arms (2 infections and infestations, and 2 COVID-19 pneumonia). While this result is not statistically significant, it may be in part due to randomization failure..
Sep 2021, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857921013571, https://c19p.org/buonfrate
Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment. Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. Authors note that for every week or month later that a person was admitted, their risk of death dropped by 16% and 49%, respectively, yet they do not consider time based confounding.
May 2021, PLOS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251262, https://c19p.org/sammartino
Retrospective 168 hospitalized COVID-19 patients in China showing higher risk of severe cases with acid suppression drugs.
Mar 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.03.19.20038539, https://c19p.org/yan6
RCT 156 COVID-19 patients showing higher mortality with favipiravir and remdesivir overall. Favipiravir and remdesivir were more effective when started earlier, however note that Table 10 compares earlier favipiravir/remdesivir+standard care with standard care at any time, which will exaggerate the benefits/harms of earlier/later treatment. The confidence intervals for the Cox results are unusually narrow suggesting a possible error in calculation.
Jan 2024, Infectious Diseases in Clinical Practice, https://journals.lww.com/10.1097/IPC.0000000000001336, https://c19p.org/alsaraja
Retrospective analysis of seven databases in the USA, showing higher mortality with treatment. Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confounding by indication. Time based confounding is very likely because HCQ became highly controversial and usage dramatically declined over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. This study includes anyone PCR+ during or prior to their visit, and anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore some patients in the control groups may be asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. Authors do not mention the possibility of any of these likely confounding factors.
Mar 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248128, https://c19p.org/stewart
PSM retrospective in South Korea, showing no significant differences in outcomes with acetaminophen use vs. NSAID use. Adherence and dosage are unknown.
Feb 2023, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/20/5/3832, https://c19p.org/kim7
Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subject to significant confounding by indication and confounding by time.
Sep 2021, Int. J. General Medicine, https://www.dovepress.com/getfile.php?fileID=73585, https://c19p.org/alotaibi
Retrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. [ijidonline.com] point out serious limitations that they say should be corrected on the record: patients receiving HCQ with or without AZ were overall sicker on presentation and had multiple other risk factors including much higher risk based on ethnicity; patients receiving HCQ were more likely to be obese, diabetic, have chronic lung disease, and cardiovascular conditions; yet these sicker patients had approximately the same mortality rates compared to patients with a milder course of the disease and less risk factors. However, the authors conclude that "there are no significant benefits." It is noteworthy that HCQ was associated with a significant survival benefit in a larger cohort of patients from New York City as reported by [Mikami]. See also [worldtribune.com].
May 2020, JAMA, May 11, 2020, https://jamanetwork.com/journals/jama/fullarticle/2766117, https://c19p.org/rosenberg
Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Mar 2021, Eurosurveillance, https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.9.2001202, https://c19p.org/vivancohidalgo
Retrospective 848 ICU patients in Saudi Arabia, showing higher mortality with azithromycin in unadjusted results.
May 2023, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170223000122, https://c19p.org/alqadheebazaz
Small RCT of zinc plus resveratrol in COVID-19+ outpatients, showing no significant differences in viral clearance or symptoms. Although the treatment group was older (46.3 vs. 38.5) and had more severe baseline symptoms, they had similar symptomatic recovery by the second week.
Sep 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3934228, https://c19p.org/kaplan
Small RCT of zinc plus resveratrol in COVID-19+ outpatients, showing no significant differences in viral clearance or symptoms. Although the treatment group was older (46.3 vs. 38.5) and had more severe baseline symptoms, they had similar symptomatic recovery by the second week.
Sep 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3934228, https://c19p.org/kaplanrsv
Retrospective 529 hospitalized COVID-19 patients with type 2 diabetes, showing no significant difference in outcomes with metformin use. This does not account for the different risk of being hospitalized based on metformin use. Authors note that "there is a lower-than-expected proportion of metformin prescription in our population (28%) compared to the general US population", without noting that this may reflect the lower risk of being hospitalized for metformin patients, as shown in other studies [c19early.org].
Jun 2023, Endocrine Practice, https://www.sciencedirect.com/science/article/pii/S1530891X23004299, https://c19p.org/obiriyeboah
RCT in Iran showing shorter time to recovery and shorter hospitalization time with ivermectin. There were no adverse effects. There was one death in the treatment group, the patient was in critical condition at baseline and died within 24 hours of admission. Also see [sciencedirect.com] and the author response [clinicaltherapeutics.com].
Jan 2021, Clinical Therapeutics, https://www.sciencedirect.com/science/article/abs/pii/S0149291821002010, https://c19p.org/shahbaznejad
Retrospective 7,580 hospitalized patients in Brazil, showing longer hospitalization, and no significant difference in mortality, mechanical ventilation, and ICU admission with HCQ treatment. Authors note confounding by indication due to selected use in a compassionate use context. Authors match only on age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid, and only 10% of patients received HCQ/CQ, therefore confounding by indication is likely to be significant. A different matching list is included in the text, but neither includes COVID-19 severity. In the first line of the abstract authors falsely state that there is no evidence of benefit for HCQ treatment. While misrepresenting prior research is common, this is an extreme case and raises concern for validity of the analysis. In reality controlled studies show statistically significant positive results for one or more outcomes (including RCTs). Authors discussion of prior research shows similar bias.
Sep 2023, Arquivos Brasileiros de Cardiologia, https://abccardiol.org/article/dados-de-vida-real-sobre-o-uso-da-hidroxicloroquina-ou-da-cloroquina-combinadas-ou-nao-a-azitromicina-em-pacientes-com-covid-19-uma-analise-retrospectiva-no-brasil/, https://c19p.org/souzasilva
Retrospective 72,105 COVID+ hospitalized patients in France, showing no significant difference in mortality with antihistamine H1RAs desloratadine and hydroxyzine.
Aug 2023, Pharmaceuticals, https://www.mdpi.com/1424-8247/16/8/1107, https://c19p.org/hoertel5h1
RCT with 501 relatively low-risk outpatients in Argentina showing hospitalization OR 0.65 [0.32-1.31]. With only 7% hospitalization, this trial is underpowered. The trial primarily includes low-risk patients that recover quickly without treatment, leaving minimal room for improvement with treatment. 74 patients had symptoms for >= 7 days. Among the 7 patients requiring ventilation, authors note that the earlier requirement in the ivermectin group may be due to those patients having higher severity at baseline. However, authors know the answer to this - it is unclear why it is not reported. There were more adverse events in the placebo group than the ivermectin group, suggesting a possible issue with dispensing or non-trial medication usage. 25+% of patients were hospitalized within 2/3 days for the placebo/treatment groups (Figure S2). The companion prophylaxis study [ IVERCOR PREP ] has reported results in the press and an online presentation [ lanacion.com.ar , web.archive.org (M) ..
Jul 2021, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06348-5, https://c19p.org/vallejos2
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with zinc prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerz
RCT 524 outpatients in the USA for a nitric oxide generating lozenge, showing no significant difference in combined hospitalization, ICU admission, intubation, dialysis, and death. There were only 3 events in each arm, all occuring in 2020, with zero events in 2021 or 2022. Recovery was 11% faster with treatment, without statistical significance. Authors note that a higher dose may have been more effective. Trials showing greater efficacy have used a nasal spray.
Jun 2023, The American J. Medicine, https://www.sciencedirect.com/science/article/pii/S0002934323003911, https://c19p.org/bryan
Retrospective 255,355 adults in Israel showing no significant association between proton pump inhibitor (PPI) use and SARS-CoV-2 positivity or COVID-19 severity.
Feb 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.791074/full, https://c19p.org/shafrir
Retrospective cohort study of 9,617 patients with liver disease in Italy, divided into UDCA users and non-users. UDCA exposure was not associated with reduced SARS-CoV-2 infection or improved COVID-19 outcomes including death, hospitalization, and ICU admission in this unvaccinated cohort. The large sample size provides power, but administrative data limitations include lack of important confounders like BMI and hypertension.
Aug 2023, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13711, https://c19p.org/ojedafernandez2
Retrospective database analysis showing no significant differences with azithromycin use.
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2azaz
RCT with 462 nitazoxanide/ciclesonide and 443 paracetamol patients, up to 7 days from onset, showing no significant difference in progression. Minimal details, with the primary mortality outcome and treatment delay not being reported.
Feb 2022, ANTICOV, News, https://www.isglobal.org/en/new/-/asset_publisher/JZ9fGljXnWpI/content/ensayo-anticov-halla-combinacion-nitazoxanida-ciclesonida-no-reduce-riesgo-hospitalizacion-pacientes-covid-19-leve, https://c19p.org/anticovn
Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4% incidence. It not clear why authors did not compare with autoimmune patients not on CQ/HCQ. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the result becomes RR 0.36, p<0.001, suggesting a substantial benefit for HCQ/CQ treatment (as shown in other studies). There may also be significant survey bias - those experiencing COVID-19 may be more likely to respond to the survey. Authors note that they "could not eliminate completely the possibility of some bias due to the..
Sep 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243598, https://c19p.org/laplana
Retrospective 179 elderly patients in France, showing higher risk of COVID-19 cases with acetaminophen use, without statistical significance.
May 2020, Preprints, https://www.preprints.org/manuscript/202005.0016/v1, https://c19p.org/blanc2
Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQ treatment.
Apr 2021, Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S0954611121001396, https://c19p.org/kokturk
Retrospective COVID-19 patients in Bangladesh, showing higher mortality with acetaminophen use in unadjusted results.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/shariface
Retrospective 72,501 COVID-19 patients in the USA showing cannabis use associated with higher risk of hospitalization and ICU admission.
Jun 2024, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820235, https://c19p.org/griffith
Prospective study of 503 COVID-19 cases in Saudi Arabia, 40 using ibuprofen during infection, and 357 not using NSAIDs, showing no significant differences in outcomes. Results are subject to confounding by indication.
Nov 2020, Infectious Diseases and Therapy, http://link.springer.com/10.1007/s40121-020-00363-w, https://c19p.org/abuesba
Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overall treatment protocols improved dramatically) are likely.
Apr 2021, Clinical Epidemiology and Global Health, https://www.sciencedirect.com/science/article/pii/S2213398421000555, https://c19p.org/mohandas
1,996 patient exercise study: 42% more cases (p=0.55).
Retrospective survey of 1,997 college students in the USA, showing no significant difference in COVID-19 cases with exercise in unadjusted results.
Feb 2022, JMIR Mental Health, https://mental.jmir.org/2022/2/e34645, https://c19p.org/gilley
Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic acetaminophen use vs. sporadic NSAID use. Since acetaminophen is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2ace
Retrospective 8,426 patients in the USA, showing no significant difference in cases with zinc prophylaxis. Severity results were not reported due to the small number of events.
Oct 2022, Cureus, https://www.cureus.com/articles/119536-does-prophylactic-oral-zinc-reduce-the-risk-of-contracting-covid-19, https://c19p.org/adrean
N3C retrospective showing higher risk with vitamin D treatment for hospitalized patients. As noted by authors, confounding by indication may be significant. The more extreme ventilation result, which is a significant outlier among all studies, is consistent with such confounding. Timing, dose, and duration of treatment were not used.
Jul 2022, Nutrients, https://www.mdpi.com/2072-6643/14/15/3073, https://c19p.org/fairfield
Retrospective 83,224 SARS-CoV-2 cases and 332,799 controls in Denmark showing increased risk of infection and hospital admission with proton pump inhibitor (PPI) use, but no significant association with ICU admission or mortality.
Sep 2021, Clinical Gastroenterology and Hepatology, https://www.sciencedirect.com/science/article/pii/S1542356521005140, https://c19p.org/israelsen
RCT 90 outpatients showing no significant difference in viral load or time to clinical improvement with camostat mesylate. The trial was discontinued early and did not reach the intended sample size. Authors note that combining camostat with a cathepsin inhibitor may improve efficacy.
Sep 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222003885, https://c19p.org/tobback
Retrospective 4,251 severe COVID-19 cases and 36,738 matched controls in Scotland showing increased risk of severe COVID-19 with PPI use and antihistamine H1RA use. Adjusted results are only provided for the patients not in care homes (2,357 cases and 33,803 controls).
Feb 2021, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-01907-8, https://c19p.org/mckeigueh1
RCT 549 low risk outpatients in Iran. Reported outcomes are very different from the pre-specified outcomes [irct.ir]. The inpatient trial is listed separately. The pre-specified primary clinical outcome was not reported. The reported components of this outcome are both positive. Pre-specified outcomes (3 not reported) [irct.ir]: - reduction in persistent cough and tachypnea and O2 saturation above 94% - not reported - negative PCR - reported - main complaints recovery time - not reported (only individual symptoms) - hospitalization - reported - time to hospitalization - not reported - mortality - reported - side effects - reported in only one patient (anomalous) A new outcome "relative recovery" is reported but not mentioned in the trial registration. The reported percentages and RR do not match. Authors include a researcher caught on video admitting that conclusions on ivermectin research were influenced by a funder [c19ivm.org]. Most/many patients were also treated with..
Jun 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.919708/full, https://c19p.org/rezai3
Very small retrospective analysis of 34 patients finding slower binary PCR viral clearance with HCQ. No information on severity for treatment versus control is provided. No deaths, ICU admission, or mechanical ventilation. Binary PCR does not distinguish replication-competence. HCQ treatment started very late for many patients with >= 9 days for 25%.
May 2020, Medicine, https://journals.lww.com/md-journal/Fulltext/2020/12240/Hydroxychloroquine_is_associated_with_slower_viral.34.aspx, https://c19p.org/mallat
PSM retrospective 72 indomethacin and 72 paracetamol patients in India, showing higher progression and worse recovery with acetaminophen.
Jul 2021, J. the Indian Medical Association, https://sapiensfoundation.org/wp-content/uploads/2021/08/Use-of-Indomethacin-in-Covid-19-patients-JIMA-2021.pdf, https://c19p.org/ravichandran2ace
This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, ICU admission, and intubation with treatment. Confounding by indication is likely. Time varying confounding is also likely due to declining usage over the early period when overall treatment protocols were also improving dramatically. Authors and reviewers appear to be unfamiliar with either of these.
Feb 2021, American J. Health-System Pharmacy, https://academic.oup.com/ajhp/advance-article/doi/10.1093/ajhp/zxab056/6144083, https://c19p.org/awad
Retrospective 762 COVID+ hospitalized patients in the USA, 239 on antiplatelet medication (199 aspirin), showing no significant differences in outcomes. For more discussion see [sciencedirect.com].
May 2021, Heart & Lung, https://www.heartandlung.org/article/S0147-9563(21)00175-8/fulltext, https://c19p.org/pan
Retrospective 403 COVID-19 cases in Israel, showing no significant difference in outcomes with ibuprofen use. Patients were asked about ibuprofen use starting a week before diagnosis of COVID-19 - treatment time may have been early, late, or prophylactic.
Sep 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20303438, https://c19p.org/rinott
Retrospective 1,083 consecutive hospitalized COVID patients in Italy, showing no significant differences with NAC treatment. The number of patients transferred to another facility exceeds the number of deaths, which may significantly affect results.
Dec 2021, ERJ Open Research, https://openres.ersjournals.com/content/8/1/00542-2021, https://c19p.org/faverio
RCT late stage patients (median SpO2 89), 193 treated with favipiravir, 187 with lopinavir/ritonavir, showing no significant differences in mortality, intubation, or ICU admission.
Mar 2021, Int. Immunopharmacology, https://www.sciencedirect.com/science/article/pii/S1567576921001582, https://c19p.org/solaymanidodaran
Retrospective 158 COVID-19 patients in Iran, showing higher risk of mortality with ibuprofen use.
Jul 2020, Archives of Clinical Infectious Diseases, https://brief.land/archcid/articles/106847.html, https://c19p.org/samimagham2
WHO SOLIDARITY open-label trial with 954 very late stage (64% on oxygen/ventilation) HCQ patients, mortality relative risk RR 1.19 [0.89-1.59], p=0.23. HCQ dosage very high as in RECOVERY, 1.6g in the first 24 hours, 9.6g total over 10 days, only 25% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors state they do not know the weight or obesity status of patients to analyze toxicity (since they do not adjust dosage based on patient weight, toxicity may be higher in patients of lower weight). KM curves show a spike in HCQ mortality days 5-7, corresponding to ~90% of the total excess seen at day 28 (a similar spike is seen in the RECOVERY trial). Almost all excess mortality is from ventilated patients. Authors refer to a lack of excess mortality in the first few days to suggest a lack of toxicity, but they are ignoring the very long half-life of HCQ and the dosing regimen - much higher levels of HCQ will be reached later. Increased..
Oct 2020, SOLIDARITY Trial Consortium, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2023184, https://c19p.org/solidarity
Retrospective database analysis of 1,669 patients in the US showing OR 1.81, p = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in the hospital for other reasons. While authors adjust for severity, the method used is very poor. 93.5% of patients are classified as "mild", which is patients with no documented care in a critical care unit within 8 hours of admission. Therefore almost all patients are in the same category, and those in a different category may be due to symptoms unrelated to COVID-19. Lower bias toward male patients in the control group also agrees with the hypothesis that the control group is made up of more people that were in hospital for another reason. Since the analysis covers the initial period of the pandemic in the USA, it is likely that HCQ was used more often earlier in the analysis period when treatment protocols were considerably worse. It's..
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325832, https://c19p.org/sands
Case control study with 474 patients that died of COVID-19 in Sweden, showing higher risk with ADT, without statistical significance.
Dec 2021, Scandinavian J. Urology, https://www.tandfonline.com/doi/pdf/10.1080/21681805.2021.2019304, https://c19p.org/gedeborg
Retrospective 15,440 patients with hepatobiliary and pancreatic diseases in the United Kingdom, 226 with confirmed COVID-19, showing higher risk with vitamin D supplementation. Results are likely confounded by impaired vitamin D processing and propensity to prescribe supplementation based on specifics of each patient's disease and vitamin D levels. Adjustments used broad age ranges, likely adding to residual confounding.
Mar 2021, Pancreatology, https://www.sciencedirect.com/science/article/abs/pii/S1424390320307298, https://c19p.org/ullah2
RCT with 184 outpatients treated with an extended release formulation of nitazoxanide, and 195 controls, showing lower hospitalization and progression to severe disease with treatment. There was one COVID-19 related death in the treatment arm. 600mg twice daily for five days.
Apr 2021, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00040-2/fulltext, https://c19p.org/rossignol
Retrospective study of cholecalciferol and calcitriol supplementation in Catalonia showing a small but significant lower risk of cases with cholecalciferol, but no significant difference for mortality, or for calcitriol supplementation. Significant benefit was found for cases, severity, and mortality in patients achieving serum vitamin D levels ≥30ng/ml.
Jul 2021, J. Endocrinological Investigation, https://link.springer.com/article/10.1007/s40618-021-01639-9, https://c19p.org/oristrell2
Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is likely.
Aug 2020, J. Global Antimicrobial Resistance, https://www.sciencedirect.com/science/article/pii/S2213716520301934, https://c19p.org/kalligeros
Preliminary report for an RCT in Nepal with 38 favipiravir patients and 32 control patients, showing no significant differences. There were no serious side effects.
Feb 2022, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)01001-8/fulltext, https://c19p.org/adhikari
Aanlysis of prescriptions in multiple databases showing higher risk of COVID-19 hospitalization with acetaminophen use for COPD patients. Acetaminophen use was more prevalent in hospitalized patients compared to diagnosed patients (data from tables 1, 5, and S3).
Jan 2022, Wellcome Open Research, https://wellcomeopenresearch.org/articles/7-22/v3, https://c19p.org/morenomartos
Retrospective 34,936 hypertensive outpatients in Spain showing no significant difference in COVID-19 cases with PPIs and antihistamine H1RAs.
Jul 2020, The J. Clinical Hypertension, https://onlinelibrary.wiley.com/doi/10.1111/jch.13948, https://c19p.org/vilacorcoles2
Retrospective 4,251 severe COVID-19 cases and 36,738 matched controls in Scotland showing increased risk of severe COVID-19 with PPI use and antihistamine H1RA use. Adjusted results are only provided for the patients not in care homes (2,357 cases and 33,803 controls).
Feb 2021, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-01907-8, https://c19p.org/mckeigue
PrEP RCT healthcare workers in Spain, showing no significant difference in cases with melatonin prophylaxis. Most cases were asymptomatic or paucisymtomatic, there were two symptomatic cases, no moderate/severe cases, and no hospitalization. The registered primary outcome is symptomatic cases. Authors report on all cases due to the small number of symptomatic cases. They did not include the original primary outcome results in the paper, but have provided the results via email to a contributor. The dosage in this trial is very low, 2mg daily. Meta regression suggests higher doses are much more effective. EudraCT 2020-001530-35.
Feb 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/4/1139, https://c19p.org/garciagarcia
Retrospective cohort study of 10,147 chronic liver disease patients in France, with 1,322 exposed to ursodeoxycholic acid (UDCA), showing lower risk of hospitalization for COVID-19 with UDCA exposure, without statistical significance (adjusted OR 0.48, 95% CI 0.20-1.19). A case-control analysis of 88 hospitalized patients and 840 matched controls showed no significant difference, and there was no significant difference for ICU admission and mortality. The study is underpowered due to the low number of COVID-19 hospitalizations.
Jan 2024, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.29418, https://c19p.org/corpechot
Retrospective 86,652 patients in Spain, showing no significant difference in cases and hospitalization with colchicine use. The different risk for patients prescribed colchicine may not be fully adjusted for. See [onlinelibrary.wiley.com].
Jan 2023, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.28496, https://c19p.org/saenzaldea
Retrospective 317 HCQ users and 333 household contacts, showing higher risk with HCQ.
Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27731, https://c19p.org/oztas
RECOVERY trial finds no significant benefit for very late stage (9 days after symptom onset) very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) [twitter.com, twitter.com]. The overall dosage used is only 23% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors do not report results based on weight, BMI, or related conditions such as diabetes, which may provide additional evidence of toxic dosages. Authors do not adjust dosage based on patient weight, so toxicity may be higher in patients of lower weight. KM curves show a spike in HCQ mortality days 5-8, corresponding to ~85% of the total excess seen at day 28 (a similar spike is seen in the SOLIDARITY trial). Authors note: "we did not observe excess mortality in the first 2 days of treatment ... when early effects of dose-dependent toxicity might be expected", but they are ignoring the very long half-life of HCQ and the dosing..
Jun 2020, RECOVERY Collaborative Group, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2022926, https://c19p.org/recovery
COVID-OUT remotely operated RCT, showing no significant difference in outcomes. Results for other treatments are listed separately - metformin , ivermectin . The "control" group includes patients receiving metformin, which is known to be beneficial for COVID-19 [ c19early.org ] . Authors note that the dosage used in the trial is lower than that of other trials [ twitter.com (H) ] . Control arm results are very different between treatments, for example considering hospitalization/death, this was 1.0% for ivermectin vs. 2.7% for overall control, however it was 1.3% for the ivermectin-specific control. 394 control patients are shared. The rate for the non-shared 261 metformin control patients is 5%, compared to 1.3% for ivermectin control patients. The metformin arm started earlier, however it is unclear why the difference in outcomes is so large. Results were delayed for 6 months with no explanation, with followup ending Feb 14, 2022. Multiple outcomes are missing, for example time to..
Aug 2022, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2201662, https://c19p.org/covidoutf
RCT very late stage (baseline SpO2 77%) patients, showing no significant differences with rivaroxaban and aspirin treatment.
Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002983, https://c19p.org/eikelboome
1,697,522 patient ibuprofen prophylaxis study: 12% higher hospitalization (p=0.26) and 8% more cases (p=0.25).
PSM retrospective 1,697,522 osteoarthritis or back pain patients in the US, showing no significant differences in COVID-19 cases and hospitalization for ibuprofen vs. other NSAIDs.
Jul 2022, Drugs, https://link.springer.com/article/10.1007/s40265-022-01822-z, https://c19p.org/xieib
Retrospective 105 Parkinson's disease patients, 92 caregivers, and 127 hospital inpatients, showing higher, but not statistically significant mortality and hospitalization with treatment. Supplementation was defined as >=25,000IU/month for at least 3 months.
Nov 2020, Nutrition, https://www.sciencedirect.com/science/article/pii/S0899900720303385, https://c19p.org/cereda2
44,866 patient acetaminophen prophylaxis study: 21% higher mortality (p<0.0001).
Retrospective 44,866 hospitalized COVID-19 patients in Sweden, showing higher mortality with vitamin D deficiency and with acetaminophen use. The study focuses on cardiorenal disease, finding higher risk of mortality with CRD. Authors also show that COVID-19 mortality was about 1.5x higher when compared with influenza in the first two pandemic waves, but there was no significant difference in the third wave (HR 1.53 [1.45-1.62] and 1.52 [1.44-1.61] in the first two waves and 1.07 [0.99-1.14] in the third).
Apr 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-069037, https://c19p.org/ritsinger
Retrospective 110 hospitalized COVID-19 patients with diabetes in China, showing increased risk of severity with metformin.
Oct 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.12897, https://c19p.org/gao4
Retrospective 2,200 healthcare workers in India, 996 taking HCQ prophylaxis, showing no significant differences. There were large differences in the occupation of participants and therefore exposure, and the authors make no adjustments.
Jan 2022, J. Basic and Clinical Physiology and Pharmacology, https://www.degruyter.com/document/doi/10.1515/jbcpp-2021-0221/html, https://c19p.org/juneja
Retrospective 650,317 COVID-19 patients in Japan showing higher risk of severe COVID-19 with low-dose apirin use. Although cardiovascular disease should have been adjusted for (details of adjustments are not provided), there may be significant residual confounding because aspirin use might indicate more severe or complex cardiovascular issues not fully captured by the adjustment.
Sep 2024, Discover Public Health, https://ete-online.biomedcentral.com/articles/10.1186/s12982-024-00225-7, https://c19p.org/sakamakie
Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients, that positive PCR may simply reflect detection of inactive (non-infectious) viral remnants, that an alternative dosage regimen may be more effective, and that medication adherence was unknown. HCQ dosing was 600mg/day for 1 week, therapeutic levels may not be reached for several days. There were no deaths or serious adverse events. Viral load was already very high at baseline.
Nov 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303898, https://c19p.org/omraniazaz
Retrospective 309 hospitalized patients showing higher risk of severe cases (ASA≥3) with PPI use.
Nov 2023, Academic J. Gastroenterology & Hepatology, https://www.researchgate.net/publication/375801185_Effect_of_Preadmission_Proton_Pump_Inhibitor_PPI_on_the_clinical_outcome_of_Covid-19_Hospitalised_Patients_during_the_Pandemic_Academic_Journal_of, https://c19p.org/elkanzi
Retrospective 2,463,707 people in the UK, showing no significant difference in COVID-19 mortality with NSAID use. Current NSAID users were defined as those ever prescribed an NSAID in the 4 months prior to study start, and non-users were those with no record of NSAID prescription in the same time period.
Jan 2021, Annals of the Rheumatic Diseases, https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2020-219517, https://c19p.org/wong4ib
Retrospective 266 COVID-19 ICU patients in India, showing significantly lower mortality with PVP-I oral gargling and topical nasal use, and non-statistically significant higher mortality with ivermectin and lower mortality with remdesivir.
Dec 2021, Cureus, https://www.cureus.com/articles/73667-determinants-of-outcome-among-critically-ill-police-personnel-with-covid-19-a-retrospective-observational-study-from-andhra-pradesh-india, https://c19p.org/jamir
RCT with 54 favipiravir, 51 HCQ, and 52 SOC hospitalized patients in Bahrain, showing no significant differences. Viral clearance improved with both treatments, but did not reach statistical significance with the small sample size.
Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-08794-w, https://c19p.org/alqahtani2a
COVID-OUT remote RCT, showing no significant differences compared to a combined metformin/placebo "control" group. Results for other treatments are listed separately - metformin , fluvoxamine . Authors include metformin patients in the control group, allowing details of adjustments to affect results. Using standard treatment vs. placebo analysis shows 61% lower hospitalization, or 75% lower for patients with onset ≤5 days (not statistically significant with only 7 and 5 events). These results are not reported in the paper or the supplementary appendix, readers need to request the data. Authors note that "hospitalization is perhaps the most accurate and well-documented end point". There are many major issues as detailed below. We provide more detailed analysis of this study due to widespread incorrect press. Submit Updates or Corrections Severity Issue CRITICAL 1. Ivermectin vs. placebo analysis - 61% lower hospitalization CRITICAL 2. Severity mismatch for ivermectin treatment but not..
Aug 2022, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2201662, https://c19p.org/covidoutivm
Retrospective 1,816 famotidine users and 26,820 non-users hospitalized for COVID-19 in the USA, showing no significant differences with treatment.
Sep 2020, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000001153, https://c19p.org/shoaibif
Retrospective 86,602 patients in Spain, showing lower COVID-19 risk SSRIs citalopram and paroxetine. There were no significant difference for fluvoxamine, which few patients were taking.
Apr 2023, European Neuropsychopharmacology, https://www.sciencedirect.com/science/article/pii/S0924977X23000639, https://c19p.org/visosvarela
RCT 77 outpatients in Iran, showing increased hospitalization with treatment, without statistical significance. Favipiravir 1600mg daily for five days. 21% of favipiravir patients did not complete treatment.
Jan 2023, Advances in Respiratory Medicine, https://www.mdpi.com/2543-6031/91/1/4, https://c19p.org/vaezi
High conflict of interest RCT with very low risk patients, high existing immunity, and a post-hoc change to exclude patients more likely to benefit. There was no significant difference in viral clearance with favipiravir among patients with high viral load at baseline. Patients in both arms had very short viral clearance half-life times. With rapid viral clearance and very low risk patients, infection is less likely to spread to other tissues. Systemic treatment is less applicable, and has less time to reach therapeutic concentrations before self-recovery. Treatment administered directly to the respiratory tract, e.g. as in [Yildiz Pekoz], may be more effective for COVID-19 in general, and extend applicability to fast-resolving cases with infection primarily localized to the respiratory tract. Authors note that "all-cause hospitalisation for clinical deterioration (until day 28) was a secondary endpoint", but do not provide the result. For more discussion of the post-hoc..
Apr 2023, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08835-3, https://c19p.org/luvira
Case control analysis with 149 multiple sclerosis patients and 292 matched controls in Italy, showing lower risk of COVID-19 cases with smoking.
Feb 2023, J. Neurology, https://link.springer.com/10.1007/s00415-023-11618-0, https://c19p.org/montinism
Retrospective 650,317 COVID-19 patients in Japan showing higher risk of severe COVID-19 with UDCA use. There may be significant residual confounding because authors do not appear to have adjusted for liver diseases (details of adjustments are not provided), and UDCA use is a strong indicator of certain liver conditions.
Sep 2024, Discover Public Health, https://ete-online.biomedcentral.com/articles/10.1186/s12982-024-00225-7, https://c19p.org/sakamakiudca
RCT 152 hospitalized patients in Italy, showing no significant difference in outcomes with colchicine treatment. Table 2 shows 13% of patients treated with antivirals in the colchicine arm, however 16.9% were treated with one specific antiviral (HCQ).
Oct 2022, European J. Internal Medicine, https://www.sciencedirect.com/science/article/pii/S0953620522003739, https://c19p.org/perricone
Case control study in China with 105 cases and 210 matched controls, showing COVID-19 cases associated with physical activity ≥5 times per week. Authors note that people may choose gyms for exercise in winter, leading to higher exposure risk.
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241540, https://c19p.org/gao5
Retrospective 226 COVID-19 pneumonia patients, 110 treated with favipiravir, showing higher mortality (p=0.1) and ICU admission (p=0.02) with treatment in multivariate analysis.
Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002410, https://c19p.org/almoosa
Retrospective 468,569 adults in the UK, showing no significant difference in COVID-19 mortality based on diet quality, however significantly lower mortality was seen with higher diet quality for pneumonia and infectious diseases.
Aug 2021, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912100180X, https://c19p.org/ahmadi2dt
RCT 180 moderate hospitalized COVID-19 patients in Egypt, showing higher ICU admission and longer hospitalization with acetaminophen compared with ibuprofen.
Apr 2023, The Open Anesthesia J., https://openanesthesiajournal.com/VOLUME/17/ELOCATOR/e258964582303020/, https://c19p.org/sobhyace
Small low-risk patient RCT with 30 low-dose ivermectin and 26 control patients, with no primary outcome events in either arm. Viral load was significantly better with ivermectin on day 5, while there was no significant difference on day 1 or day 14. There was no significant difference in combined symptoms, however authors include cough which was the most frequent symptom and may persist long after infection has been cleared. Ivermectin patients were 4 years older with a higher standard deviation, had higher prevalence of obesity, diabetes, hypertension, and cardiovascular disease, and lower prevalence of hepatic and kidney disease. SOC included acetaminophen, which has . The slow viral clearance seen may be in part due to acetaminophen use. Authors conclude that "ivermectin is not effective to prevent progression to a severe state", however there was no progression to severe in either group. Authors report 92.9% of ivermectin patients compliant with the symptom diary,..
May 2022, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-022-07890-6, https://c19p.org/delarocha
290 patient observational trial in the USA, not showing a significant difference with HCQ treatment overall, but showing significantly lower mortality in a subgroup of patients where HCQ is expected to be beneficial based on a machine learning algorithm.
Nov 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/12/3834, https://c19p.org/burdick
Retrospective 272 acute respiratory failure patients in the USA treated with high-flow nasal cannula, 66 treated with inhaled nitric oxide, showing increased mortality with inhaled nitric oxide. There were significant differences in the usage of several other treatments between the groups.
Jan 2021, Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, http://journals.sagepub.com/doi/10.1177/11795484211047065, https://c19p.org/chandel
Retrospective 1,779 prostate cancer patients, showing no significant differences in COVID-19 outcomes with ADT.
Jan 2021, J. Urology, https://www.auajournals.org/doi/10.1097/JU.0000000000001338, https://c19p.org/klein
Retrospective 228 rheumatic disease and 228 non-rheumatic disease hospitalized COVID-19 patients in Spain, showing higher risk of severe COVID-19 with HCQ treatment.
Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2020-218296, https://c19p.org/pablos
RCT 17,278 low-risk patients (zero mortality) treated with 5mL/day cod liver oil (~400IU vitamin D) and 17,323 placebo patients in Norway with, showing no significant differences with treatment. The placebo group had higher vitamin D at baseline, and both groups had comparable vitamin D during treatment (74 vs. 63 nmol/L). 23% of control patients took vitamin D supplements and 62% consumed fatty fish (typically a good source of vitamin D). Adherence was low (<70% for "strict" compliance, which only required >0.5L consumed, or treatment for > "2-3" months).
Sep 2022, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj-2022-071245, https://c19p.org/brunvoll
PSM retrospective 303 hospitalized patients treated with azvudine and 303 matched controls in China, showing shorter hospital stay and higher lymphocyte improvement rate, particularly for non-severe patients, however there were no significant differences for mortality, ICU admission, or mechanical ventilation.
Oct 2024, Infection and Drug Resistance, https://www.dovepress.com/efficacy-of-azvudine-therapy-in-patients-with-severe-and-non-severe-co-peer-reviewed-fulltext-article-IDR, https://c19p.org/zhang35
Retrospective 635 HCQ users and 643 household contacts, showing higher risk with colchicine in unadjusted results. Patients with conditions leading to the use of colchicine may have significantly different baseline risk, e.g. [Topless].
Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27731, https://c19p.org/oztaso
Retrospective 1,472 hospitalized patients in Turkey, showing a higher ICU admission and ventilation with favipiravir. Results may be subject to confounding by indication.
Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full, https://c19p.org/babayigit
Late stage RCT with 115 patients treated with a single dose of 500,000IU cholecalciferol and 103 placebo patients, showing no significant differences. Authors do not explain why they did very late treatment with cholecalciferol instead of calcifediol or calcitriol, which would avoid several days delay in conversion. Baseline vitamin D levels were relatively high, limiting the potential benefit.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267918https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0267918&type=printable, https://c19p.org/mariani
RCT very late stage (baseline SpO2 80%) patients, showing no significant differences with colchicine treatment.
Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002983, https://c19p.org/eikelboom
Retrospective hospitalized COVID-19 patients in Indonesia showing higher mortality with high dose proton pump inhibitor (PPI) use compared to low dose.
Aug 2022, J. Of The Indonesian Medical Association, https://mki-ojs.idionline.org/jurnal/article/view/802, https://c19p.org/liwang
Prospective study showing COVID- PPI users had higher salivary ACE2 expression, and retrospective analysis of 694 hospitalized COVID-19 patients, showing higher mortality with PPI use.
May 2021, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000001311, https://c19p.org/liu22
Retrospective 230 low risk healthcare workers taking HCQ prophylaxis, and 106 that declined, showing higher cases without statistical significance. No case severity information is provided. The point estimate favored HCQ when excluding the first 14 days and including participants that worked for at least 16 days. Authors note a significant dose response relationship.
Dec 2022, Life, https://www.mdpi.com/2075-1729/12/12/2047, https://c19p.org/shahrin
Retrospective 1,769 hospitalized patients in the USA showing no significant differences for HCQ, and higher intubation for HCQ+AZ.
Jun 2021, American J. Epidemiology, https://academic.oup.com/aje/advance-article/doi/10.1093/aje/kwab183/6308675, https://c19p.org/gerlovin
Retrospective 1,087 hospitalized COVID-19 patients showing significantly increased risk of secondary bacterial infections (SBIs) and secondary bacterial sepsis (SBS) sepsis with pre-admission proton pump inhibitor (PPI) use. Combined ICU admission/mortality was higher but without statistical significance.
Oct 2024, Annals of Medicine, https://www.tandfonline.com/doi/full/10.1080/07853890.2024.2399761, https://c19p.org/bianconi2
Retrospective 672 COVID-19 patients in Zimbabwe, showing higher mortality with dexamethasone treatment.
Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombedxdex
98 patient vitamin C early treatment RCT: 18% faster recovery (p=0.15).
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. A secondary analysis concludes that vitamin C increases recovery rate by 71% (p = 0.036) [pubpeer.com]. See also [patrickholford.com].
Feb 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305, https://c19p.org/thomasc
Retrospective 1,000 frontline healthcare workers in South Africa showing higher risk of COVID-19 for non-smokers.
Mar 2024, Vaccines, https://www.mdpi.com/2076-393X/12/3/329, https://c19p.org/mockeliunas
Retrospective 230 hospitalized patients in Brazil showing higher mortality with HCQ treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors note that they do not know if treatment was started before or after ICU admission and intubation. Dosage is unknown.
Nov 2021, Revista da Associação Médica Brasileira, https://www.scielo.br/j/ramb/a/kzbmDvJqjJdQR9GfqK65CZs/, https://c19p.org/ferreira2h
Retrospective 254 hospitalized COVID-19 patients in Jordan showing higher rates of gastrointestinal symptoms such as abdominal pain and diarrhea with proton pump inhibitor (PPI) use. There were no significant differences for mortality, ventilation, and ICU admission. Authors hypothesize that PPIs may facilitate SARS-CoV-2 survival and invasion in the gastrointestinal tract.
Jun 2024, Annals of Medicine, https://www.tandfonline.com/doi/full/10.1080/07853890.2024.2355581, https://c19p.org/almomani
Early terminated RCT 84 patients in Japan, showing no significant difference in outcomes with favipiravir treatment. There was a trend for improved efficacy for patients enrolled within 48 hours of symptom onset.
Oct 2023, J. Infection and Chemotherapy, https://www.sciencedirect.com/science/article/pii/S1341321X23002556, https://c19p.org/iwata
Retrospective 295 hospitalized COVID-19 patients showing higher mortality and acute respiratory distress syndrome (ARDS) with pre-hospitalization proton pump inhibitor (PPI) use. Authors hypothesize that hypochlorhydria caused by PPIs may allow SARS-CoV-2 to more easily infect the gastrointestinal tract.
Nov 2021, European J. Gastroenterology & Hepatology, https://journals.lww.com/10.1097/MEG.0000000000002013, https://c19p.org/ramachandran
Retrospective 92 hospitalized patients not showing significant differences in outcomes based on vitamin D status or supplementation.
Aug 2021, J. Primary Care & Community Health , https://journals.sagepub.com/doi/full/10.1177/21501327211041206, https://c19p.org/pecina
Proof of concept RCT with 30 ivermectin patients and 15 control patients, showing a concentration dependent antiviral activity, but no significant difference in clinical outcomes. There was no significant difference in viral load reduction between groups overall, but a significant difference was found in patients with higher median plasma ivermectin levels (72% vs. 42%, p=0.004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r=0.47, p=0.02). The change in viral load is provided for the <160ng/mL and >160ng/mL groups, but not the overall treatment group. The corrigendum provides individual viral decay rates for computing the overall treatment group viral decay rate. Authors published a corrigendum: [sciencedirect.com].
Jun 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S258953702100239X, https://c19p.org/krolewiecki
Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ.
Sep 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-233.php?jid=jide, https://c19p.org/babalola2h
PSM retrospective 29 hospitals in Saudi Arabia, showing higher mortality with favipiravir treatment, without statistical significance.
Feb 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000348, https://c19p.org/alshamrania
Retrospective 1,047 pneumonia patients in 5 COVID-19 geriatric units in France and Switzerland, significantly higher ICU admission and longer hospital stays with existing aspirin treatment. Numbers in this study appear to be inconsistent, for example the abstract says 147 of 301 aspirin patients died, shown as 34.3%, while Table 1 shows 104 of 301 (34.6%).
Jan 2022, GeroScience, https://link.springer.com/article/10.1007%2Fs11357-021-00499-8, https://c19p.org/sullerot
Retrospective 20,641 hospitalized patients in Spain, showing no significant difference in outcomes with existing aspirin use.
Nov 2021, Internal and Emergency Medicine, https://link.springer.com/10.1007/s11739-021-02870-1, https://c19p.org/formiga2
Retrospective 113 hospitalized COVID-19 patients in Spain showing higher mortality and ICU admission with PPI use.
Sep 2020, Frontiers in Pharmacology, https://www.frontiersin.org/article/10.3389/fphar.2020.570721/full, https://c19p.org/garciamenaya
Retrospective 834 elderly patients in France showing higher risk of severe COVID-19 with PPI use, and increasing risk with increasing dosage.
Apr 2024, Age and Ageing, https://academic.oup.com/ageing/article/doi/10.1093/ageing/afae082/7645558, https://c19p.org/gramont
RCT with 107 paracetamol and 103 indomethacin patients, showing higher progression and worse recovery with paracetamol.
Apr 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-10370-1, https://c19p.org/ravichandranace
RCT 295 outpatients in the USA, showing no significant differences with camostat.
Mar 2021, Sagent Pharmaceuticals, NCT04583592, https://clinicaltrials.gov/study/NCT04583592, https://c19p.org/sagent
RCT 205 hospitalized COVID-19 patients showing no significant difference in lung injury (PaO2:FiO2 ratio) at day 7 with losartan treatment, and no difference in clinical outcomes including mortality. Losartan was associated with more adverse events including acute kidney injury and need for vasopressors. Results suggest losartan is not beneficial and may cause harm in this setting.
Mar 2022, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790162, https://c19p.org/puskarich2
Low-dose prophylaxis RCT with low-risk healthcare workers in India, showing no significant differences. Symptomatic case results are not provided. Followup was over 6 months, however treatment ended after 3 months. 21% of patients discontinued treatment before 3 months (Table S2).
May 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2021-059540, https://c19p.org/tirupakuzhi
Retrospective 4,445 COVID+ patients in China, showing higher risk of combined death/intubation/ICU with famotidine and with PPIs.
Dec 2020, Gut, https://gut.bmj.com/content/70/10/2012.full, https://c19p.org/zhou3
Retrospective 4,445 COVID+ patients in China, showing higher risk of combined death/intubation/ICU with famotidine and with PPIs.
Dec 2020, Gut, https://gut.bmj.com/content/70/10/2012.full, https://c19p.org/zhou3ppi
Early terminated RCT with 47 ER patients in the USA, less than 12 days of symptoms, showing no significant difference in outcomes with a single high-dose administration of inhaled nitric oxide by mask, 250ppm for 30 min.
May 2022, The American J. Emergency Medicine, https://www.sciencedirect.com/science/article/pii/S0735675722002832, https://c19p.org/strickland
Retrospective 2,196 COVID-19 patients in Taiwan (49% mild cases, 44% moderate, 7% severe) showing significantly higher mortality with dexamethasone. Authors report that all infected patients were hospitalized at the time of the study in Taiwan.
Aug 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09654-w, https://c19p.org/yen2dexdex
Very high COI low-risk patient RCT in South Africa, showing no significant differences with favipiravir plus nitazoxanide. There were no deaths and no COVID-19 hospitalizations for favipiravir plus nitazoxanide. More patients were seropositive at baseline in the treatment arm (28% vs 22%). Favipiravir 1600mg 12-hourly for 1 day, then 600mg 12-hourly for 6 days. Nitazoxanide 1000mg 12-hourly for 7 days.
Oct 2022, eBioMedicine, https://www.sciencedirect.com/science/article/pii/S2352396422005047, https://c19p.org/chandiwana
Very high COI low-risk patient RCT in South Africa, showing no significant differences with favipiravir plus nitazoxanide. There were no deaths and no COVID-19 hospitalizations for favipiravir plus nitazoxanide. More patients were seropositive at baseline in the treatment arm (28% vs 22%). Favipiravir 1600mg 12-hourly for 1 day, then 600mg 12-hourly for 6 days. Nitazoxanide 1000mg 12-hourly for 7 days.
Oct 2022, eBioMedicine, https://www.sciencedirect.com/science/article/pii/S2352396422005047, https://c19p.org/chandiwanan
Retrospective 1,106 prostate cancer patients, showing higher mortality with HCQ treatment.
Nov 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786026, https://c19p.org/schmidth
Retrospective 1,213 hospitalized diabetic COVID-19 patients in China, showing no significant difference in mortality with pre-existing metformin use.
Aug 2021, Cell Metabolism, https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30426-5, https://c19p.org/cheng2
Small RCT on very late stage use of HCQ, with 48% on oxygen at baseline. 67 HCQ patients, 61 control. Baseline states were not comparable - 82% more HCQ patients had the highest severity at baseline, there was 32% more male HCQ patients, and 44% more control patients used AZ. The HCQ group also had significantly more patients with cerebrovascular disease, cardiovascular disease (non-hypertension), renal disease (non-dialysis), and a history of organ transplants.
Sep 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa446/5910201, https://c19p.org/ulrich
Retrospective 3,024 hospitalized COVID-19 patients in China showing increased risk of the composite outcome of ICU admission, mechanical ventilation, or death with proton pump inhibitor (PPI) use. Intravenous administration was significantly worse than oral. Authors hypothesize that PPIs may lead to worse COVID-19 outcomes by increasing the risk of secondary infections, cardiac damage, renal damage, and liver complications.
Jan 2022, Therapeutic Advances in Gastroenterology, http://journals.sagepub.com/doi/10.1177/17562848221104365, https://c19p.org/yao3
RCT 135 severe stage patients in Brazil, showing no significant differences. NAC 21g (~300mg/kg) for 20 hours. U1111-1250-356 [ensaiosclinicos.gov.br].
Sep 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/72/11/e736/5910353, https://c19p.org/dealencar
UK Biobank retrospective with 160,923 patients showing increased risks of influenza, pneumonia, COVID-19 severity, and COVID-19 mortality with proton pump inhibitor (PPI) use.
Jul 2024, eLife, https://elifesciences.org/articles/94973, https://c19p.org/zeng2
Small late stage RCT with 10 favipiravir, 10 baloxavir marboxil, and 10 control patients in China, showing no significant differences.
Oct 2020, European J. Pharmaceutical Sciences, https://www.sciencedirect.com/science/article/pii/S092809872030419X, https://c19p.org/lou
RCT 1,126 patients in Brazil showing no significant differences with low dose spirulina. The dose used was 7.6 times lower than the dose used by [Aghasadeghi] which shows significantly lower mortality. eFigure 1 shows 12 events in the treatment group before the first event in the placebo group. The probability of this happening is very low, ~ 0.001. One possible cause would be if some process resulted in patients expected to visit the ER soon being more likely to be placed in the treatment group. (Another possibility is treatment side effects causing ER visits, however the were fewer adverse events and fewer severe adverse events in the treatment group).
Aug 2024, The American J. Clinical Nutrition, https://www.sciencedirect.com/science/article/pii/S0002916524005884, https://c19p.org/reis13spi
RCT 222 non-hospitalized low risk COVID-19 patients showing lower SARS-CoV-2 viral load, faster viral clearance, and improvements in symptoms, particularly anosmia, with astodrimer sodium nasal spray compared to placebo. The reduction in viral load and benefits were statistically significant in patients aged 45 years and older, with greater effects in older age groups. There was only one hospitalization event. Treatment delay is not specified and may be relatively late - authors suggest that patients were "already at or past the time of peak viral load, and the infection was already in its decline phase".
Sep 2024, Pharmaceutics, https://www.mdpi.com/1999-4923/16/9/1173, https://c19p.org/winchester2
Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.
Nov 2021, PAMJ - Clinical Medicine, https://www.clinical-medicine.panafrican-med-journal.com/content/article/7/15/full/, https://c19p.org/calderon2h
Retrospective 244 Behçet disease patients in Spain, showing no significant difference in outcomes with colchicine treatment. Confounding by indication may significantly affect results - colchicine may be prescribed more often for more serious cases, which may have a higher baseline risk for COVID-19.
Sep 2022, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S238702062200417X, https://c19p.org/correarodriguez
Retrospective 800 e-cigarette users in the USA, showing higher risk of COVID-19 diagnosis and symptoms with cannabis use.
Mar 2022, Addictive Behaviors, https://www.sciencedirect.com/science/article/pii/S0306460321003555, https://c19p.org/merianos
Retrospective 489 COVID+ hospitalized patients in the USA, showing higher mortality with famotidine treatment.
Oct 2021, American J. Gastroenterology, https://journals.lww.com/ajg/Fulltext/2021/10001/S1301_A_Retrospective_Review__Famotidine_Use_Is.1305.aspx, https://c19p.org/stolow
Delayed publication of an early terminated late treatment RCT with low-risk (no mortality) outpatients in the USA, showing no significant differences with HCQ. Authors do not provide symptom onset data, but the subgroup analysis suggests that more patients may have been in the 5+ days group (the estimate for the 5+ days group has a smaller confidence interval, and the overall mean/median for HCQ is much closer to the 5+ days group). Treatment was started one day after enrollment according to Table S1 (authors report "commonly 1 day after randomization" in the text). This suggests that most patients were treated 6+ days after onset. Subgroup analysis for <5, ≥5 days is provided only for viral shedding duration, and shows improved results for earlier treatment. Adherence was only 66% (Figure 1). Publication was 21 months after the trial ended. Registered outcomes were modified November 2022, December 2022, and January 2023, all over a year after completion of the trial. For..
Mar 2023, Microbiology Spectrum, https://journals.asm.org/doi/10.1128/spectrum.04674-22, https://c19p.org/spivak
RCT 250 late stage (80% on oxygen) hospitalized patients in the USA, showing no significant differences with combined colchicine/rosuvastatin treatment. There was a trend towards increased risk, which authors note may be due to chance because the patients enrolled in the treatment arm were in more serious condition, for example, patients in the treatment arm were more frequently on oxygen, more frequently on HFNC/NIV, and had higher mean SOFA scores. Colchicine 0.6mg two times daily for 3 days followed by 0.6mg daily, and high-intensity rosuvastatin 40mg daily.
Feb 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-067910, https://c19p.org/shah6
Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with smoking. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2sm
Late stage RCT with 353 hospitalized patients, showing no significant differences with favipiravir treatment overall, however a trend towards benefit was seen within patients treated relatively early, including a statistically significant shorter time to discharge with treatment.
Nov 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.11.08.21265884v1, https://c19p.org/shenoy
Small PrEP RCT of low risk healthcare workers, showing no significant differences. Authors report that there was no hospitalization, ICU care, or death from COVID-19, however table 3 of the preprint shows severe events labeled as "requiring hospitalization". Symptomatology and disease severity results in tables 3 and 4 appear inconsistent. NCT04359537.
May 2021, Cureus, https://www.cureus.com/articles/77806-pre-exposure-prophylaxis-with-various-doses-of-hydroxychloroquine-among-healthcare-personnel-with-high-risk-exposure-to-covid-19-a-randomized-controlled-trial, https://c19p.org/syed
Retrospective 152 hospitalized COVID-19 patients showing increased risk of secondary infections, ARDS, and mortality with proton pump inhibitor (PPI) use. Authors hypothesize that reduced gastric acid production from PPIs leads to bacterial overgrowth and microaspiration, increasing the risk of secondary lung infections. PPIs may also have immunomodulatory effects.
Jul 2020, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13121, https://c19p.org/luxenburger
PSM retrospective 132,316 patients in South Korea, showing significantly higher risk of severe COVID-19 with PPI use, but no significant difference in cases.
Jul 2020, Gut, https://gut.bmj.com/lookup/doi/10.1136/gutjnl-2020-322248, https://c19p.org/lee15
RCT 327 outpatients in Thailand, showing no significant difference with 50mg fluvoxamine bid added to favipiravir. Authors note that trials showing benefit mostly used 100mg bid.
Jun 2023, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(23)00641-0/fulltext, https://c19p.org/siripongboonsitti2
PSM retrospective 6,556 COVID-19 patients in South Korea, showing higher risk of poor outcomes with famotidine vs. other H2-blocker use.
May 2023, Heliyon, https://www.sciencedirect.com/science/article/pii/S2405844023033789, https://c19p.org/kwon2
Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity, depression, anxiety, stress, and poor health-related quality of life.
Nov 2023, Diseases, https://www.mdpi.com/2079-9721/11/4/165, https://c19p.org/pavlidousm
Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients showing no significant difference in outcomes. For the subgroup not on supplemental oxygen at baseline (relatively early treatment), the odds ratio for the 7 point outcome scale is: aOR 0.61 [0.34-1.08]. Dosage may be too low: Dose in first 24 hours - 1g (compare to Boulware et al. 2g) Dose in 5 days - 2.4g (compare to Boulware et al. 3.8g) Dosage note: Boulware 2g within 24 hours includes the second day dose. Note two important differences with the RECOVERY/SOLIDARITY dosage which is believed to be dangerously high - in RECOVERY/SOLIDARITY the total dose is much higher, which is problematic because the half-life of HCQ is very long, and it is given to patients that are already in very serious condition. Note the paper reports primary outcome values with OR>1 favoring HCQ, we have converted to OR<1 favoring HCQ. Subgroup analysis is in the supplemental appendix.
Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2772922, https://c19p.org/self
Retrospective database analysis of 22,660 patients tested for COVID-19 in South Korea. There was no significant difference in cases according to aspirin use. Aspirin use before COVID-19 was related to an increased death rate and aspirin use after COVID-19 was related to a higher risk of oxygen therapy. Results for late treatment are listed separately [Kim].
Sep 2021, Medicina, https://www.mdpi.com/1648-9144/57/9/931, https://c19p.org/kim2
Retrospective 4,634 hospitalized COVID-19 patients in China, showing higher mortality and slower viral clearance with proton pump inhibitor (PPI) use. Authors hypothesize that PPIs may increase susceptibility to COVID-19 by increasing ACE2 expression.
Feb 2022, J. Global Health, http://jogh.org/documents/2022/jogh-12-05005.pdf, https://c19p.org/wu12
Small very late treatment RCT in the USA, with 25 favipiravir and 25 control patients, showing faster viral clearance with treatment. The benefit was only seen in patients <8 days from symptom onset. There were no significant differences in clinical outcomes. The death in the favipiravir group occurred after discharge and was believed to be unrelated to COVID-19 or favipiravir.
Dec 2021, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/8/12/ofab563/6455602, https://c19p.org/finberg
RCT 84 low risk patients, 42 treated with HCQ/AZ, showing no significant differences. There was only one hospitalization which was in the treatment arm.
Aug 2021, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857921002065, https://c19p.org/rodrigues
Retrospective 31 million people without cardiovascular disease in France, showing no significant difference in hospitalization or combined intubation/death with low dose aspirin prophylaxis.
Jun 2022, Research and Practice in Thrombosis and Haemostasis, https://onlinelibrary.wiley.com/doi/10.1002/rth2.12743, https://c19p.org/botton
RCT very low risk patients (mean age 35.7, SpO2 97.4) showing no significant differences with rapid recovery and almost no progression in both groups. The groups were unbalanced. There were 41% more patients with dyspnea at baseline in the treatment group. Similarly, at baseline patients with 4+ symptoms scored 2+ were more common in the treatment group - 7% for ivermectin vs. 4% for placebo. Table S8 shows only one case of COVID-19 pneumonia. Authors report 3 and 1 cases of progression, this matches the 3 and 1 cases of the adverse event "COVID-19" in Table S8. It's unclear how the COVID-19 adverse events were defined since all patients are meant to have COVID-19. Authors definition of progression includes "use of COVID-19 therapeutic agents" and therefore the significance for progression of disease is not clear. The study is designed to produce a null result with very low risk patients, administration on an empty stomach, the primary outcome including symptoms..
Sep 2022, J. Infection and Chemotherapy, https://www.sciencedirect.com/science/article/pii/S1341321X23003161, https://c19p.org/mikamo
Survey of 53,130 individuals with a history of GI symptoms showing increased risk of COVID-19 positivity with proton pump inhibitor (PPI) use, especially twice-daily PPI use. There was a dose-response relationship between PPI use and COVID-19 risk. Those taking PPIs twice daily had 3.67 times higher odds of testing positive compared to those not taking PPIs. The authors hypothesize that PPI-induced hypochlorhydria may impair the body's defense against ingested pathogens like SARS-CoV-2.
Aug 2020, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000000798, https://c19p.org/almario
N3C retrospective 250,533 patients showing significantly higher mortality with aspirin use. Note that aspirin results were not included in the journal version or v2 of this preprint.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reesee
RCT 15 hospitalized COVID-19 patients showing no significant differences with losartan treatment. The study was terminated early due to low enrollment.
Oct 2022, Contemporary Clinical Trials Communications, https://www.sciencedirect.com/science/article/pii/S2451865422000850, https://c19p.org/freilich
RCT with 5,610 colchicine and 5,730 control patients showing mortality RR 1.01 [0.93-1.10]. Very late stage treatment, median 9 days after symptom onset, baseline 32% ventilation (5% invasive). ISRCTN 50189673. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor, patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m², and those with an estimated bodyweight of less than 70kg.
May 2021, Recovery Collaborative Group, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260021004355, https://c19p.org/recoveryc
Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences. Different results were reported at IDWeek from the AIM results. The study enrolled people with their last exposure within 4 days, i.e., if someone was exposed for 30 days in a row, they could be enrolled anywhere from day 1 to day 34. Therefore many were likely infected earlier than the enrollment date. Note that PCR has a very high false negative rates, e.g., 100% on day 1 and 67% on day 4 here [ncbi.nlm.nih.gov]. 50% of infections were detected by day 4. With the PCR false negatives and treatment delays it is likely that a majority of infections happened before enrollment or before HCQ can reach therapeutic levels. Significantly more cases were caught at baseline in the control group (54 vs. 29 for HCQ) and excluded from analysis. The early presentation stated that therapy started one day after enrollment and study supplies were sent to the..
Dec 2020, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M20-6519, https://c19p.org/barnabas
Early terminated healthcare worker PrEP RCT with only 68 patients and 8 cases, showing no significant difference with HCQ. No information on symptoms per group, case severity, or the timing of cases is provided.
Feb 2023, BMC Research Notes, https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-023-06281-7, https://c19p.org/llanoscuentas
RCT 156 mild/moderate COVID-19 patients, 77 treated with hen egg white and bovine colostrum, showing faster recovery of severe symptoms with treatment. There were no significant differences in overall symptom duration, viral clearance, or post-COVID symptoms. Only one participant progressed to severe COVID-19.
Jul 2023, Future Science OA, https://www.future-science.com/doi/10.2144/fsoa-2023-0024, https://c19p.org/mann
Long-term followup for the REMAP-CAP very late stage ICU trial, showing higher risk with HCQ, not quite reaching statistical significance.
Dec 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2799870, https://c19p.org/higgins
874 patient proton pump inhibitor prophylaxis PSM study: 28% higher mortality (p=0.63), 75% higher ventilation (p=0.37), 150% higher ICU admission (p=0.11), and 21% higher progression (p=0.6).
PSM retrospective in South Korea, showing lower risk of COVID-19 cases with H2RA (including famotidine) and PPI use, but no significant difference in severe outcomes (results provided for the combined groups only).
Mar 2023, J. Korean Medical Science, https://jkms.org/DOIx.php?id=10.3346/jkms.2023.38.e99, https://c19p.org/kim11ppi
Small RCT in Norway showing no significant differences with HCQ treatment. Add-on trial to WHO Solidarity.
Jul 2021, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M21-0653, https://c19p.org/barratdue
RCT 218 hospitalized patients in Italy, showing no significant differences with lactoferrin treatment. Authors note that in several previous studies showing clinical improvement, lactoferrin was given at an earlier stage of disease. Authors also note that potential benefits with the late treatment in this study could be masked by other SOC medications - corticosteroids may have masked immunomodulatory effects of lactoferrin, and there may be heparin-dependent reduction in lactoferrin antiviral activity. 800mg oral bovine lactoferrin daily.
Mar 2023, Nutrients, https://www.mdpi.com/2072-6643/15/5/1285, https://c19p.org/matino
Underpowered RCT with 44 hospitalized patients in Spain, showing no significant difference with favipiravir treatment in the primary outcome of time to clinical improvement, or in the secondary efficacy outcomes. Adverse events were more frequent in the favipiravir group (68%) compared to placebo (32%), but most were mild.
Aug 2023, Pneumonia, https://pneumonia.biomedcentral.com/articles/10.1186/s41479-023-00124-6, https://c19p.org/horcajada
Retrospective 627,514 patients in Hong Kong showing slightly higher risk of COVID-19 with pre-vaccination proton pump inhibitor (PPI) use in two-dose or three-dose vaccine recipients, and higher risk of hospitalization and severe outcomes only in two-dose recipients.
May 2024, J. Gastroenterology and Hepatology, https://onlinelibrary.wiley.com/doi/10.1111/jgh.16601, https://c19p.org/cheung2
240 patient RCT comparing favipiravir, favipiravir + LPV/r, LPV/r, and placebo, showing improved viral clearance with favipiravir. Efficacy was lower in the combined favipiravir + LPV/r arm, where plasma levels of favipiravir were lower. Favipiravir 1800mg twice daily on day 1 followed by 400mg four times daily on days 2-7.
Feb 2022, PLOS Medicine, https://journals.plos.org/plosone/article?id=10.1371/journal.pmed.1004120, https://c19p.org/lowe
RCT with 99 favipiravir and 100 placebo patients in Australia, all except one being outpatients, showing no significant differences with treatment.
Jun 2022, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00433-3/fulltext, https://c19p.org/mcmahon
N3C retrospective 250,533 patients showing significantly higher mortality with acetaminophen use. Note that acetaminophen results were not included in the journal version or v2 of this preprint, which focuses on NSAID analysis.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reese
RCT 200 nursing home residents over 60 years old in Spain showing Loigolactobacillus coryniformis K8 probiotic administration enhanced IgG antibody response in subjects previously infected with SARS-CoV-2 and tended to improve IgA antibody response in those over 85 years old not previously infected, in the context of COVID-19 vaccination. There was no significant difference in incidence of COVID-19 infection between the probiotic and placebo groups during the study. The probiotic group had a higher percentage of asymptomatic COVID-19 cases compared to placebo, without statistical significance.
Jan 2022, Nutrients, https://www.mdpi.com/2072-6643/14/1/228, https://c19p.org/fernandezferreiro
RCT 40 hospitalized COVID-19 patients showing vitamin K2 supplementation was well-tolerated and reduced dp-ucMGP levels, reflecting improved vitamin K status, but did not affect desmosine, a marker of elastic fiber degradation. The study was not powered to assess effects on clinical outcomes. Authors suggest that the dose may have been insufficient to fully correct the vitamin K deficiency seen in COVID-19, and that higher doses might be required to achieve potential protective effects against inflammation or lung damage.
Jun 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/12/3476, https://c19p.org/visser
RCT 117 symptomatic outpatients showing no significant difference in hospitalization, functional status, dyspnea, or viral load with losartan treatment. The trial was terminated early due to low event rates. Losartan 25mg twice daily for 10 days.
Jul 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537021002376, https://c19p.org/puskarich
Remote RCT 547 outpatients a median of 5 days from onset, showing no significant differences with fluvoxamine. The trial was stopped early and underpowered due to low event rates. The trial does not report outcomes that may not be underpowered like time to recovery. Authors note that treatment may have been too late.
Aug 2021, Open Forurm Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofad419/7238414, https://c19p.org/reiersen
Very late stage (APACHE II 8 and 12 for non-critical and critical) RCT with publication delayed over a year showing higher ventilation and no significant difference in mortality with vitamin C. Authors have combined what was to be two separate trials into one trial, however there are very large differences between the trials. The results for each source trial are shown separately here [Adhikari, Adhikari]. eTable 15 shows that results in LOVIT-COVID were substantially better than those in REMAP-CAP. eTable 13 shows improved survival for LOVIT-COVID and worse survival for REMAP-CAP (authors provide mortality breakdown only for hospital survival): LOVIT-COVID shows 85% and 82% probability of superiority of vitamin C (critical and non-critical). REMAP-CAP shows 12% and 7% probability of superiority of vitamin C. Notably, LOVIT-COVID patients were blinded, while REMAP-CAP was open-label, introducing additional opportunity for bias on this highly politicized treatment. REMAP-CAP had more..
Oct 2023, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2811212, https://c19p.org/adhikari2
RCT 105 patients recruited in an ER in Brazil, 49 treated with CBD, showing no significant differences with treatment. 300mg CBD for 14 days. For discussion see [liebertpub.com].
Oct 2021, Cannabis and Cannabinoid Research, https://www.liebertpub.com/doi/full/10.1089/can.2021.0093, https://c19p.org/crippa
Retrospective 1,472 hospitalized patients in Turkey, showing a higher risk of ICU admission and ventilation with HCQ, without statistical significance.
Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full, https://c19p.org/babayigith
Retrospective 524 hospitalized patients in the USA, showing higher mortality and progression with acetaminophen use.
Oct 2021, Chest, https://www.sciencedirect.com/science/article/pii/S0012369221024430, https://c19p.org/manjani
Retrospective 19,915 hospitalized COVID-19 patients with gastrointestinal symptoms, showing that use of proton pump inhibitors or H2 receptor antagonists was associated with higher mortality, ARDS, sepsis, and ventilator or oxygen requirement among patients
Dec 2023, Gastro Hep Advances, https://www.sciencedirect.com/science/article/pii/S277257232200142X, https://c19p.org/patil3
RCT 245 people in South Africa, showing no significant difference in COVID-19 cases with PPE use.
Oct 2021, NCT05119348, https://clinicaltrials.gov/study/NCT05119348, https://c19p.org/bekker
RCT 216 patients, 55% >5 days from symptom onset, showing no significant difference with camostat treatment.
Jun 2023, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad342/7190261, https://c19p.org/jilg
Late (5.4 days) outpatient RCT showing no significant difference in outcomes with colchicine treatment. Authors include a meta analysis of 6 colchicine RCTs, however there were 19 RCTs as of the publication date [c19colchicine.com].
Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002995, https://c19p.org/eikelboom2
Early terminated low-risk patient prophylaxis RCT in Peru, showing no significant difference in cases with lactoferrin. There were no moderate or severe cases.
Dec 2022, BioMetals, https://link.springer.com/10.1007/s10534-022-00477-3, https://c19p.org/navarro
UK Biobank retrospective showing higher cases and mortality with folic acid supplementation.
Aug 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-062945, https://c19p.org/topless2
RCT 392 patients, median treatment delay 5 days, showing improved viral recovery at 5 days. Symptom recovery was no different at 5 days, and the treatment arm had two ICU admissions compared to zero for control. There were no serious adverse events.
Oct 2020, European Respiratory J., https://erj.ersjournals.com/content/early/2020/12/17/13993003.03725-2020, https://c19p.org/rocco
Interim results for a small RCT with 40 favipiravir and 20 control patients showing faster viral clearance with favipiravir. There is limited data in this report to evaluate the results. 75% of the control group received HCQ/CQ.
Aug 2020, Clinical Infectious Diseases, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454388/, https://c19p.org/ivashchenko
RCT 122 hospitalized patients in India, showing improved recovery with colchicine treatment. All patients received aspirin. There was one death and higher progression in the colchicine arm, however 3 patients in the colchicine arm had baseline ordinal scores ≥5, while no patients in the control arm did.
Jan 2023, Contemporary Clinical Trials Communications, https://www.sciencedirect.com/science/article/pii/S2451865423000169, https://c19p.org/sunilnaik
Small early terminated late treatment RCT showing no significant differences. The HCQ group was a median of 7 days from symptom onset at baseline, which may not include the delay delivering the medication. From the 4 HCQ hospitalizations, only one is in the per-protocol analysis, and that patient was hospitalized one day after randomization (authors do not specify if the patient received and took any HCQ before the hospitalization). The trial was terminated early due to the fraudulent Lancet article (wording here is notably different between the submitted and published versions). Per-protocol analysis, the submitted version, and the peer-review comments (two reviewers, only one with substantial feedback) are in the supplementary material. Long-term recovery results are reported in [Ganesh]. When a patient reported a symptom, they were asked whether they were still experiencing that symptom, and to choose between these three options when comparing the symptom to their pre-COVID-19..
Jun 2021, CMAJ Open, http://cmajopen.ca/content/9/2/E693.full, https://c19p.org/schwartz2
RCT 126 hospitalized COVID-19 pneumonia patients not requiring oxygen at admission, showing no significant difference in outcomes with dexamethasone treatment.
Jul 2024, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2024.1385833/full, https://c19p.org/francomorenodexdex
RCT low risk hospitalized patients in Thailand showing no significant difference with the addition of ivermectin to favipiravir based SOC. Only the abstract is currently available. The trial was registered retrospectively [thaiclinicaltrials.org]. The primary outcome was WHO-category ordinal scale improvement of 2 points at days 3, 7, 14, 21, for which only a single unspecified time point (when almost all patients have recovered) is provided in the abstract (details may be in the full paper). The registration indicates that the intervention was only provided "after laboratory result", without explanation.
Dec 2022, Infection & Chemotherapy, https://icjournal.org/DOIx.php?id=10.3947/ic.2022.0127, https://c19p.org/sarojvisut
Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247.
Apr 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-88509-9, https://c19p.org/reanato
RCT 500 hospitalized patients in Malaysia, showing no significant differences with favipiravir treatment.
Nov 2021, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab962/6432025, https://c19p.org/chuah
RCT with 112 favipiravir and 119 control patients showing no significant differences in outcomes. Viral clearance and clinical recovery for patients treated within 48 hours was better than those treated later. NCT04464408.
Jan 2022, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X21007345, https://c19p.org/bosaeed2
RCT low-risk outpatients with very late treatment (median 6 days, 25% ≥8 days) in the USA, showing 98% probability of efficacy for clinical progression at day 14, a treatment delay-response relationship, and significant efficacy for patients with severe symptoms at baseline. The posterior probability ivermectin is effective was 99%, 98%, 97% for mean time unwell and clinical progression @14 and 7 days. All exceed the pre-specified threshold for superiority [ fnih.org ] . Note that the clinical progression results exceeding the superiority threshold in the preprint [ medrxiv.org (C) ] changed in the journal version for the 400µg/kg arm, with no explanation for over 700 days). The 600µg/kg arm was reported separately [ Naggie ] . When not specified, comments refer to the 400µg/kg arm. We provide more detailed analysis of this study due to widespread incorrect press. There was one death reported in each of the 400µg/kg and 600µg/kg ivermectin arms. For 400µg/kg, the patient did not take..
Jun 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2797483, https://c19p.org/activ6ivm
RCT 5,979 low risk patients (0 COVID-19 deaths) in the UK, showing no significant differences with vitamin D prophylaxis. CORONAVIT. NCT04579640. For more discussion see [ reddit.com , twitter.com (I) ] . 51% of confirmed COVID-19 cases were hospitalized in the control arm which is 7 times the median rate in other studies reporting both cases and hospitalization as of Sep 2022 (7.2%), suggesting possible issues with the data or major differences between the study population and the general population. Authors do not provide exact start/end dates (month only) or specify when infections occurred, however based on cases in the UK, most infections may have been closer to the start of the trial when vitamin D levels may still have been relatively low. Reportedly, authors do not plan to analyze this issue, and have declined to allow one of the funders access to the data. [ Villasis-Keever ] present an RCT showing conflicting results, 78% lower cases with vitamin D prophylaxis. In..
Mar 2022, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj-2022-071230, https://c19p.org/jolliffe2
1. Schilling et al., Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial
4,652 patient HCQ prophylaxis RCT: 57% fewer symptomatic cases (p=0.0002).RCT 4,652 low-risk participants, published days after completion, showing significantly lower PCR+ COVID-19 cases with HCQ/CQ prophylaxis, p = 0.0004. Authors include a meta-analysis of this and 11 other RCTs confirming significantly lower COVID-19 cases. Authors conclude that HCQ/CQ could have been deployed with benefit early in the pandemic. HCQ/CQ was well tolerated with no serious drug-related adverse events. There were significantly fewer severe adverse events with treatment. (Serious adverse events refer to serious outcomes while severe adverse events refer to intensity, e.g., severe headache). Authors note that "the primary outcome was subsequently changed to include seroconversion" rather than only PCR+ cases. The date of this change is not reported. The PCR+ results are the most reliable. Inclusion of seroconversion means that participants with asymptomatic COVID-19 and symptomatic non-COVID-19 infections will be counted as symptomatic COVID-19 cases...
Sep 2024, PLOS Medicine, https://journals.plos.org/plosone/article?id=10.1371/journal.pmed.1004428, https://c19p.org/schilling3
2. Choudhury et al., Effect of 1% Povidone Iodine Mouthwash/Gargle, Nasal and Eye Drop in COVID-19 patient
606 patient povidone-iodine early treatment RCT: 88% lower mortality (p=0.0006), 84% lower hospitalization (p<0.0001), and 96% improved viral clearance (p<0.0001).RCT 606 patients in Bangladesh for povidone iodine mouthwash/gargle, nasal drops and eye drops showing significantly lower death, hospitalization, and PCR+ at day 7.
Dec 2020, Bioresearch Communications, https://www.banglajol.info/index.php/BRC/article/view/54245, https://c19p.org/choudhury
3. Wannigama et al., Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial
995 patient fluvoxamine early treatment RCT: 98% lower ventilation (p<0.0001), 89% lower need for oxygen therapy (p<0.0001), 94% lower hospitalization (p<0.0001), and 40% lower PASC (p<0.0001).RCT 995 outpatients showing significantly lower progression with early treatment within 48 hours using fluvoxamine, fluvoxamine+bromhexine, fluvoxamine+cyproheptadine, and niclosamide+bromhexine. 70% of patients received treatment within 12 hours of symptom onset. Treatments groups showed significantly lower long COVID (PASC). The combined treatment groups showed significantly lower viral load as early as day 3. The 3 combination arms were superior to fluvoxamine alone. The study was open-label. 593 out of 1,900 randomized participants did not receive the treatment, mostly due to inability to confirm eligibility, however baseline characteristics were similar for these patients. There was a very high hospitalization rate in the control arm. Authors note that the majority of cases were mild - the threshold for hospitalization may have been very low (in some places/times all cases were hospitalized). Authors also note that the patients requiring high flow oxygen all had the delta/alpha..
Mar 2024, eClinicalMedicine, 10.1016/j.eclinm.2024.102517, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00096-8/fulltext, https://c19p.org/wannigama
778 patient proxalutamide antiandrogen late treatment RCT: 78% lower mortality (p<0.0001), 45% improved recovery (p<0.0001), and 33% shorter hospitalization (p=0.0001).
RCT 778 hospitalized patients in Brazil, 423 treated with proxalutamide, showing significantly lower mortality and improved recovery with treatment. NCT04728802 and NCT05126628. Authors note that cases in this trial were predominantly the P.1 Gamma variant, for which proxalutamide may be more effective compared to other variants.
Dec 2021, Cureus, https://www.cureus.com/articles/80171-final-results-of-a-randomized-placebo-controlled-two-arm-parallel-clinical-trial-of-proxalutamide-for-hospitalized-covid-19-patients-a-multiregional-joint-analysis-of-the-proxa-rescue-androcov-trial, https://c19p.org/cadegiani10
5. Desort-Henin et al., The SAIVE Trial, Post-Exposure use of ivermectin in Covid-19 prevention: Efficacy and Safety Results
399 patient ivermectin prophylaxis RCT: 96% fewer cases (p<0.0001).PEP RCT 399 patients in Bulgaria showing significantly lower COVID-19 cases with ivermectin prophylaxis, and significantly lower cases with high viral load. No participant had severe symptoms, required oxygen, or was hospitalized. All patients with COVID-19 were treated with vitamin C and vitamin D. This trial makes the Cochrane analysis report statistically significant efficacy for prophylaxis, although they do not appear to have acknowledged this yet. There are currently 4 prophylaxis RCTs, and all 4 show statistically significant efficacy of ivermectin. Cochrane ignored them by simply choosing to only include post-exposure prophylaxis RCTs, even though they were included for the paxlovid analysis with many of the same authors. At the time there were no post-exposure RCTs and they knew that including any one of the 3 pre-exposure prophylaxis RCTs would show statistically significant efficacy.
Jan 2023, ECCMID 2023, https://www.medincell.com/wp-content/uploads/2024/03/Poster-SAIVE-April2023-OK3.pdf, https://c19p.org/desorthenin
6. Chahla et al., Intensive Treatment With Ivermectin and Iota-Carrageenan as Pre-exposure Prophylaxis for COVID-19 in Health Care Workers From Tucuman, Argentina
234 patient ivermectin prophylaxis RCT: 95% fewer moderate/severe cases (p=0.002) and 84% fewer cases (p=0.004).Prophylaxis RCT for ivermectin and iota-carrageenan in Argentina, 117 healthcare workers treated with ivermectin and iota-carrageenan, and 117 controls, showing significantly lower cases with treatment. There were no moderate/severe cases with treatment vs. 10 in the control group. There were 4 cases with treatment (all mild) vs. 25 for the control group.
Jan 2021, American J. Therapeutics, https://journals.lww.com/10.1097/MJT.0000000000001433, https://c19p.org/ivercartuc
7. Rahman et al., Efficacy of colchicine in patients with moderate COVID-19: A double-blinded, randomized, placebo-controlled trial
292 patient colchicine late treatment RCT: 71% lower mortality (p=0.04) and 71% lower progression (p=0.04).RCT 300 patients in Bangladesh, published 2 years after completion, showing significantly lower mortality with treatment at 28 days (not significant at 14 days). 1.2mg colchicine on day 1 followed by 0.6mg for 13 days.
Nov 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0277790, https://c19p.org/rahman3
8. Kerget et al., Effect of montelukast therapy on clinical course, pulmonary function, and mortality in patients with COVID‐19
180 patient montelukast late treatment RCT: 92% lower mortality (p=0.01), 81% lower progression (p=0.007), and 15% shorter hospitalization (p=0.04).RCT 180 hospitalized COVID-19 patients in Turkey showing faster reduction in inflammatory markers, improved pulmonary function, and lower rates of macrophage activation syndrome, respiratory failure and mortality with montelukast treatment (10mg or 20mg daily) in addition to standard care. The higher dose of 20mg daily showed greater improvement in pulmonary function compared to 10mg daily. There was no mortality in the montelukast groups compared to 6.7% mortality with standard care alone.
Jan 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27552, https://c19p.org/kerget2
9. Barnette et al., Oral Sabizabulin for High-Risk, Hospitalized Adults with Covid-19: Interim Analysis
150 patient sabizabulin antiandrogen late treatment RCT: 55% lower mortality (p=0.002), 49% shorter ventilation (p=0.001), 44% shorter ICU admission (p=0.001), and 26% shorter hospitalization (p=0.03).RCT with 98 hospitalized moderate/severe patients treated with sabizabulin and 52 control patients, showing lower mortality with treatment. Sabizabulin 9mg for up to 21 days. For more discussion see [twitter.com, twitter.com, twitter.com].
Jul 2022, NEJM Evidence, https://evidence.nejm.org/doi/10.1056/EVIDoa2200145, https://c19p.org/barnette
10. Jing et al., Effective early strategy to prevent olfactory and gustatory dysfunction in COVID-19: a randomized controlled trial
260 patient saline early treatment RCT: 71% lower progression (p<0.0001) and 97% lower severe cases (p<0.0001).RCT 379 mild COVID-19 cases showing significantly lower prevalence and severity of olfactory and gustatory dysfunction with budesonide nasal spray, chlorhexidine mouthwash, and saline nasal irrigation. The control group received no intervention, the saline group received saline nasal irrigation plus saline nasal spray and mouthwash, and the drug group received saline nasal irrigation plus budesonide nasal spray and chlorhexidine mouthwash. Saline nasal irrigation plus nasal spray and mouthwash were administered once and four times daily, respectively. Both treatment groups had significantly lower prevalence and severity olfactory and gustatory dysfunction. Prevalence was lower for the drug vs. saline group, without statistical significance.
Nov 2023, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcad262/7439598, https://c19p.org/jingnacl
11. af Geijerstam et al., Fitness, strength and severity of COVID-19: a prospective register study of 1 559 187 Swedish conscripts
655,173 patient exercise study: 50% lower mortality (p=0.005), 40% lower ICU admission (p=0.0003), and 27% lower hospitalization (p<0.0001).Prospective study of 1,559,187 men in Sweden with cardiorespiratory fitness levels measured on military conscription, showing high cardiorespiratory fitness associated with lower risk of COVID-19 hospitalization, ICU admission, and death.
Jul 2021, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2021-051316, https://c19p.org/afgeijerstam
12. Zhang et al., Efficacy and safety of Xiyanping injection in the treatment of COVID‐19: A multicenter, prospective, open‐label and randomized controlled trial
130 patient andrographolide late treatment RCT: 92% lower severe cases (p=0.03), 48% improved recovery (p=0.008), and 53% improved viral clearance (p=0.0001).RCT 130 hospitalized COVID-19 patients in China, showing lower progression and improved recovery with Xiyanping injection (9-dehydro-17-hydro-andrographolide and sodium 9-dehydro-17-hydro-andrographolide-19-yl sulfate, which are derived from andrographis).
May 2021, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7141, https://c19p.org/zhang14
13. Steenkamp et al., Small steps, strong shield: directly measured, moderate physical activity in 65 361 adults is associated with significant protective effects from severe COVID-19 outcomes
42,835 patient exercise study: 42% lower mortality (p<0.0001), 45% lower ventilation (p<0.0001), 41% lower ICU admission (p<0.0001), and 34% lower hospitalization (p<0.0001).Retrospective 65,361 COVID-19 patients in South Africa, showing significantly lower hospitalization, ICU admission, ventilation, and mortality with exercise.
Feb 2022, British J. Sports Medicine, https://bjsm.bmj.com/content/early/2022/02/08/bjsports-2021-105159.long, https://c19p.org/steenkamp
14. Abdallah et al., Twice daily oral zinc in the treatment of patients with Coronavirus Disease-19: A randomized double-blind controlled trial
470 patient zinc early treatment RCT: 30% lower mortality (p=0.27), 38% lower combined mortality/ICU admission (p=0.04), 54% lower ICU admission (p=0.01), and 42% lower need for oxygen therapy (p=0.009).RCT 470 patients with symptoms ≤7 days, showing significantly lower ICU admission and combined mortality/ICU admission with zinc treatment. Greater benefit was seen for patients treated within 3 days. 25mg elemental zinc bid for 15 days. See also [academic.oup.com] and the author's reply [academic.oup.com].
Nov 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac807/6795268, https://c19p.org/abdallah
15. Ramakrishnan et al., Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial
146 patient budesonide early treatment RCT: 82% fewer combined hospitalization/ER visits (p=0.02) and 67% improved recovery (p=0.003).RCT with 73 budesonide patients and 73 control patients, showing significantly lower combined risk of an ER visit or hospitalization, and lower risk of no recovery at day 14.
Feb 2021, Lancet Respiratory Medicine, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00160-0/fulltext, https://c19p.org/ramakrishnan
16. de Gabory et al., Seawater nasal wash to reduce symptom duration and viral load in COVID-19 and upper respiratory tract infections: a randomized controlled multicenter trial
173 patient alkalinization early treatment RCT: 75% lower progression (p<0.0001), 24% faster recovery (p=0.02), and 37% improved viral clearance (p=0.54).RCT 355 adults with COVID-19 or other upper respiratory tract infections (URTIs). For COVID-19 patients there was lower progression and faster symptom resolution with alkaline seawater nasal wash (pH ~8) 4 times daily for 21 days. There was significantly lower transmission for patients with the delta variant and for patients with high viral load. The seawater nasal wash was safe and well-tolerated.
Feb 2024, European Archives of Oto-Rhino-Laryngology, https://link.springer.com/10.1007/s00405-024-08518-y, https://c19p.org/degabory
17. McCoy et al., Proxalutamide (GT0918) Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial
268 patient proxalutamide antiandrogen early treatment RCT: 97% lower ventilation (p<0.0001) and 91% lower hospitalization (p<0.0001).RCT 268 male patients in Brazil, 134 treated with proxalutamide, showing significantly lower hospitalization and mechanical ventilation. This paper was retracted, however no specific reason is provided, the editors have ignored the authors, and the "external expert" was reportedly funded by Pfizer. For details see [twitter.com]. The retraction notice states: "The investigation found that the claims made in the conclusions were not adequately supported by the methodology of the study. In particular, as confirmed by an external expert, the process of allocation to treatment and control was not sufficiently random." The lack of any detail on what conclusion is not supported and why, or details of any issues in randomization, suggests the paper was censored rather than retracted. This study was censored.
Dec 2020, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.668698/abstract, https://c19p.org/mccoy
18. Yates et al., Obesity, walking pace and risk of severe COVID-19 and mortality: analysis of UK Biobank
194,031 patient exercise study: 45% lower mortality (p=0.001) and 47% lower severe cases (p<0.0001).UK Biobank retrospective 412,596 people, showing severe COVID-19 and COVID-19 mortality inversely associated with self-reported walking pace.
Feb 2021, Int. J. Obesity, http://www.nature.com/articles/s41366-021-00771-z, https://c19p.org/yates
52,365 patient exercise study: 74% lower mortality (p=0.05), 58% lower severe cases (p=0.03), and 16% fewer cases (p=0.03).
Retrospective 212,768 adults in South Korea, showing lower risk of COVID-19 cases, severity, and mortality with physical activity. Notably, results for aerobic and muscle strengthening activities combined were much better than results for either one in isolation.
Jul 2021, British J. Sports Medicine, https://bjsm.bmj.com/content/early/2021/07/21/bjsports-2021-104203, https://c19p.org/lee6
25 patient nitric oxide ICU RCT: 90% lower mortality (p=0.03), 90% lower ventilation (p=0.03), 42% greater improvement (p=0.47), and 64% faster viral clearance (p=0.005).
RCT 29 ICU patients in India, showing improved clinical outcomes and faster viral clearance with inhaled nitric oxide treatment. The treatment group was younger (mean 54 vs. 66) and had more patients on NIV at baseline (29% vs. 18%).
Apr 2021, Infectious Microbes and Diseases, https://journals.lww.com/10.1097/IM9.0000000000000079, https://c19p.org/moni
21. Mayberry et al., Zinc use is associated with improved outcomes in COVID-19: results from the CRUSH-COVID registry
2,028 patient zinc early treatment study: 53% lower mortality (p<0.0001), 64% lower ventilation (p<0.0001), 60% lower ICU admission (p<0.0001), and 58% lower combined mortality/ICU admission (p<0.0001).Retrospective 2,028 COVID patients in the USA, showing significantly lower mortality, ventilation, ICU admission, and progression to ARDS with zinc use, defined as at least one dose from one week prior to admission to 48 hours after admission.
Dec 2021, Critical Care Medicine, https://journals.lww.com/ccmjournal/Citation/2022/01001/195__ZINC_USE_IS_ASSOCIATED_WITH_IMPROVED_OUTCOMES.161.aspx, https://c19p.org/mayberry
22. Balmforth et al., Evaluating the efficacy and safety of a novel prophylactic nasal spray in the prevention of SARS-CoV-2 infection: A multi-centre, double blind, placebo-controlled, randomised trial.
648 patient pHOXWELL prophylaxis RCT: 47% fewer symptomatic cases (p<0.0001) and 63% lower IgG positivity (p<0.0001).648 patient RCT pHOXWELL nasal spray in India, showing significantly lower IgGS+ and significantly lower symptomatic cases with treatment. pHOXWELL includes a combination of natural virucidal agents and is designed to mimic the fluid surrounding healthy cells. The spray included xylitol, zinc chloride, polyethylene glycol 400, poloxamer, disodium hydrogen phosphate, sodium chloride, hydroxypropyl methylcellulose, ginger oil, eucalyptus oil, basil oil, clove oil, sodium hydrogen carbonate, potassium dihydrogen phosphate, ethylenediaminetetraacetic acid, sodium hyaluronate, calcium chloride dihydrate, benzalkonium chloride, magnesium chloride hexahydrate, potassium chloride, and glycerol. The spray was administered up to three times per day (TID) 140 μl/nostril for 45 days, with a gap of 6-8 hours between doses.
Jul 2022, J. Clinical Virology, https://www.sciencedirect.com/science/article/pii/S1386653222001809, https://c19p.org/balmforthphx
23. Balmforth et al., Evaluating the efficacy and safety of a novel prophylactic nasal spray in the prevention of SARS-CoV-2 infection: A multi-centre, double blind, placebo-controlled, randomised trial.
648 patient xylitol prophylaxis RCT: 47% fewer symptomatic cases (p<0.0001) and 63% lower IgG positivity (p<0.0001).648 patient RCT pHOXWELL nasal spray in India, showing significantly lower IgGS+ and significantly lower symptomatic cases with treatment. pHOXWELL includes a combination of natural virucidal agents and is designed to mimic the fluid surrounding healthy cells. The spray included xylitol, zinc chloride, polyethylene glycol 400, poloxamer, disodium hydrogen phosphate, sodium chloride, hydroxypropyl methylcellulose, ginger oil, eucalyptus oil, basil oil, clove oil, sodium hydrogen carbonate, potassium dihydrogen phosphate, ethylenediaminetetraacetic acid, sodium hyaluronate, calcium chloride dihydrate, benzalkonium chloride, magnesium chloride hexahydrate, potassium chloride, and glycerol. The spray was administered up to three times per day (TID) 140 μl/nostril for 45 days, with a gap of 6-8 hours between doses.
Jul 2022, J. Clinical Virology, https://www.sciencedirect.com/science/article/pii/S1386653222001809, https://c19p.org/balmforthxy
24. Seet et al., Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
1,354 patient povidone-iodine prophylaxis RCT: 45% fewer symptomatic cases (p=0.002) and 31% fewer cases (p=0.01).Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seetp
25. Wong et al., Glycemic Control and Clinical Outcomes in U.S. Patients With COVID-19: Data From the National COVID Cohort Collaborative (N3C) Database
39,616 patient metformin prophylaxis study: 51% lower mortality (p<0.0001), 41% lower ventilation (p<0.0001), and 40% lower hospitalization (p<0.0001).N3C retrospective 39,616 COVID-19 patients with diabetes in the USA, showing lower mortality, ventilation, and hospitalization with metformin use.
Feb 2022, Diabetes Care, https://diabetesjournals.org/care/article/doi/10.2337/dc21-2186/144605/Glycemic-Control-and-Clinical-Outcomes-in-U-S, https://c19p.org/wong2
26. Jing et al., Effective early strategy to prevent olfactory and gustatory dysfunction in COVID-19: a randomized controlled trial
260 patient chlorhexidine early treatment RCT: 79% lower progression (p<0.0001) and 97% lower severe cases (p<0.0001).RCT 379 mild COVID-19 cases showing significantly lower prevalence and severity of olfactory and gustatory dysfunction with budesonide nasal spray, chlorhexidine mouthwash, and saline nasal irrigation. The control group received no intervention, the saline group received saline nasal irrigation plus saline nasal spray and mouthwash, and the drug group received saline nasal irrigation plus budesonide nasal spray and chlorhexidine mouthwash. Saline nasal irrigation plus nasal spray and mouthwash were administered once and four times daily, respectively. Both treatment groups had significantly lower prevalence and severity olfactory and gustatory dysfunction. Prevalence was lower for the drug vs. saline group, without statistical significance.
Nov 2023, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcad262/7439598, https://c19p.org/jing
27. Kolesnyk et al., The role of nutritional support with probiotics in outpatients with symptomatic acute respiratory tract infections: a multicenter, randomized, double-blind, placebo-controlled dietary study
73 patient probiotics early treatment RCT: 60% improved recovery (p=0.02) and 68% lower PASC (p=0.008).RCT 73 outpatients with mild COVID-19 showing improved recovery and increased RBD/spike antibody response with 28 days of a multi-strain probiotic (Bifidobacterium (B.) lactis BI040, B. longum BL020, Lactobacillus (L) rhamnosus LR110, L. casei LC130, L. acidophilus LA120, 5 billion CFU total).
Jan 2024, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-023-00816-8, https://c19p.org/kolesnyk
28. Seet et al., Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
1,253 patient zinc prophylaxis RCT: 50% fewer symptomatic cases (p=0.0007) and 27% fewer cases (p=0.03).Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seetz
394 patient iota-carrageenan prophylaxis RCT: 80% fewer symptomatic cases (p=0.03).
Prophylaxis RCT with 394 healthcare workers, 196 treated with iota-carrageenan, showing significantly lower symptomatic cases with treatment. There were no deaths or hospitalizations. There was a significant number of PCR- symptomatic cases (7.6% treatment and 8.6% control). The two treatment cases occurred shortly after randomization - infection may have occurred before the start of treatment.
Apr 2021, Int. J. General Medicine, https://www.dovepress.com/efficacy-of-a-nasal-spray-containing-iota-carrageenan-in-the-postexpos-peer-reviewed-fulltext-article-IJGM, https://c19p.org/figueroa
30. Lenze et al., Fluvoxamine vs Placebo and Clinical Deterioration in Outpatients With Symptomatic COVID-19: A Randomized Clinical Trial
152 patient fluvoxamine early treatment RCT: 93% lower progression (p=0.009) and 82% lower hospitalization (p=0.009).RCT 152 outpatients, 80 treated with fluvoxamine showing lower progression with treatment (0 of 80 versus 6 of 72 control).
Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2773108, https://c19p.org/lenze
31. Kintor et al., Kintor Pharma's Proxalutamide Demonstrated Reduction in Hospitalization/Mortality for Patients with Mild to Moderate COVID-19 in Phase III MRCT Study
730 patient proxalutamide antiandrogen early treatment RCT: 50% lower hospitalization (p=0.38) and 74% improved viral clearance (p=0.0001).RCT 733 outpatients, 99% in the USA, showing lower hospitalization/death, and significantly reduced viral load with proxalutamide treatment. The viral clearance result is from [Ma]
Apr 2022, Kintor, Press Release, https://www.prnewswire.com/news-releases/kintor-pharmas-proxalutamide-demonstrated-reduction-in-hospitalizationmortality-for-patients-with-mild-to-moderate-covid-19-in-phase-iii-mrct-study-301518525.html, https://c19p.org/kintorpx3
94,731 patient exercise study: 74% lower mortality (p<0.0001) and 48% lower hospitalization (p<0.0001).
Retrospective 194,191 COVID-19 patients in the USA, showing lower risk of hospitalization and mortality with physical activity, with a dose response relationship.
Dec 2022, American J. Preventive Medicine, https://www.sciencedirect.com/science/article/pii/S0749379722005268, https://c19p.org/young
33. Sulaiman et al., The Effect of Early Hydroxychloroquine-based Therapy in COVID-19 Patients in Ambulatory Care Settings: A Nationwide Prospective Cohort Study
7,892 patient HCQ early treatment study: 64% lower mortality (p=0.01), 44% lower combined mortality/ICU admission (p=0.02), 37% lower ICU admission (p=0.13), and 39% lower hospitalization (p<0.0001).Observational prospective 5,541 patients, adjusted HCQ mortality odds ratio OR 0.36, p = 0.012. Adjusted hospitalization OR 0.57, p < 0.001. Zinc supplementation was used in all cases. Early treatment in ambulatory fever clinics in Saudi Arabia.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.09.20184143v1, https://c19p.org/sulaiman
34. Mahmud et al., Ivermectin in combination with doxycycline for treating COVID-19 symptoms: a randomized trial
366 patient ivermectin early treatment RCT: 86% lower mortality (p=0.25), 57% lower progression (p=0.001), 94% improved recovery (p<0.0001), and 39% improved viral clearance (p=0.002).RCT for ivermectin+doxycycline showing improvements in mortality, recovery, progression, and virological cure. 183 treatment and 183 control patients with no deaths in the treatment arm vs. 3 in the control arm (the 3 control deaths are not included in the analysis of other outcomes). Results may reflect the use of ivermectin, doxycycline, and potential synergistic effects of the combination. In the PRINCIPLE trial, no mortality benefit was seen for doxycycline alone [thelancet.com] (0.6% mortality with doxycycline vs. 0.2% control).
Oct 2020, J. Int. Medical Research, https://journals.sagepub.com/doi/10.1177/03000605211013550, https://c19p.org/mahmud
35. Matsuyama et al., A prospective, randomized, open-label trial of early versus late povidone-iodine gargling in patients with COVID-19
279 patient povidone-iodine early treatment RCT: 69% improved viral clearance (p=0.03).RCT 430 COVID+ patients in Japan, showing significantly lower viral infectivity from culture, and significantly faster PCR viral clearance with PVP-I. For days 2-4 the study compares treatment with PVP-I vs. water (on day 5 both groups received PVP-I). Most patients were asymptomatic. 4 times per day mouthwashing and gargling with 20mL of 15-fold diluted PVP–I 7% or water.
Nov 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-24683-8, https://c19p.org/matsuyama
36. Rahman et al., Safety and Efficacy of Favipiravir for the management of COVID-19 Patients: A Randomized Control Trial
50 patient favipiravir late treatment RCT: 89% greater improvement (p=0.005) and 92% improved viral clearance (p=0.0008).RCT hospitalized patients in Bangladesh, showing faster recovery and viral clearance with favipiravir treatment.
May 2022, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170222000139, https://c19p.org/rahman2
1,214 patient metformin prophylaxis study: 59% lower mortality (p=0.01), 61% improved recovery (p=0.005), 64% greater improvement (p=0.009), and 56% higher hospital discharge (p=0.009).
Retrospective 1,214 COVID+ type 2 diabetes patients in Hong Kong, showing lower mortality and improved recovery with metformin use.
Mar 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.810914/full, https://c19p.org/wong
38. Seet et al., Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
1,236 patient ivermectin prophylaxis RCT: 50% fewer symptomatic cases (p=0.0009) and 6% fewer cases (p=0.61).Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. The ivermectin dosage was low for 42 days prophylaxis - only a single dose of 200µg/kg, with a maximum of 12mg. Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seet
39. Million et al., Early Treatment with Hydroxychloroquine and Azithromycin in 10,429 COVID-19 Outpatients: A Monocentric Retrospective Cohort Study
10,429 patient HCQ early treatment study: 83% lower mortality (p=0.0007), 44% lower ICU admission (p=0.18), and 4% lower hospitalization (p=0.77).Retrospective 10,429 outpatients in France, 8,315 treated with HCQ+AZ a median of 4 days from symptom onset, showing significantly lower mortality with treatment.
May 2021, Reviews in Cardiovascular Medicine, https://www.imrpress.com/journal/RCM/22/3/10.31083/j.rcm2203116, https://c19p.org/million4
40. Shouman et al., Use of Ivermectin as a Potential Chemoprophylaxis for COVID-19 in Egypt: A Randomised Clinical Trial
304 patient ivermectin prophylaxis RCT: 91% fewer symptomatic cases (p=0.001) and 93% lower severe cases (p=0.002).PEP trial for asymptomatic close contacts of COVID-19 patients, 203 ivermectin patients and 101 control patients. 7.4% of contacts developed COVID-19 in the ivermectin group vs. 58.4% in the control group. Efficacy for symptomatic cases and severe cases is very similar. Adjusted results are provided only for symptomatic cases. See also [trialsitenews.com].
Aug 2020, J. Clinical and Diagnostic Research, https://www.jcdr.net/articles/PDF/14529/46795_CE[Ra]_F(Sh)_PF1(SY_OM)_PFA_(OM)_PN(KM).pdf, https://c19p.org/shouman
41. Merino et al., Diet quality and risk and severity of COVID-19: a prospective cohort study
296,285 patient diet study: 41% lower severe cases (p<0.0001) and 18% fewer cases (p<0.0001).Retrospective 592,571 participants in the UK and USA with 31,815 COVID-19 cases, showing lower risk or COVID-19 cases and severity for higher healthful plant-based diet scores. Notably, the assocation was less evident with higher levels of physical activity.
Jun 2021, Gut, https://gut.bmj.com/content/70/11/2096, https://c19p.org/merino2
42. Sallis et al., Physical inactivity is associated with a higher risk for severe COVID-19 outcomes: a study in 48 440 adult patients
10,102 patient exercise study: 59% lower mortality (p=0.005), 42% lower ICU admission (p=0.006), and 53% lower hospitalization (p<0.0001).Retrospective 48,440 COVID-19 patients in the USA, showing significantly lower mortality, ICU admission, and hospitalization with exercise.
Apr 2021, British J. Sports Medicine, https://bjsm.bmj.com/content/55/19/1099, https://c19p.org/sallis
43. Tardif et al., Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial
4,488 patient colchicine late treatment RCT: 44% lower mortality (p=0.3), 20% lower combined mortality/hospitalization (p=0.08), 47% lower ventilation (p=0.09), and 20% lower hospitalization (p=0.09).RCT for relatively low risk outpatients, 2235 treated with colchicine a mean of 5.3 days after the onset of symptoms, and 2253 controls, showing lower mortality, ventilation, and hospitalization with treatment. This study was submitted to NEJM which delayed for ~6 months and then said they were not interested, then to JAMA which delayed for ~6 months and then said they were not interested, and then to the Lancet which delayed for ~6 months and then said they were not interested, and finally was published in Lancet Respiratory Medicine [twitter.com].
Jan 2021, The Lancet Respiratory Medicine, https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(21)00222-8/fulltext, https://c19p.org/tardif
44. Zaccardi et al., Ethnicity and risks of severe COVID-19 outcomes associated with glucose-lowering medications: A cohort study
624,771 patient metformin prophylaxis study: 34% lower mortality (p<0.0001) and 31% lower hospitalization (p<0.0001).Retrospective 624,771 people with type 2 diabetes in the UK, showing lower COVID-19 mortality and hospitalization with metformin use.
Sep 2022, Diabetes, Obesity and Metabolism, https://onlinelibrary.wiley.com/doi/10.1111/dom.14872, https://c19p.org/zaccardi
45. Singh et al., Therapeutic high-dose vitamin D for vitamin D-deficient severe COVID-19 disease: randomized, double-blind, placebo-controlled study (SHADE-S)
90 patient vitamin D late treatment RCT: 45% lower mortality (p=0.05) and 40% improved recovery (p=0.01).RCT 90 vitamin D deficient moderate/severe COVID-19 ARDS patients in India, showing lower mortality with vitamin D treatment. 600,000IU nanoformulation cholecalciferol.
May 2022, J. Public Health, https://academic.oup.com/jpubhealth/advance-article-abstract/doi/10.1093/pubmed/fdae007/7591923?redirectedFrom=fulltext&login=false, https://c19p.org/singh7
46. Sirijatuphat et al., Early Treatment of Favipiravir in COVID-19 Patients Without Pneumonia: A Multicentre, Open-Labelled, Randomized Control Study
93 patient favipiravir early treatment RCT: 64% faster improvement (p=0.0005), 43% lower progression (p=0.25), and 4% worse viral clearance (p=0.87).RCT 93 patients in Thailand showing significantly faster clinical improvement with favipiravir treatment. 1800mg favipiravir bid day 1, 800mg bid 5-14 days until PCR-.
Jun 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.06.06.22275902v1, https://c19p.org/sirijatuphat2
173 patient chlorhexidine late treatment RCT: 85% improved viral clearance (p<0.0001).
RCT 294 hospitalized patients in the USA, showing faster oropharyngeal viral clearance with chlorhexidine. Results were better with a combination of oropharyngeal rinse and posterior oropharyngeal spray compared with the rinse alone.
Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jmv.26954, https://c19p.org/huang8
48. Villasis-Keever et al., Efficacy and Safety of Vitamin D Supplementation to Prevent COVID-19 in Frontline Healthcare Workers. A Randomized Clinical Trial
302 patient vitamin D prophylaxis RCT: 78% fewer cases (p=0.001).RCT 321 healthcare workers in Mexico, showing significantly lower SARS-CoV-2 infection with vitamin D prophylaxis. 4,000IU daily for 30 days. In comparison to [Jolliffe], this study used a higher dose, the participants had much higher exposure to SARS-CoV-2 patients, and the study was prior to vaccination. In [Jolliffe], 89% of participants had received a vaccine dose by the end of the study period, and the period overlapped with increasing solar UVB. For more discussion see [twitter.com].
Apr 2022, Archives of Medical Research, https://www.sciencedirect.com/science/article/abs/pii/S0188440922000455, https://c19p.org/villasiskeever
49. Pineda et al., Impact of fluvoxamine on outpatient treatment of COVID-19 in Honduras in a prospective observational real-world study
657 patient fluvoxamine early treatment study: 94% lower mortality (p=0.01), 73% lower need for oxygen therapy (p=0.0002), and 51% lower hospitalization (p=0.04).Prospective study of 657 COVID+ outpatients in Honduras, 594 accepting fluvoxamine treatment, showing significantly lower mortality and hospitalization with treatment.
Oct 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.1054644/full, https://c19p.org/pineda
50. Winchester et al., Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment of mild COVID-19 infection
80 patient nitric oxide early treatment RCT: 42% greater improvement (p=0.008) and 51% improved viral clearance (p=0.001).RCT with 40 nitric oxide and 40 placebo patients in the UK, showing faster viral clearance and greater improvement with treatment.
May 2021, J. Infection, https://www.journalofinfection.com/article/S0163-4453(21)00251-6/fulltext, https://c19p.org/winchester
51. Cho et al., Physical Activity and the Risk of COVID-19 Infection and Mortality: A Nationwide Population-Based Case-Control Study
97,123 patient exercise study: 53% lower mortality (p=0.01) and 10% fewer cases (p<0.0001).Retrospective 6,288 COVID+ patients and 125,772 matched controls in South Korea, showing significantly lower risk of COVID-19 infection and mortality with higher physical activity.
Apr 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/7/1539, https://c19p.org/cho
1,407 patient nitazoxanide prophylaxis RCT: 43% lower progression (p=0.02), 50% faster recovery (p=0.1), and 3% fewer cases (p=1).
RCT 1,407 healthcare workers and others at high risk of SARS-CoV-2 exposure, showing no difference in COVID-19 cases (13 in each group). There was lower symptom severity for nitazoxanide and a trend towards shorter illness duration. There is no publication, results are only available on clinicaltrials.gov, posted 3 years after completion (FDA pre-notice of noncompliance [fda.gov]).
Jun 2024, Romark, NCT04359680, https://clinicaltrials.gov/study/NCT04359680?term=NCT04359680&rank=1&tab=results, https://c19p.org/romark
53. Wadhwa et al., Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi
120 patient spironolactone antiandrogen late treatment RCT: 72% lower progression (p=0.03), 49% higher hospital discharge (p=0.05), and 18% faster recovery (p=0.06).RCT 120 hospitalized patients in India, 74 treated with spironolactone and dexamethasone, and 46 with dexamethasone, showing lower progression with treatment. Spironolactone 50mg once daily day 1, 25mg once daily until day 21.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277163, https://c19p.org/wadhwa
54. Wadhwa et al., Phase 2 randomised placebo-controlled trial of spironolactone and dexamethasone versus dexamethasone in COVID-19 hospitalised patients in Delhi
120 patient spironolactone late treatment RCT: 72% lower progression (p=0.03), 49% higher hospital discharge (p=0.05), and 18% faster recovery (p=0.06).RCT 120 hospitalized patients in India, 74 treated with spironolactone and dexamethasone, and 46 with dexamethasone, showing lower progression with treatment. Spironolactone 50mg once daily day 1, 25mg once daily until day 21.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277163, https://c19p.org/wadhwasp
55. Gibbons et al., Association between vitamin D supplementation and COVID-19 infection and mortality
398,996 patient vitamin D prophylaxis PSM study: 33% lower mortality (p<0.0001) and 20% fewer cases (p<0.0001).PSM retrospective in the USA, showing lower COVID-19 mortality and cases with vitamin D prophylaxis.
Nov 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-24053-4, https://c19p.org/gibbons
123,709 patient metformin prophylaxis PSM study: 25% lower mortality (p=0.001), 25% lower ventilation (p=0.01), 19% lower ICU admission (p=0.005), and 15% lower hospitalization (p<0.0001).
TriNetX retrospective 123,709 vaccinated patients with type 2 diabetes, showing significantly lower risk of COVID-19 mortality, mechanical ventilation, and hospitalization with metformin use. There was no significant difference for cases. The increasing benefit for more serious outcomes matches the results of studies to date.
May 2023, Diabetes Research and Clinical Practice, https://www.sciencedirect.com/science/article/pii/S0168822723004540, https://c19p.org/yen
57. Valerio-Pascua et al., Chlorpheniramine Intranasal Spray to Accelerate COVID-19 Clinical Recovery in an Outpatient Setting: The ACCROS Trials
101 patient chlorpheniramine early treatment RCT: 61% improved recovery (p=0.0002) and 74% lower PASC (p=0.001).RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The RCT included 101 outpatients showing significantly faster recovery with treatment. The retrospective study results are listed separately [Valerio-Pascua]. Long COVID results are from [Valerio-Pascua].
Oct 2022, Research Square, https://www.researchsquare.com/article/rs-2167465/v1, https://c19p.org/valeriopascua3
58. Valerio-Pascua et al., Chlorpheniramine Intranasal Spray to Accelerate COVID-19 Clinical Recovery in an Outpatient Setting: The ACCROS Trials
101 patient chlorpheniramine early treatment RCT: 61% improved recovery (p=0.0002) and 74% lower PASC (p=0.001).RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The RCT included 101 outpatients showing significantly faster recovery with treatment. The retrospective study results are listed separately [Valerio-Pascua]. Long COVID results are from [Valerio-Pascua].
Oct 2022, Research Square, https://www.researchsquare.com/article/rs-2167465/v1, https://c19p.org/valeriopascua3cpm
59. Oristrell et al., Association of Calcitriol Supplementation with Reduced COVID-19 Mortality in Patients with Chronic Kidney Disease: A Population-based Study
5,703 patient vitamin D prophylaxis study: 43% lower mortality (p=0.001), 43% lower severe cases (p=0.0008), and 22% fewer cases (p=0.01).Retrospective study of calcitriol supplementation with chronic kidney disease patients in Catalonia showing lower cases, severe cases, and mortality with supplementation. A dose-response relationship was found for severe cases and mortality.
Apr 2021, Biomedicines, https://www.mdpi.com/2227-9059/9/5/509, https://c19p.org/oristrell
60. Dhanger et al., To estimate the efficacy of inhaled corticosteroid in-patient of moderate COVID-19 pneumonia - randomized controlled study
80 patient budesonide late treatment RCT: 43% lower mortality (p=0.52), 78% lower ICU admission (p<0.0001), and 70% improved recovery (p<0.0001).RCT inhaled budesonide with 80 moderate COVID-19 pneumonia patients. The budesonide group had significantly faster time to clinical improvement, fewer ICU admissions, shorter oxygen therapy duration, and lower mortality. Inhaled budesonide 400mcg twice daily for 14 days.
Sep 2023, Int. J. Academic Medicine and Pharmacy, https://academicmed.org/Uploads/Volume5Issue5/101.%20[1518.%20JAMP_Bhavani%20Vaidiyanathan]%20517-521.pdf, https://c19p.org/dhanger
61. Bradbury et al., Effect of Antiplatelet Therapy on Survival and Organ Support–Free Days in Critically Ill Patients With COVID-19: A Randomized Clinical Trial
1,084 patient aspirin late treatment RCT: 16% lower mortality (p=0.05), 17% higher hospital discharge (p=0.08), and 21% lower progression (p=0.02).RCT 1,557 critical patients, showing significantly lower mortality with aspirin, with 97.5% posterior probability of efficacy.
Mar 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2790488, https://c19p.org/bradbury
62. Montopoli et al., Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532)
42,434 patient various antiandrogen prophylaxis study: 95% lower mortality (p=0.15), 75% lower severe cases (p=0.01), and 75% fewer cases (p=0.004).Retrospective 5,273 prostate cancer patients on androgen-deprivation therapy (ADT), and 37,161 not on ADT, showing lower risk of cases with treatment.
May 2020, Annals of Oncology, https://www.sciencedirect.com/science/article/pii/S0923753420397970, https://c19p.org/montopoli
63. Mayer et al., Safety and Efficacy of a MEURI Program for the Use of High Dose Ivermectin in COVID-19 Patients
21,232 patient ivermectin early treatment study: 55% lower mortality (p<0.0001) and 66% lower ICU admission (p<0.0001).Retrospective 21,232 patients in Argentina, 3,266 assigned to ivermectin treatment, showing lower mortality with treatment. Greater benefits were seen for patients >40, and a dose dependent response was found. For more discussion see [twitter.com].
Sep 2021, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2022.813378/full, https://c19p.org/mayer
64. Hellou et al., Effect of ArtemiC in patients with COVID-19: A Phase II prospective study
50 patient curcumin late treatment RCT: 77% improved recovery (p=0.04), 92% lower need for oxygen therapy (p=0.01), 13% shorter hospitalization (p=0.92), and 10% improved viral clearance (p=0.77).RCT 50 hospitalized patients in Israel, 33 treated with curcumin, vitamin C, artemisinin, and frankincense oral spray, showing improved recovery with treatment.
May 2022, J. Cellular and Molecular Medicine, https://onlinelibrary.wiley.com/doi/10.1111/jcmm.17337, https://c19p.org/hellou
65. Di Pierro et al., The administration of S. salivarius K12 to children may reduce the rate of SARS-CoV-2 infection
128 patient probiotics prophylaxis RCT: 98% fewer cases (p<0.0001).Interim report on an RCT for prophylactic treatment with S. salivarius K12, showing significantly lower cases with treatment. Only patients with symptoms or known positive contacts were tested. Trial identification/registration details are not provided.
Mar 2021, Minerva Medica, https://www.minervamedica.it/en/journals/minerva-medica/article.php?cod=R10Y2021N04A0514, https://c19p.org/dipierro3
66. Rondanelli et al., Promising Effects of 3-Month Period of Quercetin Phytosome® Supplementation in the Prevention of Symptomatic COVID-19 Disease in Healthcare Workers: A Pilot Study
120 patient quercetin prophylaxis RCT: 93% fewer symptomatic cases (p=0.04).RCT 120 healthcare workers, 60 treated with quercetin phytosome, showing lower risk of cases with treatment. Quercetin phytosome 250mg twice a day.
Jan 2022, Life, https://www.mdpi.com/2075-1729/12/1/66/htm, https://c19p.org/rondanelli
67. Seet et al., Positive impact of oral hydroxychloroquine and povidone-iodine throat spray for COVID-19 prophylaxis: an open-label randomized trial
1,051 patient HCQ prophylaxis RCT: 35% fewer symptomatic cases (p=0.05) and 32% fewer cases (p=0.009).Prophylaxis RCT in Singapore with 3,037 low risk patients, showing lower serious cases, lower symptomatic cases, and lower confirmed cases of COVID-19 with all treatments (ivermectin, HCQ, PVP-I, and Zinc + vitamin C) compared to vitamin C. Only 71.4% reported >70% adherence, limiting efficacy. QTc did not statistically significantly differ between baseline and follow-up readings (mean 379 vs 378ms, paired t-test p=0.387). Meta-analysis of vitamin C in 6 previous trials shows a benefit of 16%, so the actual benefit of ivermectin, HCQ, and PVP-I may be higher. Cluster RCT with 40 clusters. There were no hospitalizations and no deaths.
Apr 2021, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)00345-3/fulltext, https://c19p.org/seeth
68. Wang et al., Modifiable lifestyle factors and the risk of post-COVID-19 multisystem sequelae, hospitalization, and death
68,896 patient exercise study: 30% lower mortality (p<0.0001), 12% lower hospitalization (p<0.0001), and 14% lower PASC (p<0.0001).Prospective study of 68,896 UK Biobank participants with COVID-19 showing adherence to a healthy lifestyle prior to infection, characterized by 10 factors including adequate physical activity and sleep, not smoking, and a healthy BMI, was associated with a significantly lower risk of mortality, hospitalization, and post-COVID multisystem sequelae. Risk decreased monotonically for increasing numbers of healthy lifestyle factors from 5-10. Reduced risks were evident across cardiovascular, metabolic, neurologic, respiratory, and other disorders over 210 days following infection, during both acute and post-acute phases, regardless of age, sex, ethnicity, test setting, vaccination status, or SARS-CoV-2 variant.
Jan 2024, Nature Communications, https://www.nature.com/articles/s41467-024-50495-7, https://c19p.org/wang24
69. John et al., Ursodeoxycholic acid is associated with a reduction in SARS‐CoV‐2 infection and reduced severity of COVID‐19 in patients with cirrhosis
3,214 patient ursodeoxycholic acid prophylaxis PSM study: 42% lower mortality (p=0.28), 54% lower severe cases (p=0.03), 55% fewer moderate/severe cases (p=0.002), and 50% fewer symptomatic cases (p<0.0001).Retrospective 3,214 veterans with cirrhosis comparing 1,607 participants taking ursodeoxycholic acid (UDCA) to 1,607 propensity score matched controls not taking UDCA. UDCA use was associated with significantly lower odds of SARS-CoV-2 infection, symptomatic COVID-19, moderate or worse COVID-19, and severe/critical COVID-19.
Apr 2023, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13630, https://c19p.org/john
70. Cousins et al., Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19
64,349 patient spironolactone antiandrogen prophylaxis PSM study: 81% lower ventilation (p=0.006) and 66% lower ICU admission (p=0.002).PSM retrospective 64,349 COVID-19 patients in the USA, showing spironolactone associated with lower ICU admission. Authors also present In Vitro research showing dose-dependent inhibition in a human lung epithelial cell line.
Jul 2022, Cell Reports Methods, https://www.sciencedirect.com/science/article/pii/S2667237523001327, https://c19p.org/cousins
71. Cousins et al., Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19
64,349 patient spironolactone prophylaxis PSM study: 81% lower ventilation (p=0.006) and 66% lower ICU admission (p=0.002).PSM retrospective 64,349 COVID-19 patients in the USA, showing spironolactone associated with lower ICU admission. Authors also present In Vitro research showing dose-dependent inhibition in a human lung epithelial cell line.
Jul 2022, Cell Reports Methods, https://www.sciencedirect.com/science/article/pii/S2667237523001327, https://c19p.org/cousinssp
72. Jang et al., Impact of Antidiabetic Drugs on Clinical Outcomes of COVID-19: A Nationwide Population-Based Study
556 patient metformin prophylaxis study: 60% lower mortality (p=0.02), 72% lower ventilation (p=0.008), 39% lower ICU admission (p=0.12), and 30% lower need for oxygen therapy (p=0.23).Retrospective 556 diabetic patients in South Korea with COVID-19 showing lower risk of mechanical ventilation and death with metformin, lower risks of oxygen treatment and death with DPP-4 inhibitors, and increased risk of mechanical ventilation with sulfonylureas. The study used nationwide data to analyze the impact of common antidiabetic medications on COVID-19 outcomes. Authors note that South Korea had a policy early in the pandemic of hospitalizing nearly all confirmed COVID-19 patients regardless of severity.
Jan 2024, Endocrinology and Metabolism, http://www.e-enm.org/journal/view.php?doi=10.3803/EnM.2024.1857, https://c19p.org/jang6
73. Ghany et al., Metformin is associated with lower hospitalizations, mortality and severe coronavirus infection among elderly medicare minority patients in 8 states in USA
1,139 patient metformin prophylaxis study: 66% lower mortality (p=0.0002), 29% lower hospitalization (p=0.008), and 68% lower ARDS (p<0.0001).Retrospective 1,139 elderly COVID+ patients in the USA, 392 with pre-existing metformin use, showing significantly lower mortality, hospitalization, and ARDS with treatment.
Mar 2021, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://www.sciencedirect.com/science/article/pii/S187140212100045X, https://c19p.org/ghany
74. Al-Haidari et al., Clinical Trial of Black Seeds Against COVID – 19 in Kirkuk City / Iraq
419 patient nigella sativa early treatment RCT: 96% lower mortality (p=0.001) and 93% lower severe cases (p<0.0001).Open-label RCT with 419 patients in Iraq, 160 treated with Nigella Sativa, showing lower mortality and severe cases with treatment. Black seeds 40mg/kg orally once daily for 14 days.
Jan 2021, Indian J. Forensic Medicine & Toxicology, https://www.researchgate.net/publication/352134969_Clinical_Trial_of_Black_Seeds_Against_COVID_-19_in_Kirkuk_City_Iraq, https://c19p.org/alhaidari
75. Sánchez-Zuno et al., Vitamin D Levels in COVID-19 Outpatients from Western Mexico: Clinical Correlation and Effect of Its Supplementation
42 patient vitamin D early treatment RCT: 89% lower severe cases (p=0.04) and 81% improved recovery (p=0.22).Very small 42 PCR+ outpatient RCT in Mexico, 22 treated with vitamin D. Most patients had insufficient vitamin D levels, there were more symptoms in those with insufficient levels, and there were less cases with fever or with >3 symptoms at day 14 for treatment with vitamin D.
May 2021, Sánchez-Zuno, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/11/2378, https://c19p.org/sanchezzuno
76. de Souza et al., Phase III, randomized, double-blind, placebo-controlled clinical study: a study on the safety and clinical efficacy of AZVUDINE in moderate COVID-19 patients
179 patient azvudine late treatment RCT: 82% improved recovery (p=0.01) and 13% faster viral clearance (p=0.03).RCT 179 hospitalized patients in Brazil, showing improved recovery with azvudine treatment.
Oct 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1215916/full, https://c19p.org/desouza2
77. Chahla et al., Randomized trials - Ivermectin repurposing for COVID-19 treatment of outpatients with mild disease in primary health care centers
254 patient ivermectin early treatment RCT: 87% higher hospital discharge (p=0.004).Cluster RCT outpatients in Argentina showing significantly faster recovery with ivermectin. There were no deaths. Outpatients in Tucumán were assigned to the ivermectin group and outpatients from San Miguel de Tucumán and Gran San Miguel de Tucumán were assigned to the control group. All comorbidities, percentage of male patients, and age were higher in the ivermectin group, favoring the control group.
Mar 2021, Research, Society and Development, https://rsdjournal.org/index.php/rsd/article/view/30844, https://c19p.org/chahla
78. Deftereos et al., Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial
105 patient colchicine late treatment RCT: 77% lower mortality (p=0.19), 82% lower ventilation (p=0.1), and 87% lower progression (p=0.05).RCT with 55 patients treated with colchicine and 50 control patients, showing lower mortality and ventilation with treatment.
Jun 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2767593, https://c19p.org/deftereos
4,922 patient metformin prophylaxis PSM study: 52% lower mortality (p=0.01), 54% lower ventilation (p=0.007), and 72% lower ARDS (p=0.04).
Retrospective 4,922 COVID-19 patients with type 2 diabetes in China, showing lower mortality with metformin and alpha-glucosidase inhibitor treatment and higher mortality with insulin treatment.
May 2024, Molecular Biomedicine, https://link.springer.com/10.1186/s43556-024-00183-1, https://c19p.org/xu13
80. Cousins et al., Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19
64,349 patient metformin prophylaxis PSM study: 50% lower ventilation (p=0.01) and 51% lower ICU admission (p<0.0001).PSM retrospective 64,349 COVID-19 patients in the USA, showing metformin associated with lower ICU admission and mechanical ventilation.
Jul 2022, Cell Reports Methods, https://www.sciencedirect.com/science/article/pii/S2667237523001327, https://c19p.org/cousinsmf
81. Nogués et al., Calcifediol Treatment and COVID-19-Related Outcomes
838 patient vitamin D late treatment study: 79% lower mortality (p=0.001) and 87% lower ICU admission (p<0.0001).Quasi-randomized trial with 930 hospitalized patients, 447 treated with calcifediol, showing significantly lower ICU admission and death with treatment. Note that the randomization in this trial is by ward. Authors report that patients were allocated to empty beds available at admission time regardless of patient conditions, and that staff in all wards followed the same protocol. The earlier preprint for this article was censored by the Lancet. The Lancet reportedly requested a review from a Twitter user that posted negative comments [github.com]. The review provides useful feedback for the authors to improve the reporting of the cluster nature of the RCT, and to explain the delay in registration, however it is highly unusual to censor a preprint in this way. Authors responded to the issues raised here: [pubpeer.com]
Jan 2021, The J. Clinical Endocrinology & Metabolism , https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgab405/6294179, https://c19p.org/nogues
82. Behera et al., Prophylactic Role of Ivermectin in Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Healthcare Workers
3,346 patient ivermectin prophylaxis study: 83% fewer cases (p=0.001).Prospective prophylaxis study with 3,532 healthcare workers, 2,199 receiving two-dose ivermectin prophylaxis, showing adjusted relative risk of confirmed COVID-19 with treatment 0.17 [0.12-0.23] p<0.001. 186 patients took only the first dose, and no significant difference was observed for this group. The same group published an earlier small study with 117 ivermectin patients. There were no serious adverse events. T/IM-NF/CM&FM/20/142.
Feb 2021, Cureus, https://www.cureus.com/articles/64807-prophylactic-role-of-ivermectin-in-severe-acute-respiratory-syndrome-coronavirus-2-infection-among-healthcare-workers, https://c19p.org/behera2
83. Pascual-Figal et al., Colchicine in Recently Hospitalized Patients with COVID-19: A Randomized Controlled Trial (COL-COVID)
103 patient colchicine late treatment RCT: 80% lower mortality (p=0.24), 80% lower ventilation (p=0.24), 87% improved 7-point scale results (p=0.03), and 15% longer hospitalization (p=0.34).RCT with 52 colchicine patients and 51 control patients, showing lower risk of clinical deterioration with treatment. COL-COVID. NCT04350320.
Sep 2021, Int. J. General Medicine, https://www.dovepress.com/colchicine-in-recently-hospitalized-patients-with-covid-19-a-randomize-peer-reviewed-fulltext-article-IJGM, https://c19p.org/pascualfigal
305 patient N-acetylcysteine early treatment RCT: 80% lower hospitalization (p=0.25) and 83% improved recovery (p<0.0001).
RCT 304 low-risk outpatients, 229 treated with N-acetylcysteine, l-carnitine tartrate, nicotinamide riboside chloride, and serine, showing significantly faster recovery with treatment. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism were significantly improved in treated patients.
Jun 2021, Advanced Science, https://onlinelibrary.wiley.com/doi/10.1002/advs.202101222, https://c19p.org/altay
248 patient ivermectin late treatment study: 87% lower mortality (p=0.02), 89% lower ICU admission (p=0.007), 83% lower progression (p=0.0004), and 87% improved recovery (p=0.02).
Retrospective 115 ivermectin patients and 133 control patients showing significantly lower death and faster viral clearance. Some potential issues and the authors' response can be found in [sciencedirect.com, sciencedirect.com].
Sep 2020, Archivos de Bronconeumología, https://www.archbronconeumol.org/en-ivermectin-treatment-may-improve-prognosis-articulo-S030028962030288X, https://c19p.org/khan
40 patient hydrogen peroxide late treatment RCT: 46% lower need for oxygen therapy (p<0.0001), 36% faster recovery (p<0.0001), and 45% faster viral clearance (p<0.0001).
RCT 40 patients in India, showing improved recovery with nebulized hydrogen peroxide.
Apr 2022, J. South Asian Federation of Obstetrics and Gynaecology, https://www.jsafog.com/doi/10.5005/jp-journals-10006-1986, https://c19p.org/agrawal
87. Koshak et al., Nigella sativa for the treatment of COVID-19: An open-label randomized controlled clinical trial
183 patient nigella sativa early treatment RCT: 75% lower hospitalization (p=0.37) and 43% improved recovery (p=0.0002).RCT 183 mild COVID-19 outpatients in Saudi Arabia, 91 treated with Nigella Sativa, showing lower hospitalization and faster recovery with treatment. 500mg Nigella Sativa oil (MARNYS Cuminmar) twice daily for 10 days. NCT04401202.
Aug 2021, Complementary Therapies in Medicine, https://www.sciencedirect.com/science/article/pii/S0965229921001102, https://c19p.org/koshak
88. Golan et al., Favipiravir in patients with early mild-to-moderate COVID-19: a randomized controlled trial
1,187 patient favipiravir early treatment RCT: 2% lower progression (p=1), 4% improved recovery (p=0.79), and 14% faster viral clearance (p<0.0001).RCT low-risk (1 death in the control arm) patients in the USA, showing no significant differences with favipiravir. A majority of trial outcomes were modified after completion: [clinicaltrials.gov]. 44% of patients had no detectable viral load at baseline in the viral shedding sub-study. The primary outcome required 4 days of sustained clinical recovery and occurred after a median of 7 days, suggesting there was limited room for improvement in the population studied. The percentages for viral clearance at day 10 do not match any number of the reported group sizes. Authors write "of the six RCTs conducted", however there has been at least 24 other RCTs at the time of publication [c19favipiravir.com]. 1800mg bid day 1, 800mg bid days 2-10.
Sep 2022, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac712/6692456, https://c19p.org/golan
754 patient HCQ late treatment RCT: 66% improved viral clearance (p<0.0001).
RCT 754 patients comparing HCQ+AZ along with other treatment groups using lopinavir/ritonavir and doxycycline to a control group taking AZ, finding significantly faster viral clearance with all treatment groups. (The labels in Figure 2 appear to be reversed).
Feb 2021, Biochemistry Research Int., https://www.hindawi.com/journals/bri/2021/6685921/, https://c19p.org/purwati
90. da Silva Santos et al., Beneficial effects of a mouthwash containing an antiviral phthalocyanine derivative on the length of hospital stay for COVID-19: randomised trial
41 patient phthalocyanine late treatment RCT: 85% lower mortality (p=0.23), 92% lower ICU admission (p=0.02), and 54% lower hospitalization (p=0.03).RCT 41 patients in Brazil, 20 treated with a phthalocyanine derivative mouthwash, showing shorter hosptalization and lower ICU admission with treatment. One minute gargling/rinsing 5 times per day.
Oct 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-99013-5, https://c19p.org/dasilvasantos
91. Pushkar et al., Study of Favipiravir Compared to Standard of Care in Hospitalized Patients With COVID-19
200 patient favipiravir late treatment RCT: 14% improved recovery (p=0.06), 70% higher hospital discharge (p=0.0001), 33% lower pneumonia (p=0.007), and 90% improved viral clearance (p<0.0001).RCT 200 patients showing improvements in clinical recovery and viral clearance with favipiravir. There is no paper available but results are posted in clinicaltrials.gov.
Nov 2020, NCT04542694, https://clinicaltrials.gov/ct2/show/results/NCT04542694?view=results, https://c19p.org/pushkar
92. Blum et al., Nitazoxanide superiority to placebo to treat moderate COVID-19 – A Pilot prove of concept randomized double-blind clinical trial
50 patient nitazoxanide late treatment RCT: 67% lower mortality (p=0.25), 62% lower ventilation (p=0.17), 20% lower severe cases, and 56% shorter hospitalization (p=0.02).RCT with 25 nitazoxanide patients and 25 control patients, showing improved virological and clinical outcomes with treatment. Authors also perform an in vitro study in Vero E6 cells showing 90% inhibition with 0.5µM, with no cytotoxicity. NCT04348409.
Jan 2021, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00261-3/fulltext, https://c19p.org/blum
93. Entrenas Castillo et al., Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study
76 patient vitamin D late treatment RCT: 85% lower mortality (p=0.11) and 94% lower ICU admission (p=0.008).RCT on calcifediol (25-hydroxyvitamin D) treatment for hospitalized COVID-19 patients showing significantly reduced intensive care unit admissions. All patients received standard care including HCQ+AZ. For additional analysis see Jungreis et al. [Jungreis].
Aug 2020, J. Steroid Biochemistry and Molecular Biology, 203, October 2020, https://www.sciencedirect.com/science/article/pii/S0960076020302764, https://c19p.org/entrenascastillo
94. Gérain et al., NASAFYTOL® supplementation in adults hospitalized with COVID-19 infection: results from an exploratory open-label randomized controlled trial
49 patient curcumin late treatment RCT: 91% lower combined mortality/ICU admission (p=0.02), 89% lower ventilation (p=0.05), 89% lower ICU admission (p=0.05), and 73% higher hospital discharge (p=0.07).RCT 49 hospitalized COVID-19 patients, 25 treated with curcumin and quercetin, shower lower mortality/ICU admission and improved recovery with treatment. All patients received vitamin D. 336mg curcumin, 520mg quercetin, and 18μg vitamin D3 daily for 14 days. The control arm received 20μg vitamin D3 daily. Baseline fever favored treatment while vaccination favored control.
Jun 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1137407/full, https://c19p.org/geraint
95. Gérain et al., NASAFYTOL® supplementation in adults hospitalized with COVID-19 infection: results from an exploratory open-label randomized controlled trial
49 patient quercetin late treatment RCT: 91% lower combined mortality/ICU admission (p=0.02), 89% lower ventilation (p=0.05), 89% lower ICU admission (p=0.05), and 73% higher hospital discharge (p=0.07).RCT 49 hospitalized COVID-19 patients, 25 treated with curcumin and quercetin, shower lower mortality/ICU admission and improved recovery with treatment. All patients received vitamin D. 336mg curcumin, 520mg quercetin, and 18μg vitamin D3 daily for 14 days. The control arm received 20μg vitamin D3 daily. Baseline fever favored treatment while vaccination favored control.
Jun 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1137407/full, https://c19p.org/gerain
490 patient ivermectin late treatment RCT: 69% lower mortality (p=0.09), 59% lower ventilation (p=0.17), 22% lower ICU admission (p=0.79), and 31% lower progression (p=0.29).
RCT 490 late stage (>65% lung change chest radiography at baseline) hospitalized patients in Malaysia, showing no significant differences. Mortality was 1.2% for ivermectin vs. 4% for control. If the same event rates continue, the trial would need to add ~13% more patients to reach statistical significance. i.e., by continuing the trial for ~2 weeks, there is a reasonable chance of the result being a statistically significant ~69% reduction in mortality, which would equate to ~4 million lives saved if adopted at the start of the pandemic. The mortality reduction is consistent with the results from all trials to date. While not reaching the significance threshold with the specified test, Bayesian analysis shows a 97% probability that ivermectin reduces mortality [normanfenton.com]. Authors describe the mortality results as "similar" and they are not mentioned in the visual abstract or the conclusion, suggesting substantial investigator bias with a preference for a null..
Nov 2021, JAMA, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2789362, https://c19p.org/lim
1,856 patient budesonide late treatment RCT: 39% lower mortality (p=0.45), 6% lower ventilation (p=1), 52% lower ICU admission (p=0.07), and 25% lower combined mortality/hospitalization (p=0.96).
Results from the PRINCIPLE trial, 1,073 treated with budesonide starting a median of 6 days after symptom onset, showing lower hospitalization/death, and faster recovery with treatment.
Apr 2021, The Lancet, https://www.sciencedirect.com/science/article/pii/S014067362101744X, https://c19p.org/yu3
89 patient ivermectin early treatment RCT: 70% lower hospitalization (p=0.34) and 62% improved viral clearance (p=0.02).
Double blind RCT for mild-moderate COVID-19 outpatients in Israel showing significantly faster reduction in viral load with treatment, and lower hospitalization with treatment. The one treatment hospitalization was a few hours after treatment and the patient improved and was discharged quickly. Authors also examine culture viability on days 2-6, with 13% positive in the ivermectin group vs. 48% in the control group. There were no safety issues. Ivermectin was taken one hour before a meal. Sheba IRB-7156/20.
Feb 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S120197122200399X, https://c19p.org/biber
99. Ashraf et al., Honey and Nigella sativa against COVID-19 in Pakistan (HNS-COVID-PK): A multi-center placebo-controlled randomized clinical trial
313 patient nigella sativa early treatment RCT: 82% lower mortality (p=0.01), 84% improved recovery (p<0.0001), and 82% improved viral clearance (p<0.0001).RCT with 157 patients treated with honey and nigella sativa, and 156 control patients, showing significantly faster recovery and viral clearance. Honey (1gm/kg/day) plus encapsulated nigella sativa seeds (80mg/kg/day) orally in 2-3 divided doses daily for up to 13 days.
Nov 2020, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7640, https://c19p.org/ashraf2
100. Bozek et al., Montelukast’s ability to fight COVID-19 infection
445 patient montelukast prophylaxis study: 91% lower hospitalization (p=0.02) and 82% fewer cases (p=0.004).Retrospective 445 elderly patients with severe asthma showing reduced risk of COVID-19 infection with montelukast treatment.
Sep 2020, J. Asthma, https://www.tandfonline.com/doi/full/10.1080/02770903.2020.1786112, https://c19p.org/bozek
101. Sugimoto et al., Biguanides Associate with Decreased Early Mortality and Risk of Acute Kidney Injury In Hospitalized COVID-19 Patients: a nationwide retrospective cohort study in Japan
168,550 patient metformin late treatment study: 40% lower mortality (p<0.0001).Retrospective 168,370 hospitalized COVID-19 patients with diabetes in Japan showing lower mortality and reduced risk of acute kidney injury with biguanide (likely primarily or only metformin) use. Authors hypothesize that metformin's activation of AMPK in renal tubular epithelium may provide a protective effect against COVID-19-induced kidney damage.
Jul 2024, medRxiv, https://www.medrxiv.org/content/10.1101/2024.07.20.24310736v1, https://c19p.org/sugimoto
102. Mokhtari et al., Clinical outcomes of patients with mild COVID-19 following treatment with hydroxychloroquine in an outpatient setting
28,759 patient HCQ early treatment study: 70% lower mortality (p<0.0001) and 35% lower hospitalization (p<0.0001).Retrospective 28,759 adult outpatients with mild COVID-19 in Iran, 7,295 treated with HCQ, showing significantly lower hospitalization and mortality with treatment.
Apr 2021, Int. Immunopharmacology, https://www.sciencedirect.com/science/article/pii/S1567576921002721, https://c19p.org/mokhtari
103. Wang et al., Modifiable lifestyle factors and the risk of post-COVID-19 multisystem sequelae, hospitalization, and death
68,896 patient sleep study: 19% lower mortality (p=0.0008), 15% lower hospitalization (p<0.0001), and 23% lower PASC (p<0.0001).Prospective study of 68,896 UK Biobank participants with COVID-19 showing adherence to a healthy lifestyle prior to infection, characterized by 10 factors including adequate physical activity and sleep, not smoking, and a healthy BMI, was associated with a significantly lower risk of mortality, hospitalization, and post-COVID multisystem sequelae. Risk decreased monotonically for increasing numbers of healthy lifestyle factors from 5-10. Reduced risks were evident across cardiovascular, metabolic, neurologic, respiratory, and other disorders over 210 days following infection, during both acute and post-acute phases, regardless of age, sex, ethnicity, test setting, vaccination status, or SARS-CoV-2 variant.
Jan 2024, Nature Communications, https://www.nature.com/articles/s41467-024-50495-7, https://c19p.org/wang24sl
104. Mody et al., Effect of 8.4% Soda-Bicarbonate Steam Inhalation on the Course of Disease in Mild to Moderate Cases of Covid-19
60 patient alkalinization late treatment RCT: 64% greater improvement (p=0.0007).RCT 60 hospitalized patients in India, showing significantly greater clinical improvement with inhaled sodium bicarbonate. Nasal and oral inhalation of nebulized 50ml 8.4% sodium bicarbonate for 5 minutes twice daily for 5 days.
Mar 2021, Acta Scientific Orthopaedics, https://actascientific.com/ASOR/ASOR-04-0290.php, https://c19p.org/mody2
105. Mody et al., Effect of 8.4% Soda-Bicarbonate Steam Inhalation on the Course of Disease in Mild to Moderate Cases of Covid-19
60 patient sodium bicarbonate late treatment RCT: 64% greater improvement (p=0.0007).RCT 60 hospitalized patients in India, showing significantly greater clinical improvement with inhaled sodium bicarbonate. Nasal and oral inhalation of nebulized 50ml 8.4% sodium bicarbonate for 5 minutes twice daily for 5 days.
Mar 2021, Acta Scientific Orthopaedics, https://actascientific.com/ASOR/ASOR-04-0290.php, https://c19p.org/mody2sb
106. Khunti et al., Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England
2,851,465 patient metformin prophylaxis study: 23% lower mortality (p<0.0001).Retrospective 2,851,465 people with type 2 diabetes in the UK, showing lower mortality with existing metformin use. Results are subject to confounding by indication because metformin is typically used early in the progression of type 2 diabetes.
Mar 2021, The Lancet Diabetes & Endocrinology, https://www.thelancet.com/journals/landia/article/PIIS2213-8587(21)00050-4/fulltext, https://c19p.org/khunti
107. de Jesús Ascencio-Montiel et al., A Multimodal Strategy to Reduce the Risk of Hospitalization/death in Ambulatory Patients with COVID-19
28,048 patient ivermectin early treatment study: 59% lower combined mortality/hospitalization (p<0.0001), 15% lower mortality (p=0.16), 9% lower ventilation (p=0.51), and 48% lower hospitalization (p<0.0001).Retrospective 28,048 COVID+ patients in Mexico, 7,898 receiving a treatment kit including low dose ivermectin, AZ, aspirin, and acetaminophen, shower lower mortality/hospitalization for those receiving the kit. Delivery of the treatment kit was based on availability in the medical units. Adherence is unknown and may be low. Adjusted results are only provided for combined mortality/hospitalization.
Jan 2022, Archives of Medical Research, https://www.sciencedirect.com/science/article/pii/S0188440922000029, https://c19p.org/dejesusascenciomontiel
108. Mitjà et al., A Cluster-Randomized Trial of Hydroxychloroquine as Prevention of Covid-19 Transmission and Disease
2,497 patient HCQ prophylaxis RCT: 46% lower mortality (p=0.39), 17% lower hospitalization (p=0.71), and 32% fewer cases (p=0.27).For positive symptomatic cases, a greater effect is seen for nursing home residents, RR=0.49 [0.21 - 1.17], vs. overall 0.89, possibly because the exposure events are identified faster in this context, versus home exposure where testing of the source may be more delayed. The trial is too small for significance here. If the trend continued this result would be significant at p<0.05 after about 25% more patients were added. There are 2 groups in this study: PCR+ at baseline (n=314) and PCR- at baseline (n=2000), which should be separated as they are different populations (primary outcome rates 18.6% and 22.2% compared to 3.0% and 4.3%). PCR+ already have COVID-19, so PEP analysis should be for the 2,000 PCR-, showing symptomatic COVID-19 of 4.3% (control) and 3.0% (treatment), RR 0.7, p=0.154. The paper has different RR values here, stating that they are adjusted for contact-level variables. It is not clear how they are computed - the adjusted RR for the overall sample is 4% lower, for..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2021801, https://c19p.org/mitjapep
109. Sokhela et al., Randomized clinical trial of nitazoxanide or sofosbuvir/daclatasvir for the prevention of SARS-CoV-2 infection
505 patient nitazoxanide prophylaxis RCT: 66% lower mortality (p=1), 79% lower hospitalization (p=0.5), 17% fewer symptomatic cases (p=0.49), and 21% more cases (p=0.67).Prophylaxis RCT 828 high-risk participants in South Africa, showing no significant difference with nitazoxanide and sofosbuvir/daclatasvir treatment. FLU-PRO results were available for 74% of the nitazoxanide arm compared to 54% of the control arm.
Aug 2022, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkac266/6661458, https://c19p.org/sokhela
110. Wolak et al., A safety evaluation of intermittent high-dose inhaled nitric oxide in viral pneumonia due to COVID-19: a randomised clinical study
35 patient nitric oxide late treatment RCT: 64% lower need for oxygen therapy (p=0.03) and 41% shorter hospitalization (p=0.24).RCT 35 hospitalized patients with viral pneumonia (34 with COVID-19) showing improved recovery with high-dose inhaled nitric oxide (iNO) treatment. The treatment group received intermittent inhalations of 150 ppm iNO for 40 minutes, 4 times daily for up to 7 days. The treatment group had significantly reduced oxygen support duration and a greater number of patients reaching oxygen saturation ≥93%. There was also a trend towards earlier hospital discharge in the iNO group, without statistical significance. The study was terminated early. There was no ICU admission or mortality in either group.
Jul 2024, Scientific Reports, https://www.nature.com/articles/s41598-024-68055-w, https://c19p.org/wolak
111. Götberg et al., Effect of Adding Losartan to Standard of Care Treatment on the Risk of Death and Icu Admission Among Hospitalized COVID-19 Patients: A Randomized Trial
300 patient losartan late treatment RCT: 77% lower ventilation (p=0.01) and 36% lower ICU admission (p=0.24).RCT 302 hospitalized COVID-19 patients showing lower mechanical ventilation but no significant difference in ICU admission or mortality with losartan treatment.
Dec 2022, SSRN Electronic J., https://www.ssrn.com/abstract=4278529, https://c19p.org/gotberg
112. Hunt et al., Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans
26,508 patient metformin early treatment study: 67% lower mortality (p<0.0001).Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including metformin. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/huntmf
113. Guo et al., Effects of Metformin on COVID-19 Patients with Type 2 Diabetes: A Retrospective Study
571 patient metformin prophylaxis study: 62% lower combined mortality/intubation (p=0.03) and 81% lower progression (p=0.003).Retrospective 571 type 2 diabetes patients with COVID-19 in China, showing lower combined mortality/mechanical ventilation with metformin.
Aug 2023, Diabetes, Metabolic Syndrome and Obesity, https://www.dovepress.com/effects-of-metformin-on-covid-19-patients-with-type-2-diabetes-a-retro-peer-reviewed-fulltext-article-DMSO, https://c19p.org/guo2
1,323 patient azithromycin late treatment RCT: 16% lower need for oxygen therapy (p=0.69), 9% lower hospitalization (p=0.87), and 7% improved recovery (p=0.23).
RCT 1,388 outpatients in the UK showing no significant benefit with azithromycin. There was no significant difference in time to first reported recovery or risk of hospitalization or death by 28 days with azithromycin compared to usual care alone. Only 31% of participants had PCR-confirmed SARS-CoV-2 infection.
Mar 2021, The Lancet, https://www.sciencedirect.com/science/article/pii/S014067362100461X, https://c19p.org/butler4az
115. Karolyi et al., Camostat Mesylate Versus Lopinavir/Ritonavir in Hospitalized Patients With COVID-19—Results From a Randomized, Controlled, Open Label, Platform Trial (ACOVACT)
201 patient camostat late treatment RCT: 72% lower mortality (p=0.1), 70% lower ventilation (p=0.02), 60% lower combined mortality/intubation (p=0.04), and 18% faster recovery (p=0.005).RCT 201 hospitalized COVID-19 patients showing faster clinical improvement, less progression to mechanical ventilation or death, and shorter hospital stay with camostat mesylate compared to lopinavir/ritonavir. There was also a trend towards lower 29-day mortality with camostat. Authors note that the lopinavir/ritonavir dose likely did not reach effective levels, so it may be considered similar to a placebo group.
Jul 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.870493/full, https://c19p.org/karolyi
116. Huang et al., Efficacy and safety of ultra-short wave diathermy on COVID-19 pneumonia: a pioneering study
50 patient thermotherapy late treatment RCT: 67% improved recovery (p=0.002).RCT 50 hospitalized COVID-19 pneumonia patients showing faster recovery with ultra-short wave diathermy (USWD). The USWD group received standard treatment plus USWD applied to the chest for 10 minutes twice daily for 12 days. The USWD group had significantly faster clinical recovery by 6.7 days, lower systemic inflammation, and better outcomes on the 7-point clinical status scale on days 21 and 28 compared to the control group receiving only standard treatment. There was no significant difference in SARS-CoV-2 viral clearance. Pulmonary fibrosis observed prior to treatment was recovered in most patients in both groups, alleviating concerns over potential harms of USWD. Baseline severe cases were more common in the treatment group, 52 vs. 28%.
Jan 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1149250/full, https://c19p.org/huang11
117. Moon et al., Association between ursodeoxycholic acid use and COVID-19 in individuals with chronic liver disease: a nationwide case-control study in South Korea
74,074 patient ursodeoxycholic acid prophylaxis PSM study: 33% lower severe cases (p=0.04) and 20% fewer cases (p<0.0001).Retrospective 74,074 individuals with chronic liver disease in South Korea, showing lower risk of COVID-19 infection and related severe outcomes with ursodeoxycholic acid (UDCA) use. The risk reduction was dose-dependent, with greater benefits seen with higher UDCA exposure. Authors hypothesize that UDCA may reduce viral entry by downregulating the ACE2 receptor and modulate the cytokine storm implicated in severe COVID-19.
Aug 2024, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-024-02464-1, https://c19p.org/moon
118. Yu et al., Beneficial effects exerted by hydroxychloroquine in treating COVID-19 patients via protecting multiple organs
2,882 patient HCQ late treatment study: 83% lower progression (p=0.05) and 85% lower mortality (p=0.02).Retrospective 2,882 patients in China, median age 62, 278 receiving HCQ, median 10 days post hospitalization, showing that HCQ treatment can reduce systemic inflammation and inhibit the cytokine storm, thus protecting multiple organs from inflammatory injuries, such as detoxification in the liver and attenuation of cardiac injury. IL-6 levels significantly reduced after HCQ treatment, p<0.05, and elevated after HCQ withdrawal. The significantly lower dose used here is potentially related to the different observations from the RECOVERY trial results. Authors suggest that treatment should be started as soon as possible. The 550 patients that were critically ill at baseline are reported in a separate paper. For the non-critically-ill patients at baseline, the proportion of patients that became critically ill was significantly lower for those treated with HCQ. For the subset of patients that started HCQ treatment early only 1.4% died versus 3.9% for HCQ started late and 9.1% for control..
Aug 2020, Science China Life Sciences, 2020 Aug 3, https://link.springer.com/article/10.1007/s11427-020-1782-1, https://c19p.org/yu2
119. Šebić et al., Influence of the Level of Physical Activity on Symptoms and Duration of Recovery From Covid-19
100 patient exercise study: 89% lower need for oxygen therapy (p=0.05), 91% lower hospitalization (p=0.02), 84% lower progression (p<0.0001), and 47% improved recovery (p=0.0002).Retrospective 100 COVID-19 patients in Bosnia and Herzegovina, showing lower symptom severity and faster recovery with a history of regular physical activity.
Jul 2023, Sports Science and Health, https://doisrpska.nub.rs/index.php/sportskenaukeizdravlje/article/view/9896, https://c19p.org/sebic
120. Vila Méndez et al., Efficacy of Bromhexine versus Standard of Care in Reducing Viral Load in Patients with Mild-to-Moderate COVID-19 Disease Attended in Primary Care: A Randomized Open-Label Trial
191 patient bromhexine early treatment RCT: 67% lower hospitalization (p=0.49) and 7% worse viral clearance (p=0.82).RCT 191 low risk (no mortality) outpatients in Spain, showing no significant differences with bromhexine. Authors note that "statistical differences between the study groups were observed in the percentage of patients treated with bronchodilators (p = 0.033) and receiving symptomatic treatment (p = 0.034), which were higher in the SOC alone group", but do not provide details or perform adjustments. There were more moderate/severe cases in the treatment group (9 vs. 5). Many results appear to be missing including: reduction in the severity of each symptom (0–10 NRS score) at days 4, 7, 14, and 28 as compared with baseline; proportion of patients with clinical improvement and time to clinical improvement; proportion of patients with disappearance of each symptom at days 4, 7, 14, and 28, and time to disappearance; proportion of asymptomatic patients at days 4, 7, 14, and 28. Bromhexine 48 mg/day for seven days. SOC included acetaminophen.
Dec 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/1/142, https://c19p.org/vilamendez
120 patient curcumin late treatment RCT: 86% lower mortality (p=0.24), 86% lower ventilation (p=0.24), 10% shorter hospitalization (p=0.4), and 32% faster recovery (p=0.001).
RCT with 60 hospitalized patients treated with Ayurcov and 60 control patients in India, showing improved viral clearance and faster symptom resolution in the mild/moderate group, but no significant differences in the severe group. Ayurcov contains curcuma longa, go ark, sphatika (alum), sita (rock candy), godugdham (bos indicus) milk, and goghritam (bos indicus ghee).
Mar 2022, Complementary Therapies in Medicine, https://www.sciencedirect.com/science/article/pii/S0965229922000267, https://c19p.org/sankhe2
864 patient HCQ late treatment study: 80% lower mortality (p<0.0001), 20% lower progression (p=0.43), and 31% faster viral clearance (p=0.26).
Retrospective 863 COVID-19 patients in Burkina Faso, showing lower mortality, lower progression for outpatients, and faster viral clearance with HCQ/CQ treatment. Only the lower mortality was statistically significant. NCT04445441.
Feb 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222001114, https://c19p.org/rouamba
123. Pantazopoulos et al., A Hypertonic Seawater Nasal Irrigation Solution Containing Algal and Herbal Natural Ingredients Reduces Viral Load and SARS-CoV-2 Detection Time in the Nasal Cavity
56 patient alkalinization late treatment RCT: 42% improved viral clearance (p=0.04).RCT 56 severe COVID-19 patients, showing significantly decreased viral load with Sinomarin Plus Algae nasal irrigation. Sinomarin Plus Algae is a hypertonic seawater solution with algal and herbal natural ingredients with a pH of 7.5-8 [sinomarin.com]. The treatment group received nasal irrigation every 4 hours, 16 hours per day, for 2 days. Nasopharyngeal swabs were taken at baseline and 48 hours later to measure viral load. The treatment group showed a significant increase in cycle threshold values, indicating decreased viral load, while no difference was seen in the control group. The treatment was well tolerated with only mild adverse effects. Alkalinization is one possible mechanism of action - SARS-CoV-2 requires acidic pH for infection [Kreutzberger] and the solution has pH 7.5-8. Other possible mechanisms include antiviral activity of ingredients (e.g., fucoidan from Undaria pinnatifida) and physical removal of viral particles.
Jul 2023, J. Personalized Medicine, https://www.mdpi.com/2075-4426/13/7/1093, https://c19p.org/pantazopoulos
124. Di Fenza et al., High-Dose Inhaled Nitric Oxide in Acute Hypoxemic Respiratory Failure Due to COVID-19: A Multicenter Phase II Trial
193 patient nitric oxide ICU RCT: 23% lower mortality (p=0.36), 30% lower progression (p=0.67), and 83% improvement (p=0.01).RCT 193 mechanically ventilated COVID-19 patients showing improved oxygenation at 48 hours but no difference in mortality with high-dose (80ppm) inhaled nitric oxide (NO) for 48 hours. The NO group had a higher proportion attaining PaO2/FiO2 > 300 mmHg and reduced rates of neurologic symptoms at 90 days. NO was associated with faster viral clearance. No serious adverse events were reported with NO.
Dec 2023, American J. Respiratory and Critical Care Medicine, https://www.atsjournals.org/doi/10.1164/rccm.202304-0637OC, https://c19p.org/difenza
125. Elamir et al., A Randomized Pilot Study Using Calcitriol in Hospitalized Patients
50 patient vitamin D late treatment RCT: 86% lower mortality (p=0.23), 38% lower ICU admission (p=0.33), 40% shorter hospitalization (p=0.14), and 86% improved recovery (p=0.03).RCT 50 hospitalized patients in the USA, 25 treated with calcitriol, showing significantly improved oxygenation with treatment. Mortality, intubation, ICU admission, and hospitalization time also favored treatment, while not reaching statistical significance with the very small sample size.
Sep 2021, Bone, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425676/, https://c19p.org/elamir
126. Tian et al., Efficacy and safety of short-wave diathermy treatment for moderate COVID-19 patients: a prospective, double-blind, randomized controlled clinical study
40 patient diathermy late treatment RCT: 84% lower ventilation (p=0.09), 76% lower ICU admission (p=0.07), and 67% improved recovery (p=0.005).RCT 42 moderate COVID-19 inpatients showing significantly faster clinical and CT scan improvement with short-wave diathermy (SWD) treatment added to standard care, compared to placebo SWD plus standard care. 92.6% of the SWD group had clinical improvement at 14 days, compared to 69.2% in the control group. The SWD group also had significantly faster CT scan improvement. There was no significant difference in adverse events between groups, with only minor side effects like headache and dizziness reported.
Mar 2022, European J. Physical and Rehabilitation Medicine, https://www.minervamedica.it/index2.php?show=R33Y2022N01A0137, https://c19p.org/tian2
127. Kerr et al., Ivermectin Prophylaxis Used for COVID-19: A Citywide, Prospective, Observational Study of 223,128 Subjects Using Propensity Score Matching
159,561 patient ivermectin prophylaxis PSM study: 70% lower mortality (p<0.0001), 67% lower hospitalization (p<0.0001), and 44% fewer cases (p<0.0001).PSM retrospective 220,517 patients in Brazil,133,051 taking ivermectin as part of a citywide prophylaxis program, showing significantly lower hospitalization and mortality with treatment. Additional results are presented here: [odysee.com], including improved efficacy with analysis based on irregular/regular use, and a strong dose-response relationship. Confirmation from independent analysis of the raw data: [web.archive.org]. See [Mills] regarding [medrxiv.org].
Dec 2021, Cureus, https://www.cureus.com/articles/82162-ivermectin-prophylaxis-used-for-covid-19-a-citywide-prospective-observational-study-of-223128-subjects-using-propensity-score-matching, https://c19p.org/kerr
237 patient vitamin C early treatment RCT: 31% improved recovery (p=0.008).
RCT 237 patients in Turkey, 162 treated with IV vitamin C in addition to HCQ/AZ/zinc/vitamin D used for all patients, showing significantly faster recovery with the addition of IV vitamin C. 97% of patients were vitamin D deficient, and lower vitamin D levels were associated with ICU admission and longer hospital stay. Only 1 of 237 hospitalized patients died (average age 63, range 22-99) - a 70-year-old patient with heart and lung disease and severely deficient vitamin D levels (6 nmol/L). IV vitamin C (sodium ascorbate) was given as 50 mg/kg every six hours on day 1, followed by 100 mg/kg every six hours (four times daily, 400 mg/kg/day) for seven days. NCT04395768.
Nov 2021, Cureus, https://www.cureus.com/articles/76496-therapies-to-prevent-progression-of-covid-19-including-hydroxychloroquine-azithromycin-zinc-and-vitamin-d3-with-or-without-intravenous-vitamin-c-an-international-multicenter-randomized-trial, https://c19p.org/ried
129. Aref et al., Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19
114 patient ivermectin early treatment RCT: 63% improved recovery (p=0.0001) and 79% improved viral clearance (p=0.004).RCT 114 patients in Egypt, 57 treated with ivermectin mucoadhesive nanosuspension intranasal spray, showing faster recovery and viral clearance with treatment. NCT04716569.
Jun 2021, Int. J. Nanomedicine, https://www.dovepress.com/clinical-biochemical-and-molecular-evaluations-of-ivermectin-mucoadhes-peer-reviewed-fulltext-article-IJN, https://c19p.org/aref
130. Sankhe et al., A prospective, multi center, single blind, randomized controlled study evaluating “AyurCoro3” as an adjuvant in the treatment of mild to moderate COVID
174 patient curcumin early treatment RCT: 89% lower mortality (p=0.12), 75% lower ventilation (p=0.37), 46% improved recovery (p=0.002), and 10% shorter hospitalization (p=0.4).RCT 174 patients in India, 87 treated with AyurCoro-3 (turmeric, gomutra, potassium alum, khadisakhar, bos indicus milk, ghee), showing faster recovery with treatment. EC/NEW/INST/2019/245.
Aug 2021, J. Ayurveda and Integrated Medical Sciences, https://jaims.in/jaims/article/view/1386/1425, https://c19p.org/sankhe
131. Pourdowlat et al., Efficacy and safety of colchicine treatment in patients with COVID-19: A prospective, multicenter, randomized clinical trial
202 patient colchicine late treatment RCT: 73% lower hospitalization (p=0.004) and 38% improved recovery (p=0.03).RCT 202 patients in Iran, 102 treated with colchicine, showing lower hospitalization and improved clinical outcomes with treatment.
Feb 2022, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7319?af=R, https://c19p.org/pourdowlat
132. Green et al., A higher frequency of physical activity is associated with reduced rates of SARS-CoV-2 infection
113,075 patient exercise study: 42% fewer cases (p<0.0001).Retrospective 113,075 people in Israel, showing lower risk of COVID-19 cases with physical activity and a dose dependent response.
Nov 2022, European J. General Practice, https://www.tandfonline.com/doi/full/10.1080/13814788.2022.2138855, https://c19p.org/green
133. Muñoz-Vergara et al., Prepandemic Physical Activity and Risk of COVID-19 Diagnosis and Hospitalization in Older Adults
61,557 patient exercise study: 27% lower hospitalization (p=0.002) and 9% fewer cases (p=0.004).Prospective study of 61,557 adults aged 45+ years showing reduced risk of COVID-19 diagnosis and hospitalization for those meeting physical activity guidelines of ≥7.5 MET-hours/week before the pandemic compared to inactive individuals.
Feb 2024, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2814993, https://c19p.org/munozvergara
134. Stewart et al., Higher-Dose Fluvoxamine and Time to Sustained Recovery in Outpatients With COVID-19
1,175 patient fluvoxamine late treatment RCT: 31% lower progression (p=0.34), 34% improved recovery (p=0.32), and 49% lower hospitalization (p=0.59).Late treatment low risk population RCT showing lower progression to hospitalization or urgent care/ER visits with fluvoxamine, without statistical significance. There was no mortality and only three hospitalizations. Authors provide no details on the cause of hospitalization, but they appear to be unrelated to COVID-19. eFigure 5 shows no COVID-19 clinical progression to hospitalization (note that a hospitalization can be seen in the equivalent plot for the low dose arm), and the text indicates that the "COVID clinical progression scale simplified into a self-reported evaluation of home levels (limited vs not)". Note that the urgent care/ER visit outcome is also likely diluted due to inclusion of all-cause events, and could be statistically significant for only COVID-19 events. The sustained recovery outcome, which shows no difference, was a post-hoc creation used to hide efficacy for ivermectin, and is not logical for evaluating efficacy in this trial. The..
Sep 2023, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2812204, https://c19p.org/stewart8
135. Marcus et al., Predictors of incident viral symptoms ascertained in the era of COVID-19
14,335 patient exercise study: 42% fewer symptomatic cases (p<0.0001).Prospective survey based study with 14,335 participants, showing lower risk of viral symptoms with regular exercise.
Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253120, https://c19p.org/marcus
136. Ahmadi et al., Lifestyle risk factors and infectious disease mortality, including COVID-19, among middle aged and older adults: Evidence from a community-based cohort study in the United Kingdom
468,569 patient exercise study: 30% lower mortality (p=0.005).Retrospective 468,569 adults in the UK, showing significantly lower COVID-19 mortality with physical activity.
Aug 2021, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912100180X, https://c19p.org/ahmadi2
137. Gertner et al., Colchicine and/or Naltrexone for Hospitalized COVID-19 Patients Not Requiring High Levels of Ventilatory Support (COLTREXONE): A Prospective, Randomized, Open-Label Trial
137 patient colchicine late treatment RCT: 65% lower ICU admission (p=0.11), 43% improved recovery (p=0.14), 34% lower need for oxygen therapy (p=0.34), and 20% shorter hospitalization (p=0.13).Open-label RCT 137 hospitalized COVID-19 patients, showing lower progression to ICU/step-down ICU and improved recovery with colchicine, both without statistical significance. The primary outcome was changed mid-trial due to the low number of patients progressing to severe disease.
May 2024, Cureus, https://www.cureus.com/articles/240800-colchicine-andor-naltrexone-for-hospitalized-covid-19-patients-not-requiring-high-levels-of-ventilatory-support-coltrexone-a-prospective-randomized-open-label-trial, https://c19p.org/gertner
3,462 patient azithromycin late treatment study: 67% lower mortality (p=0.0001).
Retrospective 3,462 hospitalized COVID-19 patients across 13 states in Nigiera, showing lower mortality with AZ. Authors note the worse results with a combination of CQ/HCQ and AZ, compared to either alone, may be related to the side effects becoming more significant for late stage patients.
May 2023, Nigerian Medical J., https://nigerianmedjournal.org/index.php/nmj/article/view/174, https://c19p.org/yilgwanazaz
139. Ameri et al., Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial
226 patient melatonin ICU RCT: 29% lower mortality (p<0.0001), 28% lower ventilation (p=0.003), 25% improved recovery (p=0.001), and 29% shorter hospitalization (p=0.03).RCT 226 ICU patients in Iran, showing lower mortality with melatonin treatment.
Nov 2022, Inflammopharmacology, https://link.springer.com/10.1007/s10787-022-01096-7, https://c19p.org/ameri
140. Xu et al., Systematic evaluation of therapeutic effectiveness of Azvudine in treating COVID-19 hospitalized patients: a retrospective cohort study
264 patient azvudine late treatment PSM study: 75% lower mortality (p=0.02) and 63% lower progression (p=0.02).Retrospective 264 hospitalized COVID-19 patients in China showing lower risk of composite disease progression and all-cause mortality with azvudine treatment.
Nov 2024, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2024.1453234/full, https://c19p.org/xu17
441 patient HCQ late treatment RCT: 24% lower hospitalization (p=0.57) and 4% improved viral clearance (p=0.1).
Early terminated RCT in Brazil showing lower mortality and hospitalization with HCQ, but not reaching statistical significance. Although the title includes "early treatment", treatment was relatively late, with most patients being over 5 days from the onset of symptoms. Adverse events were lower in the HCQ group compared to the control group. This trial appears to have been terminated at 45% enrollment while showing ≥70% probability of superiority. The futility threshold was not reported, but it would be highly unusual for it to be as high as 70% [doyourownresearch.substack.com]. The paper indicates the placebo was talc, however the trial protocol shows the "placebo" as vitamin C, for which there are 7 COVID-19 treatment studies as of April 2021 that collectively show significant efficacy. Results differ significantly from those reported prior to publication. Prior to publication, authors reported an RR for hospitalization or death of 1.0 [0.45-2.21] [ajtmh.org].
Apr 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2779044, https://c19p.org/reis
142. De Niet et al., Positive Effects of Vitamin D Supplementation in Patients Hospitalized for COVID-19: A Randomized, Double-Blind, Placebo-Controlled Trial
43 patient vitamin D late treatment RCT: 45% faster recovery (p=0.06) and 50% shorter hospitalization (p=0.003).RCT with 21 vitamin D and 22 placebo hospitalized patients in Belgium with vitamin D deficiency, showing significantly shorter hospitalization and improved clinical recovery with treatment.
Jul 2022, Nutrients, https://www.mdpi.com/2072-6643/14/15/3048, https://c19p.org/deniet
143. Aghasadeghi et al., Effect of high-dose Spirulina supplementation on hospitalized adults with COVID-19: a randomized controlled trial
189 patient spirulina late treatment RCT: 85% lower mortality (p=0.0002) and 75% higher hospital discharge (p=0.003).RCT 189 hospitalized COVID-19 patients showing lower mortality and faster recovery with spirulina. Spirulina treatment also resulted in greater reductions in inflammatory markers such as IL-6, TNF-a, IP-10, CRP, ESR, and ferritin. All patients received remdesivir. Spirulina contains many components including calcium spirulan, a sulfated polysaccharide shown to inhibit the replication of various enveloped viruses in vitro, and many nutrients showing benefits for COVID-19 including vitamins A, C, and D, selenium, and zinc.
Apr 2024, Frontiers in Immunology, https://www.frontiersin.org/articles/10.3389/fimmu.2024.1332425/full, https://c19p.org/aghasadeghispi
144. Corradini et al., Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI)
1,713 patient HCQ late treatment study: 70% lower mortality (p<0.0001).Retrospective 3,044 hospitalized COVID-19 patients in Italy, showing HCQ significantly associated with survival in light, mild, and moderate cases in multivariable analysis, but not in severe cases.
Apr 2021, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-021-02742-8, https://c19p.org/corradini
145. Silveira et al., Standardized Brazilian green propolis extract (EPP-AF®) in COVID-19 outcomes: a randomized double-blind placebo-controlled trial
188 patient propolis late treatment RCT: 22% lower ventilation (p=0.54), 11% lower ICU admission (p=0.65), 16% shorter hospitalization (p=0.19), and 68% improvement (p=0.02).RCT 188 patients in Brazil, showing shorter hospitalization and improved outcomes with propolis, but without statistical significance. The incidence of secondary infections was significantly lower in the treatment group.
Oct 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-43764-w, https://c19p.org/silveira
146. Hunt et al., Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans
26,508 patient antihistamine H1RA prophylaxis study: 43% lower mortality (p<0.0001).Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including antihistamines. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/hunth1
147. Ventura-López et al., Treatment with metformin glycinate reduces SARS-CoV-2 viral load: An in vitro model and randomized, double-blind, Phase IIb clinical trial
20 patient metformin late treatment RCT: 44% lower need for oxygen therapy (p=0.03), 10% shorter hospitalization (p=0.35), and 41% faster viral clearance (p=0.03).RCT 20 hospitalized COVID-19 patients showing faster viral load reduction and lower oxygen use with metformin glycinate 620mg twice daily for 14 days compared to placebo. The in vitro portion demonstrated inhibition of viral replication and cytopathic effects with metformin glycinate pretreatment.
Aug 2022, Biomedicine & Pharmacotherapy, https://www.sciencedirect.com/science/article/pii/S0753332222006126, https://c19p.org/venturalopez
148. Zhao et al., Associations between the Dietary Inflammatory Index and COVID-19 Outcomes in the UK Biobank Cohort
196,154 patient diet study: 24% lower mortality (p=0.13), 28% lower severe cases (p=0.0003), and 15% fewer cases (p<0.0001).UK Biobank retrospective 196,154 participants with 11,288 COVID-19 cases, showing lower COVID-19 mortality, severity, and incidence for lower dietary inflammatory scores.
Dec 2022, SSRN Electronic J., https://www.ssrn.com/abstract=4300209, https://c19p.org/zhao6
149. Shestakova et al., Risk factors for COVID-19 case fatality rate in people with type 1 and type 2 diabetes mellitus: A nationwide retrospective cohort study of 235,248 patients in the Russian Federation
189,998 patient metformin prophylaxis study: 22% lower mortality (p=0.001).Retrospective 224,190 type 2 diabetes patients in Russia, showing lower mortality with metformin use.
Aug 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.909874/full, https://c19p.org/shestakova
150. Lora-Tamayo et al., Early Lopinavir/ritonavir does not reduce mortality in COVID-19 patients: results of a large multicenter study
8,553 patient HCQ late treatment study: 50% lower mortality (p<0.0001).Lopinavir/ritonavir retrospective study also showing univariate results for HCQ, with significantly lower mortality.
Feb 2021, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445321000773, https://c19p.org/loratamayo
151. Cadegiani et al., Proxalutamide (GT0918) Reduces the Rate of Hospitalization in mild-to-moderate COVID-19 Female Patients: A Randomized Double-Blinded Placebo-Controlled Two-Arm Parallel Trial
177 patient proxalutamide antiandrogen early treatment RCT: 90% lower ventilation (p=0.07) and 86% lower hospitalization (p=0.0008).RCT 177 women in Brazil, 75 treated with proxalutamide, showing significantly lower hospitalization with treatment.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.06.21260086v1, https://c19p.org/cadegiani5
152. Wallace et al., Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study
8,173 patient metformin prophylaxis study: 72% lower mortality (p<0.0001).Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing lower mortality with metformin use. The study provides results for use before, after, and before+after. Before+after should more accurately represent prophylaxis up to COVID-19 infection (and continued use). Before included use up to 2 years before, and after included use up to 60 days later.
Dec 2021, BMJ Open, https://bmjopen.bmj.com/content/11/12/e050051.info, https://c19p.org/wallace
153. Siripongboonsitti et al., Efficacy of Andrographis paniculata extract treatment in mild to moderate COVID-19 patients being treated with favipiravir: A double-blind, randomized, placebo-controlled study (APFaVi trial)
146 patient andrographolide early treatment RCT: 86% lower need for oxygen therapy (p=0.24), 37% improved recovery (p=0.28), and 5% worse viral clearance (p=0.46).RCT 146 mild/moderate COVID-19 patients in Thailand, showing no significant difference in clinical outcomes. There were very few serious outcomes.
Aug 2023, Phytomedicine, https://www.sciencedirect.com/science/article/pii/S0944711323003793, https://c19p.org/siripongboonsitti3
154. Osborne et al., Association of mortality and aspirin prescription for COVID-19 patients at the Veterans Health Administration
13,628 patient aspirin prophylaxis PSM study: 59% lower mortality (p<0.0001).Retrospective PSM analysis of pre-existing aspirin use in the USA, showing lower mortality with treatment.
Feb 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246825, https://c19p.org/osborne
155. Christensen et al., The association of estimated cardiorespiratory fitness with COVID-19 incidence and mortality: A cohort study
1,072 patient exercise study: 63% lower mortality (p=0.02) and 23% fewer cases (p=0.2).Prospective study of 2,690 adults in the UK Biobank showing lower cardiorespiritory fitness associated with COVID-19 mortality.
May 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250508, https://c19p.org/christensen
156. Zhu et al., Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study
3,998 patient azvudine late treatment PSM study: 22% lower mortality (p=0.001), 13% higher hospital discharge (p=0.05), 1% shorter hospitalization (p=0.43), and 10% faster viral clearance (p<0.0001).PSM retrospective 3,998 hospitalized COVID-19 patients aged 60 years and older in China showing lower all-cause mortality, higher rate of discharge, and shorter time to viral clearance with azvudine treatment.
Dec 2024, Acta Pharmaceutica Sinica B, https://www.sciencedirect.com/science/article/pii/S2211383524004611, https://c19p.org/zhu9
157. Shinkai et al., Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial
156 patient favipiravir late treatment RCT: 37% faster recovery (p=0.01).RCT 156 patients in Japan, 107 treated with favipiravir, showing significant improvement in a composite outcome defined as the time to improvement in temperature, SpO2, CT findings, and recovery to PCR-.
Aug 2021, Infectious Diseases and Therapy, https://link.springer.com/article/10.1007/s40121-021-00517-4, https://c19p.org/shinkai
138,475 patient exercise study: 35% lower hospitalization (p=0.007).
UK Biobank retrospective 235,928 participants using walking pace as a proxy for physical fitness, showing lower risk of COVID-19 hospitalization with an average vs. slow walking pace.
Nov 2020, BMJ Open, https://bmjopen.bmj.com/content/10/11/e040402, https://c19p.org/ho
159. Rathod et al., Risk Factors associated with COVID-19 Patients in India: A Single Center Retrospective Cohort Study
565 patient HCQ early treatment study: 73% lower mortality (p=0.02).Retrospective 565 COVID-19 patients in India, showing lower mortality with HCQ+AZ treatment. Most patients (66%) had mild disease at baseline.
May 2023, The J. the Association of Physicians of India, https://pubmed.ncbi.nlm.nih.gov/37355843/, https://c19p.org/rathod2
160. Tandon et al., SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial
207 patient nitric oxide early treatment RCT: 68% greater improvement (p=0.08) and 20% improved viral clearance (p<0.0001).RCT with 153 patients treated with a nitric oxide nasal spray, and 153 placebo patients, showing faster viral clearance with treatment. NO generated by a nasal spray (NONS) self-administered six times daily as two sprays per nostril (0.45mL of solution/dose) for seven days.
Jun 2022, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368222000464, https://c19p.org/tandon
161. Tsanovska et al., Hydroxychloroquine (HCQ) treatment for hospitalized patients with COVID-19
140 patient HCQ late treatment PSM study: 58% lower mortality (p=0.03), 74% lower ventilation (p=0.0007), and 70% lower ICU admission (p=0.0004).PSM prospective study of 260 COVID-19 patients in Bulgaria, showing lower mortality, ventilation, and ICU admission with HCQ treatment.
Mar 2022, Infectious Disorders - Drug Targets, https://www.eurekaselect.com/article/121288, https://c19p.org/tsanovska
3,462 patient HCQ late treatment study: 93% lower mortality (p<0.0001).
Retrospective 3,462 hospitalized COVID-19 patients across 13 states in Nigiera, showing lower mortality with HCQ. Authors note that the improved results compared with many other late stage studies may be related to the dose and experience of the physicians - in other studies beneficial effects may be offset by the side effects of high cumulative doses in late stage patients. Authors also note the worse results with a combination of CQ/HCQ and AZ may be related to the side effects becoming more significant for late stage patients.
May 2023, Nigerian Medical J., https://nigerianmedjournal.org/index.php/nmj/article/view/174, https://c19p.org/yilgwan
163. Mannumbeth Renjithlal et al., Cannabis Use and COVID-19 Hospitalization Outcomes. A Retrospective Study
39,285 patient cannabidiol prophylaxis PSM study: 56% lower mortality (p<0.0001), 25% lower ventilation (p<0.0001), and 6% longer hospitalization (p=0.0009).Retrospective 1,657,800 COVID-19 hospitalizations in the USA including 13,095 patients with cannabis use disorder, showing lower risk of mortality with cannabis use disorder. The text and Table S2 have conflicting results for mortality: 0.45 [0.36-0.57] versus 0.43 [0.34-0.55].
Jan 2023, SSRN Electronic J., https://www.ssrn.com/abstract=4336513, https://c19p.org/mannumbethrenjithlal
164. Hamrouni et al., Associations of obesity, physical activity level, inflammation and cardiometabolic health with COVID-19 mortality: a prospective analysis of the UK Biobank cohort
153,833 patient exercise study: 29% lower mortality (p=0.009).Prospective UK Biobank analysis, showing a history of low physical activity associated with COVID-19 mortality.
Nov 2021, BMJ Open, https://bmjopen.bmj.com/content/11/11/e055003.info, https://c19p.org/hamrouni
165. Comunale et al., Vitamin D Supplementation and Prior Oral Poliovirus Vaccination Decrease Odds of COVID-19 Outcomes among Adults Recently Inoculated with Inactivated Poliovirus Vaccine
282 patient vitamin D prophylaxis study: 91% fewer symptomatic cases (p=0.0006) and 88% fewer cases (p=0.001).Retrospective 282 adults recently vaccinated against poliovirus showing vitamin D supplementation associated with lower COVID-19 PCR+ cases, lower symptomatic cases, and shorter duration of symptoms.
Jan 2024, Vaccines, https://www.mdpi.com/2076-393X/12/2/121, https://c19p.org/comunale
166. Ren et al., Real-world effectiveness and safety of Azvudine in hospitalized patients with SARS-CoV-2 infection: a multicenter, retrospective cohort study
32,864 patient azvudine late treatment PSM study: 32% lower mortality (p<0.0001) and 12% lower progression (p=0.01).PSM retrospective 32,864 hospitalized COVID-19 patients in China showing lower all-cause mortality and disease progression with azvudine treatment.
Nov 2024, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445324002901, https://c19p.org/ren2
167. Lopes et al., Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial
72 patient colchicine late treatment RCT: 22% shorter hospitalization (p=0.01).RCT with 36 colchicine and 36 control patients, showing reduced length of hospitalization and oxygen therapy with treatment.
Aug 2020, RMD Open, https://rmdopen.bmj.com/content/7/1/e001455, https://c19p.org/lopes
168. Ferri et al., COVID-19 and rheumatic autoimmune systemic diseases: report of a large Italian patients series
1,641 patient HCQ prophylaxis study: 63% fewer cases (p=0.02).Analysis of 1641 systemic autoimmune disease patients showing csDMARD (HCQ etc.) RR 0.37, p=0.015. csDMARDs include HCQ, CQ, and several other drugs, so the effect of HCQ/CQ alone could be higher. This study also confirms that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, OR 4.42, p<0.001 (this is the observed real-world risk which takes into account factors such as these patients potentially being more careful to avoid exposure). (results are for "definite + highly suspected" cases and the main result is presented in the paper as the OR for not taking csDMARDs, we have converted this to RR for taking csDMARDs).
Aug 2020, Clinical Rheumatology, https://link.springer.com/article/10.1007/s10067-020-05334-7, https://c19p.org/ferri
169. Chen et al., Metformin alleviates inflammatory response and severity rate of COVID-19 infection in elderly individuals
413 patient metformin prophylaxis study: 81% lower ICU admission (p=0.008), 39% lower progression (p=0.009), and 17% shorter hospitalization (p=0.001).Retrospective 413 hospitalized COVID-19 patients with type 2 diabetes in China showing lower ICU admission, lower pneumonia incidence, and shorter hospital stay with metformin use.
Jun 2024, Translational Medicine of Aging, https://www.sciencedirect.com/science/article/pii/S2468501124000026, https://c19p.org/chen28
170. Silveira et al., Efficacy of Brazilian green propolis (EPP-AF®) as an adjunct treatment for hospitalized COVID-19 patients: A randomized, controlled clinical trial
84 patient propolis late treatment RCT: 62% lower ventilation (p=0.19), 24% lower ICU admission (p=0.73), and 35% shorter hospitalization (p=0.001).RCT 124 hospitalized COVID-19 patients in Brazil. The treatment groups received standardized green propolis extract (EPP-AF) at doses of 400mg/day or 800mg/day for 7 days, in addition to standard care. The EPP-AF groups had significantly shorter hospital stays post-intervention. The high dose EPP-AF group also had lower rates of acute kidney injury. No significant differences were seen for other outcomes like oxygen therapy duration or need for mechanical ventilation. The propolis adjunct treatment appeared safe with no discontinuations due to side effects.
Jun 2021, Biomedicine & Pharmacotherapy, https://www.sciencedirect.com/science/article/pii/S0753332221003115, https://c19p.org/silveira2
171. Signes-Costa et al., Prevalence and 30-day mortality in hospitalized patients with COVID-19 and prior lung diseases
5,847 patient HCQ late treatment study: 47% lower mortality (p=0.0005).47% lower mortality with HCQ/CQ. Retrospective 1,271 patients with lung disease in Canada, China, Cuba, Ecuador, Germany, Italy and Spain, 83% treated with HCQ/CQ. Multivariable Cox regression HCQ/CQ mortality hazard ratio HR 0.53, p < 0.001.
Dec 2020, Archivos de Bronconeumología, https://www.sciencedirect.com/science/article/pii/S0300289620305354, https://c19p.org/signescosta
363 patient vitamin B9 prophylaxis RCT: 88% fewer cases (p<0.0001).
Cluster RCT 526 healthcare workers in Egypt, showing lower COVID-19 cases with folic acid supplementation, and a dose-response relationship. Each wave of health care workers was randomized within 14 day isolation periods, introducing potential confounding by time.
Nov 2022, Microbes and Infectious Diseases, https://mid.journals.ekb.eg/article_270589.html, https://c19p.org/farag
412 patient aspirin late treatment study: 47% lower mortality (p=0.02), 44% lower ventilation (p=0.007), and 43% lower ICU admission (p=0.007).
Retrospective 412 hospitalized patients, 98 treated with aspirin, showing lower mortality, ventilation, and ICU admission with treatment.
Mar 2021, Anesthesia & Analgesia, https://journals.lww.com/anesthesia-analgesia/fulltext/2021/04000/aspirin_use_is_associated_with_decreased.2.aspx, https://c19p.org/chow
174. Wagner et al., A retrospective analysis of clinical outcomes between hospitalized patients with COVID‐19 who received famotidine or pantoprazole
1,457 patient famotidine late treatment study: 64% lower mortality (p<0.0001) and 6% lower ventilation (p=0.77).Retrospective 2,184 hospitalized patients in the USA, 638 treated with famotidine, showing lower mortality with treatment.
Oct 2021, JGH Open, https://onlinelibrary.wiley.com/doi/10.1002/jgh3.12905, https://c19p.org/wagner
175. Di Pierro et al., Possible Therapeutic Effects of Adjuvant Quercetin Supplementation Against Early-Stage COVID-19 Infection: A Prospective, Randomized, Controlled, and Open-Label Study
152 patient quercetin early treatment RCT: 86% lower mortality (p=0.25), 94% lower ICU admission (p=0.006), and 68% lower hospitalization (p=0.003).RCT 152 outpatients in Pakistan, 76 treated with quercetin phytosome, showing lower mortality, ICU admission, and hospitalization with treatment.
Jun 2021, Int. J. General Medicine, https://www.dovepress.com/possible-therapeutic-effects-of-adjuvant-quercetin-supplementation-aga-peer-reviewed-fulltext-article-IJGM#, https://c19p.org/dipierro
176. Ravichandran et al., An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients
210 patient indomethacin late treatment RCT: 30% improved recovery (p=0.002), 98% lower progression (p<0.0001), and 17% improved viral clearance (p=0.19).RCT with 103 indomethacin and 107 paracetamol patients, showing lower progression and improved recovery with indomethacin. Notably, improvements include faster resolution of cough. [Alkotaji] previously hypothesised the benefit of indomethacin for reducing cough via bradykinin inhibition.
Apr 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-10370-1, https://c19p.org/ravichandran
177. Chowdhury et al., Role of H2 receptor blocker famotidine over the clinical recovery of COVID-19 patients: A randomized controlled trial
208 patient famotidine ICU RCT: 16% lower mortality (p=0.53), 9% shorter ICU admission (p=0.33), 33% faster improvement (p<0.0001), and 7% faster recovery (p=0.14).RCT 208 ICU patients in Bangladesh, showing improved recovery with famotidine. Famotidine 40mg (<60kg) or 60mg every 8 hours.
Aug 2022, World J. Clinical Cases, https://www.wjgnet.com/2307-8960/full/v10/i23/8170.htm, https://c19p.org/chowdhury2
178. Ma et al., Metformin is associated with favorable outcomes in patients with COVID-19 and type 2 diabetes mellitus
1,356 patient metformin prophylaxis study: 74% lower mortality (p=0.03) and 25% lower ventilation (p=0.44).PSM/IPTW retrospective 1,356 hospitalized COVID-19 patients with type 2 diabetes in China, showing lower mortality/hospice with metformin use.
Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-09639-2, https://c19p.org/ma5
179. Stambouli et al., COVID-19 prophylaxis with Doxycycline and Zinc in Health Care Workers: A prospective randomized double-blind clinical tria
115 patient zinc prophylaxis RCT: 68% fewer symptomatic cases (p=0.36), 5% fewer cases (p=1), and 21% improved viral load (p<0.0001).Prophylaxis RCT with 59 zinc + doxycycline, 56 doxycycline, and 57 placebo healthcare workers, showing lower symptomatic cases and significantly improved Ct values with the addition of zinc to doxycycline treatment. Doxycycline 100mg/day and zinc 15 mg/day.
Jun 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222003496, https://c19p.org/stambouli
350 patient probiotics early treatment RCT: 50% fewer combined hospitalization/ER visits (p=0.13) and 20% faster recovery (p=0.1).
RCT 350 COVID+ outpatients in the USA, 174 treated with prebiotic KB109 (a microbiome metabolic therapy candidate), showing lower combined hospitalization, ER, and urgent care visits with treatment. NCT04414124.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.26.21254422, https://c19p.org/haran
181. Varnaseri et al., Ivermectin as a Potential Addition to the Limited Anti-COVID-19 Arsenal: A Double-Blinded Clinical Trial
110 patient ivermectin late treatment RCT: 82% lower ventilation (p=0.02), 83% lower ICU admission (p=0.0004), 33% shorter hospitalization (p=0.001), and 28% faster recovery (p<0.0001).Double-blind RCT 110 hospitalized moderate to severe COVID-19 patients showing significantly reduced ICU admission, shorter hospitalization, faster resolution of symptoms, and improved CRP and LDH levels with ivermectin treatment compared to placebo. No deaths occurred in either group. There were no serious adverse events. Note that preclinical research predicts synergistic effects with the standard treatment protocol used in both groups.
Apr 2024, Jundishapur J. Health Sciences, https://brieflands.com/articles/jjhs-146703, https://c19p.org/varnaseri
182. Shimizu et al., Ivermectin administration is associated with lower gastrointestinal complications and greater ventilator-free days in ventilated patients with COVID-19: A propensity score analysis
88 patient ivermectin late treatment study: 100% lower mortality (p=0.001), 48% lower ventilation (p=0.03), 43% lower ICU admission (p=0.06), and 78% lower progression (p=0.03).Retrospective 88 ventilated COVID-19 patients in Japan, 39 treated with ivermectin within 3 days of admission, showing significantly reduced incidence of GI complications and mortality, and increased ventilator-free days with treatment.
Dec 2021, J. Infection and Chemotherapy, https://www.jiac-j.com/article/S1341-321X(21)00360-3/fulltext, https://c19p.org/shimizu
183. Bramante et al., Outpatient metformin use is associated with reduced severity of COVID‐19 disease in adults with overweight or obesity
9,555 patient metformin prophylaxis PSM study: 62% lower mortality (p=0.03), 9% higher ICU admission (p=0.78), and 22% lower hospitalization (p=0.1).Retrospective 17,396 PCR+ patients in the USA, showing lower mortality with metformin use.
Mar 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26873, https://c19p.org/bramante4
184. Gaynitdinova et al., N-acetylcysteine as a part of complex treatment of moderate COVID-associated pneumonia
46 patient N-acetylcysteine late treatment RCT: 15% shorter hospitalization (p=0.001) and 51% improved recovery (p=0.001).RCT 46 hospitalized patients with moderate COVID-19 pneumonia, 24 treated with N-acetylcysteine, showing significantly shorter hospitalization with treatment. NAC 1,200 – 1,500mg/day intravenously.
Feb 2021, Pulmonologiya, https://journal.pulmonology.ru/pulm/article/viewFile/2263/1813, https://c19p.org/gaynitdinova
185. Udwadia et al., Efficacy and Safety of Favipiravir, an Oral RNA-Dependent RNA Polymerase Inhibitor, in Mild-to-Moderate COVID-19: A Randomized, Comparative, Open-Label, Multicenter, Phase 3 Clinical Trial
148 patient favipiravir early treatment RCT: 29% faster recovery (p=0.07) and 27% faster viral clearance (p=0.1).RCT with 75 favipiravir patients and 75 control patients showing improved recovery with treatment.
Nov 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S120197122032453X, https://c19p.org/udwadia
147 patient curcumin long COVID RCT: 44% greater improvement (p=0.02).
RCT 147 long COVID patients in the UK, 56 treated with a phytochemical-rich concentrated food capsule, showing improved recovery with treatment. Treatment included curcumin, bioflavonoids, chamomile, ellagic acid, and resveratrol.
Mar 2022, COVID, https://www.mdpi.com/2673-8112/2/4/31, https://c19p.org/thomas3
187. Pavlidou et al., Association of COVID-19 Infection with Sociodemographic, Anthropometric and Lifestyle Factors: A Cross-Sectional Study in an Older Adults’ Population Aged over 65 Years Old
5,197 patient sleep study: 40% fewer cases (p=0.01).Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity, depression, anxiety, stress, and poor health-related quality of life.
Nov 2023, Diseases, https://www.mdpi.com/2079-9721/11/4/165, https://c19p.org/pavlidousl
188. Lal et al., Pre-hospital aspirin use and patient outcomes in COVID-19: Results from the International Viral Infection and Respiratory Illness Universal Study (VIRUS)
21,579 patient aspirin prophylaxis study: 11% lower mortality (p=0.01), 22% lower ICU admission (p<0.0001), and 9% lower progression (p=0.02).Retrospective 21,579 hospitalized COVID-19 patients mostly in the USA, showing lower risk of mortality and severity with existing aspirin use.
May 2022, Archivos de Bronconeumología, https://www.sciencedirect.com/science/article/pii/S0300289622005105, https://c19p.org/lal
189. Di Castelnuovo et al., Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering
4,270 patient HCQ late treatment study: 40% lower mortality (p<0.0001).Retrospective 4,396 hospitalized patients in Italy showing significantly lower mortality with HCQ treatment, and identifying greater efficacy for a subgroup of patients in clustering analysis.
Jan 2021, J. Healthcare Engineering, https://www.hindawi.com/journals/jhe/2021/5556207/, https://c19p.org/dicastelnuovo2
190. Lagier et al., Outcomes of 3,737 COVID-19 patients treated with hydroxychloroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis
3,737 patient HCQ late treatment study: 59% lower mortality (p=0.05).Early treatment leads to significantly better clinical outcome and faster viral load reduction. Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737 patients. This study includes both outpatients and hospitalized patients.
Jun 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/pii/S1477893920302817, https://c19p.org/lagier
191. Badyal et al., Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers – A Multicentric Cohort Study Assessing Effectiveness and Safety
2,090 patient HCQ prophylaxis study: 60% fewer cases (p<0.0001).Prophylaxis study with 12,089 Indian healthcare workers, showing lower risk of COVID-19 cases with treatment, and increasingly lower risk for longer durations of HCQ prophylaxis. The appendices are not currently available.
Jun 2021, J. the Association of Physicians of India, June 2021, https://www.researchgate.net/publication/357700064_Hydroxychloroquine_for_SARS_CoV2_Prophylaxis_in_Healthcare_Workers_-_A_Multicentric_Cohort_Study_Assessing_Effectiveness_and_Safety, https://c19p.org/badyal
192. Lee et al., A population-level analysis of the protective effects of androgen deprivation therapy against COVID-19 disease incidence and severity
39,153 patient various antiandrogen prophylaxis study: 21% lower severe cases (p=0.03) and 11% fewer cases (p=0.001).Retrospective 3,057 androgen deprivation therapy patients in the USA, and 36,096 control patients with cancer, showing lower risk of cases and severity with ADT.
Mar 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.774773/full, https://c19p.org/lee5
193. Merzon et al., The use of aspirin for primary prevention of cardiovascular disease is associated with a lower likelihood of COVID-19 infection
10,477 patient aspirin prophylaxis study: 28% fewer cases (p=0.04) and 10% faster viral clearance (p=0.05).Retrospective 10,477 patients in Israel, showing lower risk of COVID-19 cases with existing aspiring use.
Feb 2021, The FEBS J., https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15784, https://c19p.org/merzon2
194. Sadeghizadeh et al., Promising clinical outcomes of nano‐curcumin treatment as an adjunct therapy in hospitalized COVID‐19 patients: A randomized, double‐blinded, placebo‐controlled trial
42 patient curcumin late treatment RCT: 92% lower progression (p=0.02), 25% shorter hospitalization (p=0.007), and 68% improved recovery (p<0.0001).RCT 42 hospitalized moderate/severe COVID-19 patients in Iran, showing lower progression and improved recovery with nano-curcumin. Nano-curcumin 70mg bid for 14 days.
Apr 2023, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7844, https://c19p.org/sadeghizadeh
195. Majeed et al., A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of a Nutritional Supplement (ImmuActive) for COVID-19 Patients
92 patient curcumin early treatment RCT: 43% improved recovery (p=0.004) and 6% faster viral clearance (p=0.47).RCT 100 patients in India, 50 treated with ImmuActive (curcumin, andrographolides, resveratrol, zinc, selenium, and piperine), showing improved recovery with treatment.
Oct 2021, Evidence-Based Complementary and Alternative Medicine, https://www.hindawi.com/journals/ecam/2021/8447545/, https://c19p.org/majeed
196. Kirenga et al., Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study
316 patient fluvoxamine late treatment study: 68% lower mortality (p<0.0001) and 53% improved recovery (p=0.04).Prospective study of 316 hospitalized patients in Uganda, 94 receiving fluvoxamine, showing significantly lower mortality and improved recovery with treatment.
Mar 2023, Molecular Psychiatry, https://www.nature.com/articles/s41380-023-02004-3, https://c19p.org/kirenga2
197. Ojeda-Fernández et al., Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy
13,112 patient metformin prophylaxis PSM study: 16% lower mortality (p<0.0001), 22% lower ICU admission (p=0.01), and 3% lower hospitalization (p=0.11).Retrospective 31,966 COVID+ patients using anti-hyperglycemic drugs in Italy, showing lower mortality and ICU admission with metformin use.
Jan 2022, Diabetes, Obesity and Metabolism, https://dom-pubs.onlinelibrary.wiley.com/doi/10.1111/dom.14648, https://c19p.org/ojedafernandez
198. Pereira et al., Cardiopulmonary and hematological effects of infrared LED photobiomodulation in the treatment of SARS-COV2
30 patient sunlight RCT: 32% shorter hospitalization (p=0.02) and 38% faster recovery (p=0.0006).RCT 30 hospitalized COVID-19 patients investigating the effectiveness of photobiomodulation (PBM) using a vest with near-infrared LEDs (simulating part of the sunlight spectrum). The treatment group showed shorter hospitalization, significant improvement in cardiopulmonary function, and improvements in leukocyte, neutrophil, and lymphocyte counts post-treatment. The treatment group had higher pneumonia severity at baseline. For more discussion see [youtube.com].
Dec 2022, J. Photochemistry and Photobiology B: Biology, https://www.sciencedirect.com/science/article/pii/S1011134422002342, https://c19p.org/pereira2
199. Karami et al., A Comparison of the Effects of Chlorhexidine and Sodium Bicarbonate Mouthwashes on COVID-19–Related Symptoms
76 patient chlorhexidine prophylaxis RCT: 61% lower progression (p=0.04) and 57% fewer cases (p=0.03).RCT 116 healthcare workers comparing 0.2% chlorhexidine mouthwash (n=36), 7.5% sodium bicarbonate mouthwash (n=40), and placebo (n=40) twice daily for 2 weeks, with symptoms followed for 4 weeks. There were lower symtoms and cases in both treatment groups, with statistical significance for chlorhexidine only. The treatments were stopped after two weeks, results may be better with continued use, more frequent use, and with the addition of nasal use.
Jan 2024, Iranian J. Nursing and Midwifery Research, https://journals.lww.com/jnmr/fulltext/2024/29010/a_comparison_of_the_effects_of_chlorhexidine_and.8.aspx, https://c19p.org/karami
200. Dimnjaković et al., Association of anti-diabetic drugs and covid-19 outcomes in patients with diabetes mellitus type 2 and chronic kidney disease: Nationwide registry analysis
7,539 patient metformin prophylaxis study: 23% lower hospitalization (p=0.004) and 12% fewer cases (p=0.04).Retrospective 7,539 patients with diabetes mellitus type 2 and chronic kidney disease in Croatia showing lower risk of SARS-CoV-2 infection with SGLT-2 inhibitors, metformin, and repaglinide use, and lower risk of COVID-19 hospitalization with SGLT-2 inhibitors and metformin use.
Mar 2024, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0301056, https://c19p.org/dimnjakovic
201. Saviano et al., COVID-19 Pneumonia and Gut Inflammation: The Role of a Mix of Three Probiotic Strains in Reducing Inflammatory Markers and Need for Oxygen Support
80 patient probiotics late treatment RCT: 86% lower ICU admission (p=0.24) and 26% shorter hospitalization (p=0.52).RCT 80 COVID-19 interstitial pneumonia patients in Italy, 40 treated with probiotics, showing significantly reduced gut inflammatory markers with treatment, and lower ICU admission and mortality, without statistical significance. Bifidobacterium lactis LA 304, lactobacillus salivarius LA 302, and lactobacillus acidophilus LA 201 bid for 10 days.
Jun 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/13/3758, https://c19p.org/saviano
334,374 patient aspirin prophylaxis PSM study: 46% lower mortality (p=0.001).
PSM retrospective 334,374 COVID-19 patients showing decreased risk of venous thromboembolism, including pulmonary embolism and deep vein thrombosis, but increased risk of arterial thromboembolic disorders, including ischemic stroke and acute ischemic heart disease, with aspirin use prior to COVID-19 diagnosis. The increased risk of arterial disease may be associated with preexisting cardiovascular disease for which aspirin was already prescribed. All cause mortality was lower in the aspirin group, however authors do not discuss this result.
Apr 2024, medRxiv, https://www.medrxiv.org/content/10.1101/2024.04.10.24305647, https://c19p.org/ware
203. Ma et al., Associations between predicted vitamin D status, vitamin D intake, and risk of SARS-CoV-2 infection and Coronavirus Disease 2019 severity
39,315 patient vitamin D prophylaxis study: 49% lower hospitalization (p=0.04), 7% more symptomatic cases (p=0.25), and 17% fewer cases (p=0.07).Analysis of 39,915 patients with 1,768 COVID+ cases based on surveys in the Nurses' Health Study II, showing higher predicted vitamin D levels associated with lower risk of COVID-19 cases. There was significantly lower risk of hospitalization with vitamin D supplementation (≥400 IU/d), but no significant differences for cases based on supplementation.
Dec 2021, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqab389/6448988, https://c19p.org/ma2
204. Pavlidou et al., Association of COVID-19 Infection with Sociodemographic, Anthropometric and Lifestyle Factors: A Cross-Sectional Study in an Older Adults’ Population Aged over 65 Years Old
5,197 patient diet study: 55% fewer cases (p=0.0009).Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity, depression, anxiety, stress, and poor health-related quality of life.
Nov 2023, Diseases, https://www.mdpi.com/2079-9721/11/4/165, https://c19p.org/pavlidoudt
205. Lima-Morales et al., Effectiveness of a multidrug therapy consisting of ivermectin, azithromycin, montelukast and acetylsalicylic acid to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico
768 patient ivermectin late treatment study: 78% lower mortality (p=0.001), 52% lower ventilation (p=0.15), 67% lower hospitalization (p=0.001), and 59% improved recovery (p=0.001).Prospective trial of 768 COVID-19 outpatients in Mexico, 481 treated with ivermectin, AZ, montelukast, and aspirin, and 287 control patients with various treatments, showing significantly lower mortality and hospitalization, and significantly higher recovery at 14 days with treatment.
Feb 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221001004, https://c19p.org/limamorales
206. Cecconi et al., Efficacy of short-course colchicine treatment in hospitalized patients with moderate to severe COVID-19 pneumonia and hyperinflammation: a randomized clinical trial
240 patient colchicine late treatment RCT: 29% lower mortality (p=0.62), 50% lower ventilation (p=0.29), 21% lower ICU admission (p=0.67), and 15% improvement (p=0.62).RCT 240 hospitalized patients with COVID-19 pneumonia, mean 9 days from the onset of symptoms, showing no significant differences with colchicine treatment. EudraCT 2020-001841-38.
Jun 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-13424-6, https://c19p.org/cecconi
207. Mather et al., Impact of Famotidine Use on Clinical Outcomes of Hospitalized Patients With COVID-19
772 patient famotidine prophylaxis PSM study: 61% lower mortality (p=0.004) and 50% lower combined mortality/intubation (p=0.003).PSM retrospective 878 hospitalized patients in the USA, 83 with existing famotidine use, showing significantly lower mortality with treatment.
Aug 2020, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000000832, https://c19p.org/mather
208. Mathai et al., Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 in health-care workers: A single-center experience
604 patient HCQ prophylaxis study: 90% fewer cases (p<0.0001).90% reduction in cases with HCQ pre-exposure prophylaxis. Retrospective 604 healthcare workers.
Nov 2020, J. Marine Medical Society, https://www.marinemedicalsociety.in/preprintarticle.asp?id=300159, https://c19p.org/mathai
209. Elavarasi et al., Clinical features, demography, and predictors of outcomes of SARS-CoV-2 infection at a tertiary care hospital in India: A cohort study
1,687 patient zinc late treatment study: 65% lower mortality (p<0.0001).Retrospective 2017 hospitalized patients in India, showing lower mortality with zinc treatment.
Aug 2021, Lung India, https://journals.lww.com/lungindia/Fulltext/2022/01000/Clinical_features,_demography,_and_predictors_of.5.aspx, https://c19p.org/elavarasiz
210. Poleti et al., Use of mouthwash and dentifrice containing antimicrobial phthalocyanine derivative for the reduction of clinical symptoms of COVID-19: A randomized triple-blinded clinical trial
134 patient phthalocyanine early treatment RCT: 29% improved recovery (p=0.02).RCT 500 patients in Brazil, showing improved recovery with a phthalocyanine derivative mouthwash and toothpaste. Toothbrushing for 2 minutes, three times per day, and gargling/rising (5ml) for one minute, three times a day, for 7 days.
Dec 2021, J. Evidence-Based Dental Practice, https://www.sciencedirect.com/science/article/pii/S1532338222001002, https://c19p.org/poleti
211. Arefin et al., Virucidal effect of povidone iodine on COVID-19 in the nasopharynx: an open-label randomized clinical trial
189 patient povidone-iodine early treatment RCT: 79% improved viral clearance (p=0.02).RCT with 189 patients showing significantly greater viral clearance with a single application of PVP-I. Authors recommend using PVP-I prophylactically in the nasopharynx and oropharynx. NCT04549376 [trialsjournal.biomedcentral.com].
May 2021, Indian J. Otolaryngology and Head & Neck Surgery, https://link.springer.com/article/10.1007/s12070-021-02616-7, https://c19p.org/arefin
212. Hobbs et al., Favipiravir for COVID-19 in adults in the community in PRINCIPLE, an open-label, randomised, controlled, adaptive platform trial of short- and longer-term outcomes
3,622 patient favipiravir late treatment RCT: 86% lower mortality (p=0.11), 1% lower combined mortality/hospitalization (p=0.51), and 17% improved recovery (p=0.003).RCT 3,622 (concurrent and eligible) COVID-19 outpatients in the UK showing significantly faster recovery with favipiravir, and significantly greater full recovery at 3, 6, and 12 months. Authors note: "From 16 Dec 2021, a minority of extremely clinically vulnerable patients could also access antiviral treatment or a monoclonal antibody infusion". However, there is no information on treatments provided or procedures for determining eligibility. This change invalidates hospitalization/death data after 16 Dec 2021. Hospitalization/death events occured in a small minority of patients and are expected to be strongly biased towards the extremely clinically vulnerable patients. Patients randomized to usual care are more likely to obtain alternative treatment. During the trial extension period sotrovimab was the most common treatment, with paxlovid and molnupiravir also being used [england.nhs.uk]. Sotrovimab showed very high efficacy during this period [Behzad, De Vito]. It..
Aug 2024, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445324001828, https://c19p.org/hobbs
213. Hellwig et al., A COVID-19 Prophylaxis? Lower incidence associated with prophylactic administration of Ivermectin
1,216,000,000 patient ivermectin prophylaxis study: 78% fewer cases (p=0.02).Analysis of COVID-19 cases vs. widespread prophylactic use of ivermectin for parasitic infections showing significantly lower incidence of COVID-19 cases.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304684, https://c19p.org/hellwig
214. Mikami et al., Risk Factors for Mortality in Patients with COVID-19 in New York City
6,000 patient HCQ late treatment study: 47% lower mortality (p<0.0001).HCQ decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients in New York City.
Jun 2020, J. Gen. Intern. Med., https://link.springer.com/article/10.1007/s11606-020-05983-z, https://c19p.org/mikami
215. Chouhdari et al., The prophylactic effect of hydroxychloroquine on the severity of COVID-19 infection in an asymptomatic population: A randomized clinical trial
1,000 patient HCQ prophylaxis RCT: 80% lower hospitalization (p=0.25) and 43% fewer cases (p=0.005).RCT of 1,000 people showing lower risk of COVID-19 infection with HCQ prophylaxis. There was no significant difference in side effects or adherence, no severe side effects, and blinding was well maintained. There are now PrEP RCTs, showing significant efficacy for COVID-19 cases with .
Jan 2024, Social Determinants of Health, https://journals.sbmu.ac.ir/sdh/article/view/43032, https://c19p.org/chouhdari
216. Karaaltin et al., Effect of the povidone iodine, hypertonic alkaline solution and saline nasal lavage on nasopharyngeal viral load in COVID-19
60 patient povidone-iodine early treatment RCT: 83% improved viral load (p=0.007).RCT 120 outpatients in Turkey, showing improved reduction in viral load with PVP-I nasal irrigation. PVP-I prepared with hypertonic alkaline solution had better results. [Kreutzberger] show that SARS-CoV-2 requires acidic pH to infect cells, therefore alkalinization may add additional benefits. All patients received favipiravir. PVP-I 1% 4 times per day.
Oct 2022, Authorea, https://www.authorea.com/users/337860/articles/592062-effect-of-the-povidone-iodine-hypertonic-alkaline-solution-and-saline-nasal-lavage-on-nasopharyngeal-viral-load-in-covid-19?commit=bcb03d2ad8d86742ebd473271b70f5ab7211094d, https://c19p.org/karaaltin
217. Morgenstern et al., Ivermectin as a SARS-CoV-2 Pre-Exposure Prophylaxis Method in Healthcare Workers: A Propensity Score-Matched Retrospective Cohort Study
542 patient ivermectin prophylaxis PSM study: 74% fewer cases (p=0.008).Propensity matched retrospective prophylaxis study of healthcare workers in the Dominican Republic showing significantly lower cases with treatment, and no hospitalization with treatment (versus 2 in the PSM matched control group). The cases with treatment were mostly in the first week, with only one case in the second and third weeks, and none in the fourth week. There were no severe side effects. In post-hoc analysis, as the treatment group discontinued treatment over time, their protection also decreased. NCT04832945.
Apr 2021, Cureus, https://www.cureus.com/articles/63131-ivermectin-as-a-sars-cov-2-pre-exposure-prophylaxis-method-in-healthcare-workers-a-propensity-score-matched-retrospective-cohort-study, https://c19p.org/morgenstern2
218. Abaluck et al., Impact of community masking on COVID-19: A cluster-randomized trial in Bangladesh
342,183 patient PPE prophylaxis RCT: 9% fewer symptomatic cases (p=0.05).RCT 342,183 adults in Bangladesh showing lower COVID-19 cases with a community-level mask promotion and distribution intervention. The reduction in symptoms and seroprevalence was larger with surgical masks compared to cloth masks, and in older adults. Villages were randomly assigned to receive free cloth or surgical masks along with education and promotion of mask-wearing, or no intervention. Author do not report any information on the severity of cases.
Jan 2022, Science, https://www.science.org/doi/10.1126/science.abi9069, https://c19p.org/abaluck
219. Mikhaylov et al., Bromhexine Hydrochloride Prophylaxis of COVID-19 for Medical Personnel: A Randomized Open-Label Study
50 patient bromhexine prophylaxis RCT: 91% fewer symptomatic cases (p=0.05) and 71% fewer cases (p=0.14).Small prophylaxis RCT with 25 treatment and 25 control health care workers, showing lower PCR+, symptomatic cases, and hospitalization with treatment, although not statistically significant with the small sample size.
Mar 2021, Interdisciplinary Perspectives on Infectious Diseases, https://www.hindawi.com/journals/ipid/2022/4693121/, https://c19p.org/mikhaylov
220. Ayerbe et al., The association of treatment with hydroxychloroquine and hospital mortality in COVID-19 patients
2,075 patient HCQ late treatment study: 52% lower mortality (p=0.001).2075 hospital patients in Spain showing HCQ reduces mortality 52%, odds ratio OR 0.39, p<0.001, after adjustment for age, gender, temperature > 37 °C, and saturation of oxygen < 90% treatment with azithromycin, steroids, heparin, tocilizumab, a combination of lopinavir with ritonavir, and oseltamivir, and date of admission (model 4).
Sep 2020, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-020-02505-x, https://c19p.org/ayerbe
221. Manenti et al., Reduced mortality in COVID-19 patients treated with colchicine: Results from a retrospective, observational study
141 patient colchicine late treatment study: 76% lower mortality (p=0.005) and 44% improved recovery (p=0.05).IPTW retrospective 141 COVID-19 patients (83% hospitalized), 71 treated with colchicine and 70 matched control patients, showing lower mortality and faster recovery with treatment.
Mar 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248276, https://c19p.org/manenti
222. Fiore et al., Effectiveness of Vitamin D Supplements among Patients Hospitalized for COVID-19: Results from a Monocentric Matched-Cohort Study
116 patient vitamin D late treatment study: 93% lower mortality (p=0.02), 50% lower ventilation (p=0.36), 50% lower ICU admission (p=0.36), and 48% lower progression (p=0.04).Retrospective 116 patients with D levels < 30ng/mL, 58 treated with vitamin D 100,000IU daily for two days, and 58 matched controls, showing significantly lower mortality with treatment.
May 2022, Healthcare, https://www.mdpi.com/2227-9032/10/5/956, https://c19p.org/fiore2
223. Gutiérrez-Castrellón et al., Probiotic improves symptomatic and viral clearance in Covid19 outpatients: a randomized, quadruple-blinded, placebo-controlled trial
293 patient probiotics early treatment RCT: 35% improved recovery (p<0.0001).RCT 293 outpatients in Mexico, 147 treated with a probiotic composed of three L. plantarum strains (KABP022, KABP023 and KABP033) and one P. acidilacti strain (KABP021), showing improved recovery with treatment. There were no hospitalizations or deaths.
May 2021, Gut Microbes, https://www.tandfonline.com/doi/pdf/10.1080/19490976.2021.2018899, https://c19p.org/gutierrezcastrellon
224. Hunt et al., Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans
26,508 patient colchicine early treatment study: 68% lower mortality (p=0.003).Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including colchicine. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/hunto
225. Simova et al., Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
38 patient HCQ early treatment study: 94% lower hospitalization (p=0.01) and 96% improved viral clearance (p=0.001).100% reduction in hospitalization and cases with early treatment using HCQ+AZ+zinc. Brief report on healthcare workers in Bulgaria. 0 hospitalizations with treatment vs. 2 for control 0 PCR+ at day 14 with treatment vs. 3 for control 33 treatment patients and 5 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297520301657, https://c19p.org/simova
226. Chung et al., A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID
24 patient vitamin A long COVID RCT: 75% lower PASC (p=0.05).RCT 24 patients with olfactory dysfunction post-COVID-19 in Hong Kong, showing significantly improved recovery with the addition of vitamin A to aerosolised diffuser olfactory training. 25,000IU vitamin A for 14 days.
Jun 2023, Brain Sciences, https://www.mdpi.com/2076-3425/13/7/1014, https://c19p.org/chung
227. Connors et al., Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19
280 patient aspirin early treatment RCT: 67% lower hospitalization (p=0.49) and 19% lower progression (p=0.78).Early terminated RCT with 164 aspirin and 164 control patients in the USA with very few events, showing no significant difference with aspirin treatment for the combined endpoint of all-cause mortality, symptomatic venous or arterial thromboembolism, myocardial infarction, stroke, and hospitalization for cardiovascular or pulmonary indication. There was no mortality and no major bleeding events among participants that started treatment (there was one ITT placebo death).
Oct 2021, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2785218, https://c19p.org/connors
228. Campi et al., Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy
155 patient vitamin D prophylaxis study: 88% lower severe cases (p<0.0001).Prospective study of 103 hospitalized patients in Italy, showing very high prevalence of vitamin D deficiency, and increased severity for lower vitamin D levels. Vitamin D supplementation was significantly less common for cases.
Jun 2021, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06281-7, https://c19p.org/campi
229. Ahmed et al., A five day course of ivermectin for the treatment of COVID-19 may reduce the duration of illness
72 patient ivermectin early treatment RCT: 85% improved symptoms (p=0.09), 76% improved viral clearance (p=0.03), and 1% shorter hospitalization.Small 72 patient RCT of ivermectin and ivermectin + doxycycline showing faster recovery with ivermectin. The ivermectin + doxycycline group uses only a single dose of ivermectin vs. 5 daily doses for the ivermectin group. PCR testing was only done weekly after day 7, therefore hospitalization time may not match symptomatic recovery. Ivermectin group: 12mg daily for 5 days Ivermectin + doxycycline: 12mg ivermectin single dose, 200mg doxycycline + 100mg bid 4 days
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325066, https://c19p.org/ahmed
435 patient HCQ prophylaxis RCT: 51% fewer symptomatic cases (p=0.79) and 27% fewer cases (p=0.31).
Early terminated healthcare worker prophylaxis RCT in Spain, showing lower risk of symptomatic cases with HCQ prophylaxis, without statistical significance due to the small number of events.
Aug 2022, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X22003706, https://c19p.org/polo
231. Cousins et al., Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study
898,303 patient spironolactone antiandrogen prophylaxis PSM study: 18% lower mortality (p=0.004) and 17% lower ventilation (p<0.0001).PSM retrospective 898,303 hospitalized COVID-19 patients in the USA, 16,324 on spironolactone, showing lower mortality and ventilation with spironolactone use.
Mar 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.02.28.23286515v1, https://c19p.org/cousins2
232. Cousins et al., Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study
898,303 patient spironolactone prophylaxis PSM study: 18% lower mortality (p=0.004) and 17% lower ventilation (p<0.0001).PSM retrospective 898,303 hospitalized COVID-19 patients in the USA, 16,324 on spironolactone, showing lower mortality and ventilation with spironolactone use.
Mar 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.02.28.23286515v1, https://c19p.org/cousins2sp
233. Reis et al., The Association between Lifestyle Risk Factors and COVID-19 Hospitalization in a Healthcare Institution
546 patient diet study: 75% lower hospitalization (p=0.0003).Retrospective 546 COVID+ patients in the USA, showing lower risk of hospitalization with higher consumption of vegetables.
Oct 2022, American J. Lifestyle Medicine, http://journals.sagepub.com/doi/10.1177/15598276221135541, https://c19p.org/reis6
234. Sakamaki et al., Insights from a multicenter nationwide cohort analysis in Japan on the association of underlying conditions and pharmacological interventions with COVID-19 disease severity
650,317 patient metformin prophylaxis study: 23% lower severe cases (p<0.0001).Retrospective 650,317 COVID-19 patients in Japan showing lower risk of severe COVID-19 with metformin use.
Sep 2024, Discover Public Health, https://ete-online.biomedcentral.com/articles/10.1186/s12982-024-00225-7, https://c19p.org/sakamaki
235. Shaseb et al., Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19
189 patient metformin late treatment RCT: 74% lower mortality (p=0.06), 79% lower ventilation (p=0.05), 63% lower ICU admission (p=0.07), and 5% shorter hospitalization (p=0.52).RCT 189 hospitalized patients showing lower mortality, ICU admission, and intubation with metformin, statistically significant only for intubation. Treatment patients may have also taken metformin prior to admission. Authors note that patients receiving metformin prior to the study were not matched, and diabetes and hyperlipidemia differed between groups.
Jul 2022, Advanced Pharmaceutical Bulletin, https://apb.tbzmed.ac.ir/Article/apb-33452, https://c19p.org/shaseb
236. Wargny et al., Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study
2,794 patient metformin prophylaxis study: 28% lower mortality (p=0.03) and 15% higher hospital discharge (p=0.02).Retrospective 2,796 hospitalized diabetes patients with COVID-19 in France, showing lower mortality with metformin use.
Feb 2021, Diabetologia, https://link.springer.com/article/10.1007/s00125-020-05351-w, https://c19p.org/wargny
621 patient povidone-iodine early treatment RCT: 91% lower hospitalization (p=0.06), 15% faster recovery (p=0.008), 68% improved viral clearance (p<0.0001), and 92% lower transmission (p<0.0001).
RCT with 200 patients and 421 contacts, with 100 patients and their contacts treated with nasal and oropharyngeal sprays containing povidone-iodine and glycyrrhizic acid, showing significantly faster viral clearance and recovery, and significantly lower transmission. SOC included vitamin C and zinc. The spray active ingredients included a compound of glycyrrhizic acid in the form of ammonium glycyrrhizate 2.5 mg/ml plus PVI 0.5% for oropharyngeal and dipotassium glycyrrhizinate 2.5 mg/ml plus PVI 0.5% for nasal spray. Patients were advised to concomitantly use oropharyngeal and nasal sprays 6 times per day. They were instructed to abstain from food, drink, and smoke for 20min, particularly after oropharyngeal spray. The oropharyngeal spray bottle contains an atomizer that ends with a long arm applicator to insert inside the mouth cavity and can be directed up, down, right, or left to cover the entire pharyngeal area.
Apr 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.863917/full, https://c19p.org/elsersy
238. Mondal et al., Prevalence of COVID-19 Infection and Identification of Risk Factors among Asymptomatic Healthcare Workers: A Serosurvey Involving Multiple Hospitals in West Bengal
1,470 patient ivermectin prophylaxis study: 88% fewer symptomatic cases (p=0.006).Retrospective 1,470 healthcare workers in India, showing significantly lower risk of symptomatic COVID-19 with ivermectin prophylaxis.
May 2021, J. the Indian Medical Association, https://onlinejima.com/read_journals.php?article=683, https://c19p.org/mondal
239. Chertok Shacham et al., Impact of blood glucose control on clinical outcomes in type 2 diabetes patients hospitalized with COVID-19 infection
857 patient metformin prophylaxis study: 70% lower mortality (p=0.01).Retrospective 857 hospitalized type 2 diabetes patients showing lower mortality with pre-admission metformin use. Authors report no significant difference in mortality with in-hospital metformin use, but do not report the actual result.
Nov 2024, Diabetes and Vascular Disease Research, https://journals.sagepub.com/doi/10.1177/14791641241288390, https://c19p.org/chertokshacham2
240. Ravikirti et al., Ivermectin as a potential treatment for mild to moderate COVID-19: A double blind randomized placebo-controlled trial
112 patient ivermectin early treatment RCT: 89% lower mortality (p=0.12), 79% lower ventilation (p=0.1), 14% lower ICU admission (p=0.8), and 89% higher hospital discharge (p=0.12).RCT with 112 mild and moderate COVID-19 patients in India, showing lower mortality, ventilation, and ICU admission, although not statistically significant due to the small number of events. There was no mortality in the treatment arm (55 patients) versus 7% (4 of 57) in the control arm. The PCR result is subject to confounding by biased loss of followup, with 23 lost in the treatment group and 13 in the control group, and 8 more people in the treatment group discharged before day 6.
Jan 2021, J. Pharmacy & Pharmaceutical Sciences, https://journals.library.ualberta.ca/jpps/index.php/JPPS/article/view/32105, https://c19p.org/ravikirti
241. Shen et al., Real-world effectiveness of Azvudine in hospitalized patients with COVID-19: a retrospective cohort study
452 patient azvudine late treatment PSM study: 74% lower mortality (p=0.04), 91% lower ventilation (p=0.06), 75% lower ICU admission (p=0.37), and 57% lower progression (p=0.05).PSM retrospective 900 hospitalized COVID-19 patients in China showing lower risk of disease progression and death with azvudine treatment.
Jan 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.01.23.23284899, https://c19p.org/shen3
242. Rastogi et al., Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomised, placebo-controlled, study (SHADE study)
40 patient vitamin D late treatment RCT: 53% improved viral clearance (p=0.02).53% reduction in PCR+ with high-dose cholecalciferol supplementation. RCT with 16 treatment patients and 24 control patients. 25(OH)D levels at day 14 were 52 ng/ml vs. 15 ng/ml in the intervention and control group.
Nov 2020, Postgraduate Medical J., https://pmj.bmj.com/content/early/2020/11/12/postgradmedj-2020-139065.full, https://c19p.org/rastogi
243. Colado Simão et al., Effect of phthalocyanine oral and nasal antiseptic solutions on the infectivity of SARS-CoV-2 in patients with COVID-19: a randomized controlled trial
75 patient phthalocyanine late treatment RCT: 51% improved viral clearance (p=0.008).RCT 75 patients in Brazil, showing significantly lower viral load with phthalocyanine mouthwash and nasal spray. The combination was more effective than mouthwash alone.
Jun 2023, German Medical Science GMS Publishing House, https://www.egms.de/en/journals/gms/2023-21/000321.shtml, https://c19p.org/coladosimao
244. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient HCQ prophylaxis study: 69% lower mortality (p=0.0002).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3h
245. Azhar et al., Effectiveness of early pharmaceutical interventions in symptomatic COVID-19 patients: A randomized clinical trial
471 patient HCQ early treatment RCT: 71% lower mortality (p=0.03), 4% greater improvement (p=0.64), and 10% improved viral clearance (p=0.52).RCT 471 mild COVID-19 patients in Pakistan showing no significant differences in clinical improvement and viral clearance between HCQ, azithromycin, oseltamivir, and combinations. Mortality was significantly lower in HCQ vs. non-HCQ arms. The best results for viral clearance and clinical improvement were seen with the combination of all treatments. There was no placebo group (the study compares different combinations of treatments). No serious adverse events were reported. All patients had mild COVID-19 and the paper indicates early treatment, however time from onset is not reported and minimal baseline information is provided.
Mar 2024, Pakistan J. Medical Sciences, https://www.pjms.org.pk/index.php/pjms/article/view/8757, https://c19p.org/azhar
246. Behera et al., Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
372 patient ivermectin prophylaxis study: 54% fewer cases (p=0.0007).Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/beherai
247. Cardoso et al., Patterns of physical activity and SARS-CoV-2 severe pneumonia: A case–control study
614 patient exercise study: 73% lower severe cases (p<0.0001).Case control study with 307 severe COVID-19 ICU patients and 307 matched COVID-19 outpatients in Brazil, showing significantly higher risk of severe cases with low physical activity.
May 2023, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775323002518, https://c19p.org/cardoso
248. Ferreira et al., Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection
26,815 patient HCQ prophylaxis study: 47% fewer cases (p<0.0001).Chronic treatment with HCQ provides protection against COVID, odds ratio 0.51 (0.37-0.70). The actual benefit is likely to be larger becasue research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall. Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure.
Jun 2020, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.26286, https://c19p.org/ferreira
249. Finkelstein et al., The Efficacy of Long-Term Hydroxychloroquine Use in the Prevention of COVID-19: A Retrospective Cohort Study
110,038 patient HCQ prophylaxis PSM study: 21% fewer cases (p=0.0007).PSM retrospective SLE/RA patients in the USA, showing lower COVID-19 cases with HCQ prophylaxis.
Jun 2023, Studies in Health Technology and Informatics, https://ebooks.iospress.nl/doi/10.3233/SHTI230489, https://c19p.org/finkelstein
250. Ansarin et al., Effect of bromhexine on clinical outcomes and mortality in COVID-19 patients: A randomized clinical trial
78 patient bromhexine early treatment RCT: 91% lower mortality (p=0.05), 89% lower ventilation (p=0.01), and 82% lower ICU admission (p=0.01).RCT with 39 bromhexine and 39 control patients showing lower mortality, intubation, and ICU admission with treatment. The treatment group received bromhexine hydrochloride 8 mg three times a day for two weeks. All patients received SOC including HCQ.
Jul 2020, Bioimpacts, https://bi.tbzmed.ac.ir/Article/bi-23240, https://c19p.org/ansarin
251. Dhibar et al., The ‘myth of Hydroxychloroquine (HCQ) as post-exposure prophylaxis (PEP) for the prevention of COVID-19’ is far from reality
1,168 patient HCQ prophylaxis RCT: 27% fewer symptomatic cases (p=0.32) and 21% fewer cases (p=0.21).Low dose low-risk patient HCQ PEP RCT, showing lower symptomatic cases with treatment, without statistical significance. There were no moderate or severe cases. HCQ 800mg on day one followed by 400mg once weekly for 3 weeks.
Jan 2023, Scientific Reports, https://www.nature.com/articles/s41598-022-26053-w, https://c19p.org/dhibar2
252. Prasoppokakorn et al., Efficacy and Safety of Andrographolide and Favipiravir Versus Favipiravir Monotherapy in Patients with Mild COVID-19 Infection: A Multicenter Randomized Controlled Trial
82 patient andrographolide early treatment RCT: 37% improved recovery (p=0.005).Randomized controlled trial of 82 mild COVID-19 outpatients showing significantly greater reduction in cough and lower inflammatory markers at day 7. Symptomatic improvement was significant at day 7 when combining all symptoms reported, but not for other symptoms individually. There was no progression to severe pneumonia in either group.
Feb 2024, OBM Integrative and Complementary Medicine, https://www.lidsen.com/journals/icm/icm-09-01-013, https://c19p.org/prasoppokakorn
253. Lauriola et al., Effect of combination therapy of hydroxychloroquine and azithromycin on mortality in COVID-19 patients
360 patient HCQ late treatment study: 74% lower mortality (p=0.001).Retrospective 377 patients, 73% reduction in mortality with HCQ+AZ, adjusted hazard ratio HR 0.27 [0.17-0.41]. Mean age 71.8. No serious adverse events. Subject to incomplete adjustment for confounders.
Sep 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/abs/10.1111/cts.12860, https://c19p.org/lauriola
254. Cui et al., Efficacy of ursodeoxycholic acid in the prevention and treatment of COVID-19 in patients with chronic hepatitis B
215 patient ursodeoxycholic acid prophylaxis PSM study: 48% faster recovery (p=0.01) and 83% fewer cases (p=0.001).Retrospective 215 patients with chronic hepatitis B in China, showing lower risk of COVID-19 infection, milder symptoms, and faster recovery with ursodeoxycholic acid (UDCA) treatment.
Mar 2024, J. Clinical Hepatology, https://www.lcgdbzz.org/en/article/doi/10.12449/JCH240309, https://c19p.org/cui2
255. Costello et al., Ursodeoxycholic acid and severe COVID-19 outcomes in a cohort study using the OpenSAFELY platform
11,305 patient ursodeoxycholic acid prophylaxis study: 24% lower mortality (p=0.13), 19% lower hospitalization (p=0.02), and 21% lower combined mortality/hospitalization (p=0.005).OpenSAFELY retrospective 11,305 primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) patients showing lower risk of COVID-19 hospitalization or death with ursodeoxycholic acid (UDCA) treatment.
Dec 2023, Communications Medicine, https://www.nature.com/articles/s43856-024-00664-y, https://c19p.org/costello
256. Nguyen et al., Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses
2,424 patient cannabidiol prophylaxis study: 50% fewer cases (p=0.006).Retrospective 1,212 patients in the USA with a history of seizure-related conditions, showing patients treated with CBD100 had significantly lower incidence of COVID-19 cases compared to a matched control group. In Vitro study showing CBD inhibits SARS-CoV-2 with Vero E6 and Calu-3 cells. Mouse study showing CBD significantly inhibited viral replication in the lung and nasal turbinate. Authors note that CBD does not inhibit ACE2 expression or the main viral proteases, inhibition occurs after viral entry. Authors stress several limitations for use at this time, including purity, quality, and the formulation of products, and potential lung damage based on administration method. Authors recommend clinical trials, but do not mention the existing RCT by Crippa et al.
Jan 2022, Science Advances, https://www.science.org/doi/10.1126/sciadv.abi6110, https://c19p.org/nguyen
257. Hong et al., Early Hydroxychloroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication
90 patient HCQ early treatment study: 65% improved viral clearance (p=0.001).HCQ 1-4 days from diagnosis was the only protective factor against prolonged viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4 days delay vs. 22.9% for 5+ days delayed treatment. Authors report that early administration of HCQ significantly ameliorates inflammatory cytokine secretion and that COVID-19 patients should be administrated HCQ as soon as possible. 42 patients with HCQ 1-4 days from diagnosis, 48 with HCQ 5+ days from diagnosis.
Jul 2020, Infection & Chemotherapy, 2020, https://icjournal.org/DOIx.php?id=10.3947/ic.2020.52.3.396, https://c19p.org/hong
258. Arshad et al., Treatment with Hydroxychloroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19
2,541 patient HCQ late treatment study: 51% lower mortality (p=0.009).HCQ decreases mortality from 26.4% to 13.5% (HCQ) or 20.1% (HCQ+AZ). Propensity matched HCQ HR 0.487, p=0.009. Michigan 2,541 patients retrospective. Before propensity matching the HCQ group average age is 5 years younger and the percentage of male patients is 4% higher which is likely to favor the treatment and the control respectively in the before-propensity matching results. Some reported limtiations of this study are inaccurate [ijidonline.com]. Corticosteroids were controlled for in the multivariate and propensity analyses as were age and comorbidities including cardiac disease and severity of illness. Age was an independent risk factor associated with mortality. HCQ was independently associated with decreased mortality, distinct from the steroid effect. 91% of all patients began treatment within two days of admission. HCQ was used throughout the study period, limiting time bias. Patients assigned to HCQ group had moderate and severe illness at presentation, which would favor..
Jun 2020, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(20)30534-8/fulltext, https://c19p.org/arshad
259. Lavilla Olleros et al., Use of glucocorticoids megadoses in SARS-CoV-2 infection in a spanish registry: SEMI-COVID-19
14,921 patient HCQ late treatment study: 36% lower mortality (p<0.0001).Retrospective 14,921 hospitalized patients in Spain, showing lower mortality with HCQ treatment.
Jan 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261711, https://c19p.org/lavillaolleros
260. Sheshah et al., Prevalence of Diabetes, Management and Outcomes among Covid-19 Adult Patients Admitted in a Specialized Tertiary Hospital in Riyadh, Saudi Arabia
300 patient HCQ late treatment study: 80% lower mortality (p=0.001).Retrospective 300 hospitalized patients in Saudi Arabia showing HCQ adjusted odds ratio aOR 0.12, p < 0.001.
Nov 2020, Diabetes Research and Clinical Practice, https://www.sciencedirect.com/science/article/pii/S0168822720307956, https://c19p.org/sheshah
261. Morrison et al., COVID-19 outcomes in patients taking cardioprotective medications
13,585 patient metformin prophylaxis PSM study: 41% lower mortality (p=0.003), 16% higher ventilation (p=0.49), 3% lower ICU admission (p=0.85), and 4% higher hospitalization (p=0.72).Retrospective 13,585 COVID+ patients in the USA, showing lower mortality with metformin use, but no significant difference for ventilation, ICU admission, and hospitalization.
Oct 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0275787, https://c19p.org/morrison
262. Bernabeu-Wittel et al., Effectiveness of a On-Site Medicalization Program for Nursing Homes with COVID-19 Outbreaks
272 patient HCQ early treatment study: 94% lower mortality (p=0.001).Retrospective 272 nursing home residents showing significantly improved survival after establishing a treatment program including HCQ with or without lopinavir/ritonavir and with the addition of adjuvant and antimicrobial treatments depending on circumstances. HCQ (114 patients), HCQ+LPV/RTV (18 patients), and HCQ+AZ (7 patients). Dosage details are in the supplementary appendix.
Jul 2020, J. Gerontol. A Biol. Sci. Med. Sci., https://academic.oup.com/biomedgerontology/advance-article/doi/10.1093/gerona/glaa192/5879759, https://c19p.org/bernabeuwittel
263. Kadnur et al., Hydroxychloroquine pre-exposure prophylaxis for COVID-19 among healthcare workers: Initial experience from India
358 patient HCQ prophylaxis study: 62% fewer cases (p=0.01).Prophylaxis study with 334 low-risk healthcare workers in India, showing significantly lower risk of cases with treatment. Symptomatic patients received PCR results, but only some asymptomatic patients did, so there may have been additional asymptomatic cases. There were no severe adverse events.
Jul 2020, J. Family Medicine and Primary Care, https://journals.lww.com/10.4103/jfmpc.jfmpc_1177_21, https://c19p.org/kadnur
264. Wischmeyer et al., Daily Lactobacillus Probiotic versus Placebo in COVID-19-Exposed Household Contacts (PROTECT-EHC): A Randomized Clinical Trial
182 patient probiotics prophylaxis RCT: 33% fewer moderate/severe cases (p=0.15), 38% fewer symptomatic cases (p=0.02), 27% faster recovery (p=0.37), and 43% fewer cases (p=0.17).RCT 182 COVID-19 exposed patients, 91 treated with daily probiotic Lactobacillus rhamnosus GG starting a median of 3 days from exposure, showing lower symptomatic COVID-19 with treatment. There were no hospitalizations or deaths.
Jan 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.01.04.21268275, https://c19p.org/wischmeyer
265. Hunt et al., Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans
26,508 patient vitamin D early treatment study: 47% lower mortality (p=0.0007).Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including vitamin D. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/hunt
266. Hasan et al., The Effect of Melatonin on Thrombosis, Sepsis and Mortality Rate in COVID-19 Patients
158 patient melatonin late treatment RCT: 93% lower mortality (p=0.0004).RCT 158 severe condition patients in Iraq, 82 treated with melatonin, showing lower mortality, thrombosis, and sepsis with treatment.
Oct 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221007980, https://c19p.org/hasan
267. McCreary et al., Randomized double-blind placebo-controlled proof-of-concept trial of resveratrol for outpatient treatment of mild coronavirus disease (COVID-19)
100 patient resveratrol early treatment RCT: 67% lower hospitalization (p=0.62) and 43% lower progression (p=0.52).RCT 100 outpatients in the USA, showing lower hospitalization and progression with resveratrol, without statistical significance.
Jun 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-13920-9, https://c19p.org/mccreary3
268. Yadav et al., Sero-survey for health-care workers provides corroborative evidence for the effectiveness of Hydroxychloroquine prophylaxis against COVID-19 infection
500 patient HCQ prophylaxis study: 82% lower hospitalization (p=0.01) and 42% fewer cases (p=0.05).ICMR seroprevalence survey of 500 healthcare workers in India, 279 taking HCQ prophylaxis, showing a significantly lower risk with treatment, and lower severity.
Sep 2020, ResearchGate, https://www.researchgate.net/publication/344221734_Sero-survey_for_health-care_workers_provides_corroborative_evidence_for_the_effectiveness_of_Hydroxychloroquine_prophylaxis_against_COVID-19_infection, https://c19p.org/yadav3
269. Araldi et al., Effects of antidiabetic drugs on mortality risks in individuals with type 2 diabetes: A prospective cohort study of UK Biobank participants
43,610 patient metformin prophylaxis study: 60% lower mortality (p<0.0001).UK Biobank retrospective including 43,610 type 2 diabetes patients, showing lower mortality with metformin use within matched type 2 diabetes patients.
May 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.05.19.23290214, https://c19p.org/araldi
270. Yang et al., Oral azvudine for mild‐to‐moderate COVID‐19 in high risk, nonhospitalized adults: Results of a real‐world study
804 patient azvudine early treatment study: 91% lower mortality (p=0.09), 75% lower hospitalization (p=0.05), and 16% improved recovery (p=0.19).PSM retrospective 804 high-risk, nonhospitalized adults with mild to moderate COVID-19 in China. The study compared outcomes between 317 patients who received azvudine with 487 patients who received standard supportive treatment only. The azvudine group had a lower rate of disease progression (composite of death or COVID-19 hospitalization) at 28 days, as well as a lower rate of COVID-19 hospitalization specifically after adjusting for factors. In addition, azvudine shortened the duration of fever if given within 3 days of symptom onset. However, azvudine treatment was associated with a higher incidence of adverse effects, including mainly mild gastrointestinal and nervous system effects.
Jul 2023, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.28947, https://c19p.org/yang8
271. Ghati et al., Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial)
661 patient aspirin late treatment RCT: 22% lower mortality (p=0.62), 9% lower ventilation (p=0.8), and 30% lower progression (p=0.46).RCT hospitalized patients in India, 224 treated with atorvastatin, 225 with aspirin, and 225 with both, showing lower serum interleukin-6 levels with aspirin, but no statistically significant changes in other outcomes. Low dose aspirin 75mg daily for 10 days.
Jul 2022, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-022-07570-5, https://c19p.org/ghati
272. Bishop et al., REsCue Trial: Randomized Controlled Clinical Trial with Extended-Release Calcifediol in Symptomatic COVID-19 Outpatients
134 patient vitamin D late treatment RCT: 85% lower progression (p=0.25) and 34% improved recovery (p=0.56).Small RCT with low-risk patients in the USA showing no significant differences in overall recovery. Minimal details on outcomes are provided in the preprint. Authors note significantly faster resolution of respiratory symptoms when treatment increased vitamin D levels. Baseline vitamin D was relatively high, mean 37±1 ng/mL, 95% >20ng/mL, leaving little room for improvement. Treatment delay is not specified but is likely relatively late based on the symptoms at baseline, PCR testing delay, and exclusion with FLU-PRO scores <1.5. ER/urgent care data from clinicaltrials.gov.
Feb 2022, Nutrition, https://www.sciencedirect.com/science/article/pii/S0899900722003100, https://c19p.org/bishop
273. Rocco et al., Nitazoxanide in Patients Hospitalized With COVID-19 Pneumonia: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial
405 patient nitazoxanide late treatment RCT: 5% higher mortality (p=0.95), 31% lower ICU admission (p=0.18), 40% lower need for oxygen therapy (p=0.06), and 64% faster improvement (p<0.0001).RCT late stage patients with COVID-19 pneumonia, 202 treated with nitazoxanide and 203 placebo patients, showing improved recovery, but no significant difference in mortality.
Apr 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.844728/full, https://c19p.org/rocco2
381 patient nigella sativa late treatment RCT: 61% lower ICU admission (p=0.28), 70% shorter hospitalization (p=0.001), and 67% improved recovery (p=0.001).
RCT 358 hospitalized patients in Iran, 184 receiving treatment with a combination of nigella sativa and several other herbal medicines, showing shorter hospitalization time and improved recovery with treatment. IR.TUMS.VCR.REC.1399.024.
Oct 2021, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7277, https://c19p.org/karimi
275. Pavlidou et al., Association of COVID-19 Infection with Sociodemographic, Anthropometric and Lifestyle Factors: A Cross-Sectional Study in an Older Adults’ Population Aged over 65 Years Old
5,197 patient exercise study: 42% fewer cases (p=0.001).Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity, depression, anxiety, stress, and poor health-related quality of life.
Nov 2023, Diseases, https://www.mdpi.com/2079-9721/11/4/165, https://c19p.org/pavlidou
276. Lengelé et al., Frailty but not sarcopenia nor malnutrition increases the risk of developing COVID-19 in older community-dwelling adults
241 patient exercise study: 74% fewer cases (p=0.03).Analysis of 241 adults >65yo in Belgium, showing lower risk of COVID-19 with a history of physical activity.
Oct 2021, Aging Clinical and Experimental Research, https://link.springer.com/10.1007/s40520-021-01991-z, https://c19p.org/lengele
80 patient favipiravir late treatment study: 69% lower pneumonia (p=0.04) and 71% improved viral clearance (p=0.03).
Comparison of 35 FPV patients and 35 LPV/RTV patients, showing significant improvements in chest CT and faster viral clearance with FPV.
Mar 2020, Engineering, https://www.sciencedirect.com/science/article/pii/S2095809920300631, https://c19p.org/cai
278. Salgado-Aranda et al., Influence of Baseline Physical Activity as a Modifying Factor on COVID-19 Mortality: A Single-Center, Retrospective Study
520 patient exercise study: 83% lower mortality (p=0.003).Retrospective 520 COVID-19 patients in Spain, showing significantly lower mortality with a history of physical activity.
Mar 2022, Infectious Diseases and Therapy, https://link.springer.com/article/10.1007/s40121-021-00418-6/fulltext.html, https://c19p.org/salgadoaranda
279. Somasundaram et al., Metformin use and its association with various outcomes in COVID-19 patients with diabetes mellitus: a retrospective cohort study in a tertiary care facility
421 patient metformin prophylaxis study: 89% lower mortality (p<0.0001).Retrospective 421 hospitalized COVID-19 patients with type 2 diabetes in India, showing significantly lower mortality with metformin use compared to other antidiabetic medications.
Nov 2024, Annals of Medicine, https://www.tandfonline.com/doi/full/10.1080/07853890.2024.2425829, https://c19p.org/somasundaram
499 patient favipiravir late treatment RCT: 26% lower mortality (p=0.24), 24% lower ventilation (p=0.21), and 6% improved recovery (p=0.53).
PIONEER very late treatment RCT showing lower mortality and mechanical ventilation with favipiravir, without statistical significance. The conclusion "favipiravir is not efficacious in treating hospitalised adult patients with COVID-19" is incorrect. Authors show 26% and 24% lower mortality and mechanical ventilation. While these results are not statistically significant, they predict efficacy, and cannot be used to rule out efficacy. Favipiravir 1,800mg bid day 1, 800mg bid days 2-10.
Sep 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S221326002200412X, https://c19p.org/shah5
281. Nasri et al., Efficacy of hydroxychloroquine in pre-exposure severe acute respiratory syndrome coronavirus 2 prophylaxis among high-risk healthcare workers: A multicenter study
143 patient HCQ prophylaxis RCT: 92% fewer symptomatic cases (p=0.03).RCT 143 healthcare workers in Iran, showing lower cases with HCQ prophylaxis, statistically significant only for moderate/severe cases. Baseline details are not provided.
Jan 2023, Advanced Biomedical Research, https://www.advbiores.net/article.asp?issn=2277-9175;year=2023;volume=12;issue=1;spage=3;epage=3;aulast=Nasri, https://c19p.org/nasri
282. Pawar et al., Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial
140 patient curcumin early treatment RCT: 82% lower mortality (p=0.02).RCT 140 patients, 70 treated with curcumin and piperine (for absorption), and 70 treated with probiotics, showing faster recovery, lower progression, and lower mortality with curcumin.
May 2021, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2021.669362/full, https://c19p.org/pawar
283. Brunetti et al., Colchicine to Weather the Cytokine Storm in Hospitalized Patients with COVID-19
66 patient colchicine late treatment PSM study: 73% lower mortality (p=0.03) and 73% higher hospital discharge (p=0.03).PSM matched analysis from consecutive hospitalized patients, with 33 colchicine and 33 control matched patients, showing lower mortality with treatment.
Sep 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/9/2961, https://c19p.org/brunetti
284. Sandhu et al., A Case Control Study to Evaluate the Impact of Colchicine on Patients Admitted to the Hospital with Moderate to Severe COVID-19 Infection
112 patient colchicine late treatment study: 42% lower mortality (p=0.0006), 53% lower ventilation (p<0.0001), 42% higher hospital discharge (p=0.0006), and 5% shorter hospitalization.Prospective cohort study of hospitalized patients in the USA, 34 treated with colchicine, showing lower mortality and intubation with treatment.
Oct 2020, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2020/8865954/, https://c19p.org/sandhu
285. Bramante et al., Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19
1,307 patient metformin early treatment RCT: 52% lower combined mortality/hospitalization (p=0.09), 40% lower progression (p=0.03), and 37% improved viral clearance (p=0.0008).COVID-OUT remotely operated RCT, showing lower combined ER/hospitalization/death with metformin. Results for other treatments are listed separately - ivermectin , fluvoxamine . The "control" group includes patients receiving active treatments fluvoxamine and ivermectin. Control arm results are very different between treatments, for example considering hospitalization/death, this was 1.0% for ivermectin vs. 2.7% for overall control, however it was 1.3% for the ivermectin-specific control. 394 control patients are shared. The rate for the non-shared 261 metformin control patients is 5%, compared to 1.3% for ivermectin control patients. The metformin arm started earlier, however it is unclear why the difference in outcomes is so large. Results were delayed for 6 months with no explanation, with followup ending Feb 14, 2022. Adherence was very low, with 77% overall reporting 70+% adherence. Numbers for 100% adherence are not provided. Multiple outcomes are missing, for example time to..
Aug 2022, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2201662, https://c19p.org/covidoutmf
286. Dubee et al., Hydroxychloroquine in mild-to-moderate COVID-19: a placebo-controlled double blind trial
247 patient HCQ late treatment RCT: 46% lower mortality (p=0.21) and 26% lower combined mortality/intubation (p=0.48).Small early terminated late stage (60% on oxygen) RCT in France showing 46% lower mortality. mortality at 28 days relative risk RR 0.54 [0.21-1.42] combined mortality/intubation at 28 days relative risk RR 0.74 [0.33-1.70] If not stopped early and the same trend continued, statistical significance would be reached on 28 day mortality after ~550 patients (1,300 patients were planned). Mortality results are not provided for subgroups. For the subgroups receiving AZ: No safety concerns were identified. This study has been presented as negative, however the results do not support that conclusion.
Oct 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X21001403, https://c19p.org/dubee
287. Huang et al., Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19
373 patient HCQ late treatment study: 67% faster viral clearance (p=0.0001).197 CQ patients, 176 control. Mean time to undetectable viral RNA and duration of fever significantly reduced. No serious adverse events.
May 2020, National Science Review, https://academic.oup.com/nsr/advance-article/doi/10.1093/nsr/nwaa113/5848167, https://c19p.org/huangnsr
288. Zong et al., Azvudine reduces the in-hospital mortality of COVID-19 patients: A retrospective cohort study
1,072 patient azvudine late treatment PSM study: 62% lower mortality (p=0.0002).PSM retrospective 1072 hospitalized patients with COVID-19 pneumonia in China, showing lower mortality with azvudine treatment.
Jul 2023, Acta Pharmaceutica Sinica B, https://www.sciencedirect.com/science/article/pii/S2211383523002575, https://c19p.org/zong
289. Piarulli et al., Association of renin-angiotensin-aldosterone system inhibitors with best COVID-19 outcomes in a diabetic population of the Veneto Region (north-east Italy): a lesson for endemic phase?
4,014 patient metformin prophylaxis study: 53% lower combined mortality/ICU admission (p=0.08) and 45% lower hospitalization (p=0.0002).Retrospective diabetic COVID-19 patients in Italy, showing lower risk of hospitalization with metformin use.
Jun 2023, Nutrition, Metabolism and Cardiovascular Diseases, https://www.sciencedirect.com/science/article/pii/S0939475323002491, https://c19p.org/piarulli
290. Di Pierro et al., Role of S. salivarius K12 in the prevention of URTI and AGE in nursery-aged children
287 patient probiotics prophylaxis study: 78% fewer cases (p=0.007).Retrospective study of 287 nursery school children in Italy, 186 treated with S. salivarius K12 probiotic. The probiotic group had significantly lower rates of COVID-19, bronchitis, sinusitis, and laryngitis as well as lower antibiotic use. The study was registered retrospectively and details of COVID-19 diagnosis are not provided. Parents that administer the treatment may also use other treatments or take other actions that reduce risk for their children.
Sep 2023, Minerva Medica, https://www.minervamedica.it/index2.php?show=R10Y9999N00A23092804, https://c19p.org/dipierro7
291. Lakkireddy et al., Effect of Short Term High Dose Oral Vitamin D Therapy on the Inflammatory Markers in Patients with COVID 19 Disease
87 patient vitamin D late treatment RCT: 61% lower mortality (p=0.27), 22% lower ICU admission (p=0.74), and 7% shorter hospitalization (p=0.9).RCT 44 treatment and 43 control patients with vitamin D levels <30ng/ml, showing significant reduction in inflammatory markers with treatment of 60,000IU vitamin D per day for 8 days (10 days for BMI >25). Death and ICU admission was lower in the treatment group but not statistically significant. Randomization was simple alternation, with the allocation officer unaware of which group patients were being assigned to as detailed in the study. An earlier version of this study was censored based on incorrect claims from an anti-treatment researcher. For discussion see [c19early.org].
Jul 2022, Archives of Clinical and Biomedical Research, https://www.fortunejournals.com/articles/effect-of-short-term-high-dose-oral-vitamin-d-therapy-on-the-inflammatory-markers-in-patients-with-covid-19-disease.html, https://c19p.org/lakkireddy
292. Uz et al., Role of intravenous vitamin C on outcomes in hospitalized patients with moderate or severe COVID-19: a real life data of Turkish patients
270 patient vitamin C late treatment study: 84% lower mortality (p=0.05).Retrospective 270 moderate/severe hospitalized COVID-19 patients, showing lower mortality with high (25 g/day) or low-dose (2 g/day) intraveneous vitamin C.
Nov 2024, Inflammopharmacology, https://link.springer.com/10.1007/s10787-024-01597-7, https://c19p.org/uz
293. Friedland et al., Phase II Trial of the Impact 0.5% Povidone‐Iodine Nasal Spray (Nasodine®) on Shedding of SARS‐CoV‐2
23 patient povidone-iodine early treatment RCT: 60% improved viral clearance (p=0.03) and 6% improved recovery.RCT 23 early COVID-19 outpatients showing significantly improved reduction in viral load and significantly faster viral clearance with povidone-iodine nasal spray compared to placebo. The study was underpowered due to low recruitment, enrolling only 23 patients from a target of 144. Authors report generally mild symptoms and a 6% benefit over placebo on symptom scores (AUC symptom score days 2–5) without statistical significance, but do not provide details. Notably, no benefit was seen for rapid antigen test positivity, which is unable to distinguish viable and non-viable virus. The relatively poor diagnostic information from viral positivity using methods that cannot distinguish viable virus may present misleading results in many COVID-19 studies. Treatment 8 times daily for a total of 20 doses.
Mar 2024, The Laryngoscope, https://onlinelibrary.wiley.com/doi/10.1002/lary.31430, https://c19p.org/friedland2
568 patient exercise study: 71% lower severe cases (p=0.001).
Retrospective 568 convalescent COVID-19 patients in Poland, showing lower risk of severe cases with regular physical activity in the 3 months before COVID-19.
Dec 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034122003495, https://c19p.org/kapusta
295. Ugarte-Gil et al., Characteristics associated with poor COVID-19 outcomes in individuals with systemic lupus erythematosus: data from the COVID-19 Global Rheumatology Alliance
895 patient HCQ prophylaxis study: 44% lower severe cases (p=0.007).Retrospective 1,606 SLE patients showing lower risk of severe COVID-19 outcomes with HCQ/CQ use.
Feb 2022, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2022/02/15/annrheumdis-2021-221636.long, https://c19p.org/ugartegil
296. Yilmaz et al., Effects of hypertonic alkaline nasal irrigation on COVID‐19
60 patient alkalinization early treatment RCT: 86% lower hospitalization (p=0.24) and 62% improved viral clearance (p=0.87).RCT 60 outpatients with mild COVID-19 showing improved viral clearance with hypertonic alkaline (pH 9.3) nasal irrigation. All patients received HCQ. The nasal irrigation group had no hospitalizations, while 3 patients in the control group required hospitalization, associated with viral load increase at day 3.
Nov 2021, Laryngoscope Investigative Otolaryngology, https://onlinelibrary.wiley.com/doi/10.1002/lio2.686, https://c19p.org/yilmaz4
21,026 patient famotidine prophylaxis PSM study: 36% fewer cases (p<0.0001).
PSM retrospective in South Korea, showing lower risk of COVID-19 cases with H2RA (including famotidine) and PPI use, but no significant difference in severe outcomes (results provided for the combined groups only).
Mar 2023, J. Korean Medical Science, https://jkms.org/DOIx.php?id=10.3346/jkms.2023.38.e99, https://c19p.org/kim11
298. Li et al., Protective effect of ursodeoxycholic acid on COVID-19 in patients with chronic liver disease
450 patient ursodeoxycholic acid prophylaxis study: 80% lower severe cases (p=0.22), 80% fewer moderate/severe cases (p<0.0001), and 11% fewer cases (p=0.05).Retrospective propensity score matched cohort study of 225 chronic liver disease patients on UDCA therapy matched to 225 controls without UDCA in China. UDCA use was associated with lower COVID-19 infection rate (85% vs 94%), lower maximum temperature, less severe symptoms, shorter recovery time (5 vs 7 days median), and lower risk of infection on regression (OR 0.32). The results rely on patient self-report rather than lab confirmed COVID-19 diagnosis.
May 2023, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2023.1178590/full, https://c19p.org/li26
299. Zhang et al., Efficacy of azvudine plus dexamethasone in severe hospitalized patients with Omicron infection: a prospective multicenter study
209 patient azvudine late treatment study: 43% lower progression (p=0.03) and 14% faster viral clearance (p=0.02).Prospective multicenter study of 209 severe hospitalized COVID-19 patients in China showing improved 28-day composite outcomes, faster viral clearance, and higher PaO2/FiO2 levels with azvudine plus dexamethasone compared to dexamethasone alone.
Nov 2024, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2024.1390098/full, https://c19p.org/zhang39
300. Kinoshita et al., A multicenter, double-blind, randomized, parallel-group, placebo-controlled study to evaluate the efficacy and safety of camostat mesilate in patients with COVID-19 (CANDLE study)
155 patient camostat early treatment RCT: 67% lower progression (p=1), 50% lower need for oxygen therapy (p=0.37), 1% worse recovery (p=1), and 1% worse viral clearance (p=0.97).RCT 155 hospitalized patients showing no significant differences with camostat.
Sep 2022, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02518-7, https://c19p.org/kinoshita
301. Núñez-Gil et al., Hydroxychloroquine and Mortality in SARS-Cov-2 Infection; The HOPE- Covid-19 Registry.
6,217 patient HCQ late treatment PSM study: 53% lower mortality (p<0.0001).PSM retrospective 6,217 hospitalized patients in Spain, showing lower mortality with HCQ. The higher efficacy reported with obesity is consistent with the greater efficacy predicted for higher cholesterol [Yuan].
Sep 2022, Anti-Infective Agents, https://www.eurekaselect.com/204783/article, https://c19p.org/nunezgil2
302. Okumuş et al., Evaluation of the Effectiveness and Safety of Adding Ivermectin to Treatment in Severe COVID-19 Patients
60 patient ivermectin late treatment RCT: 33% lower mortality (p=0.55), 43% greater improvement (p=0.18), and 80% improved viral clearance (p=0.02).Small RCT for severe COVID-19 comparing the addition of ivermectin to SOC (low dose HCQ+AZ+favipiravir), with 30 treatment and 30 control patients in Turkey, showing lower mortality and faster clinical recovery. Authors also investigate the presence of gene mutations that alter ivermectin metabolism, predicting that ivermectin can be used safely without serious side effects in patients without MDR-1/ABCB1 and/or CYP3A4 gene mutation, and recommending monitoring and appropriate treatment if necessary when sequencing is unavailable. NCT04646109.
Jan 2021, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06104-9, https://c19p.org/okumus
303. Simova et al., Hydroxychloroquine for prophylaxis and treatment of COVID-19 in health care workers
204 patient HCQ prophylaxis study: 93% fewer cases (p=0.01).100% reduction in cases with HCQ+zinc post-exposure prophylaxis. Brief report for healthcare workers in Bulgaria. 0 cases with treatment vs. 3 for control. 156 treatment patients and 48 control patients. No serious adverse events. This paper reports on both PEP and early treatment, we have separated the two studies.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297520301657, https://c19p.org/simovapep
82,069 patient fluvoxamine prophylaxis PSM study: 28% fewer cases (p<0.0001).
TriNetX PSM retrospective 82,069 OCD patients, showing lower risk of COVID-19 with fluvoxamine use.
Oct 2022, The Primary Care Companion For CNS Disorders, https://www.psychiatrist.com/pcc/ocd/protective-effect-fluvoxamine-covid-19-obsessive-compulsive-disorder-real-world-case-control-study/, https://c19p.org/diaz3
305. Catteau et al., Low-dose Hydroxychloroquine Therapy and Mortality in Hospitalized Patients with COVID-19: A Nationwide Observational Study of 8075 Participants
8,075 patient HCQ late treatment study: 32% lower mortality (p<0.0001).Retrospective 8,075 hospitalized patients, 4,542 low-dose HCQ, 3,533 control. 35% lower mortality for HCQ (17.7% vs. 27.1%), adjusted HR 0.68 [0.62–0.76]. Low-dose HCQ monotherapy was independently associated with lower mortality in hospitalized patients. Patients exposed to others therapies (TCZ, AZ, LPV/RTV) were excluded. Statistical analysis was performed by an independent group. Calendar time of prescription and immortal time bias was taken into account. Corticosteroids prescriptions was low in both groups.
Aug 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920303423, https://c19p.org/catteau
306. Derwand et al., COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study
518 patient HCQ early treatment study: 79% lower mortality (p=0.12) and 82% lower hospitalization (p=0.001).79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. No cardiac side effects. Retrospective 518 patients (141 treated, 377 control).
Jul 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304258, https://c19p.org/derwand
11,672 patient melatonin prophylaxis study: 58% fewer cases (p<0.0001).
Retrospective 11,672 patients tested for COVID-19 with 818 testing positive, showing significantly lower risk with melatonin use.
Jun 2020, Chest, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286244/, https://c19p.org/jehi
308. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient ibuprofen prophylaxis study: 48% lower mortality (p=0.002).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3ib
309. Mancilla-Galindo et al., Regional moderate hyperthermia for mild-to-moderate COVID-19 (TherMoCoV study): a randomized controlled trial
105 patient thermotherapy late treatment RCT: 43% lower mortality (p=0.28), 21% lower ventilation (p=0.76), and 17% lower progression (p=0.67).RCT 105 hospitalized patients with mild-to-moderate COVID-19, evaluating the efficacy and safety of local thermotherapy (heating pads applied to the chest for 90 minutes twice daily for 5 days) to prevent disease progression, compared to standard care alone. The thermotherapy was well-tolerated with no significant adverse events. Reduction in NEWS-2 score was significantly faster with treatment. There was lower progression and mortality with treatment, without statistical significance. The study was underpowered due to early termination. The temperature used may be too low. Lung temperature is expected to be lower than the external skin surface temperature measured on the thorax, due to heat diffusion and dissipation that occurs in transferring thermal energy across the tissue layers of skin, adipose, muscle, connective tissue and bone between the heating pad and the lung. The treatment group had greater severity at baseline, NEWS-2 7 vs. 5, and PH-COVID-19 high-risk 7.5% vs. 0%...
Dec 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1256197/full, https://c19p.org/mancillagalindo2
310. Gorial et al., Randomized controlled trial of colchicine add on to the standard therapy in moderate and severe corona virus Disease-19 infection
160 patient colchicine late treatment RCT: 63% improved recovery (p=0.001).RCT with 80 colchicine and 80 control patients, showing improved recovery with treatment. SOC included vitamin C, vitamin D, and zinc.
Apr 2022, Annals of Medicine and Surgery, https://www.sciencedirect.com/science/article/pii/S2049080122003533, https://c19p.org/gorial2
311. Gunst et al., Efficacy of the TMPRSS2 inhibitor camostat mesilate in patients hospitalized with Covid-19-a double-blind randomized controlled trial
205 patient camostat late treatment RCT: 18% lower mortality (p=0.75), 31% lower ventilation (p=0.65), 20% lower ICU admission (p=0.61), and 15% improved recovery (p=0.28).RCT 205 hospitalized patients showing no significant benefit with camostat. There was a trend towards lower risk of ICU admission or death in the camostat group (10% vs. 18% for placebo), but the study was not powered for this endpoint. Viral load and inflammatory markers were not significantly different between groups. The study was underpowered due to faster than expected clinical improvement.
May 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537021001292, https://c19p.org/gunst
312. Zhao et al., Treatments Associated with Lower Mortality among Critically Ill COVID-19 Patients: A Retrospective Cohort Study
2,070 patient aspirin late treatment study: 43% lower mortality (p=0.0006).Retrospective 2,070 hospitalized patients in the USA, showing lower mortality with aspirin treatment.
Sep 2021, Anesthesiology, https://pubs.asahq.org/anesthesiology/article-abstract/doi/10.1097/ALN.0000000000003999/117698/Treatments-Associated-with-Lower-Mortality-among?redirectedFrom=fulltext, https://c19p.org/zhao5
313. Schmidt et al., Self-Reported Pre-Pandemic Physical Activity and Likelihood of COVID-19 Infection: Data from the First Wave of the CoCo-Fakt Survey
5,338 patient exercise study: 31% fewer cases (p=0.02).Retrospective 5,338 individuals with confirmed contact with a COVID-19 patient, showing lower risk of COVID-19 with exercise.
Jun 2023, Sports Medicine - Open, https://sportsmedicine-open.springeropen.com/articles/10.1186/s40798-023-00592-6, https://c19p.org/schmidt3
314. Aref et al., Possible Role of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Recovery of Post-COVID-19 Anosmia
96 patient ivermectin long COVID RCT: 74% faster recovery (p=0.0005).96 patient RCT showing faster resolution of post-COVID anosmia with an ivermectin nanosuspension nasal spray.
Sep 2022, Infection and Drug Resistance, https://www.dovepress.com/possible-role-of-ivermectin-mucoadhesive-nanosuspension-nasal-spray-in-peer-reviewed-fulltext-article-IDR, https://c19p.org/aref2
315. Alam et al., Ivermectin as Pre-exposure Prophylaxis for COVID-19 among Healthcare Providers in a Selected Tertiary Hospital in Dhaka – An Observational Study
118 patient ivermectin prophylaxis study: 91% fewer cases (p<0.0001).91% reduction in COVID-19 cases with ivermectin prophylaxis. 118 healthcare workers in Bangladesh, 58 receiving ivermectin 12mg monthly, showing RR 0.094, p < 0.0001.
Dec 2020, European J. Medical and Health Sciences, https://ejmed.org/index.php/ejmed/article/view/599, https://c19p.org/alam2
316. Skipper et al., Hydroxychloroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial
465 patient HCQ early treatment RCT: 37% lower combined mortality/hospitalization (p=0.58), 49% lower hospitalization (p=0.38), and 20% improved recovery (p=0.21).Update: we have not received details for treatment delay. An author reports that treatment initiation time was not recorded: [osf.io]. Conflicting estimates are provided in a comment of the article and independent analysis, with reports indicating missing data in the dataset. Also see [medrxiv.org] (companion PEP trial), and Pullen et al. [ncbi.nlm.nih.gov], which shows shipping delay for these trials of 19 - 68 hours. Only one third of participants completed enrollment weekdays between 8:00am and 4:00pm, with 44% outside of these hours during the week, and 22% during the weekend. With enrollment up to 4 days after symptom onset, this implies delivery 19 - 164 hours after onset (19 hours would require instantaneous enrollment). ~70 to 140 hour (inc. shipping) delayed outpatient treatment with HCQ showing lower hospitalization/death and faster recovery, but not reaching statistical significance. There was one hospitalized control death and one non-hospitalized HCQ death. It is unclear..
Jul 2020, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M20-4207, https://c19p.org/skipper
317. Lee et al., Association Between Ursodeoxycholic Acid and Clinical Outcomes in Patients With COVID-19 Infection: Population-Based Cohort Study
413,226 patient ursodeoxycholic acid prophylaxis study: 57% lower severe cases (p=0.19) and 15% fewer cases (p=0.21).Retrospective 1,675,593 patients in the Jeonbuk CDM cohort and 8,528,533 patients in the NHIS cohort, showing ursodeoxycholic acid (UDCA) intake associated with significantly lower risk of COVID-19 infection and severe COVID-19.
Aug 2024, JMIR Public Health and Surveillance, http://preprints.jmir.org/preprint/59274/accepted, https://c19p.org/lee16
318. Chen et al., Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial
62 patient HCQ late treatment RCT: 57% lower pneumonia (p=0.04).62 patients. RCT showing significantly faster recovery with HCQ. 13% progressed to severe cases in the control group, versus 0% for the treatment group. Significant improvement seen in pneumonia on chest CT for 61% of treated patients and 16% of control patients.
Mar 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.03.22.20040758v3, https://c19p.org/chenrct
117 patient camostat late treatment RCT: 8% lower progression (p=1) and 40% higher hospital discharge (p=0.04).
RCT 117 hospitalized patients with moderate COVID-19 pneumonia in Japan, showing a shorter time to discharge with favipiravir, camostat, and ciclesonide combination therapy compared to favipiravir monotherapy. Subgroup analysis showed greater benefit in patients ≤60 years old and those with less severe disease not requiring oxygen. There were no significant differences between groups in clinical findings, laboratory values, or adverse events. The mortality numbers in the main results table and the text are different, without explanation.
Jun 2022, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537022002140, https://c19p.org/terada
320. Huang et al., Reduced Sleep in the Week Prior to Diagnosis of COVID-19 is Associated with the Severity of COVID-19
136 patient sleep study: 81% lower severe cases (p=0.02).Retrospective 164 COVID-19 patients and 188 controls in China, showing the risk of severe cases associated with lack of sleep.
Nov 2021, Nature and Science of Sleep, https://www.dovepress.com/reduced-sleep-in-the-week-prior-to-diagnosis-of-covid-19-is-associated-peer-reviewed-article-NSS, https://c19p.org/huang5sl
321. Ceccarelli et al., Oral Bacteriotherapy in Patients With COVID-19: A Retrospective Cohort Study
200 patient probiotics late treatment study: 64% lower mortality (p=0.003) and 15% lower ICU admission (p=0.6).Retrospective 200 severe condition hospitalized patients in Italy, 88 treated with probiotic Sivomixx, showing lower mortality with treatment.
Jan 2021, Frontiers in Medicine, https://internal-journal.frontiersin.org/articles/10.3389/fnut.2020.613928/full, https://c19p.org/ceccarelli
322. Strangfeld et al., Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry
1,165 patient HCQ prophylaxis study: 48% lower mortality (p<0.0001).Retrospective 3,729 rheumatic disease patients showing lower risk of mortality with HCQ/CQ use (HCQ/CQ vs. no DMARD therapy).
Jan 2021, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/80/7/930, https://c19p.org/strangfeld
323. Wang et al., Efficacy of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance for COVID-19 patients
55 patient alkalinization late treatment RCT: 39% shorter hospitalization (p=0.0009).RCT 55 mild/moderate patients in China, showing shorter hospitalization with sodium bicarbonate nasal irrigation and oral rinsing. Oral rinse with 5% sodium bicarbonate solution three times daily. Nasal irrigation two times with the solution entering through one nostril and exiting from the other. 30–40mL of solution was used every time and irrigation was performed for at least 30s. Details of randomization are not provided.
Mar 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1145669/full, https://c19p.org/wang12
324. Wang et al., Efficacy of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance for COVID-19 patients
55 patient sodium bicarbonate late treatment RCT: 39% shorter hospitalization (p=0.0009).RCT 55 mild/moderate patients in China, showing shorter hospitalization with sodium bicarbonate nasal irrigation and oral rinsing. Oral rinse with 5% sodium bicarbonate solution three times daily. Nasal irrigation two times with the solution entering through one nostril and exiting from the other. 30–40mL of solution was used every time and irrigation was performed for at least 30s. Details of randomization are not provided.
Mar 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1145669/full, https://c19p.org/wang12sb
325. Gentry et al., Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study
32,109 patient HCQ prophylaxis study: 91% lower mortality (p=0.1) and 21% fewer cases (p=0.27).Retrospective patients with rheumatologic conditions showing zero of 10,703 COVID-19 deaths for HCQ patients versus 7 of 21,406 propensity matched control patients (not statistically significant). The average age of HCQ patients is slightly lower 64.8 versus 65.4 control. COVID-19 cases OR 0.79, p=0.27. There are several significant differences in the propensity matched patients that could affect results, e.g., 20.9% SLE versus 24.7%.
Sep 2020, Lancet Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30305-2/fulltext, https://c19p.org/gentry
262 patient colchicine late treatment study: 85% lower mortality (p<0.0001).
Retrospective 122 colchicine patients and 140 control patients in Italy, showing lower mortality with treatment.
Sep 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/79/10/1286, https://c19p.org/scarsi
327. Heras et al., COVID-19 mortality risk factors in older people in a long-term care center
100 patient HCQ early treatment study: 96% lower mortality (p=0.004).Retrospective 100 COVID+ elderly nursing home patients, HCQ+AZ mortality 11.4% vs. control 61.9%, RR 0.18, p<0.001. Median age 85.
Sep 2020, European Geriatric Medicine, https://link.springer.com/article/10.1007/s41999-020-00432-w, https://c19p.org/heras
328. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
2,148 patient vitamin D prophylaxis study: 33% lower hospitalization (p=0.001) and 29% lower severe cases (p=0.01).Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin D prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimer
329. Wander et al., Prior Glucose-Lowering Medication Use and 30-Day Outcomes Among 64,892 Veterans With Diabetes and COVID-19
64,892 patient metformin prophylaxis study: 15% lower mortality (p<0.0001), 2% lower ICU admission (p=0.62), and 3% lower hospitalization (p=0.09).Retrospective 64,892 veterans with diabetes in the USA, showing lower mortality with existing metformin use.
Oct 2021, Diabetes Care, https://care.diabetesjournals.org/content/early/2021/10/06/dc21-1351.article-info, https://c19p.org/wander
87 patient dutasteride antiandrogen early treatment RCT: 62% improved recovery (p=0.009).
RCT 130 outpatients in Brazil, 54 treated with dutasteride, showing faster recovery with treatment. All patients received nitazoxanide. There were no hospitalizations, mechanical ventilation, or deaths. Some percentages for viral clearance in Table 3 do not match the group sizes, and a third-party analysis suggests possible randomization failure. 34110420.2.0000.0008.
Jan 2021, Cureus, https://www.cureus.com/articles/50511-early-antiandrogen-therapy-with-dutasteride-reduces-viral-shedding-inflammatory-responses-and-time-to-remission-in-males-with-covid-19-a-randomized-double-blind-placebo-controlled-interventional-trial-eat-duta-androcov-trial---biochemical, https://c19p.org/cadegiani7
1,991 patient alcohol study: 50% fewer cases (p=0.05).
Retrospective survey of 1,997 college students in the USA, showing higher risk of COVID-19 cases with alcohol consumption.
Feb 2022, JMIR Mental Health, https://mental.jmir.org/2022/2/e34645, https://c19p.org/gilleyac
332. Malisoux et al., Associations between physical activity prior to infection and COVID-19 disease severity and symptoms: results from the prospective Predi-COVID cohort study
224 patient exercise study: 63% lower progression (p=0.05).Retrospective 452 participants in Luxembourg, showing lower risk of moderate cases with higher physical activity.
Apr 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2021-057863, https://c19p.org/malisoux
333. Nguyen et al., Single and Combinative Impacts of Healthy Eating Behavior and Physical Activity on COVID-19-like Symptoms among Outpatients: A Multi-Hospital and Health Center Survey
3,947 patient exercise study: 20% fewer symptomatic cases (p<0.0001).Analysis of 3,947 participants in Vietnam, showing significantly lower risk of COVID-19-like symptoms with physical activity and with a healthy diet. The combination of being physically active and eating healthy reduced risk further compared to either alone. The analyzed period was Feb 14 to Mar 2, 2020, which may have been before testing was widely available.
Sep 2021, Nutrients, https://www.mdpi.com/2072-6643/13/9/3258, https://c19p.org/nguyen2
334. Tamura et al., Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies
188 patient metformin late treatment study: 97% lower mortality (p=0.02).Retrospective 188 hospitalized patients in Brazil, showing lower risk of mortality with metformin use. Authors note that, although pre-hospital metformin use improved clinical parameters at admission, continuous use during hospitalization is essential. Patients that used pre-hospital metformin therapy but interrupted the treatment during hospitalization showed higher mortality than those that continued metformin therapy.
Jul 2021, Diabetology & Metabolic Syndrome, https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-021-00695-8, https://c19p.org/tamura
335. Esper et al., Empirical treatment with hydroxychloroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine
636 patient HCQ early treatment study: 64% lower hospitalization (p=0.02).636 patients. HCQ+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.
Apr 2020, Prevent Senior Institute, São Paulo, Brazil, https://pgibertie.com/wp-content/uploads/2020/04/2020.04.15-journal-manuscript-final.pdf, https://c19p.org/esper
336. Salman et al., Role of vitamin-D supplementation in COVID-19 patients
300 patient vitamin D late treatment RCT: 60% lower mortality (p=0.07), 17% lower ventilation (p=0.55), 12% lower ICU admission (p=0.85), and 18% shorter hospitalization (p=0.001).RCT 300 hospitalized COVID-19 patients in Pakistan receiving either 4,000 IU vitamin D3 supplementation or standard care daily for 14 days. The vitamin D group had significantly faster time to clinical improvement (7 vs 9 days) and shorter length of stay (9 vs 11 days). 65% of patients were vitamin D deficient at baseline.
Jun 2023, Biological and Clinical Sciences Research J., https://bcsrj.com/ojs/index.php/bcsrj/article/view/322, https://c19p.org/salman
337. Di Castelnuovo et al., Use of hydroxychloroquine in hospitalised COVID-19 patients is associated with reduced mortality: Findings from the observational multicentre Italian CORIST study
3,451 patient HCQ late treatment study: 30% lower mortality (p<0.0001).Retrospective 3,451 hospitalized patients, 30% reduction in mortality with HCQ after propensity adjustment, HR 0.70 [0.59 - 0.84].
Aug 2020, European J. Internal Medicine, https://www.sciencedirect.com/science/article/abs/pii/S0953620520303356, https://c19p.org/dicastelnuovo
338. Jimenez et al., Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics
285 patient vitamin D prophylaxis study: 50% lower mortality (p=0.02).Retrospective 288 hemodialysis patients in Spain, 137 with existing vitamin D treatments (94 with paricalcitol), showing lower mortality with treatment. There was no significant difference in outcomes based on serum levels, however authors do not separate patients that received vitamin D treatment.
Jul 2021, Nutrients, https://www.mdpi.com/2072-6643/13/8/2559, https://c19p.org/jimenez
339. Sanz et al., Vitamin D3 supplementation in COVID-19 patients with cardiovascular disease and gut dysbiosis
22 patient vitamin D late treatment RCT: 83% lower ventilation (p=0.06) and 60% lower ICU admission (p=0.36).Small RCT 22 hospitalized COVID-19 patients with cardiovascular disease in Argentina showing lower mortality, ventilation, and ICU admission with vitamin D treatment, without statistical significance. Treatment was associated with lower levels of inflammatory markers IL-6, IL-8 and TNF-α, higher levels of anti-inflammatory IL-10, and improvements in gut microbiome markers. 10,000 IU/day vitamin D3 for 10 days.
Jun 2024, Hipertensión y Riesgo Vascular, https://www.sciencedirect.com/science/article/pii/S1889183724000564, https://c19p.org/sanz
340. Cadegiani et al., Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients
296 patient HCQ early treatment study: 81% lower mortality (p=0.21), 95% lower ventilation (p=0.0008), and 98% lower hospitalization (p<0.0001).Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297521000792, https://c19p.org/cadegiani
341. Bencheqroun et al., A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2
52 patient nigella sativa early treatment RCT: 9% faster improvement (p=0.78) and 43% improved viral clearance (p=0.31).52 patient RCT in the USA with nigella sativa component thymoquinone, showing improved recovery with treatment. There was a significantly faster decline in the total symptom burden, and a significant increase in CD8+ and helper CD4+ central memory T lymphocytes. The treatment group contained 5 more vaccinated patients and 7 more overweight patients. Authors also present in vitro results showing an inhibitory effect with five SARS-CoV-2 variants including omicron.
May 2022, Pathogens, https://www.mdpi.com/2076-0817/11/5/551, https://c19p.org/bencheqroun
342. Şengül et al., Serum Vitamin D Concentrations and Covid-19 In Pregnant Women, Does Vitamin D Supplementation Impact Results? A Comprehensive Study
318 patient vitamin D prophylaxis study: 69% fewer cases (p=0.004).Retrospective 318 pregnant women, 54 COVID+ and 264 healthy controls, showing lower risk of COVID-19 with vitamin D supplementation, and with higher vitamin D levels.
Dec 2022, Cukurova Anestezi ve Cerrahi Bilimler Dergisi, https://dergipark.org.tr/en/doi/10.36516/jocass.1185181, https://c19p.org/sengul
343. Wu et al., Azvudine for the Treatment of COVID‐19 in Pre‐Existing Cardiovascular Diseases: A Single‐Center, Real‐World Experience
351 patient azvudine early treatment PSM study: 81% lower mortality (p=0.0008).Retrospective 351 hospitalized COVID-19 patients with pre-existing cardiovascular diseases in China, showing lower mortality with azvudine treatment.
Mar 2024, Advanced Science, https://onlinelibrary.wiley.com/doi/10.1002/advs.202306050, https://c19p.org/wu10
344. Luo et al., Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis
283 patient metformin prophylaxis study: 75% lower mortality (p=0.02).Retrospective 283 COVID-19+ diabetes patients in China, showing lower mortality with existing metformin treatment.
May 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/configurable/content/journals$002ftpmd$002f103$002f1$002farticle-p69.xml?t:ac=journals%24002ftpmd%24002f103%24002f1%24002farticle-p69.xml, https://c19p.org/luo3
345. Fasano et al., COVID-19 in Parkinson’s Disease Patients Living in Lombardy, Italy
1,486 patient vitamin D prophylaxis study: 42% fewer cases (p=0.05).Retrospective phone survey of 1,486 Parkinson's disease patients in Italy, showing lower risk of COVID-19 cases with vitamin D supplementation. This paper also presents a case control study of PD patients and family member control patients.
Jun 2021, Movement Disorders, https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28176, https://c19p.org/fasano
346. Holubar et al., Favipiravir for treatment of outpatients with asymptomatic or uncomplicated COVID-19: a double-blind randomized, placebo-controlled, phase 2 trial
149 patient favipiravir early treatment RCT: 89% lower hospitalization (p=0.06), 30% lower progression (p=0.56), 19% worse recovery (p=0.43), and 32% worse viral clearance (p=0.24).Small RCT 116 mITT patients in the USA, 59 treated with favipiravir, showing no significant differences with treatment.
Nov 2021, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciac312/6572081, https://c19p.org/holubar
347. Sánchez-Álvarez et al., Status of SARS-CoV-2 infection in patients on renal replacement therapy. Report of the COVID-19 Registry of the Spanish Society of Nephrology (SEN)
375 patient HCQ late treatment study: 46% lower mortality (p=0.005).Analysis of 868 patients on renal replacement therapy. Statistically significant reduction in mortality with HCQ for patients on dialysis (OR 0.47, p=0.005). No statistically significant change was found for transplant patients (the result is not given but likely the sample size is too small - the number of transplant patients was half the number of dialysis patients).
Apr 2020, Nefrología, https://www.sciencedirect.com/science/article/pii/S201325142030050X, https://c19p.org/sanchezalvarez
348. Meizlish et al., Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: A propensity score-matched analysis
638 patient aspirin late treatment PSM study: 48% lower mortality (p=0.004).Retrospective 638 matched hospitalized patients in the USA, 319 treated with aspirin, showing lower mortality with treatment.
Jan 2021, American J. Hematology, https://onlinelibrary.wiley.com/doi/10.1002/ajh.26102, https://c19p.org/meizlish
349. Lobelo et al., Clinical, behavioural and social factors associated with racial disparities in COVID-19 patients from an integrated healthcare system in Georgia: a retrospective cohort study
5,712 patient exercise study: 20% lower hospitalization (p=0.02).Retrospective 5,712 COVID-19 patients in the USA, showing higher risk of COVID-19 hospitalization with a history of physical inactivity.
May 2021, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2020-044052, https://c19p.org/lobelo
350. Carlucci et al., Zinc sulfate in combination with a zinc ionophore may improve outcomes in hospitalized COVID-19 patients
932 patient zinc late treatment study: 38% lower combined mortality/hospice (p=0.002), 18% lower ventilation (p=0.4), and 23% lower ICU admission (p=0.17).Retrospective 932 patients showing that the addition of zinc to HCQ+AZ reduced mortality / transfer to hospice, ICU admission, and the need for ventilation.
May 2020, J. Medical Microbiology, https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.001250, https://c19p.org/carlucciz
351. Jeon et al., Effect of Spironolactone on COVID-19 in Patients With Underlying Liver Cirrhosis: A Nationwide Case-Control Study in South Korea
294 patient spironolactone antiandrogen prophylaxis study: 77% fewer cases (p=0.005).Retrospective 6,462 liver cirrhosis patients in South Korea, with 67 COVID+ cases, showing significantly lower cases with spironolactone treatment. Death and ICU results per group are not provided.
Feb 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.629176/full, https://c19p.org/jeon
352. Jeon et al., Effect of Spironolactone on COVID-19 in Patients With Underlying Liver Cirrhosis: A Nationwide Case-Control Study in South Korea
294 patient spironolactone prophylaxis study: 77% fewer cases (p=0.005).Retrospective 6,462 liver cirrhosis patients in South Korea, with 67 COVID+ cases, showing significantly lower cases with spironolactone treatment. Death and ICU results per group are not provided.
Feb 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.629176/full, https://c19p.org/jeonsp
353. Tsuzuki et al., Impact of dementia, living in a long-term care facility, and physical activity status on COVID-19 severity in older adults
4,868 patient exercise study: 56% lower severe cases (p<0.0001).Retrospective 4,868 elderly COVID-19 patients in Japan, showing higher risk of severe cases with poor physical activity status.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277144, https://c19p.org/tsuzuki3
354. Li et al., Evaluating the protective effectiveness and risk factors of ursodeoxycholic acid on COVID-19 among outpatients
192 patient ursodeoxycholic acid prophylaxis PSM study: 21% fewer symptomatic cases (p=0.001), 19% fewer cases (p=0.004), and 18% lower progression (p=0.04).Retrospective 1,040 outpatients in China showing lower COVID-19 cases, less severe symptoms, and shorter symptom duration with ursodeoxycholic acid (UDCA) use.
Jul 2024, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2024.1381830/full, https://c19p.org/li36
355. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient metformin prophylaxis study: 30% lower mortality (p<0.0001).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3mf
356. Siripongboonsitti et al., Assessing Favipiravir's Impact on SARS-CoV-2 Transmission within Households: Insights from a Multi-center Study (FaviPrev)
2,006 patient favipiravir early treatment study: 25% lower transmission (p=0.05).Retrospective 976 mild to moderate COVID-19 outpatients in Thailand showing significantly lower household transmission with favipiravir treatment of index cases.
Dec 2024, J. Virus Eradication, https://www.sciencedirect.com/science/article/pii/S2055664024001912, https://c19p.org/siripongboonsitti7
357. Hunt et al., Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans
26,508 patient antiandrogen early treatment study: 39% lower mortality (p<0.0001).Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including anti-androgens. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.
Jun 2022, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07701-3, https://c19p.org/huntaa
358. Yildiz et al., The prognostic significance of vitamin D deficiency in patients with COVID-19 pneumonia
207 patient vitamin D late treatment study: 81% lower mortality (p=0.04), 94% lower ICU admission (p=0.13), and 10% shorter hospitalization (p=0.32).Retrospective 207 hospitalized patients in Turkey, 37 with vitamin D levels <30ng/ml treated with a single dose of 300,000IU vitamin D, showing lower mortality with treatment.
Sep 2021, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7390&category_id=171&option=com_virtuemart&vmcchk=1&Itemid=1, https://c19p.org/yildiz
359. de Souza et al., Association of physical activity levels and the prevalence of COVID-19-associated hospitalization
938 patient exercise study: 73% lower ventilation (p=0.07) and 34% lower hospitalization (p=0.05).Retrospective survey of 938 COVID-19 recovered patients in Brazil, showing lower hospitalization with physical activity. NCT04396353.
Sep 2021, J. Science and Medicine in Sport, https://www.jsams.org/article/S1440-2440(21)00136-5/fulltext, https://c19p.org/desouza
360. Sekhavati et al., Safety and effectiveness of azithromycin in patients with COVID-19: An open-label randomised trial
111 patient azithromycin late treatment RCT: 86% lower ventilation (p=0.12), 72% lower ICU admission (p=0.09), and 23% shorter hospitalization (p=0.02).Randomized controlled trial of 111 hospitalized COVID-19 patients in Iran showing significantly shorter hospital stay, higher oxygen saturation, and lower respiratory rate at discharge with azithromycin plus hydroxychloroquine and lopinavir/ritonavir compared to hydroxychloroquine and lopinavir/ritonavir alone. There were no significant differences in ICU admission, intubation, or mortality, although there was a trend towards lower ICU admission with azithromycin (3.6% vs. 12.7%, p = 0.07). Patients with prior cardiac disease were excluded. The study is limited by the small sample size and open-label design.
Oct 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920303411, https://c19p.org/sekhavatiaz
361. Soltani et al., The effectiveness of gabapentin and gabapentin/montelukast combination compared with dextromethorphan in the improvement of COVID‐19‐ related cough: A randomized, controlled clinical trial
127 patient montelukast late treatment RCT: 20% shorter hospitalization (p=0.01) and 25% improved recovery (p=0.0006).RCT 180 hospitalized COVID-19 patients showing improved cough frequency and severity with gabapentin and gabapentin/montelukast compared to dextromethorphan, with the combination being more efficacious. The gabapentin/montelukast group had a significantly greater reduction in cough frequency (measured by the Breathlessness, Cough, and Sputum Scale) compared to the gabapentin alone group. There was no significant difference between the two groups in cough severity reduction measured by Visual Analog Scale.
Jul 2022, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13529, https://c19p.org/soltani2
362. Karonova et al., Effect of Cholecalciferol Supplementation on the Clinical Features and Inflammatory Markers in Hospitalized COVID-19 Patients: A Randomized, Open-Label, Single-Center Study
110 patient vitamin D late treatment RCT: 86% lower ICU admission (p=0.11) and 7% lower need for oxygen therapy (p=0.85).RCT with 56 cholecalciferol and 54 control hospitalized patients with vitamin D insufficiency or deficiency in Russia, showing positive effects on immune status. The median age in the treatment group was 7 years lower and deficiency was less common, while baseline treatment group CT lung involvement and supplemental oxygen use was higher in the treatment group. Treatment increased vitamin D levels and neutrophil and lymphocyte counts, decreased CRP levels, and was associated with a decrease in CD38++CD27 transitional and CD27−CD38+ mature naive B cells and an increase in CD27−CD38− DN B cells.
Jun 2022, Nutrients, https://www.mdpi.com/2072-6643/14/13/2602, https://c19p.org/karonova5
363. Wanaratna et al., Efficacy and Safety of Andrographis Paniculata Extract in Patients with Mild COVID-19: A Randomized Controlled Trial
57 patient andrographolide early treatment RCT: 86% lower progression (p=0.11) and 40% improved viral clearance (p=0.11).RCT 63 mild COVID-19 patients showing lower progression and improved viral clearance with andrographis, without statistical significance.
Jul 2021, Archives of Internal Medicine Research, https://www.fortunejournals.com/articles/efficacy-and-safety-of-andrographis-paniculata-extract-in-patients-with-mild-covid19-a-randomized-controlled-trial.html, https://c19p.org/wanaratna
364. Qadir et al., Efficacy of Favipiravir in the Treatment of Mild to Moderate COVID-19 Patients in Erbil: A Controlled Clinical Trial
250 patient favipiravir early treatment study: 97% lower mortality (p<0.0001), 60% lower hospitalization (p=0.001), and 97% improved recovery (p<0.0001).Prospective study with 125 favipiravir patients and 125 patients declining favipiravir treatment, showing lower mortality and improved recovery with treatment. All patients received vitamin C, D, and zinc. Favipiravir 3200mg day 1, followed by 600mg bid days 2-10.
May 2022, Int. J. Applied Sciences: Current and Future Research Trends, https://ijascfrtjournal.isrra.org/index.php/Applied_Sciences_Journal/article/view/1235, https://c19p.org/qadir
365. Ma et al., Associations between predicted vitamin D status, vitamin D intake, and risk of SARS-CoV-2 infection and Coronavirus Disease 2019 severity
19,535 patient sunlight study: 23% fewer cases (p=0.0001).Analysis of 39,915 patients with 1,768 COVID+ cases based on surveys in the Nurses' Health Study II, showing higher UVA/UVB exposure associated with lower risk of COVID-19 cases.
Dec 2021, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqab389/6448988, https://c19p.org/ma2sun
366. Ouedraogo et al., Factors associated with the occurrence of acute respiratory distress and death in patients with COVID-19 in Burkina Faso
456 patient HCQ late treatment study: 33% lower mortality (p=0.38) and 68% lower severe cases (p=0.001).Retrospective 456 patients in Burkina Faso showing lower risk of ARDS (p=0.001) and mortality (p=0.38) with HCQ.
Feb 2021, Revue des Maladies Respiratoires, https://www.sciencedirect.com/science/article/pii/S0761842521000383, https://c19p.org/ouedraogo
367. Obrișcă et al., Characteristics of SARS-CoV-2 Infection in an Actively Monitored Cohort of Patients with Lupus Nephritis
95 patient HCQ prophylaxis study: 87% fewer cases (p=0.01).Prospective analysis of 95 Lupus Nephritis patients in Romania, showing lower risk of COVID-19 with HCQ use.
Sep 2022, Biomedicines, https://www.mdpi.com/2227-9059/10/10/2423, https://c19p.org/obrisca
368. Ip et al., Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: A multi-center observational study
1,067 patient HCQ early treatment study: 55% lower mortality (p=0.43) and 37% lower hospitalization (p=0.04).Retrospective 1,274 outpatients, 47% reduction in hospitalization with HCQ with propensity matching, HCQ OR 0.53 [0.29-0.95]. Sensitivity analyses revealed similar associations. Adverse events were not increased (2% QTc prolongation events, 0% arrhythmias).
Aug 2020, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-05773-w, https://c19p.org/ip
523 patient vitamin D late treatment study: 80% lower mortality (p=0.001).
80% lower mortality with cholecalciferol booster therapy. Retrospective 986 hospitalized patients in the UK finding that cholecalciferol booster therapy, regardless of baseline serum levels, was associated with a reduced risk of mortality in acute COVID-19 inpatients. Primary cohort of 444 patients, adjusted mortality odds ratio aOR 0.13, p < 0.001. Validation cohort of 541 patients, adjusted mortality odds ratio aOR 0.38, p = 0.018.
Dec 2020, Nutrients, https://www.mdpi.com/2072-6643/12/12/3799, https://c19p.org/ling
370. Alcala-Diaz et al., Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study
537 patient vitamin D late treatment study: 81% lower mortality (p=0.04).Retrospective 537 patients in Spain, 79 treated with calcifediol, showing significantly lower mortality with treatment. The treated group had a higher risk of comorbidity, whereas the control group had lower O2 saturation, higher CURB-65, and higher ARDS (severity measures were included in the multivariate analysis).
May 2021, Nutrients, https://www.mdpi.com/2072-6643/13/6/1760, https://c19p.org/alcaladiaz
371. Medhat et al., Sofosbuvir/Ledipasvir in Combination or Nitazoxanide Alone are Safe and Efficient Treatments for COVID-19 Infection: A Randomized Controlled Trial for Repurposing antivirals
150 patient nitazoxanide early treatment RCT: 56% improved viral clearance (p=0.02).RCT with 77 nitazoxanide, 70 sofosbuvir/ledipasvir, and 73 SOC patients in Egypt, showing faster viral clearance with nitazoxanide and with sofosbuvir/ledipasvir. There was no mortality or progression to severe COVID-19 or ICU admission. Nitazoxanide 500mg qid for 14 days. SOC included vitamin C and zinc.
May 2022, Arab J. Gastroenterology, https://www.sciencedirect.com/science/article/pii/S1687197922000326, https://c19p.org/medhat
372. Crouse et al., Metformin Use Is Associated With Reduced Mortality in a Diverse Population With COVID-19 and Diabetes
220 patient metformin prophylaxis study: 61% lower mortality (p=0.02).Retrospective 219 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment.
Jan 2021, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2020.600439/full, https://c19p.org/crouse
373. Salva et al., Reversal of SARS-CoV2-Induced Hypoxia by Nebulized Sodium Ibuprofenate in a Compassionate Use Program
501 patient alkalinization late treatment study: 45% lower mortality (p=0.009) and 14% shorter hospitalization (p<0.0001).Retrospective 383 hospitalized COVID-19 patients in Argentina showing signifcantly lower mortality and shorter hospital stay with nebulized sodium ibuprofenate compared to 195 contemporaneous controls. The treatment appears to be the same as detailed in [Kalayan], which reports a pH of 8.5. [Kreutzberger] showed that SARS-CoV-2 requires an acidic pH (between 6.2-6.8) for membrane fusion and cell entry, even when the viral spike protein is primed by proteases like TMPRSS2. Efficacy seen here may be more due to alkalinization, which shows more consistent higher efficacy than ibuprofen in studies to date. Baseline SpO2 was significantly different for the patients on mechanical ventilation at baseline.
Aug 2021, Infectious Diseases and Therapy, https://link.springer.com/10.1007/s40121-021-00527-2, https://c19p.org/salvaph
374. Kulzhanova et al., Clinical efficacy of the antiviral drug favipiravir in the complex treatment of patients with COVID-19 coronavirus infection
80 patient favipiravir late treatment study: 88% greater improvement (p<0.0001) and 50% improved viral clearance (p=0.18).Retrospective 40 favipiravir patients in Kazakhstan and 40 controls, showing faster recovery and viral clearance with treatment.
Aug 2021, , https://newjournal.ssmu.kz/upload/iblock/026/6_15_4_23_2021.pdf, https://c19p.org/kulzhanova
375. Bhandari et al., Effectiveness of Inhaled Steroids in Post COVID Cough
120 patient budesonide late treatment study: 33% lower need for oxygen therapy (p=0.009), 26% shorter hospitalization (p=0.02), and 37% faster recovery (p=0.001).Retrospective 120 hospitalized COVID-19 patients with persistent cough in India, showing faster resolution of cough, shorter duration of oxygen support, and shorter hospitalization with inhaled budesonide treatment compared to standard of care alone.
Mar 2022, Int. J. Scientific Development and Research, https://mail.ijsdr.org/viewpaperforall.php?paper=IJSDR2203020, https://c19p.org/bhandari2
376. Isnardi et al., Sociodemographic and clinical factors associated with poor COVID-19 outcomes in patients with rheumatic diseases: data from the SAR-COVID Registry
2,066 patient HCQ prophylaxis study: 34% lower mortality (p=0.23), 48% lower severe cases (p=0.02), and 17% lower hospitalization (p=0.09).Retrospective 1,915 rheumatic disease patients with COVID-19 in Argentina, showing lower mortality, severe oxygen requirement, and hospitalization with CQ/HCQ (antimalarial) use in unadjusted results, statistically significant only for severe oxygen requirement.
Oct 2022, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-022-06393-8, https://c19p.org/isnardi
377. Wang et al., Adherence to Healthy Lifestyle Prior to Infection and Risk of Post–COVID-19 Condition
1,285 patient exercise study: 11% lower PASC (p=0.2).Prospective analysis of 32,249 women, showing lower risk of PASC with a healthy lifestyle, in a dose-dependent manner. Participants with 5 or 6 healthy lifestyle factors had significantly lower COVID-19 hospitalization and PASC. BMI and sleep were independently associated with risk of PASC.
Feb 2023, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2800885, https://c19p.org/wang10ex
378. Bowen et al., Reduction in risk of death among patients admitted with COVID-19 between first and second epidemic waves in New York City
4,631 patient HCQ late treatment study: 20% lower mortality (p=0.007).Retrospective 4,631 hospitalized patients in New York, showing higher mortality with remdesivir, and lower mortality with HCQ. Authors suggest that increased mortality during the first epidemic wave was partly due to strain on hospital resources.
Aug 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac436/6675651, https://c19p.org/bowen
379. Taccone et al., The role of organizational characteristics on the outcome of COVID-19 patients admitted to the ICU in Belgium
1,747 patient HCQ ICU study: 25% lower mortality (p=0.02).Retrospective 1,747 ICU patients in Belgium showing lower mortality with HCQ, multivariate mixed effects analysis HCQ aOR 0.64 [0.45-0.92].
Dec 2020, The Lancet Regional Health - Europe, https://www.sciencedirect.com/science/article/pii/S2666776220300193, https://c19p.org/taccone
380. Ly et al., Pattern of SARS-CoV-2 infection among dependant elderly residents living in retirement homes in Marseille, France, March-June 2020
226 patient HCQ early treatment study: 56% lower mortality (p=0.02).Retrospective analysis of retirement homes, HCQ+AZ >= 3 days mortality OR 0.37, p=0.02. 1,690 elderly residents (mean age 83), 226 infected residents, 116 treated with HCQ+AZ >= 3 days. Detection via mass screening also showed significant improvements (16.9% vs. 40.6%, OR 0.20, p=0.001), suggesting that earlier detection and treatment is more successful.
Aug 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920304301, https://c19p.org/ly
381. Frish et al., The Association of Weight Reduction and Other Variables after Bariatric Surgery with the Likelihood of SARS-CoV-2 Infection
3,038 patient exercise study: 53% fewer cases (p=0.04).Retrospective 3,038 bariatric surgery patients in Israel, showing higher risk of SARS-CoV-2 infection with vitamin D deficiency, and lower risk with physical activity.
Jun 2023, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/12/4054, https://c19p.org/frishex
382. Lagier et al., Outcomes of 2,111 COVID-19 hospitalised patients treated with 2 hydroxychloroquine/azithromycin and other regimens in Marseille, France: a 3 monocentric retrospective analysis
2,111 patient HCQ late treatment study: 32% lower mortality (p=0.004).Retrospective 2,011 hospitalized patients in France, median age 67, showing lower mortality with HCQ+AZ, and further benefit with the addition of zinc.
Jun 2021, Therapeutics and Clinical Risk Management, https://www.dovepress.com/outcomes-of-2111-covid-19-hospitalized-patients-treated-with-hydroxych-peer-reviewed-fulltext-article-TCRM, https://c19p.org/lagier2
383. Tanioka et al., Why COVID-19 is not so spread in Africa: How does Ivermectin affect it?
1,216,000,000 patient ivermectin prophylaxis study: 88% lower mortality (p=0.002).Retrospective study of the 31 onchocerciasis-endemic countries using the community-directed treatment with ivermectin (CDTI) and the 22 non-endemic countries in Africa, showing significantly lower mortality per capita in the countries using ivermectin.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.26.21254377v1, https://c19p.org/tanioka
384. Yadav et al., Hydroxychloroquine/chloroquine prophylaxis among health-care workers: Was it really preventive? – Evidence from a multicentric cross-sectional study
2,224 patient HCQ prophylaxis study: 20% lower seropositivity (p=0.1).Retrospective 2,224 healthcare workers in India, showing lower risk of seropositivity with HCQ prophylaxis, without statistical significance.
Jul 2022, Indian J. Community Medicine, http://www.ijcm.org.in/text.asp?2022/47/2/202/350357, https://c19p.org/yadav4
385. Singla et al., A randomized controlled trial to evaluate outcomes with Aggrenox in patients with SARS-CoV-2 infection
98 patient aspirin late treatment RCT: 20% lower ventilation (p=1), 29% lower ICU admission (p=0.76), and 33% lower progression (p=0.74).RCT 98 hospitalized patients in the USA, 49 treated with aspirin and dipyridamole, showing improved results with treatment, but without statistical significance.
Jan 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0274243, https://c19p.org/singla
122 patient camostat late treatment PSM study: 69% lower mortality (p=0.001), 10% lower ventilation (p=1), and 17% longer hospitalization (p=0.35).
Retrospective 371 critically ill COVID-19 patients showing lower mortality with camostat mesylate treatment.
Apr 2021, Intensive Care Medicine, https://link.springer.com/10.1007/s00134-021-06395-1, https://c19p.org/sakr
387. Fernandez et al., Intrahospital supervised exercise training improves survival rate among hypertensive COVID-19 patients
439 patient exercise study: 47% lower mortality (p=0.02).Retrospective 439 severe COVID-19 hospitalized patients with hypertension, 201 receiving a supervised exercise program, showing significantly lower mortality with exercise. Exercise included of aerobic, breathing, and musculoskeletal exercises, 3 to 4 times per week. There were significantly more control patients on beta-adrenergic blockers and thiazide diuretics. There are many possible mechanisms of action, including improved circulation, stress reduction, hormone regulation, improved sleep, increased antioxidant levels, and increased nitric oxide levels in the respiratory system. Over-exercising may be detrimental and lead to impaired immune function.
Feb 2023, J. Applied Physiology, https://journals.physiology.org/doi/10.1152/japplphysiol.00544.2022, https://c19p.org/fernandez
388. Chatterjee et al., Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19
455 patient HCQ prophylaxis study: 67% fewer cases (p=0.001).4+ doses of HCQ associated with a significant decline in the odds of getting infected, dose-response relationship exists.
May 2020, Indian J. Medical Research, https://www.ijmr.org.in/article.asp?issn=0971-5916;year=2020;volume=151;issue=5;spage=459;epage=467;aulast=Chatterjee, https://c19p.org/chatterjee
389. Galindo-Andúgar et al., Impact of N-Acetylcysteine in the mortality of patients hospitalized with COVID-19: a retrospective cohort study
378 patient N-acetylcysteine late treatment study: 43% lower mortality (p=0.05).Retrospective 378 hospitalized patients in Spain, showing lower mortality with N-acetylcysteine treatment.
Jul 2023, Revista Clínica Española, https://www.sciencedirect.com/science/article/abs/pii/S2254887423000929, https://c19p.org/galindoandugar
390. Sulli et al., Vitamin D and Lung Outcomes in Elderly COVID-19 Patients
130 patient vitamin D prophylaxis study: 76% fewer cases (p=0.0002).Retrospective 65 elderly COVID-19 patients and 65 matched controls, showing lower vitamin D levels associated with more severe lung involvement, longer disease duration, and higher mortality. Vitamin D supplementation was less common in the COVID-19 group compared to the control group.
Feb 2021, Nutrients, https://www.mdpi.com/2072-6643/13/3/717, https://c19p.org/sulli
391. Avanoglu Guler et al., COVID-19 in familial Mediterranean fever: Clinical course and complications related to primary disease
73 patient colchicine prophylaxis study: 79% lower need for oxygen therapy (p=0.04).Retrospective 73 familial Mediterranean fever patients with COVID-19 in Turkey, showing significantly higher risk of hospitalization for respiratory support with non-adherence to colchicine treatment before the infection.
Jul 2022, Modern Rheumatology, https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roac074/6647632, https://c19p.org/avanogluguler
392. Gordon et al., A Case-Control Study for the Effectiveness of Oral Zinc in the Prevention and Mitigation of COVID-19
200 patient zinc prophylaxis study: 85% fewer symptomatic cases (p=0.02).Prospective study of zinc supplementation with 104 patients randomized to receive 10mg, 25mg, or 50mg of zinc picolinate daily, and a matched sample of 96 control patients from the adjacent clinic that did not routinely recommend/use zinc, showing significantly lower symptomatic COVID-19 with treatment.
Dec 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.756707/full, https://c19p.org/gordon
393. Ong et al., Association Between Metformin Use and Mortality Among Patients with Type 2 Diabetes Mellitus Hospitalized for COVID-19 Infection
355 patient metformin prophylaxis study: 47% lower mortality (p=0.02).Retrospective 355 diabetic hospitalized COVID-19 patients in the Philippines, showing lower mortality with metformin use.
Oct 2021, J. the ASEAN Federation of Endocrine Societies, https://www.asean-endocrinejournal.org/index.php/JAFES/article/view/1155, https://c19p.org/ong
394. Kim et al., Plant-based diets, pescatarian diets and COVID-19 severity: a population-based case–control study in six countries
568 patient diet study: 72% fewer moderate/severe cases (p=0.02) and 19% fewer cases (p=0.24).Retrospective healthcare workers in six countries with exposure to COVID-19 patients, showing lower risk of moderate/severe COVID-19 with plant-based diets.
Jun 2021, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/257, https://c19p.org/kim4
395. Zhou et al., A network medicine approach to investigation and population-based validation of disease manifestations and drug repurposing for COVID-19
26,779 patient melatonin prophylaxis PSM study: 21% fewer cases (p=0.01).PSM observational study with a database of 26,779 patients in the USA, showing significantly lower risk of PCR+ with melatonin usage.
Nov 2020, PLOS Biology, https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000970, https://c19p.org/zhou2
396. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient budesonide prophylaxis study: 22% lower mortality (p=0.004).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3u
397. Pinato et al., Clinical portrait of the SARS-CoV-2 epidemic in European cancer patients
890 patient HCQ late treatment study: 59% lower mortality (p=0.0001).Retrospective 890 cancer patients with COVID-19, adjusted mortality HR for HCQ/CQ 0.41, p<0.0001. Confirmed SARS-CoV-2 infection was required, which may help focus on more severe cases. Analysis with Cox proportional hazard model. Potential unmeasured confounders.
Aug 2020, Cancer Discovery, https://cancerdiscovery.aacrjournals.org/content/early/2020/08/18/2159-8290.CD-20-0773, https://c19p.org/pinato
398. Rojas-Serrano et al., Hydroxychloroquine for prophylaxis of COVID-19 in health workers: A randomized clinical trial
127 patient HCQ prophylaxis RCT: 82% fewer symptomatic cases (p=0.12).Early terminated HCQ PrEP RCT with 62 HCQ and 65 placebo patients, showing 82% lower cases with treatment, p = 0.12. If the trial is continued and the same event rate is observed, statistical significance will be reached after adding about 16 patients per arm.
May 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261980, https://c19p.org/rojasserrano
399. Pimenta Bonifácio et al., Efficacy and safety of Ixekizumab vs. low-dose IL-2 vs. Colchicine vs. standard of care in the treatment of patients hospitalized with moderate-to-critical COVID-19: A pilot randomized clinical trial (STRUCK: Survival Trial Using Cytokine Inhibitors)
30 patient colchicine late treatment RCT: 85% greater improvement (p=0.23).Open label RCT late stage hospitalized patients in Brazil with 14 colchicine and 16 SOC patients, showing lower mortality and improved recovery with treatment, without statistical significance. Authors note that the colchicine group had one patient with SOFA ≥7 vs. zero for SOC, however both groups had one patient intubated and SOC had more patients not requiring high-flow oxygen (12 vs. 8). The journal version of this paper falsely states: "Ixekizumab, colchicine, and IL-2 were demonstrated to be safe but ineffective". The pre-print more accurately represents the improved but not statistically significant results: "The colchicine arm presented the lowest mortality rate (0%), while the low dose IL-2 had the highest (21.4%) by day 28 post-enrollment. The frequency of adverse events was lowest in the colchicine group (7.3%). None of the differences observed was statistically significant. Interpretation: Colchicine added to SOC performed better than Ixekizumab, low-dose..
Apr 2022, Revista da Sociedade Brasileira de Medicina Tropical, http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0037-86822023000100317&tlng=en, https://c19p.org/pimentabonifacio
400. Tolouian et al., Bromhexine, for Post Exposure COVID-19 Prophylaxis: A Randomized, Double-Blind, Placebo Control Trial
372 patient bromhexine prophylaxis RCT: 70% lower hospitalization (p=0.15), 53% fewer symptomatic cases (p=0.007), and 50% fewer cases (p=0.03).PEP RCT with 372 close contacts of COVID+ patients, 187 treated with bromhexine, showing significantly lower cases with treatment. IRCT20120703010178N22.
Dec 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3989849, https://c19p.org/tolouian2
401. De Rosa et al., Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry
1,538 patient HCQ late treatment study: 35% lower mortality (p=0.02).Retrospective 1,538 hospitalized patients in Italy, showing only HCQ associated with reduced mortality. Authors analyze mortality amongst those that were alive at day 7 to avoid survival time bias due to drug recording requiring a minimum of 5 days treatment.
Apr 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/9/1951, https://c19p.org/derosa
402. Calonico et al., Causal Inference During a Pandemic: Evidence on the Effectiveness of Nebulized Ibuprofen as an Unproven Treatment for COVID-19 in Argentina
5,416 patient alkalinization late treatment study: 49% lower mortality (p=0.01).Retrospective 5,146 hospitalized COVID-19 patients in Argentina, showing lower mortality associated with nebulized ibuprofen (NaIHS) treatment. Doubly robust inverse probability weighting estimators were used to control for confounding. Authors emphasize the need for randomized controlled trials. The treatment appears to be the same as detailed in [Kalayan], which reports a pH of 8.5. [Kreutzberger] showed that SARS-CoV-2 requires an acidic pH (between 6.2-6.8) for membrane fusion and cell entry, even when the viral spike protein is primed by proteases like TMPRSS2. Efficacy seen here may be more due to alkalinization, which shows more consistent higher efficacy than ibuprofen in studies to date.
May 2022, National Bureau of Economic Research, http://www.nber.org/papers/w30084.pdf, https://c19p.org/calonicoph
403. Shao et al., Composite Interventions on Outcomes of Severely and Critically Ill Patients with COVID-19 in Shanghai, China
686 patient azvudine late treatment study: 56% lower mortality (p=0.007).Retrospective 1,082 severely and critically ill COVID-19 patients in China showing lower 60 day mortality with azvudine. Mortality was also lower with paxlovid, but without statistical significance, and health related quality of life was significantly lower for paxlovid patients at 60 days.
Jul 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/7/1859, https://c19p.org/shao4azv
404. Beltran Gonzalez et al., Efficacy and Safety of Ivermectin and Hydroxychloroquine in Patients with Severe COVID-19: A Randomized Controlled Trial
70 patient HCQ late treatment RCT: 63% lower mortality (p=0.27) and 25% lower progression (p=0.57).RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 33 HCQ and 37 control patients not finding significant differences. NCT04391127.
Feb 2021, Infectious Disease Reports, https://www.mdpi.com/2036-7449/14/2/20, https://c19p.org/beltrangonzalezh
405. Seftel et al., Prospective cohort of fluvoxamine for early treatment of COVID-19
125 patient fluvoxamine early treatment study: 72% lower mortality (p=0.38), 84% lower combined mortality/ICU admission (p=0.15), 94% lower hospitalization (p=0.003), and 99% improved recovery (p<0.0001).Prospective quasi-randomized (patient choice) study with 125 outpatients, 77 treated with fluvoxamine, showing lower death/ICU admission (0 of 77 vs. 2 of 48), lower hospitalization (0 of 77 vs. 6 of 48), and faster recovery with treatment. Note that 12 treatment patients were added but are not reflected in the table in the paper (because the numbers had been previously published and the IRB did not allow updating the table).
Jan 2021, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab050/6124100, https://c19p.org/seftel
406. Rajter et al., Use of Ivermectin is Associated with Lower Mortality in Hospitalized Patients with COVID-19 (ICON study)
280 patient ivermectin late treatment PSM study: 46% lower mortality (p=0.05) and 64% lower ventilation (p=0.1).Retrospective 280 hospitalized patients showing lower mortality with ivermectin (13.3% vs 24.5%), propensity matched odds ratio OR 0.47 [0.22-0.99], p=0.045.
Oct 2020, Chest, https://www.sciencedirect.com/science/article/pii/S0012369220348984, https://c19p.org/rajter
407. Nicastri et al., A phase 2 randomized, double-blinded, placebo-controlled, multicenter trial evaluating the efficacy and safety of raloxifene for patients with mild to moderate COVID-19
41 patient raloxifene antiandrogen late treatment RCT: 52% lower need for oxygen therapy (p=0.43) and 69% improved viral clearance (p=0.22).RCT 68 patients in Italy showing improved viral clearance with raloxifene.
Jun 2022, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537022001808, https://c19p.org/nicastri
408. Vaisi et al., The association between nutrients and occurrence of COVID-19 outcomes in the population of Western Iran: A cohort study
3,955 patient selenium prophylaxis study: 53% lower hospitalization (p=0.02) and 15% fewer symptomatic cases (p=0.04).Analysis of nutrient intake and COVID-19 outcomes for 3,996 people in Iran, showing lower risk of COVID-19 hospitalization with sufficient vitamin A, vitamin C, and selenium intake, with statistical significance for vitamin A and selenium.
May 2023, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13632, https://c19p.org/vaisise
409. Sobhy et al., Early Use of Ibuprofen in Moderate Cases of COVID-19 Might be a Promising Agent to Attenuate the Severity of Disease: A Randomized Controlled Trial
180 patient ibuprofen late treatment RCT: 52% lower ICU admission (p=0.05), 52% lower need for oxygen therapy (p=0.05), and 26% shorter hospitalization (p=0.01).RCT 180 moderate hospitalized COVID-19 patients in Egypt, showing lower ICU admission and shorter hospitalization with ibuprofen compared with acetaminophen.
Apr 2023, The Open Anesthesia J., https://openanesthesiajournal.com/VOLUME/17/ELOCATOR/e258964582303020/, https://c19p.org/sobhy
410. Mohsin et al., Lifestyle and Comorbidity-Related Risk Factors of Severe and Critical COVID-19 Infection: A Comparative Study Among Survived COVID-19 Patients in Bangladesh
1,500 patient sleep study: 38% lower severe cases (p<0.0001).Retrospective 1,500 COVID+ patients in Bangladesh, showing lower risk of severe cases with good sleep.
Sep 2021, Infection and Drug Resistance, https://www.dovepress.com/lifestyle-and-comorbidity-related-risk-factors-of-severe-and-critical--peer-reviewed-fulltext-article-IDR, https://c19p.org/mohsin
411. Mohsin et al., Lifestyle and Comorbidity-Related Risk Factors of Severe and Critical COVID-19 Infection: A Comparative Study Among Survived COVID-19 Patients in Bangladesh
1,500 patient alcohol study: 28% lower severe cases (p=0.001).Retrospective 1,500 COVID+ patients in Bangladesh, showing higher risk of severe cases with alcohol/smokeless tobacco/substance abuse.
Sep 2021, Infection and Drug Resistance, https://www.dovepress.com/lifestyle-and-comorbidity-related-risk-factors-of-severe-and-critical--peer-reviewed-fulltext-article-IDR, https://c19p.org/mohsinac
412. Sánchez-Rico et al., Hydroxyzine Use and Mortality in Patients Hospitalized for COVID-19: A Multicenter Observational Study
15,103 patient hydroxyzine prophylaxis study: 46% lower mortality (p=0.02).Retrospective 15,103 hospitalized COVID-19 patients in France showing lower mortality with hydroxyzine use.
Dec 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/24/5891, https://c19p.org/sanchezrico2
413. Jamir et al., Determinants of Outcome Among Critically Ill Police Personnel With COVID-19: A Retrospective Observational Study From Andhra Pradesh, India
266 patient povidone-iodine ICU study: 57% lower mortality (p=0.0004).Retrospective 266 COVID-19 ICU patients in India, showing significantly lower mortality with PVP-I oral gargling and topical nasal use, and non-statistically significant higher mortality with ivermectin and lower mortality with remdesivir.
Dec 2021, Cureus, https://www.cureus.com/articles/73667-determinants-of-outcome-among-critically-ill-police-personnel-with-covid-19-a-retrospective-observational-study-from-andhra-pradesh-india, https://c19p.org/jamirp
414. Annweiler et al., Vitamin D and survival in COVID-19 patients: A quasi-experimental study
66 patient vitamin D early treatment study: 89% lower mortality (p=0.002).Vitamin D3 supplementation during or just before COVID-19 was associated with 68% lower mortality and less severe COVID-19 in frail elderly. Retrospective 66 French nursing home residents, mean age 87.7, 9 control patients, and 57 that received an oral bolus of 80,000 IU vitamin D3 either in the week following the suspicion or diagnosis of COVID-19, or during the previous month. 17.5% mortality in the treatment group and 55.6% in the control group.
Oct 2020, The J. Steroid Biochemistry and Molecular Biology, https://www.sciencedirect.com/science/article/pii/S096007602030296X, https://c19p.org/annweiler
415. Leal-Martínez et al., Effect of a Nutritional Support System to Increase Survival and Reduce Mortality in Patients with COVID-19 in Stage III and Comorbidities: A Blinded Randomized Controlled Clinical Trial
80 patient vitamin D late treatment RCT: 86% lower mortality (p=0.03) and 57% lower ventilation (p=0.31).80 patient RCT with 40 patients treated with a comprehensive regimen of nutritional support, showing significantly lower mortality with treatment. Treatment contained cholecalciferol, vitamin C, zinc, spirulina maxima, folic acid, glutamine, vegetable protein, selenium, resveratrol, omega-3 fatty acids, l-arginine, magnesium, probiotics, and B-complex IV. Adherence was strictly monitored.
Oct 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/19/3/1172/htm, https://c19p.org/lealmartinez
416. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient vitamin C prophylaxis study: 28% lower mortality (p=0.002).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3c
417. RECOVERY Collaborative Group et al., Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
14,892 patient aspirin late treatment RCT: 4% lower mortality (p=0.35), 5% lower ventilation (p=0.32), 6% higher hospital discharge (p=0.006), and 11% shorter hospitalization.RCT 14,892 late stage patients, 7,351 treated with aspirin, showing slightly improved discharge and hospitalization time, and no significant difference for mortality. Results are limited due to low dose (150mg daily), very late treatment (9 days post symptom onset), and 96% concurrent use of low molecular weight heparin. Greater benefits were seen for non-LMWH patients, and for very late (<= 7 days from onset) vs. extremely late (>7 days) treatment. For more discussion see [web.archive.org].
Nov 2021, RECOVERY Collaborative Group, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673621018250, https://c19p.org/recoverye
418. Loucera et al., Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients
1,604 patient vitamin D prophylaxis PSM study: 33% lower mortality (p=0.009).Retrospective 15,968 hospitalized patients in Spain showing a significant reduction in mortality associated with the prescription of vitamin D, especially calcifediol, within 15-30 days prior to hospitalization.
Apr 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-02701-5, https://c19p.org/loucera
419. Bejan et al., DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
9,748 patient curcumin prophylaxis study: 59% lower hospitalization (p=0.05).Retrospective 9,748 COVID-19 patients in the USA showing lower hospitalization with turmeric extract.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejant
420. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data
917,198 patient metformin late treatment study: 44% lower mortality (p<0.0001).Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizimf
421. Huh et al., Association of previous medications with the risk of COVID-19: a nationwide claims-based study from South Korea
65,149 patient N-acetylcysteine prophylaxis study: 28% fewer cases (p<0.0001).Retrospective database analysis of 65,149 in South Korea, showing significantly lower cases with existing N-acetylcysteine treatment. The journal version of this paper does not present the N-acetylcysteine results.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.04.20089904v2, https://c19p.org/huhnac
422. Kanokkangsadal et al., Andrographis paniculata extract versus placebo in the treatment of COVID-19: a double-blinded randomized control trial
165 patient andrographolide early treatment RCT: 51% lower progression (p=0.25) and 8% improved recovery (p=0.33).RCT 165 low-risk mild COVID-19 patients in Thailand receiving either 180mg/day of Andrographis paniculata extract or placebo for 5 days. No significant difference was found between groups for disease progression, though A. paniculata showed lower progression. Most symptoms improved similarly between groups, though A. paniculata provided faster relief for headaches and loss of smell. All patients recovered with 14 days. The main side effect was mild diarrhea.
Nov 2023, Research in Pharmaceutical Sciences, https://journals.lww.com/10.4103/1735-5362.389947, https://c19p.org/kanokkangsadal
423. Polat et al., Hydroxychloroquine Use on Healthcare Workers Exposed to COVID-19 - A Pandemic Hospital Experience
208 patient HCQ prophylaxis study: 57% fewer cases (p=0.03).Small prophylaxis study of 208 healthcare workers in Turkey, 138 with high risk exposure received HCQ, while 70 with low and medium risk exposure did not. COVID-19 cases were lower in the treatment group, relative risk RR 0.43, p = 0.026. Since the control group had lower risk, the actual benefit may be larger.
Sep 2020, Medical J. Bakirkoy, 280-6, https://cms.galenos.com.tr/Uploads/Article_47752/BTD-16-280-En.pdf, https://c19p.org/polat
424. Faisal et al., Potential use of azithromycin alone and in combination with ivermectin in fighting against the symptoms of COVID-19
100 patient ivermectin early treatment RCT: 68% improved recovery (p=0.005).RCT 100 outpatients in Pakistan, 50 treated with ivermectin, showing faster recovery with ivermectin. All patients received AZ, zinc, vitamin C, vitamin D, and paracetemol. Details of randomization were not provided. No mortality or hospitalization was reported.
May 2021, The Professional Medical J., http://theprofesional.com/index.php/tpmj/article/view/5867, https://c19p.org/faisal
425. Siraj et al., Efficacy of Various Treatment Modalities on Patient-related Outcome in Hospitalized COVID-19 Patients – A Retrospective Study
1,000 patient famotidine late treatment study: 36% lower mortality (p=0.002).Retrospective 1,000 COVID+ hospitalized patients in India, showing lower mortality with famotidine and remdesivir in multivariable logistic regression.
Feb 2022, Indian J. Clinical Practice, https://ijcp.in/Admin/CMS/PDF/6.%20OriginalResearch_IJCP_Feb2022.pdf, https://c19p.org/siraj
426. Naggie et al., Hydroxychloroquine for pre-exposure prophylaxis of COVID-19 in health care workers: A randomized, multicenter, placebo-controlled trial (HERO-HCQ)
1,359 patient HCQ prophylaxis RCT: 24% fewer symptomatic cases (p=0.18).HCQ prophylaxis RCT reporting statistically significant lower cases when pooling results with the COVID PREP RCT, OR 0.74 [0.55-1.0] p = 0.046. There were no significant safety issues. The trials were both terminated early resulting in a loss of power, however the combination shows statistically significant efficacy of HCQ. Note that this result has been censored in the journal version, see [medrxiv.org]. The journal paper still shows the COVID PREP paper in the reference list, but the analysis and discussion has been deleted. The journal version falsely states: "The prophylactic use of HCQ by HCW was safe but not effective", whereas the paper actually estimates OR 0.75, which becomes statistically significant OR 0.74 when pooled with COVID PREP. The preprint contains a different version: "...but did not produce a clinically useful treatment". It's unclear why ~25% fewer cases would not be useful. They also state "This is one of several negative studies"..
Aug 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S120197122300019X, https://c19p.org/naggie
427. Mirahmadizadeh et al., Efficacy of single-dose and double-dose ivermectin early treatment in preventing progression to hospitalization in mild COVID-19: A multi-arm, parallel-group randomized, double-blind, placebo-controlled trial
261 patient ivermectin early treatment RCT: 67% lower ventilation (p=0.37), 46% lower hospitalization (p=0.22), and 39% improved recovery (p=0.27).RCT with 131 24mg ivermectin, 130 12mg ivermectin, and 130 placebo patients, showing no significant differences in outcomes. Lower ventilation and hospitalization was seen with treatment, in a dose-dependent manner, but not reaching statistical significance with the small number of events.
Jun 2022, Respirology, https://onlinelibrary.wiley.com/doi/10.1111/resp.14318, https://c19p.org/mirahmadizadeh
428. Yu et al., Low Dose of Hydroxychloroquine Reduces Fatality of Critically Ill Patients With COVID-19
550 patient HCQ late treatment study: 60% lower mortality (p=0.002).Retrospective, 550 critically ill patients. 19% fatality for HCQ versus 47% for non-HCQ, RR 0.395, p=0.002. The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 pg/mL to 5.2 pg/mL (p<0.05) at the end of the treatment in the HCQ group but there was no change in the control group.
May 2020, Science China Life Sciences, 2020 May 15, 1-7, https://link.springer.com/article/10.1007%2Fs11427-020-1732-2, https://c19p.org/yu
429. Alamgir et al., Drug repositioning candidates identified using in-silico quasi-quantum molecular simulation demonstrate reduced COVID-19 mortality in 1.5M patient records
22,124 patient metformin prophylaxis study: 27% lower mortality (p<0.0001).In Silico study followed by PSM analysis of the National COVID Cohort Collaborative data in the USA, showing 27% lower mortality with metformin use.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.22.21254110, https://c19p.org/alamgir
430. Taieb et al., Hydroxychloroquine and Azithromycin Treatment of Hospitalized Patients Infected with SARS-CoV-2 in Senegal from March to October 2020
926 patient HCQ late treatment study: 39% higher hospital discharge (p=0.02).Retrospective 926 patients in Senegal, 674 treated with HCQ+AZ, showing significantly higher hospital discharge at day 15 with treatment.
Jun 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/13/2954, https://c19p.org/taieb
431. Ando et al., Impact of overlapping risks of type 2 diabetes and obesity on coronavirus disease severity in the United States
28,093 patient metformin prophylaxis study: 39% lower hospitalization (p=0.04).Retrospective 28,093 COVID+ patients in the USA, showing lower risk of hospitalization with metformin use.
Sep 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-96720-x, https://c19p.org/ando
432. Abbaspour-Aghdam et al., Immunomodulatory role of Nanocurcumin in COVID-19 patients with dropped natural killer cells frequency and function
60 patient curcumin late treatment RCT: 71% lower mortality (p=0.15) and 86% improved recovery (p=0.04).RCT with 30 nanocurcumin and 30 control patients in Iran, showing lower mortality and improved recovery, without statistical significance, and improved NK cell function. 160mg nanocurcumin for 21 days.
Sep 2022, European J. Pharmacology, https://www.sciencedirect.com/science/article/pii/S0014299922005283, https://c19p.org/abbaspouraghdam
433. Usanma Koban et al., The factors affecting the prolonged PCR positivity in COVID-19 patients
126 patient favipiravir early treatment study: 86% improved viral clearance (p=0.03).Retrospective 126 patients in Turkey, showing lower risk of PCR+ at day 14 with favipiravir treatment.
Jun 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7706&category_id=179&option=com_virtuemart, https://c19p.org/usanmakoban
434. Mohan et al., Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): a single-centre randomized, placebo-controlled trial
157 patient ivermectin early treatment RCT: 62% improved recovery (p=0.27) and 24% improved viral clearance (p=0.18).RCT in India with low risk patients, comparing 24mg ivermectin, 12mg ivermectin, and placebo showing non-statistically significant improvements in recovery and PCR+ status (day 5 both arms, day 7 24mg only) with treatment, and showing greater improvement for the higher dose arm. Viral load decline was similar in all arms - absolute values are lower for ivermectin in a dose-dependent manner, however the baseline value for the ivermectin groups was lower, leaving less room for change. There were no deaths or use of mechanical ventilation. There were no serious adverse events. Note that our pre-specified protocol prioritizes clinical outcomes over PCR results.
Feb 2021, J. Infection and Chemotherapy, https://www.sciencedirect.com/science/article/pii/S1341321X21002397, https://c19p.org/mohan
435. Parant et al., Vitamin D and COVID-19 Severity in Hospitalized Older Patients: Potential Benefit of Prehospital Vitamin D Supplementation
228 patient vitamin D prophylaxis study: 50% lower mortality (p=0.11), 51% lower ICU admission (p=0.008), and 39% lower severe cases (p=0.01).Retrospective 228 hospitalized COVID-19 patients, median age 78, showing significantly lower risk of ICU admission and severe cases with vitamin D prophylaxis. NCT04877509.
Apr 2022, Nutrients, https://www.mdpi.com/2072-6643/14/8/1641, https://c19p.org/parant
436. Chow et al., Association of Pre-Hospital Antiplatelet Therapy with Survival in Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis
17,347 patient aspirin prophylaxis PSM study: 19% lower mortality (p=0.005) and 3% lower ventilation (p=0.21).PSM retrospective 6,781 hospitalized patients ≥50 years old in the USA who were on pre-hospital antiplatelet therapy (84% aspirin), and 10,566 matched controls, showing lower mortality with treatment.
Aug 2021, J. Thrombosis and Haemostasis, https://onlinelibrary.wiley.com/doi/abs/10.1111/jth.15517, https://c19p.org/chow2
437. Chen et al., Efficacy and safety of chloroquine or hydroxychloroquine in moderate type of COVID-19: a prospective open-label randomized controlled study
48 patient HCQ late treatment RCT: 20% faster recovery (p=0.51) and 71% faster viral clearance (p=0.0004).RCT 48 hospitalized patients in China showing faster clinical recovery and viral clearance with CQ/HCQ.
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.19.20136093v1, https://c19p.org/chen
438. Gao et al., The efficiency and safety of high-dose vitamin C in patients with COVID-19: a retrospective cohort study
76 patient vitamin C late treatment study: 86% lower mortality (p=0.04).Retrospective 76 COVID-19 patients, 46 treated with intravenous high-dose vitamin C, showing lower mortality and improved oxygen requirements with treatment. Dosage was 6g intravenous infusion per 12hr on the first day, and 6g once for the following 4 days.
Feb 2021, Aging, https://www.aging-us.com/article/202557/text, https://c19p.org/gao3
439. Heberto et al., Implications of myocardial injury in Mexican hospitalized patients with coronavirus disease 2019 (COVID-19)
254 patient HCQ late treatment study: 54% lower mortality (p=0.04) and 65% lower ventilation (p=0.008).Observational prospective 254 hospitalized patients, HCQ+AZ mortality odds ratio OR 0.36, p = 0.04. Ventilation OR 0.20, p = 0.008.
Sep 2020, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906720303365, https://c19p.org/heberto
440. Kumari et al., The Role of Vitamin C as Adjuvant Therapy in COVID-19
150 patient vitamin C late treatment RCT: 36% lower mortality (p=0.45), 20% lower ventilation (p=0.67), 26% faster recovery (p=0.0001), and 24% shorter hospitalization (p=0.0001).RCT 150 hospitalized patients in Pakistan showing 26% faster recovery, p < 0.0001. 36% lower mortality, not statistically significant due to the small number of events. Dosage was 50 mg/kg/day of intravenous vitamin C.
Nov 2020, Cureus, https://www.cureus.com/articles/45284-the-role-of-vitamin-c-as-adjuvant-therapy-in-covid-19, https://c19p.org/kumari
441. Wang et al., Randomized trial of influence of vitamin D on the prevention and improvement of symptomatic COVID-19
202 patient vitamin D prophylaxis RCT: 25% lower progression (p=0.15), 4% fewer cases (p=0.89), and 11% faster viral clearance.RCT 214 low risk (no hospitalization) healthcare workers in China, showing no significant differences with vitamin D2 prophylaxis using two bolus treatments. Patients with higher vitamin D levels (across both groups) were less likely to be infected. The trial only lasted one month. Two thirds of the cases occurred within the first week, when treatment may have minimal impact on vitamin D levels (calcifediol or calcidiol may be more effective due to delays in conversion). Cases were lower in the intervention group during the last two weeks, after treatment is likely to have increased levels significantly. Regular rather than bolus treatment, longer term treatment, or alternative forms of vitamin D (e.g., calcifediol/calcidiol) may be more effective. Authors report that "4.5% of subjects were lost to follow-up" (1% and 7.6% per group). Figure 2 shows 2 and 0 patients at risk at day 28. This is inconsistent with the reported infection rates and loss to followup, raising..
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-024-66267-8, https://c19p.org/wang14
442. Saygili et al., Preadmission usage of metformin and mortality in COVID-19 patients including the post-discharge period
240 patient metformin prophylaxis PSM study: 42% lower mortality (p=0.02).Retrospective 586 diabetic hospitalized COVID-19 patients in Turkey, showing lower mortality with existing metformin use.
Oct 2021, Irish J. Medical Science, https://link.springer.com/article/10.1007/s11845-021-02823-9/fulltext.html, https://c19p.org/saygili
443. AlQahtani et al., Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease
103 patient HCQ late treatment RCT: 4% improved recovery (p=0.94) and 47% improved viral clearance (p=0.13).RCT with 54 favipiravir, 51 HCQ, and 52 SOC hospitalized patients in Bahrain, showing no significant differences. Viral clearance improved with both treatments, but did not reach statistical significance with the small sample size.
Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-08794-w, https://c19p.org/alqahtani2
76 patient alkalinization ICU study: 76% lower mortality (p=0.0001).
Analysis of 76 ICU patients in Brazil, 44 treated with bronchoalveolar lavage using 3% sodium bicarbonate, showing significantly lower mortality with treatment. Bronchoalveolar lavage with 10ml of sodium bicarbonate solution directly into the tube (closed circuit), 500μl for each lung segment, followed by aspiration of the solution, performed every 6 hours for 7 days.
Dec 2021, Brazilian J. Development, https://brazilianjournals.com/ojs/index.php/BRJD/article/view/40521, https://c19p.org/soares
76 patient sodium bicarbonate ICU study: 76% lower mortality (p=0.0001).
Analysis of 76 ICU patients in Brazil, 44 treated with bronchoalveolar lavage using 3% sodium bicarbonate, showing significantly lower mortality with treatment. Bronchoalveolar lavage with 10ml of sodium bicarbonate solution directly into the tube (closed circuit), 500μl for each lung segment, followed by aspiration of the solution, performed every 6 hours for 7 days.
Dec 2021, Brazilian J. Development, https://brazilianjournals.com/ojs/index.php/BRJD/article/view/40521, https://c19p.org/soaressb
446. Chow et al., Association of Early Aspirin Use With In-Hospital Mortality in Patients With Moderate COVID-19
112,070 patient aspirin late treatment study: 13% lower mortality (p<0.0001).Retrospective 112,269 hospitalized COVID-19 patients in the USA, showing lower mortality with aspirin treatment.
Mar 2022, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790439, https://c19p.org/chow3
447. Tylishchak et al., Effectiveness of the quercetin use in patients with COVID-19 with concomitant type 2 diabetes mellitus
60 patient quercetin late treatment RCT: 15% shorter hospitalization (p<0.0001).RCT 60 hospitalized COVID-19 patients with type 2 diabetes showing quercetin treatment decreased levels of inflammatory markers (interleukin-6, CRP, ferritin), reduced length of hospital stay, and improved capillaroscopy measures compared to standard care. Quercetin was administered at 0.5g intravenously once daily for 10 days. The authors hypothesize the benefits may be due to the anti-inflammatory, antioxidant and endothelium-protective effects of quercetin,
Dec 2024, Wiadomości Lekarskie, https://www.wiadomoscilekarskie.pl/Effectiveness-of-the-quercetin-use-in-patients-with-COVID-19-with-concomitant-type,191875,0,2.html, https://c19p.org/tylishchak
448. De Nicolò et al., Possible Impact of Vitamin D Status and Supplementation on SARS-CoV-2 Infection Risk and COVID-19 Symptoms in a Cohort of Patients with Inflammatory Bowel Disease
106 patient vitamin D prophylaxis study: 88% lower IgG positivity (p=0.002).Prospective study of 106 IBD patients in Italy, showing lower risk of IgG positivity with vitamin D supplementation. Vitamin D levels below 30 ng/mL were associated with a higher probability of symptomatic cases.
Dec 2022, Nutrients, https://www.mdpi.com/2072-6643/15/1/169, https://c19p.org/denicolo
449. Mura et al., Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients
1,126 patient famotidine late treatment PSM study: 21% lower mortality (p=0.02).PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with aspirin (not reaching statistical significance) and famotidine, and improved results from the combination of both.
Mar 2021, Signal Transduction and Targeted Therapy, https://www.nature.com/articles/s41392-021-00689-y, https://c19p.org/murafm
450. Wang et al., Multidimensional Sleep Health Prior to SARS-CoV-2 Infection and Risk of Post–COVID-19 Condition
1,979 patient sleep study: 36% lower PASC (p=0.0004).Retrospective 1,979 nurses in the USA, showing lower risk of long COVID with better sleep quality.
May 2023, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2805380, https://c19p.org/wang17
451. Rajasingham et al., Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial
1,483 patient HCQ prophylaxis RCT: 27% fewer cases (p=0.07).PrEP RCT showing lower cases with HCQ prophylaxis. The trial was halted after 47% enrollment, p < 0.05 would be reached at ~75% enrollment if similar results continued. HR 0.66/0.68 for full medication adherence, 0.72/0.74, p = 0.18/0.22 overall (1x/2x dosing). Efficacy for first responders was higher, OR 0.32, p = 0.01. First responders had a much higher incidence, allowing greater power, and reducing the effect of confounders such as misdiagnosis of other conditions or survey issues. Performance is similar to the control arm for the first 3 weeks. The effect may be greater with a dosage regimen that achieves therapeutic levels faster [tandfonline.com]. ~40% of participants suspected they might have had COVID-19 before the trial, the effect in people without prior COVID-19 may be higher. Research shows the treatment used in the control arm (folic acid) may have significant efficacy for COVID-19 [Deschasaux-Tanguy, Farag], so the true effectiveness of HCQ may be higher than observed...
Sep 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1571/5929230, https://c19p.org/rajasingham
452. Assimakopoulos et al., N-acetyl-cysteine reduces the risk for mechanical ventilation and mortality in patients with COVID-19 pneumonia: a two-center retrospective cohort study
82 patient N-acetylcysteine late treatment study: 97% lower mortality (p=0.006).Retrospective 42 hospitalized PCR+ COVID-19 pneumonia patients treated with NAC, and a matched control group of 40 patients, showing significantly lower severe respiratory failure and significantly lower mortality with treatment. NAC 600 mg bid orally for 14 days.
Jun 2021, Infectious Diseases, https://www.tandfonline.com/doi/full/10.1080/23744235.2021.1945675, https://c19p.org/assimakopoulos
453. Zheng et al., The Value of Ursodeoxycholic Acid and Mesenchymal Stem Cells in the Treatment of Severe COVID-19
167 patient ursodeoxycholic acid prophylaxis study: 62% lower mortality (p=0.03).Retrospective 167 severe COVID-19 patients showing lower mortality with ursodeoxycholic acid (UDCA). Timing and duration of treatment is unknown - UDCA patients may have been on UDCA since before COVID-19.
Jun 2024, Microorganisms, https://www.mdpi.com/2076-2607/12/7/1269, https://c19p.org/zheng10
454. Villamañán et al., Targeting patients with pneumonia by COVID-19 that could be beneficiated by colchicine
222 patient colchicine late treatment study: 42% lower mortality (p=0.03).Retrospective 111 hospitalized COVID-19 pneumonia patients treated with colchicine and 111 matched controls, showing lower mortality with colchicine treatment.
Mar 2023, Eur. J. Hosp. Pharm., https://ejhp.bmj.com/lookup/doi/10.1136/ejhpharm-2023-eahp.56, https://c19p.org/villamanan
455. Korkmaz et al., The effect of Hydroxychloroquine use due to rheumatic disease on the risk of Covid-19 infection and its course
694 patient HCQ prophylaxis study: 82% lower mortality (p=0.19) and 94% fewer cases (p<0.0001).Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases for HCQ users.
May 2021, Authorea, https://www.authorea.com/doi/full/10.22541/au.162257516.68665404, https://c19p.org/korkmaz
456. Ebongue et al., Factors predicting in-hospital all-cause mortality in COVID 19 patients at the Laquintinie Hospital Douala, Cameroon
580 patient HCQ late treatment study: 43% lower mortality (p=0.04).Retrospective 580 hospitalized COVID+ patients in Cameroon, showing lower mortality with HCQ+AZ treatment.
Mar 2022, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/pii/S1477893922000382, https://c19p.org/ebongue
179 patient colchicine late treatment RCT: 81% lower mortality (p=0.03), 87% lower ICU admission (p=0.002), and 35% shorter hospitalization (p<0.0001).
RCT 179 hospitalized COVID-19 patients showing lower mortality, ICU admission, and hospitalization duration with colchicine plus phenolic monoterpenes compared to standard care alone. The intervention group received 0.8 mg/day colchicine and 45 mg/day phenolic monoterpenes extracted from nigella sativa and Trachyspermum ammi in addition to standard care (lopinavir/ritonavir). No serious side effects were reported. Baseline SpO2 was significantly lower in the control group, although there was no significant difference in severity according to NIH guidelines.
Mar 2024, Heliyon, https://www.sciencedirect.com/science/article/pii/S2405844024034042, https://c19p.org/vaziri
458. Kosari et al., The influence of propolis plus Hyoscyamus niger L. against COVID‐19: A phase II, multicenter, placebo‐controlled, randomized trial
140 patient propolis late treatment RCT: 86% lower mortality (p=0.24), 86% lower ICU admission (p=0.06), and 64% improved recovery (p=0.007).RCT 140 patients showing lower progression and improved recovery with propolis plus Hyoscyamus niger L.syrup.
Nov 2023, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.8047, https://c19p.org/kosari2
459. Tsiakalos et al., Early Fluvoxamine Reduces the Risk for Clinical Deterioration in Symptomatic Outpatients with COVID-19: A Real-World, Retrospective, before–after Analysis
103 patient fluvoxamine early treatment study: 84% lower hospitalization (p=0.06) and 86% lower progression (p=0.02).Retrospective 103 outpatients in Greece, showing lower risk of progression with fluvoxamine 100mg bid for 10 days. 2 patients (4%) in the fluvoxamine group had clinical deterioration compared to 8 patients (16%) in the standard care group (p<0.05). After adjusting for confounders, fluvoxamine was associated with a lower risk of clinical deterioration (adjusted OR 0.12, p=0.02). Fluvoxamine was also associated with improved lymphocyte count. Control patients were during Sep-Nov 2021, and treatment patients Nov-Dec 2021, introducing potential confounding by time due to changes in variants, although the change in risk during this period is expected to be relatively low.
Aug 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/8/2073, https://c19p.org/tsiakalos
460. Jagielski et al., Associations of Nutritional Behavior and Gut Microbiota with the Risk of COVID-19 in Healthy Young Adults in Poland
95 patient diet study: 82% fewer cases (p=0.005).Retrospective 95 people in Poland, showing significantly lower risk of COVID-19 with higher consumption of fruits, vegetables, and nuts. Diets with higher consumption of fruits, vegetables, and nuts had a significantly lower dietary inflammatory index.
Jan 2022, Nutrients, https://www.mdpi.com/2072-6643/14/2/350, https://c19p.org/jagielski
461. Perez-Araluce et al., Components of the Mediterranean Diet and Risk of COVID-19
4,403 patient diet study: 78% lower severe cases (p=0.15), 15% fewer symptomatic cases (p=0.31), and 20% fewer cases (p=0.14).Retrospective 5,194 participants in Spain with 382 COVID-19 cases, showing lower risk of COVID-19 with high adherence to a Mediterranean diet, with statistical significance only when excluding healthcare professionals.
Jan 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2021.805533/full, https://c19p.org/perezaraluce
462. Aldwihi et al., Patients’ Behavior Regarding Dietary or Herbal Supplements before and during COVID-19 in Saudi Arabia
738 patient vitamin C prophylaxis study: 36% lower hospitalization (p=0.006).Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihic
463. Mingiano et al., Vitamin D Deficiency in COVID-19 Patients and Role of Calcifediol Supplementation
288 patient vitamin D late treatment study: 39% lower mortality (p=0.04), 23% lower need for oxygen therapy (p=0.22), and 35% shorter hospitalization (p=0.01).Retrospective 288 hospitalized COVID-19 patients in Italy, showing lower mortality and shorter hospitalization with calcifediol. Results may underestimate the benefits because only higher risk patients with vitamin D deficiency received supplementation. Treated patients also had significantly higher BMI. 83% of patients had vitamin D insufficiency (levels <30 ng/mL). Lower vitamin D levels correlated with higher inflammation markers. Patients with severe vitamin D deficiency (<10 ng/mL) had significantly higher mortality compared to those with levels >10 ng/mL.
Jul 2023, Nutrients, https://www.mdpi.com/2072-6643/15/15/3392, https://c19p.org/mingiano
164 patient exercise study: 91% lower mortality (p=0.09) and 70% lower severe cases (p=0.03).
Retrospective 164 COVID-19 patients in China, showing physical inactivity associated with an increased risk of severe COVID-19.
Jun 2021, Therapeutic Advances in Respiratory Disease, https://journals.sagepub.com/doi/10.1177/17534666211025221, https://c19p.org/yuan2
465. SaNOtize et al., Retrospective clinical study for COVID-19 prevention after exposure
625 patient nitric oxide prophylaxis study: 75% fewer cases (p<0.0001).PEP retrospective 625 university students in Thailand offered nitric oxide nasal spray, showing significantly lower cases for students that chose to use the treatment.
Apr 2022, SaNOtize, https://sanotize.com/clinical-trials-covid/, https://c19p.org/sanotizepep
466. Atceken et al., Association of High-Risk Obstructive Sleep Apnea with Artificial Intelligence-Guided, CT-Based Severity Scores in Patients with COVID-19 Pneumonia
221 patient sleep study: 67% lower severe cases (p=0.01).Retrospective 221 COVID-19 patients showing an association between high-risk obstructive sleep apnea and COVID-19 severity.
Oct 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/21/6415, https://c19p.org/atceken
467. Ramlall et al., Melatonin is significantly associated with survival of intubated COVID-19 patients
948 patient melatonin ICU study: 87% lower mortality (p<0.0001).Retrospective 948 intubated patients, 196 treated with melatonin, showing lower mortality with treatment.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.15.20213546v1, https://c19p.org/ramlall
468. Zhou et al., Impact of ultra-processed food intake on the risk of COVID-19: a prospective cohort study
20,507 patient diet study: 16% fewer cases (p<0.0001).Prospective study of 41,012 UK Biobank participants, showing higher risk of COVID-19 cases with ultra-processed food consumption.
Aug 2022, European J. Nutrition, https://link.springer.com/10.1007/s00394-022-02982-0, https://c19p.org/zhou7
469. Farnoosh et al., Efficacy of a Low Dose of Melatonin as an Adjunctive Therapy in Hospitalized Patients with COVID-19: A Randomized, Double-blind Clinical Trial
44 patient melatonin late treatment RCT: 81% lower ICU admission (p=0.2) and 49% faster recovery (p=0.004).RCT 44 hospitalized patients in Iran, 24 treated with melatonin, showing faster recovery with treatment. There was no mortality.
Jun 2021, Archives of Medical Research, https://www.sciencedirect.com/science/article/pii/S0188440921001417, https://c19p.org/farnoosh
1,497 patient fluvoxamine late treatment RCT: 30% lower mortality (p=0.24), 22% lower ventilation (p=0.33), 22% lower hospitalization (p=0.1), and 32% fewer combined hospitalization/ER visits (p=0.004).
Together Trial showing significantly lower hospitalization/extended ER visits with fluvoxamine treatment. Adherence was only 73.2%. Symptom onset was unspecified or >= 4 days for 57% of patients. The schedule of study activities specifies treatment administration only one day after randomization, adding an additional day delay. Overall mortality is high for the patient population. Results may be impacted by late treatment, poor SOC, and may be specific to local variants [science.sciencemag.org, thelancet.com]. Per-protocol analysis shows significantly improved results in this trial, however this may be subject to bias - the probability of adherence may be related to the probability of the outcome. Regarding the combined hospitalization/extended ER observation outcome, authors have noted that at the study sites, extended medical observation was essentially equivalent to being hospitalized. “These were not standard emergency rooms but instead were COVID-19 emergency centers that were..
Aug 2021, The Lancet Global Health, https://www.thelancet.com/journals/langlo/article/PIIS2214-109X(21)00448-4/fulltext, https://c19p.org/reis2
471. Zhang et al., Probiotics use is associated with improved clinical outcomes among hospitalized patients with COVID-19
300 patient probiotics late treatment study: 14% shorter hospitalization (p=0.009), 14% faster recovery (p=0.02), and 17% faster viral clearance (p=0.001).Retrospective 375 patients in China, 179 treated with probiotics (Bifidobacterium, Lactobacillus, and Enterococcus), showing improved clinical outcomes with treatment.
Aug 2021, Therapeutic Advances in Gastroenterology , https://journals.sagepub.com/doi/full/10.1177/17562848211035670, https://c19p.org/zhang3
472. Li et al., Inpatient use of metformin and acarbose is associated with reduced mortality of COVID-19 patients with type 2 diabetes mellitus
131 patient metformin late treatment study: 76% lower mortality (p=0.02).Retrospective 131 hospitalized COVID-19 patients with type 2 diabetes, showing lower mortality with metformin treatment and acarbose treatment.
Sep 2021, Endocrinology, Diabetes & Metabolism, https://onlinelibrary.wiley.com/doi/10.1002/edm2.301https://onlinelibrary.wiley.com/doi/pdf/10.1002/edm2.301, https://c19p.org/li18
473. Omrani et al., Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19
456 patient HCQ early treatment RCT: 12% lower hospitalization (p=1), 26% improved recovery (p=0.58), and 10% worse viral clearance (p=0.13).Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients, that positive PCR may simply reflect detection of inactive (non-infectious) viral remnants, that an alternative dosage regimen may be more effective, and that medication adherence was unknown. HCQ dosing was 600mg/day for 1 week, therapeutic levels may not be reached for several days. There were no deaths or serious adverse events. Viral load was already very high at baseline.
Nov 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303898, https://c19p.org/omrani
474. López et al., Telemedicine follow-ups for COVID-19: experience in a tertiary hospital
72 patient HCQ late treatment study: 64% lower progression (p=0.02).Retrospective 72 pediatric patients showing HCQ associated with a shorter duration of fever (p=0.023), less progression (p=0.016), and fewer return visits to the ER (p=0.017).
Nov 2020, Annals of Pediatrics, https://www.sciencedirect.com/science/article/pii/S1695403320304768, https://c19p.org/lopez2
475. Cadegiani et al., Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients
494 patient nitazoxanide early treatment study: 88% lower mortality (p=0.08), 97% lower ventilation (p<0.0001), and 99% lower hospitalization (p<0.0001).Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297521000792, https://c19p.org/cadegianin
476. Sarlin et al., Streptococcus salivarius Probiotics to Prevent Acute Otitis Media in Children
827 patient probiotics prophylaxis RCT: 33% fewer cases (p=1).RCT 827 children aged 1-6 years in daycare in Finland analyzing the effectiveness of daily Streptococcus salivarius K12 oral probiotic use for 6 months in preventing acute otitis media (AOM). The probiotic group did not have a significantly lower rate of AOM requiring antibiotics compared to placebo. A secondary outcome shows no significant difference in COVID-19, with only 2 and 3 cases in the treatment and placebo groups.
Nov 2023, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2811238, https://c19p.org/sarlin
477. Zurita-Cruz et al., Efficacy and safety of vitamin D supplementation in hospitalized COVID-19 pediatric patients: A randomized controlled trial
45 patient vitamin D late treatment RCT: 79% lower mortality (p=0.11), 72% lower ventilation (p=0.08), and 73% lower ICU admission (p=0.006).RCT 45 hospitalized high-risk pediatric patients requiring supplemental oxygen in Mexico, showing lower mortality, ventilation, and intensive care with vitamin D treatment, however there were less severe and critical cases at baseline in the treatment group.
Jul 2022, Frontiers in Pediatrics, https://www.frontiersin.org/articles/10.3389/fped.2022.943529/full, https://c19p.org/zuritacruz
150 patient nigella sativa ICU RCT: 6% lower mortality (p=0.87), 62% lower ventilation (p=0.01), and 23% lower ICU admission (p=0.74).
Open label randomized trial of 150 ICU patients in Bangladesh, showing shorter ICU stay and lower requirements for increased oxygen support including mechanical ventilation with nigella sativa treatment, but no significant difference in mortality. The large baseline difference in convalescent plasma usage suggests an error or randomization problem.
Aug 2023, Bangladesh Critical Care J., https://www.researchgate.net/publication/376207383_Role_of_Nigella_Sativa_black_cumin_seedsas_an_adjunct_therapy_in_treating_severe_and_critical_COVID_-19_infection_compared_to_those_with_standard_therapy_An_open_label_randomized_clinical_trial, https://c19p.org/faruq
479. Bernigaud et al., Ivermectin benefit: from scabies to COVID-19, an example of serendipity
3,131 patient ivermectin prophylaxis study: 99% lower mortality (p=0.08) and 55% fewer cases (p=0.01).69 residents of a French care home, median age 90, were treated with ivermectin for a scabies outbreak. 3,062 residents in 45 nearby comparable homes were used as controls. 7 of 69 treated patients had probable or certain COVID-19, with no serious cases and no deaths. In comparable care homes in the same district, matched by age and socio-economic level, there was 22.6% COVID-19 and 5% death.
Nov 2020, Annals of Dermatology and Venereology, https://www.sciencedirect.com/science/article/pii/S015196382030627X, https://c19p.org/bernigaud
480. Rocha et al., Physical activity status prevents symptoms of long covid: Sulcovid-19 survey
2,919 patient exercise study: 20% lower PASC (p=0.05).Retrospective 2,919 non-hospitalized COVID-19 patients in Brazil showing remaining physically active before and after COVID-19 infection reduces the probability of experiencing long COVID symptoms, particularly those affecting the musculoskeletal, neurological and respiratory systems.
Dec 2023, BMC Sports Science, Medicine and Rehabilitation, https://bmcsportsscimedrehabil.biomedcentral.com/articles/10.1186/s13102-023-00782-5, https://c19p.org/rocha
481. Freedberg et al., Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study
1,620 patient famotidine prophylaxis PSM study: 57% lower combined mortality/intubation (p=0.02).PSM retrospective 1,620 hospitalized patients in the USA, 84 with existing famotidine use, showing lower risk of combined death/intubation with treatment.
May 2020, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34706-5/fulltext, https://c19p.org/freedberg
482. Milosavljevic et al., Evaluation of Glycemic Control and Predictors of Severe Illness and Death in Patients With Diabetes Hospitalized With COVID-19
733 patient metformin prophylaxis study: 33% lower severe cases (p=0.03).Retrospective 733 hospitalized COVID-19 patients with diabetes in the USA, showing lower risk of severity with metformin use.
Nov 2022, J. Community Hospital Internal Medicine Perspectives, https://scholarlycommons.gbmc.org/jchimp/vol12/iss6/5, https://c19p.org/milosavljevic
483. Cangiano et al., Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests
98 patient HCQ late treatment study: 73% lower mortality (p=0.03).73% lower mortality with HCQ. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, showing HCQ mortality RR 0.27, p = 0.03. Subject to confounding by contraindication. The paper provides the p value for regression but not the effect size.
Dec 2020, Aging, https://www.aging-us.com/article/202307/text, https://c19p.org/cangiano
484. Dugot et al., The Association between Previous Antibiotic Consumption and SARS-CoV-2 Infection: A Population-Based Case-Control Study
156,299 patient azithromycin prophylaxis study: 12% fewer cases (p<0.0001).Retrospective 31,260 COVID-19 cases and 125,039 matched controls, showing lower risk of COVID-19 with previous azithromycin use.
Mar 2023, Antibiotics, https://www.mdpi.com/2079-6382/12/3/587, https://c19p.org/dugotaz
485. Jiang et al., Association of metformin with mortality or ARDS in patients with COVID-19 and type 2 diabetes: A retrospective cohort study
148 patient metformin prophylaxis PSM study: 46% lower mortality (p=0.4) and 80% lower progression (p=0.02).Retrospective 328 COVID-19 patients with type 2 diabetes in China, showing significantly lower risk of ARDS with existing metformin use.
Mar 2021, Diabetes Research and Clinical Practice, https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(20)30876-7/fulltext, https://c19p.org/jiang2
486. Huang et al., Reduced Sleep in the Week Prior to Diagnosis of COVID-19 is Associated with the Severity of COVID-19
164 patient exercise study: 47% lower severe cases (p=0.18) and 66% fewer cases (p=0.004).Retrospective 164 COVID-19 patients and 188 controls in China, showing lower risk of cases with regular exercise.
Nov 2021, Nature and Science of Sleep, https://www.dovepress.com/reduced-sleep-in-the-week-prior-to-diagnosis-of-covid-19-is-associated-peer-reviewed-article-NSS, https://c19p.org/huang5
487. McKinnon et al., Safety and Tolerability of Hydroxychloroquine in healthcare workers and first responders for the prevention of COVID-19: WHIP COVID-19 Study
543 patient HCQ prophylaxis RCT: 2% fewer symptomatic cases (p=1) and 51% fewer cases (p=0.6).HCQ prophylaxis RCT with 201 weekly HCQ patients, 197 daily HCQ patients, and 200 control patients, concluding the prophylaxis is safe. There were no grade 3 or 4 AEs, SAEs, ER visits, or hospitalizations. There was only 4 confirmed cases, 2 in the placebo arm and one in each HCQ arm. 60% of patients had exposure at baseline. HCQ 400mg weekly or HCQ 200mg daily after a loading dose of 400mg on day 1.
Dec 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221012431, https://c19p.org/mckinnon
488. Ma et al., Habitual use of vitamin D supplements and risk of coronavirus disease 2019 (COVID-19) infection: a prospective study in UK Biobank
8,297 patient vitamin D prophylaxis study: 30% fewer cases (p=0.03).Retrospective 8,297 adults from the UK Biobank showing the habitual use of vitamin D supplements significantly associated with lower risk of COVID-19 cases. Note that the information on vitamin D supplement use was collected a median of 10 years before the COVID-19 tests, so usage may have changed significantly.
Jan 2021, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqaa381/6123965, https://c19p.org/ma
489. Santoro et al., Aspirin Therapy on Prophylactic Anticoagulation for Patients Hospitalized With COVID-19: A Propensity Score-Matched Cohort Analysis of the HOPE-COVID-19 Registry
7,824 patient aspirin late treatment PSM study: 38% lower mortality (p=0.02).HOPE-COVID-19 PSM retrospective 7,824 patients, comparing prophylactic anticoagulation with and without additional treatment with aspirin in hospitalized patients, showing lower mortality with aspirin treatment.
Jun 2022, J. the American Heart Association, https://www.ahajournals.org/doi/10.1161/JAHA.121.024530, https://c19p.org/santoro3
490. Dhibar et al., Post Exposure Prophylaxis with Hydroxychloroquine (HCQ) for the Prevention of COVID-19, a Myth or a Reality? The PEP-CQ Study
317 patient HCQ prophylaxis study: 44% fewer symptomatic cases (p=0.21) and 50% fewer cases (p=0.04).Low dose prospective PEP study with 132 HCQ patients and 185 control patients, showing significantly lower COVID-19 cases with treatment. There were no serious adverse events. HCQ 800mg on day one followed by 400mg once weekly for 3 weeks.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304350, https://c19p.org/dhibar
491. Mohamed Hussein et al., Value of montelukast as a potential treatment of post-COVID-19 persistent cough: a non-randomized controlled pilot study
68 patient montelukast late treatment RCT: 50% improved recovery (p<0.0001).RCT 68 post-COVID-19 outpatients showing improvement in cough severity measures with montelukast treatment. The montelukast group had a greater reduction in number of cough paroxysms per day, cough severity visual analog scale, cough severity index, and improved cough quality of life scores compared to the control group. The montelukast group also had a shorter duration of cough.
Sep 2022, The Egyptian J. Bronchology, https://ejb.springeropen.com/articles/10.1186/s43168-022-00154-6, https://c19p.org/mohamedhussein
492. Sanchez-Gonzalez et al., Intranasal Chlorpheniramine Maleate for the treatment of COVID-19: Translational and Clinical Evidence
45 patient chlorpheniramine early treatment RCT: 87% lower hospitalization (p=0.08).Small RCT showing significantly improved recovery with intranasal chlorpheniramine maleate. Authors also perform an In Vitro study showing efficacy with a highly differentiated three-dimensional model of normal, human-derived tracheal/bronchial epithelial cells.
Dec 2022, Medical Research Archives, https://esmed.org/MRA/index.php/mra/article/view/2752, https://c19p.org/sanchezgonzalez2
493. Sanchez-Gonzalez et al., Intranasal Chlorpheniramine Maleate for the treatment of COVID-19: Translational and Clinical Evidence
45 patient chlorpheniramine early treatment RCT: 87% lower hospitalization (p=0.08).Small RCT showing significantly improved recovery with intranasal chlorpheniramine maleate. Authors also perform an In Vitro study showing efficacy with a highly differentiated three-dimensional model of normal, human-derived tracheal/bronchial epithelial cells.
Dec 2022, Medical Research Archives, https://esmed.org/MRA/index.php/mra/article/view/2752, https://c19p.org/sanchezgonzalez2cpm
494. Davido et al., Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time
132 patient HCQ late treatment study: 55% lower combined intubation/hospitalization (p=0.04).Retrospective of 132 hospitalized patients. HCQ+AZ(52)/AZ(28) significantly reduced death/ICU, HR=0.45, p=0.04. Adjusted for Charlson Comorbidity Index (including age), obesity, O2, lymphocyte count, and treatments. Mean delay from admission to treatment 0.7 days.
Aug 2020, Int. J. Antimicrobial Agents, 2020, https://www.sciencedirect.com/science/article/pii/S0924857920303125, https://c19p.org/davido
495. Ahmadi et al., Efficacy of Nanocurcumin as an Add-On Treatment for Patients Hospitalized with COVID-19: A Double-Blind, Randomized Clinical Trial
76 patient curcumin late treatment RCT: 58% lower need for oxygen therapy (p=0.06) and 67% improved recovery (p=0.04).RCT 76 hospitalized patients, showing improved recovery with nanocurcumin. Authors note that pure curcumin is limited due to rapid metabolism, low bio-availability, weak aqueous solubility, and systemic deletion, and that the nanocurcumin formulation used improves curcumin’s solubility, stability, half-life, and bioavailability. The dropout rate was higher in the curcumin group, in part due to discontinuation for side effects. Authors do not provide detailed discharge criteria.
Jul 2023, Int. J. Clinical Practice, https://www.hindawi.com/journals/ijclp/2023/5734675/, https://c19p.org/ahmadi4
496. Sinaci et al., Impact of vitamin D on the course of COVID-19 during pregnancy: A case control study
491 patient vitamin D prophylaxis study: 90% lower severe cases (p=0.35) and 19% more moderate/severe cases (p=0.64).Retrospective 159 COVID-19+ pregnant women in Turkey and 332 healthy pregnant controls, showing significantly lower vitamin D levels in COVID-19+ patients. 23% of COVID-19 patients where on vitamin D supplementation, while none of the 7 severe cases were on supplementation.
Aug 2021, The J. Steroid Biochemistry and Molecular Biology, https://www.sciencedirect.com/science/article/pii/S0960076021001576, https://c19p.org/sinaci
497. Wang et al., Evaluation and management of COVID-19-related severity in people with type 2 diabetes
16,504 patient metformin prophylaxis study: 12% lower ICU admission (p=0.005).Retrospective 16,504 COVID-19 type 2 diabetes patients, showing lower risk of ICU admission with existing metformin use.
Sep 2021, BMJ Open Diabetes Research & Care, https://drc.bmj.com/content/9/1/e002299.abstract, https://c19p.org/wang5
498. Agusti et al., Efficacy and safety of hydroxychloroquine in healthcare professionals with mild SARS-CoV-2 infection: prospective, non-randomized trial
142 patient HCQ early treatment study: 68% lower progression (p=0.21) and 32% faster viral clearance.Small trial of low dose HCQ for healthcare workers with mild SARS-CoV-2 showing 68% lower progression to pneumonia, p = 0.21, and faster, but not statistically significant viral clearance. There were no ICU admissions or deaths. Prospective non-randomized study. The figures and supplementary data are not currently available in the pre-proof edition.
Dec 2020, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/abs/pii/S0213005X20304134, https://c19p.org/agusti
499. Baralić et al., Significance of 1,25-Dihydroxyvitamin D3 on Overall Mortality in Peritoneal Dialysis Patients with COVID-19
52 patient vitamin D prophylaxis study: 67% lower mortality (p=0.02).Prospective analysis of 52 peritoneal dialysis patients, 31 on calcitriol (vitamin D) therapy. All patients tested positive for COVID-19 during followup (median 26 months). Mortality was significantly lower for patients on calcitriol therapy in univariate Cox regression analysis and in Kaplan-Meier analysis. Multivariate Cox regression analysis showed only diabetes mellitus with statistical significance.
Apr 2023, Nutrients, https://www.mdpi.com/2072-6643/15/9/2050, https://c19p.org/baralic
500. Ianhez et al., Androgen sensitivity in COVID‐19 and antiandrogens: Prospective data are still needed
12,732 patient antiandrogen prophylaxis study: 80% lower ICU admission (p=0.26), 66% lower hospitalization (p=0.32), and 1% more cases (p=0.9).Retrospective survey of 41,529 participants, including 571 on antiandrogen therapy, showing no significant association between antiandrogen use and COVID-19 incidence, hospitalization, or ICU admission/mechanical ventilation.
Sep 2020, Dermatologic Therapy, https://onlinelibrary.wiley.com/doi/10.1111/dth.14166, https://c19p.org/ianhez
501. Panahi et al., Evaluation the efficacy and safety of N‐acetylcysteine inhalation spray in controlling the symptoms of patients with COVID‐19: An open‐label randomized controlled clinical trial
250 patient N-acetylcysteine late treatment RCT: 92% lower mortality (p<0.0001), 36% lower ICU admission (p=0.38), and 1% shorter hospitalization (p=0.81).RCT 250 hospitalized COVID-19 patients showing reduced mortality rate and inflammatory markers with N-acetylcysteine (NAC) 400μg inhaled spray twice daily for 7 days as adjunctive treatment. There was no significant difference in hospital length of stay or ICU admission. The NAC group was older on average, while the control group had significantly lower SpO2 at baseline. 400 μg/day NAC inhaler spray for 7 days.
Dec 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.28393, https://c19p.org/panahi
502. Abbasi et al., A Randomized Trial of Sitagliptin and Spironolactone With Combination Therapy in Hospitalized Adults With COVID-19
138 patient spironolactone antiandrogen late treatment RCT: 55% lower mortality (p=0.1), 34% lower ventilation (p=0.36), 19% lower ICU admission (p=0.67), and 47% improved recovery (p<0.0001).RCT including 51 spironolactone patients and 87 control patients in Iran, showing improved recovery with spironolactone, sitagliptin, and the combination of both.
Feb 2022, J. the Endocrine Society, https://academic.oup.com/jes/article/6/4/bvac017/6523815, https://c19p.org/abbasi
503. Abbasi et al., A Randomized Trial of Sitagliptin and Spironolactone With Combination Therapy in Hospitalized Adults With COVID-19
138 patient spironolactone late treatment RCT: 55% lower mortality (p=0.1), 34% lower ventilation (p=0.36), 19% lower ICU admission (p=0.67), and 47% improved recovery (p<0.0001).RCT including 51 spironolactone patients and 87 control patients in Iran, showing improved recovery with spironolactone, sitagliptin, and the combination of both.
Feb 2022, J. the Endocrine Society, https://academic.oup.com/jes/article/6/4/bvac017/6523815, https://c19p.org/abbasisp
504. Annweiler et al., Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study
61 patient vitamin D prophylaxis study: 93% lower mortality (p=0.02).Retrospective study finding that regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly. For those receiving regular supplementation: Adjusted mortality hazard ratio with supplementation HR 0.07, p = 0.017. Risk of severe COVID-19 with supplementation OR 0.08, p = 0.033. For supplementation started after COVID-19 diagnosis: Adjusted mortality hazard ratio HR 0.37, p = 0.28. Risk of severe COVID-19 with supplementation OR 0.46, p = 0.4.
Nov 2020, Nutrients, https://www.mdpi.com/2072-6643/12/11/3377, https://c19p.org/annweiler2
505. Kishimoto et al., Efficacy of highly bioavailable oral curcumin in asymptomatic or mild COVID-19 patients: a double-blind, randomized, placebo-controlled trial
138 patient curcumin early treatment RCT: 47% lower progression (p=0.48).RCT 138 COVID-19 outpatients in Japan showing lower progression to fever and hypoxemia with curcuRouge, a highly bioavailable oral curcumin formulation, compared to placebo. The curcuRouge group also had a greater reduction in body temperature and took fewer antipyretic medications. The event rate was lower than expected and the difference in progression was not statistically significant.
Jun 2024, J. Health, Population and Nutrition, https://jhpn.biomedcentral.com/articles/10.1186/s41043-024-00584-6, https://c19p.org/kishimoto
506. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data
917,198 patient azithromycin late treatment study: 32% lower mortality (p<0.0001).Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehriziazaz
507. Chitre et al., Phase III randomized clinical trial of BV-4051, an Ayurvedic polyherbal formulation in moderate SARS-CoV-2 infections and its impact on inflammatory biomarkers
175 patient curcumin early treatment RCT: 11% faster recovery (p=0.04).RCT 208 moderate COVID-19 patients in India, 103 treated with a combination of turmeric, ashwagandha, boswellia, and ginger, showing improved recovery with treatment. The dose of curcumin is unknown and bioavailability may be poor.
Nov 2022, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7683, https://c19p.org/chitre
508. Harmon et al., Preadmission Metformin Use Is Associated with Reduced Mortality in Patients with Diabetes Mellitus Hospitalized with COVID-19
11,993 patient metformin prophylaxis study: 18% lower mortality (p<0.0001).Retrospective 11,993 hospitalized COVID-19 patients with diabetes mellitus but without chronic kidney disease or need for hemodialysis, showing lower mortality with metformin use.
Sep 2024, J. General Internal Medicine, https://link.springer.com/article/10.1007/s11606-024-08864-x, https://c19p.org/harmon
509. Dorward et al., Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial
1,301 patient colchicine late treatment RCT: 70% lower mortality (p=0.43), 30% higher combined mortality/hospitalization (p=0.66), and 6% worse recovery (p=0.67).Late treatment RCT with 156 colchicine patients in the UK, showing no significant differences. ISRCTN86534580.
Sep 2021, British J. General Practice, https://bjgp.org/content/early/2022/03/23/BJGP.2022.0083.short, https://c19p.org/dorward
510. Li et al., Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19
131 patient metformin prophylaxis study: 78% lower mortality (p=0.02).Retrospective 131 type II diabetes patients with COVID pneumonia, showing lower mortality with existing metformin use. Acarbose (commonly used in China as an initial therapy for diabetes) did not have a similar association with mortality, suggesting that the result may not be explained by metformin being used early in type II diabetes.
Sep 2020, Endocrine Practice, https://www.endocrinepractice.org/article/S1530-891X(20)48222-9/fulltext, https://c19p.org/li12
511. Tanni et al., Efficacy of BREATHOX® Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH Study): A Randomized Pilot Clinical Trial
98 patient saline early treatment RCT: 75% lower hospitalization (p=0.34) and 10% worse recovery (p=0.7).RCT 98 outpatients in Brazil, showing faster recovery from cough with inhaled hypertonic saline. Authors note that the effect on coughing may hypothetically be related to a hyperosmotic response influencing the function of different membrane channels and preventing virus entry into the cells; and that the hypertonic solution may increase mucociliary clearance and reduce the destructive inflammatory process in the airways with a decrease in respiratory symptoms.
Sep 2023, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/18/6075, https://c19p.org/tanni
512. Israel et al., Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
39,180 patient dutasteride antiandrogen prophylaxis study: 38% lower hospitalization (p=0.01).Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with dutasteride.
Jul 2021, Epidemiology and Global Health Microbiology and Infectious Disease, https://elifesciences.org/articles/68165, https://c19p.org/israel2aa
513. Derwand et al., COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxychloroquine and Azithromycin: A Retrospective Case Series Study
518 patient zinc early treatment study: 79% lower mortality (p=0.12) and 82% lower hospitalization (p=0.001).79% lower mortality and 82% lower hospitalization with early HCQ+AZ+Z. Retrospective 518 patients (141 treated, 377 control).
Jul 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304258, https://c19p.org/derwandz
514. Wang et al., Adherence to Healthy Lifestyle Prior to Infection and Risk of Post–COVID-19 Condition
798 patient diet study: 9% lower PASC (p=0.43).Prospective analysis of 32,249 women from the Nurses’ Health Study II in the USA, showing lower risk of PASC with a healthy lifestyle, and in a dose-dependent manner. Participants with 5 or 6 healthy lifestyle factors had significantly lower COVID-19 hospitalization and PASC. BMI and sleep were independently associated with risk of PASC.
Feb 2023, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2800885, https://c19p.org/wang10dt
580 patient vitamin D prophylaxis study: 34% fewer symptomatic cases (p=0.01).
Prospective study of 580 ChAdOx1 recipients, 262 treated with calcifediol (patient choice), showing lower cases with treatment. Supplementation did not significantly affect antibody levels following ChAdOx1 receipt. Calcifediol patients were older (31 vs. 26 in the exposed subgroup containing most patients). 50μg/day calcifediol.
Mar 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323001317, https://c19p.org/bhat
516. Li et al., Bromhexine Hydrochloride Tablets for the Treatment of Moderate COVID-19: An Open-Label Randomized Controlled Pilot Study
18 patient bromhexine late treatment RCT: 75% higher hospital discharge (p=0.11) and 3% slower recovery.Tiny RCT with 12 bromhexine and 6 control patients showing non-statistically significant improvements in chest CT, need for oxygen therapy, and discharge rate within 20 days. Authors recommend a larger scale trial.
Sep 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.12881, https://c19p.org/li5
517. Boye et al., Risk Factors Associated with COVID-19 Hospitalization and Mortality: A Large Claims-Based Analysis Among People with Type 2 Diabetes Mellitus in the United States
9,531 patient metformin prophylaxis study: 10% lower hospitalization (p<0.0001).Retrospective 9531 COVID+ diabetes patients in the USA, showing lower risk of hospitalization with existing biguanides treatment (defined as mainly metformin in the abstract and entirely metformin in the text).
Jul 2021, Diabetes Therapy, https://link.springer.com/article/10.1007/s13300-021-01110-1/fulltext.html, https://c19p.org/boye
518. Dev et al., Risk factors and frequency of COVID-19 among healthcare workers at a tertiary care centre in India: a case–control study
759 patient HCQ prophylaxis study: 26% fewer cases (p=0.003).Retrospective case control study of 3,100 healthcare workers in India showing lower cases with HCQ prophylaxis, and an inverse association between the number of HCQ doses taken and the risk of COVID-19 cases. Low risk population with no mortality and no severe cases.
Mar 2021, Transactions of The Royal Society of Tropical Medicine and Hygiene, https://academic.oup.com/trstmh/advance-article/doi/10.1093/trstmh/trab047/6186057, https://c19p.org/dev
106 patient vitamin D late treatment RCT: 40% lower ICU admission (p=0.42) and 17% shorter hospitalization (p=0.1).
RCT 106 hospitalized patients with vitamin D levels <30ng/ml in Iran, 53 treated with calcifediol, showing that treatment was able to correct vitamin D deficiency/insufficiency, resulting in improved immune system function. Hospitalization, ICU duration, ventilation, and mortality was lower with treatment, without reaching statistical significance with the small sample size. The dosage used in this trial was much lower than other trials.
Oct 2021, Endocrine Practice, https://www.sciencedirect.com/science/article/abs/pii/S1530891X21012593, https://c19p.org/maghbooli2
520. Kumar et al., Efficacy of montelukast in the management of COVID-19: double blind randomized placebo controlled trial
90 patient montelukast late treatment RCT: 67% lower ICU admission (p=0.62), 25% higher progression (p=0.79), and no change in hospital discharge (p=1).RCT 90 mild to moderate COVID-19 patients showing no significant differences with montelukast treatment.
Nov 2021, Int. J. Basic & Clinical Pharmacology, https://www.ijbcp.com/index.php/ijbcp/article/view/4867, https://c19p.org/kumar9
521. Zhong Nanshan (钟南山) et al., Efficacy and safety of chloroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial
197 patient HCQ late treatment study: 80% improved viral clearance (p=0.0001).197 patients. CQ effective. Day 10 viral RNA negative 91.4% HCQ versus 57.4% control. Median time to negative test 3 days versus 9 days for control.
Mar 2020, Zhong Nanshan, https://twitter.com/JamesTodaroMD/status/1243260720944480265, https://c19p.org/zhong2
522. Atipornwanich et al., Various Combinations of Favipiravir, Lopinavir-Ritonavir, Darunavir-Ritonavir, High-Dose Oseltamivir, and Hydroxychloroquine for the Treatment of COVID-19: A Randomized Controlled Trial (FIGHT-COVID-19 Study)
200 patient favipiravir late treatment RCT: 23% lower mortality (p=0.66), 60% lower progression (p=0.009), and 9% faster viral clearance (p=0.43).RCT 200 moderate/severe patients in Thailand, showing significantly lower progression with favipiravir vs. oseltamivir. NCT04303299.
Oct 2021, SSRN Electronic J., https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3936499, https://c19p.org/atipornwanicha
523. Gao et al., The impact of individual lifestyle and status on the acquisition of COVID-19: A case—Control study
315 patient sleep study: 36% fewer cases (p=0.04).Case control study in China with 105 cases and 210 matched controls, showing COVID-19 cases associated with lack of sleep.
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241540, https://c19p.org/gao5sl
524. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient antihistamine H1RA prophylaxis study: 40% lower mortality (p=0.003).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with antihistamine H1RAs, without statistical significance. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3h1
525. George et al., Single Dose of Ivermectin is not Useful in Patients with Hematological Disorders and COVID-19 Illness: A Phase II B Open Labelled Randomized Controlled Trial
112 patient ivermectin late treatment RCT: 30% lower mortality (p=0.55), 19% faster recovery (p=0.37), 33% lower progression (p=0.41), and 33% worse viral clearance (p=0.5).RCT with 35 single dose 24mg, 38 single dose 12mg, and 39 SOC hospitalized patients with hematological illnesses in India, showing no significant differences. Results were better for 24mg vs. 12mg for all symptomatic outcomes. Viral clearance results do not follow the randomization with less than 50% of patients tested at day 7, and no adjusted results are provided. Results were obtained for only 43.8% of ivermectin patients and 56.4% of control patients at day 7 and may not be comparable due to the large difference in the percentage of patients tested. Lower test coverage in the ivermectin group is likely related to faster recovery. Ct 40 for E or S was used for viral clearance which may also have low relevance to infectious disease.
May 2022, Indian J. Hematology and Blood Transfusion, https://link.springer.com/10.1007/s12288-022-01546-w, https://c19p.org/george
526. Mukhtar et al., A Randomized trial on the regular use of potent mouthwash in COVID-19 treatment
92 patient hydrogen peroxide early treatment RCT: 86% lower mortality (p=0.24), 86% lower ventilation (p=0.24), and 18% improved viral clearance (p=0.16).RCT for mouthwash containing hydrogen peroxide 2% and chlorhexidine gluconate, showing higher discharge, shorter hospital stay, less intubation, and lower mortality with treatment.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.27.20234997v2, https://c19p.org/mukhtar
527. Al Harthi et al., Evaluation of Low-Dose Aspirin use among Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study
351 patient aspirin ICU PSM study: 27% lower mortality (p=0.03) and 5% shorter ICU admission (p=0.54).Retrospective 1,033 critical condition patients, showing lower in-hospital mortality with aspirin in PSM analysis. Patients receiving aspirin also had a higher risk of significant bleeding, although not reaching statistical significance. Authors note that the use of aspirin during an ICU stay should be tailored to each patient.
Sep 2021, J. Intensive Care Medicine, https://journals.sagepub.com/doi/pdf/10.1177/08850666221093229, https://c19p.org/alharthi
528. Catinean et al., Ongoing Treatment with a Spore-Based Probiotic Containing Five Strains of Bacillus Improves Outcomes of Mild COVID-19
120 patient probiotics prophylaxis study: 40% improved recovery (p=0.008).Retrospective 60 patients in Romania taking probiotics and 60 matched controls, showing faster symptom resolution with the use of probiotics. Spore-based probiotic containing five strains of Bacillus.
Jan 2023, Nutrients, https://www.mdpi.com/2072-6643/15/3/488, https://c19p.org/catinean
8,864 patient ursodeoxycholic acid prophylaxis study: 13% fewer cases (p=0.03).
Retrospective 8,964 primary care patients prescribed ursodeoxycholic acid (UDCA) in the UK. Higher categorized UDCA adherence (≥80%) was associated with lower COVID-19 incidence (OR 0.86), whereas adherence as a continuous variable was not significant. However, adherence was measured indirectly via prescription records which may not reflect actual usage. Additionally, more adherent patients may differ systematically on unmeasured confounders (e.g., health behaviors) that influence COVID-19 risk.
Nov 2023, Microbiology and Infectious Diseases The American Medical J., https://www.emjreviews.com/microbiology-infectious-diseases/article/a-retrospective-study-in-patients-with-varying-prescription-coverage-with-ursodeoxycholic-acid-and-association-with-incidence-of-covid-19-diagnosis-in-primary-care/, https://c19p.org/ming
201 patient vitamin D prophylaxis study: 22% lower mortality (p=0.61) and 31% lower progression (p=0.26).
Prospective study of 201 COVID+ hospitalized adults in Brazil, mean age 73, showing a lower risk of mortality and respiratory failure with vitamin D supplementation in unadjusted results, without statistical significance, and a higher risk of progression to mechanical ventilation with vitamin D levels <40ng/dl.
Feb 2022, BMC Geriatrics, https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-022-02776-3, https://c19p.org/junior
531. Manomaipiboon et al., Efficacy and safety of ivermectin in the treatment of mild-to-moderate COVID-19 infection: A randomized, double blind, placebo, controlled trial
72 patient ivermectin early treatment RCT: 43% improved recovery (p=0.26) and 5% improved viral clearance (p=1).Small RCT with 72 low-risk patients in Thailand, showing improved recovery with ivermectin, without statistical significance. All patients recovered and there was no escalation of care in either group. There were no adverse events.
Feb 2022, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06649-3, https://c19p.org/manomaipiboon
532. Valerio-Pascua et al., Chlorpheniramine Intranasal Spray to Accelerate COVID-19 Clinical Recovery in an Outpatient Setting: The ACCROS Trials
660 patient chlorpheniramine early treatment study: 54% faster recovery (p<0.0001).RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The retrospective study included 660 outpatients showing fewer days with general COVID-19 symptoms, cough, anosmia, and ageusia compared to standard of care alone. The RCT results are listed separately [Valerio-Pascua].
Oct 2022, Research Square, https://www.researchsquare.com/article/rs-2167465/v1, https://c19p.org/valeriopascua3b
533. Valerio-Pascua et al., Chlorpheniramine Intranasal Spray to Accelerate COVID-19 Clinical Recovery in an Outpatient Setting: The ACCROS Trials
660 patient chlorpheniramine early treatment study: 54% faster recovery (p<0.0001).RCT and retrospective study of chlorpheniramine nasal spray for COVID-19. The retrospective study included 660 outpatients showing fewer days with general COVID-19 symptoms, cough, anosmia, and ageusia compared to standard of care alone. The RCT results are listed separately [Valerio-Pascua].
Oct 2022, Research Square, https://www.researchsquare.com/article/rs-2167465/v1, https://c19p.org/valeriopascua3bcpm
534. Zihono et al., Metformin Effectiveness in Reducing Mortality among Covid-19 Patients with Type 2 Diabetes Mellitus at a Tertiary Hospital in Indonesia
137 patient metformin prophylaxis study: 49% lower mortality (p=0.02).Retrospective 137 hospitalized mild to moderate COVID-19 patients with type 2 diabetes in Indonesia, showing a significantly lower mortality with metformin treatment.
Sep 2023, Folia Medica Indonesiana, https://e-journal.unair.ac.id/FMI/article/view/46944, https://c19p.org/zihono
535. Atipornwanich et al., Various Combinations of Favipiravir, Lopinavir-Ritonavir, Darunavir-Ritonavir, High-Dose Oseltamivir, and Hydroxychloroquine for the Treatment of COVID-19: A Randomized Controlled Trial (FIGHT-COVID-19 Study)
200 patient HCQ late treatment RCT: 56% lower mortality (p=0.07), 54% lower progression (p=0.02), and 7% faster viral clearance (p=0.51).RCT 320 patients in Thailand, showing significantly lower progression with HCQ for moderate/severe patients, and faster viral clearance with mild patients (statistically significant for 800mg). There are two sets of results - for moderate/severe patients, and for mild patients. There was no mortality for mild patients. NCT04303299.
Oct 2021, SSRN Electronic J., https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3936499, https://c19p.org/atipornwanich
536. Seely et al., Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial
90 patient vitamin D late treatment RCT: 14% improved recovery (p=0.41).Early terminated low-risk population (no hospitalization) very late treatment (mean 8 days) RCT with 44 patients treated with vitamin C, D, K, and zinc, and 46 control patients, showing no significant differences. Authors acknowledge that the very late treatment is a major limitation, noting that in an ideal setting, "patients would begin taking therapeutic interventions immediately after noticing symptoms". Authors note that patients already had a low symptom burden at baseline and that "it is likely that the majority of the participants had almost fully recovered before starting treatment." Authors note that most participants were young, had few comorbidities and had excellent self-rated health at baseline, leaving less room for improvement. There was low compliance with completing surveys. Data from only 64% of patients was in the main analysis. Authors claim "high internal validity", but the loss of data was statistically significantly..
Sep 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2023-073761, https://c19p.org/seelyd
537. Seely et al., Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial
90 patient vitamin C late treatment RCT: 14% improved recovery (p=0.41).Early terminated low-risk population (no hospitalization) very late treatment (mean 8 days) RCT with 44 patients treated with vitamin C, D, K, and zinc, and 46 control patients, showing no significant differences. Authors acknowledge that the very late treatment is a major limitation, noting that in an ideal setting, "patients would begin taking therapeutic interventions immediately after noticing symptoms". Authors note that patients already had a low symptom burden at baseline and that "it is likely that the majority of the participants had almost fully recovered before starting treatment." Authors note that most participants were young, had few comorbidities and had excellent self-rated health at baseline, leaving less room for improvement. There was low compliance with completing surveys. Data from only 64% of patients was in the main analysis. Authors claim "high internal validity", but the loss of data was statistically significantly..
Sep 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2023-073761, https://c19p.org/seely
538. Seely et al., Dietary supplements to reduce symptom severity and duration in people with SARS-CoV-2: a double-blind randomised controlled trial
90 patient zinc late treatment RCT: 14% improved recovery (p=0.41).Early terminated low-risk population (no hospitalization) very late treatment (mean 8 days) RCT with 44 patients treated with vitamin C, D, K, and zinc, and 46 control patients, showing no significant differences. Authors acknowledge that the very late treatment is a major limitation, noting that in an ideal setting, "patients would begin taking therapeutic interventions immediately after noticing symptoms". Authors note that patients already had a low symptom burden at baseline and that "it is likely that the majority of the participants had almost fully recovered before starting treatment." Authors note that most participants were young, had few comorbidities and had excellent self-rated health at baseline, leaving less room for improvement. There was low compliance with completing surveys. Data from only 64% of patients was in the main analysis. Authors claim "high internal validity", but the loss of data was statistically significantly..
Sep 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2023-073761, https://c19p.org/seelyz
539. Levy et al., Frail Older Adults with Presymptomatic SARS-CoV-2 Infection: Clinical Course and Prognosis
849 patient vitamin D prophylaxis study: 30% lower combined mortality/hospitalization (p=0.05).Retrospective 849 COVID-19+ patients in skilled nursing homes, showing lower risk of combined hospitalization/death with vitamin D prophylaxis, very close to statistical significance.
Jan 2022, Gerontology, https://www.karger.com/Article/FullText/521412, https://c19p.org/levy
540. Davarpanah et al., Combination of spironolactone and sitagliptin improves clinical outcomes of outpatients with COVID-19: a prospective cohort study
206 patient spironolactone antiandrogen late treatment study: 78% lower hospitalization (p=0.0008), 67% lower progression (p=0.003), and 64% faster recovery (p=0.0001).Prospective study of 206 outpatients in Iran, 103 treated with spironolactone and sitagliptin, showing lower hospitalization and faster recovery with treatment. spironolactone 100mg and sitagliptin 100mg daily.
Jan 2022, J. Endocrinological Investigation, https://link.springer.com/10.1007/s40618-023-02141-0, https://c19p.org/davarpanah
541. Davarpanah et al., Combination of spironolactone and sitagliptin improves clinical outcomes of outpatients with COVID-19: a prospective cohort study
206 patient spironolactone late treatment study: 78% lower hospitalization (p=0.0008), 67% lower progression (p=0.003), and 64% faster recovery (p=0.0001).Prospective study of 206 outpatients in Iran, 103 treated with spironolactone and sitagliptin, showing lower hospitalization and faster recovery with treatment. spironolactone 100mg and sitagliptin 100mg daily.
Jan 2022, J. Endocrinological Investigation, https://link.springer.com/10.1007/s40618-023-02141-0, https://c19p.org/davarpanahsp
542. Calusic et al., Safety and efficacy of fluvoxamine in COVID-19 ICU patients: an open label, prospective cohort trial with matched controls
102 patient fluvoxamine ICU PSM study: 42% lower mortality (p=0.03).Prospective PSM study of 51 COVID-19 ICU patients in Croatia and 51 matched controls, showing significantly lower mortality with treatment.
Oct 2021, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15126, https://c19p.org/calusic
543. d'Ettorre et al., Challenges in the Management of SARS-CoV2 Infection: The Role of Oral Bacteriotherapy as Complementary Therapeutic Strategy to Avoid the Progression of COVID-19
70 patient probiotics late treatment study: 87% lower mortality (p=0.14) and 88% lower progression (p=0.01).Retrospective 70 hospitalized patients in Italy, 28 treated with probiotic Sivomixx, showing lower risk of respiratory failure and faster recovery with treatment.
Jul 2020, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2020.00389/full, https://c19p.org/dettorre
544. Ghandehari et al., Progesterone in Addition to Standard of Care vs Standard of Care Alone in the Treatment of Men Hospitalized With Moderate to Severe COVID-19
40 patient antiandrogen late treatment RCT: 85% lower ventilation (p=0.24), 76% lower progression (p=0.2), and 100% improved recovery (p=0.02).RCT 42 hospitalized patients in the USA, showing improved recovery and lower progression with progesterone treatment.
Jul 2021, Chest, https://www.sciencedirect.com/science/article/pii/S0012369221002890, https://c19p.org/ghandehari
545. Mourya et al., Comparative Analytical Study of Two Different Drug Regimens in Treatment of Covid 19 Positive Patients in Index Medical College Hospital and Research Center, Indore, India
100 patient ivermectin early treatment study: 89% improved viral clearance (p<0.0001).Retrospective 100 patients in India with 50 treated with ivermectin, and SOC for all patients including HCQ+AZ, showing much higher viral clearance with ivermectin. Baseline clinical status was worse in the control group. Time of testing after treatment initiation was longer in the control group (mean 7.24 days versus 5.22 days).
Mar 2021, Int. J. Health and Clinical Research, https://ijhcr.com/index.php/ijhcr/article/view/1263, https://c19p.org/mourya
546. Hueda-Zavaleta et al., Factores asociados a la muerte por COVID-19 en pacientes admitidos en un hospital público en Tacna, Perú
351 patient colchicine late treatment study: 54% lower mortality (p=0.03).Retrospective 450 late stage (median oxygen saturation 86%) COVID+ hospitalized patients in Peru, showing lower mortality with colchicine treatment.
Jun 2021, Revista Peruana de Medicina Experimental y Salud Pública, https://rpmesp.ins.gob.pe/rpmesp/article/view/7158, https://c19p.org/huedazavaleta
547. Lammers et al., Early hydroxychloroquine but not chloroquine use reduces ICU admission in COVID-19 patients
1,064 patient HCQ late treatment study: 32% lower combined mortality/ICU admission (p=0.02).Observational study 1,064 hospitalized patients in the Netherlands, 53% reduced risk of transfer to the ICU for mechanical ventilation with HCQ treatment starting on the first day of admission. Weighted propensity score adjusted hazard ratio for transfer to the ICU with HCQ treatment, HR = 0.47, p = 0.008. For CQ, HR = 0.8, p = 0.207. Mortality results in this study are only for mortality before transfer to the ICU. The combined ICU/death HR was 0.68, p = 0.024 for HCQ, and 0.85, p = 0.224 for CQ. Observational, multicenter, cohort study of hospitalized COVID-19 patients. 189 HCQ patients, 377 CQ, 498 control.
Sep 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220321755, https://c19p.org/lammers
548. Berenguer et al., Characteristics and predictors of death among 4035 consecutively hospitalized patients with COVID-19 in Spain
3,995 patient HCQ late treatment study: 18% lower mortality (p=0.0001).Retrospective 4035 hospitalized patients in Spain showing reduced mortality with HCQ (data is in the supplementary appendix).
Aug 2020, Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30431-6/fulltext, https://c19p.org/berenguer
549. Abul et al., Association of mortality and aspirin use for COVID-19 residents at VA Community Living Center Nursing Homes
1,687 patient aspirin prophylaxis study: 33% lower mortality (p=0.03) and 20% lower hospitalization (p=0.13).Retrospective 1,687 nursing home residents in the USA, showing significantly lower risk of mortality with chronic low-dose aspirin use. Low dose 81mg aspirin users had treatment ≥10 of 14 days prior to the positive COVID date, control patients had no aspirin use in the prior 14 days.
Aug 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.03.22278392, https://c19p.org/abul
550. Guérin et al., Azithromycin and Hydroxychloroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19
88 patient HCQ early treatment study: 65% faster recovery (p=0.0001).Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HCQ+AZ) or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective study of 88 patients with case control analysis with matched patients.
May 2020, Asian J. Medicine and Health, https://www.journalajmah.com/index.php/AJMAH/article/view/30224, https://c19p.org/guerin
551. Liu et al., Effect of low-dose aspirin on mortality and viral duration of the hospitalized adults with COVID-19
232 patient aspirin late treatment PSM study: 75% lower mortality (p=0.03) and 2% slower viral clearance (p=0.94).Retrospective PSM analysis of 232 hospitalized patients, 28 treated with aspirin, showing lower mortality with treatment. There was no significant difference in viral clearance.
Feb 2021, Medicine, https://journals.lww.com/md-journal/Fulltext/2021/02120/Effect_of_low_dose_aspirin_on_mortality_and_viral.41.aspx, https://c19p.org/liu2
552. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient azithromycin prophylaxis study: 15% lower mortality (p=0.005).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3azaz
553. Shohan et al., The therapeutic efficacy of quercetin in combination with antiviral drugs in hospitalized COVID-19 patients: A randomized controlled trial
60 patient quercetin late treatment RCT: 86% lower mortality (p=0.24) and 32% faster recovery (p=0.04).Small RCT with 60 severe hospitalized patients in Iran, 30 treated with quercetin, showing shorter time until discharge. All patients received remdesivir or favipiravir, and vitamin C, vitamin D, famotidine, zinc, dexamethasone, and magnesium (depending on serum levels). Quercetin 1000mg daily for 7 days. IRCT20200419047128N2.
Dec 2021, European J. Pharmacology, https://www.sciencedirect.com/science/article/pii/S0014299921007718, https://c19p.org/shohan
554. Israel et al., Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
20,859 patient vitamin D prophylaxis study: 13% lower hospitalization (p=0.003).Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with vitamin D (defined as being picked up within 35 days prior to PCR+). Other patients may have acquired vitamin D supplements outside of the healthcare system.
Jul 2021, Epidemiology and Global Health Microbiology and Infectious Disease, https://elifesciences.org/articles/68165, https://c19p.org/israel2
555. Akbar et al., The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank
10,000 patient vitamin D prophylaxis study: 19% fewer cases (p=0.02).Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with vitamin D supplementation. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2
556. Al-Salameh et al., The association between metformin treatment and COVID-19 outcomes according to metformin continuation during hospitalisation
97 patient metformin prophylaxis study: 55% lower combined mortality/ICU admission (p=0.04).Retrospective 140 diabetic patients in France, showing lower mortality for patients where metformin use was continued after hospitalization.
Nov 2021, Diabetes & Metabolism, https://www.sciencedirect.com/science/article/pii/S126236362100080X, https://c19p.org/alsalameh
557. Bundgaard et al., Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers
4,862 patient PPE prophylaxis RCT: 18% fewer cases (p=0.33).RCT 4,862 community-dwelling adults in Denmark, showig no significant difference in COVID-19 cases with recommending the use of surgical masks outside the home. The prespecified mortality outcomes are not reported and the only severity information provided is symptom counts.
Nov 2020, Annals of Internal Medicine , https://www.acpjournals.org/doi/10.7326/M20-6817, https://c19p.org/bundgaard
558. Lally et al., Metformin is Associated with Decreased 30-Day Mortality Among Nursing Home Residents Infected with SARS-CoV2
775 patient metformin prophylaxis study: 52% lower mortality (p=0.009).Retrospective 775 nursing home residents in the USA, showing lower mortality with existing metformin use.
Jan 2021, J. the American Medical Directors Association, https://www.sciencedirect.com/science/article/pii/S1525861020309245, https://c19p.org/lally
559. Szente Fonseca et al., Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis
717 patient HCQ early treatment study: 64% lower hospitalization (p=0.0008).64% lower hospitalization with HCQ. Retrospective 717 patients in Brazil with early treatment, adjusted OR 0.32, p=0.00081, for HCQ versus no medication, and OR 0.45, p=0.0065, for HCQ vs. anything else.
Oct 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/abs/pii/S1477893920304026, https://c19p.org/fonseca
560. Cangiano et al., Mortality in an Italian nursing home during COVID-19 pandemic: correlation with gender, age, ADL, vitamin D supplementation, and limitations of the diagnostic tests
98 patient vitamin D prophylaxis study: 70% lower mortality (p=0.04).70% lower mortality with vitamin D supplementation. Analysis of 98 PCR+ nursing home residents in Italy, mean age 90, vitamin D supplementation RR 0.30, p = 0.04. The paper provides the p value for regression but not the effect size. Treatment was 2x per month 25000IU.
Dec 2020, Aging, https://www.aging-us.com/article/202307/text, https://c19p.org/cangianod
561. Brevini et al., FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2
186 patient ursodeoxycholic acid prophylaxis PSM study: 94% lower mortality (p=0.13), 75% lower ICU admission (p=0.21), and 40% lower hospitalization (p=0.03).Retrospective study from two registries of 1,096 COVID-19 patients with chronic liver disease, including 31 treated with ursodeoxycholic acid (UDCA). Propensity score matching was used to compare outcomes between UDCA-treated and untreated patients. The analysis found that UDCA treatment was associated with reduced hospitalization, ICU admission, ventilation, and death from COVID-19. The authors suggest that UDCA may decrease susceptibility to SARS-CoV-2 infection by downregulating the host receptor ACE2 through inhibition of the farnesoid X receptor. Authors also show that UDCA-mediated downregulation of ACE2 reduces susceptibility to SARS-CoV-2 infection in vitro, in vivo and in human lungs and livers perfused ex situ; and that UDCA reduces the expression of ACE2 in the nasal epithelium in humans.
Dec 2022, Nature, https://www.nature.com/articles/s41586-022-05594-0, https://c19p.org/brevini
562. Sobngwi et al., Doxycycline vs Hydroxychloroquine + Azithromycin in the Management of COVID-19 Patients: An Open-Label Randomized Clinical Trial in Sub-Saharan Africa (DOXYCOV)
187 patient HCQ early treatment RCT: 52% improved recovery (p=0.44) and 3% improved viral clearance (p=0.88).RCT 194 mild/asymptomatic low-risk patients in Cameroon, 97 treated with HCQ+AZ and 97 treated with doxycycline, showing 2.1% symptomatic patients at day 10 with HCQ+AZ, versus 4.3% with doxycycline, without statistical significance. There were only 6 patients with symptoms at day 10. There was no mortality or hospitalization, and no major adverse events.
Jul 2021, Cureus, https://www.cureus.com/articles/179159-doxycycline-vs-hydroxychloroquine--azithromycin-in-the-management-of-covid-19-patients-an-open-label-randomized-clinical-trial-in-sub-saharan-africa-doxycov, https://c19p.org/sobngwi
563. Hsieh et al., Efficacy and Safety of Complementary Therapy With Jing Si Herbal Tea in Patients With Mild-To-Moderate COVID-19: A Prospective Cohort Study
260 patient antiandrogen late treatment study: 88% lower mortality (p=0.13), 30% lower ICU admission (p=0.76), 88% improved recovery (p=0.13), and 36% improved viral clearance (p=0.0002).Prospective study of 260 hospitalized patients in Taiwan, 117 treated with herbal formula Jing Si Herbal Tea which includes antiandrogen glycyrrhiza glabra, showing improved recovery with treatment, with statistical significance for SpO2, Ct score, CRP, and Brixia score.
Mar 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.832321/full, https://c19p.org/hsieh
564. Guan et al., High-dose Vitamin C Intake and COVID-19 Related Symptoms During the SARS-CoV-2 Pandemic
2,621 patient vitamin C prophylaxis study: 31% fewer symptomatic cases (p=0.007).Retrospective 2,746 individuals in China showing significantly lower incidence of COVID-19 symptoms and fever with higher vitamin C intake, with a dose response relationship.
May 2024, The American J. the Medical Sciences, https://www.sciencedirect.com/science/article/pii/S0002962924012229, https://c19p.org/guan2
565. Zhong et al., Azvudine reduces the mortality rate of patients with Coronavirus disease 2019: a single-center retrospective analysis study
2,863 patient azvudine late treatment study: 35% lower mortality (p=0.05).Retrospective 2,862 hospitalized COVID-19 patients in China showing lower mortality with azvudine treatment.
Mar 2024, Research Square, https://www.researchsquare.com/article/rs-4157424/v1, https://c19p.org/zhong6
566. van Halem et al., Risk factors for mortality in hospitalized patients with COVID-19 at the start of the pandemic in Belgium: a retrospective cohort study
319 patient HCQ late treatment study: 32% lower mortality (p=0.05).Retrospective 319 hospitalized patients in Belgium showing significantly lower mortality with HCQ.
Nov 2020, BMC Infectious Diseases, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691970/, https://c19p.org/vanhalem
567. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient aspirin prophylaxis study: 18% lower mortality (p=0.0004).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3e
568. Coppock et al., Pharmacologic Ascorbic Acid as Early Therapy for Hospitalized Patients with COVID-19: A Randomized Clinical Trial
66 patient vitamin C late treatment RCT: 50% greater improvement (p=0.16) and 22% higher hospital discharge (p=0.07).RCT with 66 very late stage (8 days from symptom onset) hospitalized patients, 44 treated with vitamin C and 22 control patients, showing no significant differences with treatment.
Mar 2022, Life, https://www.mdpi.com/2075-1729/12/3/453, https://c19p.org/coppock
569. Goenka et al., Seroprevalence of COVID-19 Amongst Health Care Workers in a Tertiary Care Hospital of a Metropolitan City from India
962 patient HCQ prophylaxis study: 87% lower IgG positivity (p=0.03).Study of SARS-CoV-2-IgG antibodies in 1122 health care workers in India finding 87% lower positives for adequate HCQ prophylaxis, 1.3% HCQ versus 12.3% for no HCQ prophylaxis. Adequate prophylaxis is defined as 400mg 1/wk for >6 weeks.
Oct 2020, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3689618, https://c19p.org/goenka
570. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data
917,198 patient HCQ late treatment study: 26% lower mortality (p<0.0001).Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizi
840 patient HCQ late treatment study: 78% lower mortality (p<0.0001).
Retrospective 750 COVID-19 patients in Saudi Arabia, showing lower mortality with HCQ treatment in unadjusted results. Authors note that the poor results in some other trials may be related to increased dosages and later treatment.
Apr 2023, J. Multidisciplinary Healthcare, https://www.dovepress.com/profiles-of-independent-comorbidity-groups-in-senior-covid-19-patients-peer-reviewed-fulltext-article-JMDH, https://c19p.org/said2
572. Amaravadi et al., Hydroxychloroquine for SARS-CoV-2 positive patients quarantined at home: The first interim analysis of a remotely conducted randomized clinical trial
29 patient HCQ early treatment RCT: 60% improved recovery (p=0.13).Tiny early-terminated 34 patient RCT for outpatient treatment showing faster recovery with treatment (not statistically significant). All patients recovered (3 control patients recovered after crossover to the treatment arm) - as per protocol mid-recovery results have priority. There was no mortality and only one hospitalization on day 0 before treatment. There were no severe adverse events.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.22.21252228v1, https://c19p.org/amaravadi
573. Ravichandran et al., Use of indomethacin in COVID-19 patients: experience from two medical centres
144 patient indomethacin late treatment PSM study: 96% lower need for oxygen therapy (p<0.0001) and 43% faster recovery (p<0.0001).PSM retrospective 72 indomethacin and 72 paracetamol patients in India, showing lower progression and improved recovery with indomethacin.
Jul 2021, J. the Indian Medical Association, https://sapiensfoundation.org/wp-content/uploads/2021/08/Use-of-Indomethacin-in-Covid-19-patients-JIMA-2021.pdf, https://c19p.org/ravichandran2
574. Margolin et al., 20-Week Study of Clinical Outcomes of Over-the-Counter COVID-19 Prophylaxis and Treatment
113 patient quercetin prophylaxis study: 94% fewer cases (p=0.003).Retrospective 113 outpatients, 53 (patient choice) treated with zinc, quercetin, vitamin C/D/E, l-lysine, and quina, showing lower cases with treatment. Results are subject to selection bias and limited information on the groups is provided. See [journals.sagepub.com].
Jul 2021, J. Evidence-Based Integrative Medicine, https://journals.sagepub.com/doi/full/10.1177/2515690X211026193, https://c19p.org/margolinq
575. Delgado et al., Investigational medications in 9,638 hospitalized patients with severe COVID-19: lessons from the “fail-and-learn” strategy during the first two waves of the pandemic in 2020
9,638 patient HCQ late treatment study: 26% lower mortality (p=0.002).PSM retrospective 9,638 patients in the USA, showing significantly lower mortality with HCQ in early 2020 (1,157 HCQ patients), and no significant difference in late 2020 (82 HCQ patients). The few patients treated in the later period may be in more serious condition due to the effort required to overcome the politicization and censorship in the study country. Authors refer to their result as "no relevant benefit in mortality between the two surges".
Feb 2023, Research Square, https://www.researchsquare.com/article/rs-2596201/v1, https://c19p.org/delgado
576. Di Domênico et al., Effectiveness of hydrogen peroxide as auxiliary treatment for hospitalized COVID-19 patients in Brazil: preliminary results of a randomized double-blind clinical trial
40 patient hydrogen peroxide late treatment RCT: 50% lower ICU admission (p=1), 6% greater improvement (p=0.91), and 7% higher hospital discharge (p=0.61).RCT very late treatment (>10 days from onset) comparing hydrogen peroxide + mint essence with water + mint essence, showing no significant differences.
Apr 2021, Epidemiology and Health, http://e-epih.org/journal/view.php?doi=10.4178/epih.e2021032, https://c19p.org/didomenico
577. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data
917,198 patient spironolactone late treatment study: 32% lower mortality (p<0.0001).Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizisp
578. Welén et al., A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
39 patient enzalutamide antiandrogen late treatment RCT: 80% lower mortality (p=0.26), 133% lower hospital discharge (p=0.03), and 50% longer hospitalization (p=0.01).Very small late stage RCT with 10 control patients and 29 enzalutamide patients, showing mixed results. Discharge and hospitalization time favored the control group, while viral load reduction was better with treatment on days 4&6 (day 4 ΔCt −5.6 p = 0.084), and the only death occurred in the control group. 27% of enzalutamide patients had diabetes compared to 0% of the control group. This paper also includes a retrospective study which is listed separately, and an In Vitro HBEC study showing no significant differences (p = 0.084). The supplementary data is not currently available. NCT04475601. For discussion of issues with this study see [sciencedirect.com, sciencedirect.com, sciencedirect.com, sciencedirect.com].
Dec 2021, European Urology, https://www.europeanurology.com/article/S0302-2838(21)02224-7/fulltext, https://c19p.org/welen
579. Rengifo et al., A Mouthwash with Cetylpyridinium Chloride is reducing salivary SARS-CoV-2 viral load in +COVID-19
23 patient cetylpyridinium chloride late treatment RCT: 83% improved viral clearance (p=0.06).RCT 23 patients in Colombia, showing improved viral clearance with cetylpyridinium chloride plus chlorhexidine mouthwash.
May 2023, Revista Estomatologia, https://estomatologia.univalle.edu.co/index.php/revista_estomatologia/article/download/12669/15872, https://c19p.org/rengifo
580. Salehzadeh et al., The Impact of Colchicine on COVID-19 patients: A Clinical Trial Study
100 patient colchicine late treatment RCT: 23% shorter hospitalization (p=0.001).Open label RCT with 100 hospitalized patients in Iran, 50 treated with colchicine, showing shorter hospitalization time with treatment. There were no deaths.
Sep 2020, Mediterranean J. Rheumatology, http://www.mjrheum.org/assets/files/792/file382_1566.pdf, https://c19p.org/salehzadeh
581. Bejan et al., DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
9,748 patient vitamin B12 prophylaxis study: 34% lower mortality (p=0.3), 35% lower ventilation (p=0.26), 16% lower ICU admission (p=0.61), and 10% lower hospitalization (p=0.6).Retrospective 9,748 COVID-19 patients in the USA showing lower risk with vitamin B12 use, without statistical significance.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejan
582. Ogasawara et al., The effect of 1-hydroxy-vitamin D treatment in hospitalized patients with COVID-19: A retrospective study
312 patient vitamin D late treatment study: 78% lower progression (p=0.05) and 75% lower need for oxygen therapy (p=0.09).PSM retrospective 312 hospitalized patients in Japan, showing lower progression with vitamin D (alfacalcidol) treatment, statistically significant via KM log-rank.
Aug 2023, Clinical Nutrition, https://www.sciencedirect.com/science/article/pii/S0261561423002790, https://c19p.org/ogasawara
583. Mulhem et al., 3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study
3,219 patient zinc late treatment study: 46% lower mortality (p<0.0001).Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhemz
584. Vila‐Corcoles et al., Use of distinct anti‐hypertensive drugs and risk for COVID‐19 among hypertensive people: A population‐based cohort study in Southern Catalonia, Spain
34,936 patient antihistamine H1RA prophylaxis study: 61% fewer cases (p=0.1).Retrospective 34,936 hypertensive outpatients in Spain showing no significant difference in COVID-19 cases with PPIs and antihistamine H1RAs.
Jul 2020, The J. Clinical Hypertension, https://onlinelibrary.wiley.com/doi/10.1111/jch.13948, https://c19p.org/vilacorcoles2h1
36 patient HCQ late treatment study: 88% lower ICU admission (p=0.008).
Retrospective analysis of 36 hospitalized patients showing HCQ/AZ associated with lower ICU admission, p=0.008. Median age 66, no mortality. Confounding by indication, however it was patients with hypoxemic pneumonia that were treated with HCQ/AZ, patients were not treated with HCQ/AZ if they didn't need oxygen therapy.
Aug 2020, J. Global Antimicrobial Resistance, https://www.sciencedirect.com/science/article/pii/S221371652030206X, https://c19p.org/dubernet
586. Aidouni et al., The impact of asprin use on the outcome of patients admitted to the intensive care unit with COVID-19 infection
1,124 patient aspirin ICU study: 31% lower mortality (p=0.003) and 10% lower ventilation (p=0.33).Prospective study of 1,124 COVID-19 ICU patients, showing lower mortality with aspirin treatment.
Nov 2022, Research Square, https://www.researchsquare.com/article/rs-2313880/v1, https://c19p.org/aidouni
587. Li et al., Risk of severe case in COVID-19 patients and Azvudine: A Retrospective cohort study after exit from ‘zero-COVID’ policy
2,206 patient azvudine late treatment PSM study: 29% lower mortality (p=0.03).Retrospective 4,201 hospitalized COVID-19 patients in China, showing lower mortality with azvudine.
Jan 2024, Research Square, https://www.researchsquare.com/article/rs-3707560/v1, https://c19p.org/li28
588. Bologna et al., Efficacy of Prolonged-Release Melatonin 2 mg (PRM 2 mg) Prescribed for Insomnia in Hospitalized Patients for COVID-19: A Retrospective Observational Study
80 patient melatonin late treatment study: 50% lower mortality (p=0.48), 50% lower ICU admission (p=0.48), 9% shorter hospitalization (p=0.05), and 58% lower need for oxygen therapy (p<0.0001).Retrospective 40 hospitalized patients in Italy treated with melatonin and 40 control patients, showing improved sleep, reduced delirium, shorter hospitalization and oxygen times, and reduced ICU admission and mortality (not statistically significant).
Dec 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/24/5857, https://c19p.org/bologna
589. Alahmari et al., Factors Associated with Length of Hospital Stay among COVID-19 Patients in Saudi Arabia: A Retrospective Study during the First Pandemic Wave
977 patient zinc late treatment study: 30% shorter hospitalization (p<0.0001).Retrospective 977 hospitalized patients in Saudi Arabia, showing significantly shorter hospitalization with zinc treatment.
Jun 2022, Healthcare, https://www.mdpi.com/2227-9032/10/7/1201, https://c19p.org/alahmari
590. Ali et al., Effect of Aspirin Use on clinical Outcome among Critically Ill Patients with COVID-19
1,190 patient aspirin ICU study: 40% lower mortality (p<0.0001) and 37% lower ARDS (p=0.001).Retrospective 1,190 ICU patients in Egypt, showing lower mortality with aspirin treatment. 150mg daily.
Oct 2022, Egyptian J. Anaesthesia, https://www.tandfonline.com/doi/full/10.1080/11101849.2022.2139104, https://c19p.org/ali6
591. Jevalikar et al., Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19
197 patient vitamin D late treatment study: 82% lower mortality (p=0.12), 34% lower ICU admission (p=0.29), and 32% lower need for oxygen therapy (p=0.06).Prospective study of 410 hospitalized patients in India showing lower mortality and ICU admission with cholecalciferol treatment, although not statistically significant with the small number of cases. The median total dose was 60,000IU. No significant difference was found for outcomes based on baseline vitamin D deficiency, however this analysis does not appear to account for the deficient patients that were treated with vitamin D.
Dec 2020, Scientific Reports, https://www.nature.com/articles/s41598-021-85809-y, https://c19p.org/jevalikar
592. Tawfik et al., Effectiveness of Early Favipiravir Therapy in Hospitalised COVID-19 Patients
165 patient favipiravir late treatment study: 96% lower mortality (p<0.0001), 21% lower ICU admission (p=0.45), and 16% shorter hospitalization (p<0.0001).Retrospective 103 hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir in unadjusted results, and greater efficacy for treatment within 3 days of admission.
Jun 2022, Advances in Virology, https://www.hindawi.com/journals/av/2022/9240941/, https://c19p.org/tawfik
593. AlShehhi et al., Utilizing machine learning for survival analysis to identify risk factors for COVID-19 intensive care unit admission: A retrospective cohort study from the United Arab Emirates
1,797 patient HCQ late treatment study: 43% lower ICU admission (p=0.001).Retrospective 1,787 hospitalized COVID-19 patients in the United Arab Emirates, identifying hydroxychloroquine as reducing the risk of ICU admission in a machine learning model. Only unadjusted quantitative results are provided, which also show a benefit.
Jan 2024, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0291373, https://c19p.org/alshehhi
594. Zhao et al., Favipiravir in the treatment of patients with SARS-CoV-2 RNA recurrent positive after discharge: a multicenter, open-label, randomized trial
55 patient favipiravir late treatment RCT: 59% improved viral clearance (p=0.06).RCT with 55 patients (36 favipiravir, 19 control) who were PCR+ after recovery, showing improved viral clearance with treatment.
Apr 2021, Int. Immunopharmacology, https://www.sciencedirect.com/science/article/pii/S1567576921003386, https://c19p.org/zhao2
595. Zhong et al., COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study
43 patient HCQ prophylaxis study: 91% fewer cases (p=0.04).Rheumatic disease patients on HCQ had a lower risk of COVID-19 than those on other disease-modifying anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for age, sex, smoking, systemic lupus erythematosus, infection in other family members, and comorbidities. 43 patients with rheumatic disease and COVID-19 exposure.
Jul 2020, Lancent Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30227-7/fulltext, https://c19p.org/zhong
596. Chowdhury et al., A Comparative Study on Ivermectin-Doxycycline and Hydroxychloroquine-Azithromycin Therapy on COVID-19 Patients
116 patient ivermectin early treatment RCT: 81% lower hospitalization (p=0.23), 46% improved recovery (p<0.0001), and 81% improved viral clearance (p=0.23).Small 116 patient RCT with low-risk patients comparing ivermectin+doxycycline and HCQ+AZ, showing lower hospitalization, higher viral clearance, and faster symptom resolution and viral clearance with ivermectin+doxycycline. Mid-recovery resolution of symptoms is statistically significantly better with treatment, while other measures do not reach statistical significance. Instructions were to take ivermectin on an empty stomach, reducing lung tissue concentration.
Jul 2020, Eurasian J. Medicine and Oncology, https://ejmo.org/10.14744/ejmo.2021.16263/, https://c19p.org/chowdhury
597. Abaleke et al., Azithromycin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
7,763 patient azithromycin late treatment RCT: 3% lower mortality (p=0.5), 8% lower ventilation (p=0.29), and 9% higher hospital discharge.RCT 7,763 hospitalized COVID-19 patients showing no significant differences with very late (75% on oxygen at baseline) azithromycin treatment. Only 91% of treatment patients received azithromycin and 17% of control patients received azithromycin or other macrolides.
Feb 2021, The Lancet, https://www.sciencedirect.com/science/article/pii/S0140673621001495, https://c19p.org/abalekeaz
598. Mitjà et al., Hydroxychloroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial
293 patient HCQ early treatment RCT: 16% lower hospitalization (p=0.64), 34% improved recovery (p=0.38), and 2% improved viral clearance.This paper has conflicting values, table S2 shows 12 control hospitalizations, while table 2 shows 11. The original report for this paper had more conflicting values, with values reported in Table 2 and the abstract corresponding to 12 control hospitalizations, while others corresponded to 11 control hospitalizations. The counts in table S2 also do not match - n=290 is given for secondary endpoints but the three groups add up to n=238. The sum of the secondary endpoint counts for the control group in table 2 do not match the group size. One missing patient may be the 12th control hospitalization but there are 2 more missing. There was a 16% reduction in hospitalization and 34% reduction in the risk of no symptom resolution, without statistical significance due to small samples. Treatment delay is unknown at this time. They report a delay of up to 120 hours after symptoms plus an additional unspecified delay where medication was provided to patients at the first home visit. Authors..
Jul 2020, Clinical Infectious Diseases, ciaa1009, https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa1009/5872589, https://c19p.org/mitja
599. Trinchieri et al., Exploiting Bacteria for Improving Hypoxemia of COVID-19 Patients
35 patient probiotics late treatment study: 78% lower mortality (p=0.28) and 78% improvement (p=0.0001).Retrospective COVID-19 patients requiring CPAP, 21 treated with SLAB51 probiotics and 15 control patients, showing improved outcomes with treatment, despite significantly lower blood oxygenation at baseline in the treatment group.
Jul 2022, Biomedicines, https://www.mdpi.com/2227-9059/10/8/1851, https://c19p.org/trinchieri
600. Campione et al., Lactoferrin as Antiviral Treatment in COVID-19 Management: Preliminary Evidence
64 patient lactoferrin early treatment study: 47% faster viral clearance (p=0.0001).Small prospective study in Italy with 32 lactoferrin patients, 32 SOC, and 28 patients with no treatment, showing significantly faster viral clearance and improved recovery with treatment. Oral and intranasal lactoferrin.
Oct 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/20/10985, https://c19p.org/campione
601. Bhattacharya et al., Pre exposure Hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers
106 patient HCQ prophylaxis study: 81% fewer cases (p=0.001).HCQ reduced cases from 38% to 7%. 106 people. No serious adverse effects.
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.09.20116806v1, https://c19p.org/bhattacharya
602. Arslan et al., Synergistic Effect of Quercetin and Vitamin C Against COVID-19: Is a Possible Guard for Front Liners
113 patient quercetin prophylaxis RCT: 92% fewer cases (p=0.03).Small prophylaxis RCT with 113 patients showing fewer cases with quercetin + vitamin C + bromelain prophylaxis. Note that this paper disappeared from SSRN without explanation.
Nov 2020, SSRN, https://europepmc.org/article/ppr/ppr239932, https://c19p.org/arslan
603. Soliman et al., Impact of Vitamin D Therapy on the Progress COVID-19: Six Weeks Follow-Up Study of Vitamin D Deficient Elderly Diabetes Patients
56 patient vitamin D late treatment RCT: 63% lower mortality (p=0.21), 20% lower ventilation (p=0.56), and 20% improved recovery (p=0.56).Small RCT with 56 eldery diabetes patients hospitalized in Egypt, 40 treated with cholecalciferol, not showing significant differences.
Aug 2021, Proceedings of Singapore Healthcare, https://journals.sagepub.com/doi/full/10.1177/20101058211041405, https://c19p.org/soliman
604. Geriak et al., Randomized Prospective Open Label Study Shows No Impact on Clinical Outcome of Adding Losartan to Hospitalized COVID-19 Patients with Mild Hypoxemia
31 patient losartan late treatment RCT: 6% lower mortality (p=1), 53% lower ICU admission (p=0.6), 53% higher hospital discharge (p=0.6), and 10% shorter hospitalization.RCT 31 hospitalized COVID-19 patients with mild hypoxemia showing no significant difference in mechanical ventilation, ICU admission, or mortality with addition of losartan to standard care.
May 2021, Infectious Diseases and Therapy, https://link.springer.com/10.1007/s40121-021-00453-3, https://c19p.org/geriak
605. Bejan et al., DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
9,748 patient vitamin C prophylaxis study: 34% lower mortality (p=0.33), 25% lower ventilation (p=0.47), 15% lower ICU admission (p=0.65), and no change in hospitalization (p=1).Retrospective 9,748 COVID-19 patients in the USA showing lower risk of mortality, ventilation, and ICU admission with vitamin C prophylaxis, without statistical significance.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanc
606. Efimenko et al., Treatment with Ivermectin Is Associated with Decreased Mortality in COVID-19 Patients: Analysis of a National Federated Database
41,608 patient ivermectin late treatment PSM study: 69% lower mortality (p<0.0001).PSM retrospective 41,608 patients in the USA, 1,072 treated with ivermectin and 40,536 treated with remdesivir, showing lower mortality with ivermectin treatment. This study was presented at a conference (IMED 2021). Submissions were peer-reviewed. The treatment/control group sizes align with the estimated percentage of hospitals that used ivermectin vs. remdesivir. Hospitals in the USA receive financial incentives to use remdesivir. Authors have self-censored the conference report of this result, not due to any error in the analysis, but because they believe ivermectin "has proven to be ineffective in clinical trials". This is incorrect, while some studies show no statistically significant effect, studies show statistically significant positive results for one or more outcomes ( prospective and retrospective studies, including RCTs). The self-censorship and decision not to submit to a journal provide further evidence of a negative publication bias for ivermectin research. This study was self-censored by the authors.
Feb 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221009887, https://c19p.org/efimenko
607. Nguyen et al., Single and Combinative Impacts of Healthy Eating Behavior and Physical Activity on COVID-19-like Symptoms among Outpatients: A Multi-Hospital and Health Center Survey
2,136 patient diet study: 15% fewer symptomatic cases (p=0.006).Analysis of 3,947 participants in Vietnam, showing significantly lower risk of COVID-19-like symptoms with physical activity and with a healthy diet. The combination of being physically active and eating healthy reduced risk further compared to either alone. The analyzed period was Feb 14 to Mar 2, 2020, which may have been before testing was widely available.
Sep 2021, Nutrients, https://www.mdpi.com/2072-6643/13/9/3258, https://c19p.org/nguyen2dt
608. Hashim et al., Controlled randomized clinical trial on using Ivermectin with doxycycline for treating COVID-19 patients in Baghdad, Iraq
140 patient ivermectin late treatment RCT: 92% lower mortality (p=0.03), 83% lower progression (p=0.07), and 41% faster recovery (p=0.0001).RCT 70 ivermectin+doxycycline patients and 70 control patients showing reduced time to recovery and reduced mortality with treatment. Earlier treatment was more successful. For ethical reasons, critical patients were all in the treatment group. NCT04591600.
Oct 2020, Iraqi J. Medical Science, http://www.iraqijms.net/upload/pdf/iraqijms60db8b76d3b1e.pdf, https://c19p.org/hashim
609. Avezum et al., Hydroxychloroquine versus placebo in the treatment of non-hospitalised patients with COVID-19 (COPE – Coalition V): A double-blind, multicentre, randomised, controlled trial
1,372 patient HCQ early treatment RCT: 1% lower mortality (p=1), 32% higher ventilation (p=0.79), 16% lower ICU admission (p=0.61), and 23% lower hospitalization (p=0.18).Authors have not responded to a request for the data. Outpatient RCT with 687 HCQ and 682 control patients in Brazil, showing lower hospitalization with treatment, not reaching statistical significance. Higher efficacy was seen with treatment <4 days from onset, RR 0.61. The associated meta analysis includes mostly late treatment studies, for example in [Schwartz] the median delay from onset was 7 days. [Omrani] is missing. The values for [Johnston] are incorrect - the study shows 4 hospitalizations in the control arm - RR for this study should be 0.58 instead of 0.78.
Mar 2022, The Lancet Regional Health - Americas, https://www.sciencedirect.com/science/article/pii/S2667193X22000606, https://c19p.org/avezum
610. Adhikari et al., Intravenous Vitamin C for Patients Hospitalized With COVID-19 Two Harmonized Randomized Clinical Trials
1,560 patient vitamin C late treatment RCT: 28% lower mortality (p=0.19) and 35% higher ventilation (p=0.04).Very late stage (APACHE II 8 and 12 for non-critical and critical) RCT with publication delayed over a year showing higher ventilation and no significant difference in mortality with vitamin C. Authors have combined what was to be two separate trials into one trial, however there are very large differences between the trials. The results for each source trial are shown separately here [Adhikari, Adhikari]. eTable 15 shows that results in LOVIT-COVID were substantially better than those in REMAP-CAP. eTable 13 shows improved survival for LOVIT-COVID and worse survival for REMAP-CAP (authors provide mortality breakdown only for hospital survival): LOVIT-COVID shows 85% and 82% probability of superiority of vitamin C (critical and non-critical). REMAP-CAP shows 12% and 7% probability of superiority of vitamin C. Notably, LOVIT-COVID patients were blinded, while REMAP-CAP was open-label, introducing additional opportunity for bias on this highly politicized treatment. REMAP-CAP had more..
Oct 2023, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2811212, https://c19p.org/adhikari2b
611. Ersoy et al., Assessment Of The Efficacy Of Spironolactone For COVID-19 ARDS Patients
60 patient spironolactone antiandrogen ICU study: 46% lower mortality (p=0.002).Retrospective 30 COVID-19 ARDS ICU patients and 30 control patients, showing lower mortality with treatment.
Oct 2021, Aydin Sağlik Dergi̇si̇, https://dergipark.org.tr/en/pub/asder/issue/65413/959218, https://c19p.org/ersoy
612. Ersoy et al., Assessment Of The Efficacy Of Spironolactone For COVID-19 ARDS Patients
60 patient spironolactone ICU study: 46% lower mortality (p=0.002).Retrospective 30 COVID-19 ARDS ICU patients and 30 control patients, showing lower mortality with treatment.
Oct 2021, Aydin Sağlik Dergi̇si̇, https://dergipark.org.tr/en/pub/asder/issue/65413/959218, https://c19p.org/ersoysp
613. Kartika et al., Curcumin as adjuvant Therapy in Mild - Moderate Covid 19
246 patient curcumin late treatment study: 41% shorter hospitalization (p=0.05).Retrospective 246 hospitalized patients in Indonesia, 136 treated with curcumin, showing shorter hospitalization time with treatment. All patients received vitamin C, D, and zinc.
Jan 2022, ICE on IMERI, 2021, http://web.archive.org/web/20220209083251/http://writingcenter.fk.ui.ac.id/index.php/p/article/view/40, https://c19p.org/kartika
614. García-Posada et al., Clinical outcomes of patients hospitalized for COVID-19 and evidence-based on the pharmacological management reduce mortality in a region of the Colombian Caribbean
209 patient colchicine late treatment study: 57% lower mortality (p=0.01).Retrospective 209 hospitalized patients in Colombia, showing lower mortality with antibiotics + LMWH + corticosteroids + colchicine in multivariable analysis.
Mar 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121000575?via%3Dihub, https://c19p.org/garciaposada
615. Zupanets et al., Quercetin effectiveness in patients with COVID-19 associated pneumonia
200 patient quercetin late treatment RCT: 29% improved recovery (p=0.5).RCT 200 patients in Ukraine, 99 treated with IV quercetin/polyvinylirolidone followed by oral quercetin/pectin, showing improved recovery with treatment.
Aug 2021, Zaporozhye Med. J., http://zmj.zsmu.edu.ua/article/view/231714, https://c19p.org/zupanets
616. Hoertel et al., Association between Hydroxyzine Use and Reduced Mortality in Patients Hospitalized for Coronavirus Disease 2019: Results from a multicenter observational study
7,345 patient hydroxyzine prophylaxis study: 58% lower mortality (p=0.001).Retrospective 7,345 hospitalized COVID-19 patients in France showing lower mortality with hydroxyzine use, with a significant dose-response relationship. Hydroxyzine was also associated with a faster decrease in inflammatory markers.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.23.20154302, https://c19p.org/hoertel6
617. Sivapalan et al., Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19–a randomised double-blinded placebo-controlled trial
117 patient HCQ late treatment RCT: 92% lower mortality (p=0.32), 22% higher ICU admission (p=1), and 8% lower hospital discharge (p=0.36).Early terminated late stage (8 days from onset, 59% on oxygen) RCT not showing statistically significant differences. NNF20SA0062834.
Jun 2021, European Respiratory J., https://erj.ersjournals.com/content/early/2021/05/28/13993003.00752-2021.article-info, https://c19p.org/sivapalan
618. Patel et al., Factors Associated with COVID-19 Breakthrough Infection in the Pre-Omicron Era Among Vaccinated Patients with Rheumatic Diseases: A Cohort Study
11,468 patient HCQ prophylaxis study: 46% fewer cases (p=0.001).Retrospective 11,468 vaccinated rheumatic disease patients in the USA, showing lower risk of COVID-19 with HCQ/CQ use compared with all other treatments. Adjusted results are only provided with respect to specific other treatments.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.13.22277606, https://c19p.org/patel4
619. Kalayan et al., Safety and Efficacy of Nebulised Anti-Inflammatory Solution of Alkaline Hypertonic Ibuprofen (AHI) for Treatment of SARS-Cov-2 Infection: A Compassionate Study with a Comparator Arms
99 patient alkalinization late treatment study: 79% lower mortality (p=0.0009).Retrospective 99 COVID-19 patients in Argentina showing significantly lower mortality with inhaled alkaline hypertonic ibuprofen (AHI) treatment. The treatment has a pH of 8.5. 3 times daily for 7-10 days.
Dec 2022, European J. Respiratory Medicine, https://europeanjournalofrespiratorymedicine.com/safety-and-efficacy-of-nebulised-anti-inflammatory-solution-of-alkaline-hypertonic-ibuprofen-ahi-for-treatment-of-sars-cov-2-infection-a-compassionate-study-with-a-comparator-arms, https://c19p.org/kalayanph
620. AbdelGhaffar et al., Prediction of mortality in hospitalized Egyptian patients with Coronavirus disease-2019: A multicenter retrospective study
3,712 patient HCQ late treatment study: 100% lower mortality (p<0.0001).Retrospective 3,712 hospitalized patients in Egypt, showing lower mortality with HCQ treatment in unadjusted results. According to the official treatment protocol, HCQ was recommended with higher risk and/or more serious cases.
Jan 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0262348, https://c19p.org/abdelghaffar
148 patient diet study: 45% lower severe cases (p=0.06) and 32% improved viral clearance (p=0.03).
Retrospective 148 hospitalized COVID-19 patients in China, showing lower severity and faster viral clearance with improved nutrition.
Jul 2023, Infection and Drug Resistance, https://www.dovepress.com/improving-nutritional-status-was-associated-with-decreasing-disease-se-peer-reviewed-fulltext-article-IDR, https://c19p.org/wang18
622. Bagheri et al., Supplement Usage Pattern in a Group of COVID-19 Patients in Tehran
510 patient vitamin D prophylaxis study: 71% lower severe cases (p=0.02) and 38% lower hospitalization (p=0.11).Retrospective 510 patients in Iran, showing lower risk of severity with vitamin D (statistically significant) and zinc (not statistically significant) supplementation. IR.TUMS.VCR.REC.1398.1063.
Aug 2021, J. Family & Reproductive Health, https://europepmc.org/article/PMC/PMC7868648, https://c19p.org/bagheri
623. Razjouyan et al., Smoking Status and Factors associated with COVID-19 In-Hospital Mortality among US Veterans
10,074 patient famotidine prophylaxis study: 27% lower mortality (p=0.006).Retrospective 10,074 hospitalized veterans with COVID-19 in the USA, showing lower mortality with existing famotidine use.
Oct 2021, Nicotine & Tobacco Research, https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntab223/6409756?login=false, https://c19p.org/razjouyan
624. AlQadheeb et al., Impact of common comorbidities on antimicrobial consumption and mortality amongst critically ill COVID-19 patients: A retrospective two center study in Saudi Arabia
848 patient HCQ ICU study: 35% lower mortality (p=0.0001).Retrospective 848 ICU patients in Saudi Arabia, showing lower mortality with HCQ in unadjusted results.
May 2023, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170223000122, https://c19p.org/alqadheeb
625. Han et al., Effectiveness and Optimal Timing of Azvudine in COVID-19 Patients: A Multi-center Retrospective Study in Beijing, China
856 patient azvudine early treatment PSM study: 37% lower mortality (p=0.05) and 3% greater improvement (p=0.73).PSM retrospective 6,218 hospitalized COVID-19 patients in China showing lower 28-day all-cause mortality with azvudine treatment compared to controls (HR 0.63, 95% CI 0.40-1.00). Subgroup analysis found significantly faster clinical improvement when azvudine was initiated within 5 days of symptom onset compared to controls.
Jul 2023, Research Square, https://www.researchsquare.com/article/rs-3145554/v1, https://c19p.org/han
626. Avdeev et al., N-acetylcysteine for the treatment of COVID-19 among hospitalized patients
46 patient N-acetylcysteine late treatment study: 69% lower mortality (p=0.34), 77% lower ventilation (p=0.18), 77% lower ICU admission (p=0.18), and 15% shorter hospitalization (p=0.01).Prospective study of 24 hospitalized COVID-19 patients in Russia treated with NAC, and 22 matched controls, showing significantly improved SpO2/FiO2, and significantly shorter hospitalization with treatment.
Jul 2021, J. Infection, https://www.journalofinfection.com/article/S0163-4453(21)00329-7/fulltext, https://c19p.org/avdeev
627. Patel et al., Does androgen deprivation therapy protect against severe complications from COVID-19?
58 patient various antiandrogen prophylaxis study: 55% lower mortality (p=0.22), 69% lower ventilation (p=0.19), and 77% lower hospitalization (p=0.02).Retrospective 58 prostate cancer patients in the USA, showing lower risk of hospitalization with ADT.
Jul 2020, Annals of Oncology, https://www.annalsofoncology.org/article/S0923-7534(20)39933-6/fulltext, https://c19p.org/patel3
628. Absalón-Aguilar et al., Colchicine Is Safe Though Ineffective in the Treatment of Severe COVID-19: a Randomized Clinical Trial (COLCHIVID)
116 patient colchicine late treatment RCT: 29% lower mortality (p=0.74), 17% lower progression (p=0.67), and 13% worse recovery (p=0.59).Very late stage RCT with 56 colchicine and 60 control patients in Mexico, showing no significant differences.
Nov 2021, J. General Internal Medicine, https://link.springer.com/article/10.1007/s11606-021-07203-8, https://c19p.org/absalonaguilar
629. Membrillo de Novales et al., Early Hydroxychloroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study
166 patient HCQ late treatment study: 55% lower mortality (p=0.002).166 patients hospitalised with COVID-19, HCQ increased survival 1.4 - 1.8 times when patients admitted in early stages. Early is relative to hospital admission here - all patients were in relatively serious condition.
May 2020, Preprints, https://www.preprints.org/manuscript/202005.0057, https://c19p.org/membrillo
630. Asimi et al., Selenium, zinc, and vitamin D supplementation affect the clinical course of COVID-19 infection in Hashimoto’s thyroiditis
356 patient vitamin D early treatment study: 97% lower ventilation (p<0.0001), 99% lower hospitalization (p<0.0001), and 100% lower severe cases (p<0.0001).Retrospective 356 Hashimoto's thyroiditis outpatients, 270 taking vitamin D, zinc, and selenium, showing significantly lower hospitalization with treatment. Authors adjust for age, gender, BMI, and smoking status, reporting statistically significant associations with p<0.001 for hospitalization and mechanical ventilation, however they do not report the adjusted risks.
May 2021, Endocrine Abstracts, https://www.endocrine-abstracts.org/ea/0073/ea0073pep14.2, https://c19p.org/asimi
631. Asimi et al., Selenium, zinc, and vitamin D supplementation affect the clinical course of COVID-19 infection in Hashimoto’s thyroiditis
356 patient zinc early treatment study: 97% lower ventilation (p<0.0001), 99% lower hospitalization (p<0.0001), and 100% lower severe cases (p<0.0001).Retrospective 356 Hashimoto's thyroiditis outpatients, 270 taking vitamin D, zinc, and selenium, showing significantly lower hospitalization with treatment. Authors adjust for age, gender, BMI, and smoking status, reporting statistically significant associations with p<0.001 for hospitalization and mechanical ventilation, however they do not report the adjusted risks.
May 2021, Endocrine Abstracts, https://www.endocrine-abstracts.org/ea/0073/ea0073pep14.2, https://c19p.org/asimiz
632. Ramírez-García et al., Hydroxychloroquine and Tocilizumab in the Treatment of COVID-19: A Longitudinal Observational Study
403 patient HCQ late treatment study: 67% lower mortality (p<0.0001) and 6% higher ICU admission (p=1).Retrospective 403 hospitalized patients in Spain, showing lower mortality with treatment, however authors do not adjust for the differences between the groups. Confounding by indication is likely.
May 2021, Archivos de Medicina Universitaria, https://digibug.ugr.es/handle/10481/69170, https://c19p.org/ramirezgarcia
633. Brennan et al., Oral famotidine versus placebo in non-hospitalised patients with COVID-19: a randomised, double-blind, data-intense, phase 2 clinical trial
55 patient famotidine early treatment RCT: 48% improved recovery (p=0.23).Small RCT with 27 famotidine and 28 placebo patients, showing improved recovery with treatment. Recovery was faster with treatment for 14 of 16 symptoms. There was no mortality or hospitalization. NCT04724720.
Feb 2022, Gut, https://gut.bmj.com/content/early/2022/02/09/gutjnl-2022-326952, https://c19p.org/brennan
634. Goshua et al., Admission Rothman Index, Aspirin, and Intermediate Dose Anticoagulation Effects on Outcomes in COVID-19: A Multi-Site Propensity Matched Analysis
2,785 patient aspirin late treatment PSM study: 35% lower mortality (p=0.04), 49% higher ventilation (p=0.04), and 45% higher ICU admission (p=0.02).PSM retrospective 2,785 hospitalized patients in the USA, showing lower mortality and higher ventilation and ICU admission with aspirin treatment.
Nov 2020, Blood, https://ashpublications.org/blood/article/136/Supplement%201/23/470342/Admission-Rothman-Index-Aspirin-and-Intermediate, https://c19p.org/goshua
635. Beigmohammadi et al., The effect of supplementation with vitamins A, B, C, D, and E on disease severity and inflammatory responses in patients with COVID-19: a randomized clinical trial
60 patient vitamin A ICU RCT: 89% lower mortality (p=0.11), 41% lower hospitalization (p=0.25), and 45% improved recovery (p=0.001).Small RCT 60 ICU patients in Iran, 30 treated with vitamins A, B, C, D, and E, showing significant improvement in SOFA score and several inflammatory markers at day 7 with treatment. 5,000 IU vitamin A daily, 600,000 IU vitamin D once, 300 IU of vitamin E twice a day, 500 mg vitamin C four times a day, and one ampule daily of B vitamins [thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg].
Nov 2021, Trials, https://link.springer.com/article/10.1186/s13063-021-05795-4/fulltext.html, https://c19p.org/beigmohammadi2a
636. Gomaa et al., Advancing combination treatment with glycyrrhizin and boswellic acids for hospitalized patients with moderate COVID-19 infection: a randomized clinical trial
50 patient glycyrrhizin antiandrogen late treatment RCT: 91% lower mortality (p=0.05), 91% lower ventilation (p=0.05), and 44% faster recovery (p=0.001).RCT with 50 hospitalized COVID+ patients in Egypt, 25 treated with glycyrrhizin and boswellic acid, showing improved recovery with treatment. Glycyrrhizin 60mg and boswellic acid 200mg bid for 2 weeks. NCT04487964.
Feb 2022, Inflammopharmacology, https://link.springer.com/article/10.1007/s10787-022-00939-7, https://c19p.org/gomaa
97 patient HCQ late treatment study: 51% shorter hospitalization (p=0.01) and 56% faster viral clearance (p=0.005).
Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HCQ+antibiotic. Preprint withdrawn pending peer review.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.13.20094193v1?versioned=true, https://c19p.org/kim
638. Brouqui et al., SARS-CoV 2 Viral Clearance in 1276 Patients: Associated Factors and the Role of Treatment with Hydroxychloroquine and Azithromycin
1,276 patient HCQ late treatment study: 15% improved viral clearance (p=0.04).Retrospective 1,276 hospitalized patients showing significantly faster viral clearance with HCQ. Authors also perform a meta-analysis of 9 studies, with 1,461 HCQ-treated patients and 958 controls, showing significantly faster viral clearance with HCQ on day 7.
Jul 2024, Acta Scientific Microbiology, https://actascientific.com/ASMI/pdf/ASMI-07-1413.pdf, https://c19p.org/brouqui4
639. Kim et al., The Clinical Characteristics and Outcomes of Patients with Moderate-to-Severe Coronavirus Disease 2019 Infection and Diabetes in Daegu, South Korea
235 patient metformin prophylaxis study: 64% lower mortality (p=0.1) and 52% lower progression (p=0.13).Retrospective 235 hospitalized diabetes patients in South Korea, showing lower mortality and lower progression to severe disease with metformin.
Aug 2020, Diabetes & Metabolism J., https://www.e-dmj.org/journal/view.php?doi=10.4093/dmj.2020.0146, https://c19p.org/kim3
640. Gordon et al., Phase 2 study of oral sabizabulin for the treatment of SARS-CoV-2 in hospitalized patients at high risk for ARDS
sabizabulin antiandrogen late treatment RCT: 82% lower mortality (p=0.04), 76% shorter ventilation (p=0.14), and 73% shorter ICU admission (p=0.03).Phase 2 RCT of sabizabulin showing lower mortality with treatment. For more discussion see [twitter.com].
Apr 2022, European Congress of Clinical Microbiology & Infectious Diseases, https://verupharma.com/news/veru-announces-oral-late-breaking-presentation-of-phase-2-data-of-sabizabulin-for-the-treatment-of-hospitalized-severe-covid-19-patients-at-high-risk-for-acute-respiratory-distress-syndrome-at-the-32n/, https://c19p.org/gordon2
641. El-Badrawy et al., A randomized controlled trial of adjuvant inhalable sodium bicarbonate role in treatment of COVID-19
546 patient alkalinization late treatment RCT: 23% lower mortality (p=0.26) and 28% faster recovery (p<0.0001).RCT 546 patients showing significantly faster recovery and lower mortality with sodium bicarbonate (inhaled and nasal drops). The reduction in mortality is only statistically significant when excluding baseline critical cases. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Nov 2022, Research Square, https://www.researchsquare.com/article/rs-2214180/v1, https://c19p.org/elbadrawy
642. El-Badrawy et al., A randomized controlled trial of adjuvant inhalable sodium bicarbonate role in treatment of COVID-19
546 patient sodium bicarbonate late treatment RCT: 23% lower mortality (p=0.26) and 28% faster recovery (p<0.0001).RCT 546 patients showing significantly faster recovery and lower mortality with sodium bicarbonate (inhaled and nasal drops). The reduction in mortality is only statistically significant when excluding baseline critical cases. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Nov 2022, Research Square, https://www.researchsquare.com/article/rs-2214180/v1, https://c19p.org/elbadrawysb
643. Tan et al., Cohort study to evaluate the effect of combination Vitamin D, Magnesium and Vitamin B12 (DMB) on progression to severe outcome in older COVID-19 patients
43 patient vitamin D late treatment study: 80% lower need for oxygen therapy (p=0.04) and 81% lower ICU admission (p=0.07).Observational study of 43 patients >= 50 years old, with 17 patients receiving vitamin D, magnesium, and vitamin B12 (DMB); and 26 control patients, showing a significantly lower need for oxygen therapy and ICU admission with treatment. DMB OR 0.20 [0.04–0.93] for oxygen therapy and/or intensive care support with multivariate analysis.
Jun 2020, Nutrition, https://www.sciencedirect.com/science/article/pii/S0899900720303002, https://c19p.org/tan
3,885 patient HCQ late treatment study: 36% lower mortality (p=0.005).
Retrospective 352 hospitalized COVID-19 patients in Belgium and 3,533 control patients from the contemporaneous Belgian Collaborative Group, showing significantly lower mortality with HCQ treatment. The survival benefit was consistent in all age groups. No torsade de pointes or ventricular arrhythmias were observed. Mean time from onset is not provided, but 43% of patients with known onset were admitted within 5 days, making the efficacy consistent with expectations based on the treatment delay [c19hcq.org]. HCQ 800mg day one, 200mg bid for five days, according to national guidelines. Authors note that the poor results in SOLIDARITY/RECOVERY may be related to the excessively high doses used. Most patients also received AZ. Adjusted results are only provided for all HCQ patients. Publication was delayed over 3 years. Authors reported in 2021 that the paper had been rejected by the editors of four different journals, without peer review [twitter.com].
Sep 2023, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297523000914, https://c19p.org/meeus
645. Patil et al., A Prospective Longitudinal Study Evaluating The Influence of Immunosuppressives and Other Factors On COVID-19 in Autoimmune Rheumatic Diseases
9,212 patient HCQ prophylaxis study: 66% lower mortality (p=0.1) and 9% fewer cases (p=0.43).Prospective study of 9,212 autoimmune rheumatic disease patients showing lower mortality with HCQ, without reaching statistical significance. Authors incorrectly state "HCQ use did not influence occurrence of COVID-19 (RR = 0.909, CI (0.715,1.154), p = 0.432) or mortality (p = 0.097)" [nature.com]. CFR for the autoimmune rheumatic disease patients was 4.6 times higher than in the general population from the same area.
Aug 2021, Research Square, https://www.researchsquare.com/article/rs-805748/v1, https://c19p.org/patil
646. Burahee et al., Older patients with proximal femur fractures and SARS-CoV-2 infection – An observational study
14 patient vitamin D early treatment study: 93% lower mortality (p=0.01).Small retrospective study of 29 hip fracture patients in the UK, 14 with COVID-19. All COVID-19 patients were treated with vitamin D except for 2 where testing and supplementation was missed due to a clerical error. The two COVID-19 patients that died were the two that did not receive vitamin D supplementation.
Feb 2021, SICOT-J, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7888253/#!po=1.28205, https://c19p.org/burahee
647. Guenezan et al., Povidone Iodine Mouthwash, Gargle, and Nasal Spray to Reduce Nasopharyngeal Viral Load in Patients With COVID-19: A Randomized Clinical Trial
24 patient povidone-iodine early treatment RCT: 63% improved viral load (p=0.25).RCT of PCR+ patients with Ct<=20 with 12 treatment and 12 control patients, concluding that nasopharyngeal decolonization may reduce the carriage of infectious SARS-CoV-2 in adults with mild to moderate COVID-19. All patients but 1 had negative viral titer by day 3 (group not specified). There was no significant difference in viral RNA quantification over time. The mean relative difference in viral titers between baseline and day 1 was 75% [43%-95%] in the intervention group and 32% [10%-65%] in the control group. Thyroid dysfunction occurred in 42% of treated patients, with spontaneous resolution after the end of treatment. Patients in the treatment group were younger.
Feb 2021, JAMA Otolaryngol Head Neck Surg., https://jamanetwork.com/journals/jamaotolaryngology/fullarticle/2775984, https://c19p.org/guenezan
648. Pasinato et al., Lactoferrin in the Prevention of Recurrent Respiratory Infections in Preschool Children: A Prospective Randomized Study
50 patient lactoferrin prophylaxis RCT: 50% fewer cases (p=1).RCT 50 preschool children, 25 treated with bovine lactoferrin (bLf) prophylaxis, showing significantly lower frequency and duration of respiratory infections during the active phase with treatment. The only COVID-19 specific results reported are the number as patients with COVID, 1 vs. 2 for treatment vs. control. bLf 400mg bid for 4 months.
Feb 2024, Children, https://www.mdpi.com/2227-9067/11/2/249, https://c19p.org/pasinato
649. Bukhari et al., Efficacy of Ivermectin in COVID-19 Patients with Mild to Moderate Disease
86 patient ivermectin early treatment RCT: 82% improved viral clearance (p<0.0001).RCT of relatively low risk hospitalized patients with 50 ivermectin and 50 control patients showing significantly faster viral clearance with treatment. 9 patients in the treatment arm were lost to followup compared with 5 in the control arm, which could be in part due to faster recovery with treatment. There were no safety concerns. No mortality was reported. The numbers in Table 3 are the number of patients that became negative on that day, i.e., non-cumulative. SOC included vitamin C and vitamin D. NCT04392713.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.02.21250840v1, https://c19p.org/bukhari
650. Modrák et al., Detailed disease progression of 213 patients hospitalized with Covid-19 in the Czech Republic: An exploratory analysis
213 patient HCQ late treatment study: 59% lower mortality (p=0.04).Retrospective 213 hospitalized patients in Czech Republic showing lower mortality with HCQ. Subject to confounding by indication.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.03.20239863v1, https://c19p.org/modrak
651. Al-Haidari et al., Preventive Value of Black Seed in People at Risk of Infection with COVID-19
376 patient nigella sativa prophylaxis study: 62% fewer symptomatic cases (p<0.0001).Prophylaxis study with 376 mostly high-risk patients, 188 treated with nigella sativa, showing significantly lower cases with treatment. Black seeds 40mg/kg orally once daily.
Jan 2021, Pakistan J. Medical and Health Sciences, https://pjmhsonline.com/2021/jan/384.pdf, https://c19p.org/alhaidari2
652. Di Domênico et al., Hydrogen peroxide as an auxiliary treatment for COVID-19 in Brazil: a randomized double-blind clinical trial
128 patient hydrogen peroxide late treatment RCT: 34% lower ICU admission (p=1), 1% worse recovery (p=0.97), and 31% lower PASC (p=0.54).RCT very late treatment (>9 days from onset) comparing hydrogen peroxide + mint essence with water + mint essence, showing no significant differences.
Aug 2021, Epidemiology and Health, http://e-epih.org/journal/view.php?doi=10.4178/epih.e2021051, https://c19p.org/didomenico2
653. Koskinen et al., Androgen deprivation and SARS-CoV-2 in men with prostate cancer
352 patient various antiandrogen prophylaxis study: 46% lower mortality (p=1), 46% lower combined mortality/ICU admission (p=1), and 11% fewer cases (p=1).Retrospective 352 prostate cancer patients in Finland, showing no significant differences in COVID-19 with ADT.
Jun 2020, Annals of Oncology, https://www.sciencedirect.com/science/article/pii/S0923753420399257, https://c19p.org/koskinen
654. Babalola et al., Ivermectin shows clinical benefits in mild to moderate COVID19: A randomised controlled double-blind, dose-response study in Lagos
60 patient ivermectin early treatment RCT: 64% improved viral clearance (p=0.11) and 41% improved recovery (p=0.07).Small RCT comparing ivermectin 6mg & 12mg q84hr with lopinavir/ritonavir, showing a statistically significant and dose dependent effect of ivermectin on reducing the time to PCR-. The study does not report mortality, hospitalization, progression, recovery, etc. The paper does report change in SpO2 (Figure 3, ∆Spo2), where a similar improvement with a smaller p value is seen with ivermectin, however this result is unadjusted and there are large differences between groups. Specifically, baseline SpO2 is lower in the control group, giving the control group more room to improve, therefore the actual benefit of ivermectin is likely to be even larger than the benefit in ∆SpO2 shown. See also [doyourownresearch.substack.com].
Jan 2021, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcab035/6143037, https://c19p.org/babalola
49 patient potassium canrenoate antiandrogen late treatment RCT: 17% lower mortality (p=1), 11% lower ICU admission (p=1), and 30% improved recovery (p=0.51).
RCT with 24 patients treated with potassium canrenoate and 25 placebo patients in Poland, showing no significant differences.
Feb 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/2/200, https://c19p.org/kotfis
656. Tang et al., Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial
150 patient HCQ late treatment RCT: 21% improved viral clearance (p=0.51).150 patient very late stage RCT showing no significant difference. Treatment was very late, an average of 16.6 days after symptom onset. Data favorable to HCQ was deleted in the second version, see analysis [mediterranee-infection.com]. "[HCQ] accelerate[s] the alleviation of clinical symptoms"; "More rapid alleviation of clinical symptoms with SOC plus HCQ than with SOC alone was observed during the second week since randomization"; "The efficacy of HCQ on the alleviation of symptoms, HR 8.83 [1.09-71.3], was more evident when the confounding effects of other anti-viral agents were removed".
Apr 2020, BMJ 2020, 369, https://www.bmj.com/content/369/bmj.m1849, https://c19p.org/tang
657. Hartono et al., The Effect of Curcumin and Virgin Coconut Oil Towards Cytokines Levels in COVID-19 Patients at Universitas Sebelas Maret Hospital, Surakarta, Indonesia
60 patient curcumin late treatment RCT: 53% improved viral clearance (p<0.0001).RCT with 30 patients treated with curcumin and virgin coconut oil (VCO), and 30 SOC patients in Indonesia, showing faster viral clearance with treatment. Treatment also reduced IL-1β, IL-2, IL-6, IL-18, and IFN-β levels. VCO improves the bioavailability of curcumin. There were large unadjusted differences in baseline severity and age, for example 20% vs. 47% of patients >50. VCO 30ml and curcumin 1g tid for 21 days. 066/UN27.06.6.1/KEPK/EC/2020.
Feb 2022, Pharmacognosy J., https://phcogj.com/article/1755, https://c19p.org/hartono
658. Said et al., The effect of Nigella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 patients: A randomized controlled clinical trial
60 patient nigella sativa early treatment RCT: 77% improved recovery (p=0.09) and 61% improved viral clearance (p=0.08).120 patient RCT comparing vitamin D, nigella sativa, and combined vitamin D+nigella sativa, showing improved symptom recovery and viral clearance with both vitamin D and nigella sativa, and further improvements with the combination of both. All patients received vitamin C, zinc, and lactoferrin.
Nov 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.1011522/full, https://c19p.org/saidns
659. Vicenzi et al., The Efficacy of the Mineralcorticoid Receptor Antagonist Canrenone in COVID-19 Patients
69 patient canrenone antiandrogen late treatment study: 93% lower mortality (p<0.0001) and 81% lower combined mortality/intubation (p=0.002).Retrospective 69 consecutive hospitalized COVID-19 patients in Italy, 30 patients receiving canrenone, and 39 treated with vasodilator agents or renin–angiotensin–aldosterone system (RAAS) inhibitors, showing lower mortality with canrenone.
Sep 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/9/2943, https://c19p.org/vicenzi
660. McCullough et al., Hydroxychloroquine in the Prevention of COVID-19 Infection in Healthcare Workers
221 patient HCQ prophylaxis study: 52% fewer cases (p=0.01).Prospective study with 221 healthcare workers, showing lower risk of COVID-19 with HCQ prophylaxis.
Aug 2021, NCT04333225, https://clinicaltrials.gov/study/NCT04333225, https://c19p.org/mccullough4
661. Vila-Córcoles et al., Influence of prior comorbidities and chronic medications use on the risk of COVID-19 in adults: a population-based cohort study in Tarragona, Spain
79,083 patient antihistamine H1RA prophylaxis study: 53% fewer cases (p=0.05).Retrospective 79,083 adults aged ≥50 years in Spain showing lower with of PCR-confirmed COVID-19 with antihistamine use, close to statistical significance.
Dec 2020, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2020-041577, https://c19p.org/vilacorcoles
662. Di Pierro et al., Quercetin as a possible complementary agent for early-stage COVID-19: Concluding results of a randomized clinical trial
100 patient quercetin early treatment RCT: 37% improved recovery (p=0.007) and 58% improved viral clearance (p<0.0001).RCT 100 outpatients in Pakistan, 50 treated with quercetin phytosome, showing faster viral clearance and improved recovery with treatment. Patients in the treatment group were significantly younger (41 vs. 54).
Jan 2023, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.1096853/full, https://c19p.org/dipierro5
663. Ahanchian et al., Synbiotic for Prevention of SARS-Cov2 Infection in High Risk Hospital Staffs: A Randomized Controlled Trial
60 patient probiotics prophylaxis RCT: 73% fewer symptomatic cases (p=0.35) and 85% fewer cases (p=0.24).Small RCT 60 healthcare workers in Iran, showing lower cases with treatment but without statistical significance. Once daily oral synbiotic capsule (Lactocare®) containing 1 billion CFU L. (Lactobacillus) casei, L. rhamnosus, Streptococcus thermophilus, Bifidobacterium breve, L. acidophilus, Bifidobacterium infantis, L. bulgaricus, and Fructooligosacharide.
May 2021, Open J. Nursing, https://www.scirp.org/journal/paperinformation.aspx?paperid=108986, https://c19p.org/ahanchian
664. Sutkowska et al., Physical Activity Modifies the Severity of COVID-19 in Hospitalized Patients—Observational Study
131 patient exercise study: 62% lower mortality (p=0.21) and 61% improved recovery (p=0.19).Prospective study of 131 hospitalized patients in Poland, showing lower mortality and improved recovery with a history of higher physical activity.
Jun 2023, J. Clinical Medicine, https://www.mdpi.com/2077-0383/12/12/4046, https://c19p.org/sutkowska
665. Osati et al., Clinical manifestations and mortality among hospitalized COVID-19 patients in Tanzania, 2021-2022.
1,387 patient ivermectin late treatment study: 32% lower mortality (p=0.02).Retrospective 1,387 hospitalized PCR confirmed COVID-19 patients in Tanzania, showing lower mortality with ivermectin treatment and with steroid treatment in multivariable analysis.
Jul 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.07.13.23292643, https://c19p.org/osati
666. Güner et al., Comparing ICU Admission Rates of Mild/Moderate COVID-19 Patients Treated with Hydroxychloroquine, Favipiravir, and Hydroxychloroquine plus Favipiravir
704 patient HCQ late treatment study: 77% lower ICU admission (p=0.16).Retrospective 824 hospitalized patients in Turkey showing lower ICU admission for HCQ vs. favipiravir.
Dec 2020, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034120307735, https://c19p.org/guner
667. Kevorkian et al., Oral corticoid, aspirin, anticoagulant, colchicine, and furosemide to improve the outcome of hospitalized COVID-19 patients - the COCAA-COLA cohort study
68 patient colchicine late treatment study: 96% lower progression (p=0.0005).Observational study in France with 28 hospitalized patients treated with prednisone/furosemide/colchicine/salicylate/direct anti-Xa inhibitor, and 40 control patients, showing lower combined mortality, ventilation, or high-flow oxygen therapy with treatment.
Jun 2021, J. Infection, https://www.journalofinfection.com/article/S0163-4453(21)00058-X/fulltext, https://c19p.org/kevorkian
668. Alattar et al., Favipiravir for the Treatment of Coronavirus Disease 2019 Pneumonia; a Propensity Score-matched Cohort Study
774 patient favipiravir early treatment PSM study: 33% lower mortality (p=0.5), 2% worse recovery (p=0.73), and 44% improved viral clearance (p<0.0001).PSM retrospective with 1,493 patients, showing significantly improved viral clearance with favipiravir. There were no significant differences in clinical improvement or mortality. Mortality was lower (2.1% vs 3.1%), without statistical significance with the small number of events.
Nov 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S187603412200212X, https://c19p.org/alattar
669. Feter et al., Physical activity and long COVID: findings from the Prospective Study About Mental and Physical Health in Adults cohort
237 patient exercise study: 26% lower PASC (p=0.02).Analysis of 237 COVID-19 patients in Brazil, showing lower risk of long COVID with physical activity.
Jun 2023, Public Health, https://www.sciencedirect.com/science/article/pii/S0033350623001592, https://c19p.org/feter
670. Daneshfard et al., Effect of Sinamaz nasal drop on asymptomatic family members of COVID 19 patients: An open-label randomized controlled trial
173 patient nigella sativa prophylaxis RCT: 34% fewer symptomatic cases (p=0.006).RCT 173 family members of COVID-19 patients, showing lower incidence of COVID-19 symptoms with nasal drops containing nigella sativa oil and olea europaea oil. One drop in each nostril twice daily for 7 days.
Jul 2023, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/epdf/10.1002/ptr.7915, https://c19p.org/daneshfard
671. Yu et al., Ursodeoxycholic acid and COVID-19 outcomes: a cohort study and data synthesis of state-of-art evidence
115 patient ursodeoxycholic acid late treatment study: 39% faster recovery (p=0.04).Retrospective 115 hospitalized COVID-19 patients in China showing faster time to body temperature recovery with ursodeoxycholic acid (UDCA) treatment. Results were better for higher dose treatment (300mg vs. 150mg). Authors also perform a meta analysis showing lower risk of severe/critical COVID-19 with UDCA, which is listed separately [Yu].
Jul 2024, Expert Review of Anti-infective Therapy, https://www.tandfonline.com/doi/full/10.1080/14787210.2024.2376153, https://c19p.org/yu10
672. Li et al., A Retrospective Analysis of Azvudine in Patients with COVID-19 and Pre-existing Cancer
84 patient azvudine late treatment study: 11% shorter hospitalization (p=0.26) and 50% improved viral clearance (p=0.03).PSM retrospective 84 hospitalized COVID-19 patients with pre-existing cancer in China, showing faster viral clearance with azvudine. There was no significant difference in length of hospital stay or ICU admission.
Mar 2024, J. Cancer, https://www.jcancer.org/v15p2442, https://c19p.org/li29
673. Kalichuran et al., Vitamin D status and COVID-19 severity
100 patient sunlight study: 58% fewer symptomatic cases (p=0.004).Prospective study of 100 COVID-19 patients in South Africa, 50 with COVID-19 pneumonia and 50 asymptomatic, showing higher risk of symptomatic COVID-19 with lower exposure to sunlight, and with vitamin D deficiency. Sunlight exposure may be correlated with physical activity and may have additional benefits independent of vitamin D [sciencedirect.com].
Apr 2022, Southern African J. Infectious Diseases, https://sajid.co.za/index.php/sajid/article/view/359, https://c19p.org/kalichuransun
674. Alsultan et al., Efficacy of Colchicine and Budesonide in Improvement Outcomes of Patients with Coronavirus Infection 2019 in Damascus, Syria: A Randomized Control Trial
35 patient colchicine late treatment RCT: 36% lower mortality (p=0.7) and 20% shorter hospitalization.Small RCT 49 severe condition hospitalized patients in Syria, showing lower mortality with colchicine and shorter hospitalization time with both colchicine and budesonide (all of these were not statistically significant).
Dec 2021, Interdisciplinary Perspectives on Infectious Diseases, https://www.hindawi.com/journals/ipid/2021/2129006/, https://c19p.org/alsultano
675. Ramlall et al., Melatonin is significantly associated with survival of intubated COVID-19 patients
948 patient budesonide ICU study: 71% lower mortality (p=0.01).Retrospective 948 intubated patients, 33 treated with budesonide, showing lower mortality with treatment.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.15.20213546v1, https://c19p.org/ramlallu
676. Ashinyo et al., Clinical characteristics, treatment regimen and duration of hospitalization among COVID-19 patients in Ghana: a retrospective cohort study
307 patient HCQ late treatment study: 33% shorter hospitalization (p=0.03).Retrospective 307 hospital patients in Ghana showing 33% reduction in hospitalization time with HCQ, 29% reduction with HCQ+AZ, and 37% reduction with CQ+AZ.
Sep 2020, Pan African Medical J., https://www.panafrican-med-journal.com/content/series/37/1/9/full/, https://c19p.org/ashinyo
677. Rahman et al., Clinical & Demographical Status of Hospitalized and Non-Hospitalized Covid-19 Cases: A Multicenter Hospital Based Study in Bangladesh
600 patient vitamin C early treatment study: 40% lower hospitalization (p=0.0001).Retrospective 416 non-hospitalized and 184 hospitalized COVID-19 patients in Bangladesh, showing higher acetaminophen and lower vitamin C usage for hospitalized patients. Confounding may be significant and baseline details per treatment group are not provided, however fever and symptomatic patients were more common in the non-hospitalized group. Note there is an alignment mismatch in Table 1.
Nov 2023, Molecular Mechanism Research, https://ojs.as-pub.com/index.php/MMR/article/view/133, https://c19p.org/rahman5
678. Chan et al., Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes
3,136 patient metformin prophylaxis study: 59% lower mortality (p=0.66), 54% lower severe cases (p=0.37), and 42% lower progression (p=0.37).Retrospective 3,136 patients with prediabetes and 282 with PCOS, showing metformin associated with reduced COVID-19 severity.
Aug 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.29.22279355, https://c19p.org/chan
679. Sun et al., Oral Azvudine for hospitalised patients with COVID-19 and pre-existing conditions: a retrospective cohort study
490 patient azvudine late treatment study: 54% lower mortality (p=0.16), 38% lower need for oxygen therapy (p=0.15), and 48% lower progression (p=0.02).PSM retrospective 490 hospitalized COVID-19 patients with pre-existing conditions in China showing that azvudine was associated with a significantly lower risk of the composite outcome of disease progression, driven largely by lower rates of non-invasive respiratory support. However, there was no significant difference in all-cause mortality or other individual outcomes like ICU admission or invasive mechanical ventilation between the azvudine and control groups.
May 2023, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S258953702300158X, https://c19p.org/sun4
680. Saber-Moghaddam et al., Oral nano-curcumin formulation efficacy in management of mild to moderate hospitalized coronavirus disease-19 patients: An open label nonrandomized clinical trial
41 patient curcumin early treatment study: 94% lower progression (p=0.001), 38% improved recovery (p=0.04), and 45% shorter hospitalization (p=0.001).Small prospective nonrandomized trial with 41 patients, 21 treated with curcumin, showing lower disease progression and faster recovery with treatment. IRCT20200408046990N1.
Jan 2021, Phytotherapy Research, doi:10.1002/ptr.7004 , https://onlinelibrary.wiley.com/doi/10.1002/ptr.7004, https://c19p.org/sabermoghaddam
681. Pahwani et al., Efficacy of Oral Famotidine in Patients Hospitalized With Severe Acute Respiratory Syndrome Coronavirus 2
178 patient famotidine late treatment RCT: 11% lower mortality (p=1), 12% lower ventilation (p=0.73), 10% lower ICU admission (p=0.86), and 17% shorter hospitalization (p<0.0001).RCT with 89 famotidine and 89 control patients in Pakistan, showing faster recovery but no significant difference in mortality. 40mg oral famotidine daily.
Feb 2022, Cureus, https://www.cureus.com/articles/78980-efficacy-of-oral-famotidine-in-patients-hospitalized-with-severe-acute-respiratory-syndrome-coronavirus-2, https://c19p.org/pahwani
682. Novartis et al., Hydroxychloroquine Monotherapy and in Combination With Azithromycin in Patients With Moderate and Severe COVID-19 Disease
12 patient HCQ late treatment RCT: 71% lower mortality (p=0.42), 71% higher hospital discharge (p=0.42), 71% greater improvement (p=0.42), and 79% worse viral clearance (p=0.56).Early terminated RCT with only 20 patients.
Jul 2020, Novartis, NCT04358081, https://clinicaltrials.gov/study/NCT04358081, https://c19p.org/novartis
683. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data
917,198 patient famotidine late treatment study: 19% lower mortality (p<0.0001).Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizifm
684. Barania Adabi et al., The association between inflammatory and immune system biomarkers and the dietary inflammatory index in patients with COVID-19
500 patient diet study: 99% lower ICU admission (p<0.0001).Retrospective 500 COVID-19 patients, showing dietary inflammatory index (DII) and energy-adjusted dietary inflammatory index (E-DII) associated with COVID-19 severity.
Mar 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1075061/full, https://c19p.org/baraniaadabi
685. Karimpour-Razkenari et al., Evaluating the Effects of Clinical Characteristics and Therapeutic Regimens on Mortality in Hospitalized Patients with Severe COVID-19
478 patient vitamin D late treatment study: 79% lower mortality (p<0.0001).Retrospective 478 moderate to severe hospitalized patients in Iran, showing lower mortality with vitamin D treatment.
Oct 2022, J. Pharmaceutical Care, https://publish.kne-publishing.com/index.php/JPC/article/view/10790, https://c19p.org/karimpourrazkenari2
686. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data
917,198 patient aspirin late treatment study: 16% lower mortality (p<0.0001).Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizie
687. Chandra et al., Efficacy of polyherbal formulations for prevention of COVID-19 infection in high-risk subjects: A randomized open-label controlled clinical trial
105 patient nigella sativa prophylaxis RCT: 49% fewer cases (p=0.36).RCT 251 high-risk individuals in India, mostly with direct contact with COVID-19 positive patients, testing polyherbal formulations Infuza, which includes nigella sativa, and Kulzam. Both formulations showed lower risk, without statisical significance, while the best results were from the combination of both.
Jul 2022, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7531, https://c19p.org/chandra
688. Tu et al., Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective Study
180 patient vitamin C late treatment study: 83% lower mortality (p<0.0001).Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing lower mortality with vitamin C treatment in unadjusted results.
Jan 2022, Infectious Diseases & Immunity, https://journals.lww.com/10.1097/ID9.0000000000000037, https://c19p.org/tuc
689. Beydoun et al., Socio-demographic, lifestyle and health characteristics as predictors of self-reported Covid-19 history among older adults: 2006-2020 Health and Retirement Study
2,158 patient exercise study: 43% fewer cases (p=0.05).Retrospective 2,830 people in the USA, showing lower risk of COVID-19 with a history of moderate/vigorous exercise.
Mar 2022, American J. Infection Control, https://www.sciencedirect.com/science/article/pii/S0196655322001018, https://c19p.org/beydoun
690. Jabbar et al., Vitamin D Serum Levels and Its Association With COVID 19 Infection In Babylon Governorate, Iraq
240 patient sunlight study: 63% fewer cases (p=0.0002).Analysis of 120 COVID-19 and 120 control patients in Iraq, showing lower risk of cases with regular sunlight exposure (3 times/week).
Dec 2021, Natural Volatiles & Essential Oils, https://www.nveo.org/index.php/journal/article/view/1046, https://c19p.org/jabbarsun
691. Samajdar et al., Effectiveness of budesonide formoterol fixed-dose combination MDI in reducing cough symptoms in COVID-19 patients: A real-world evidence study
102 patient budesonide late treatment study: 69% lower hospitalization (p=0.07) and 29% improved recovery (p=0.008).Prospective study of 102 patients in India, showing improved recovery of cough with budesonide+formoterol. Authors note better results with earlier treatment. Budesonide 800mcg + formoterol 12mcg bid for 7 days.
Mar 2023, Lung India, https://journals.lww.com/10.4103/lungindia.lungindia_268_22, https://c19p.org/samajdar2
692. Almazrou et al., Comparing the impact of Hydroxychloroquine based regimens and standard treatment on COVID-19 patient outcomes: A retrospective cohort study
161 patient HCQ late treatment study: 65% lower ventilation (p=0.16) and 21% lower ICU admission (p=0.78).Retrospective 161 hospitalized patients in Saudi Arabia showing lower ventilation and ICU admission with HCQ, but not statistically significant with the small sample sizes.
Sep 2020, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016420302334, https://c19p.org/almazrou
693. Milan et al., Factors Associated with Adverse Outcomes among SARS-CoV-2 Positive Children in a Tertiary Government COVID-19 Referral Hospital in the Philippines
180 patient vitamin D late treatment study: 47% lower mortality (p=0.18), 21% lower ventilation (p=0.53), and 16% lower ICU admission (p=0.69).Retrospective 180 hospitalized pediatric COVID-19 patients in the Philippines showing lower mortality with vitamin D and zinc, and higher mortality with remdesivir, all without statistical significance. Remdesivir was given to few patients and authors do not provide information on the timing of treatment - confounding by indication may be significant.
Apr 2024, Acta Medica Philippina, https://actamedicaphilippina.upm.edu.ph/index.php/acta/article/view/8392, https://c19p.org/miland
694. Lyngbakken et al., A pragmatic randomized controlled trial reports lack of efficacy of hydroxychloroquine on coronavirus disease 2019 viral kinetics
53 patient HCQ late treatment RCT: 4% lower mortality (p=1) and 71% improved viral reduction rate (p=0.51).Small RCT of nasopharyngeal viral load not showing significant differences. The rate of reduction for HCQ was 0.24 [0.03-0.46] RNA copies/mL/24h, and 0.14 [-0.10-0.37] for the control group (71% faster with HCQ but not statistically significant with the small sample size of 27 HCQ and 26 control patients). Analysis only over 96 hours. NCT04316377.
Jul 2020, Nature Communications, https://www.nature.com/articles/s41467-020-19056-6, https://c19p.org/lyngbakken
695. Giancola et al., Efficacy of a Multistrain Synbiotic Treatment in Acute and Post-Acute COVID-19 Patients: A Double-Blind, Placebo-Controlled Randomized Trial
50 patient probiotics late treatment RCT: 33% improved recovery (p=0.32).RCT 52 acute COVID-19 inpatients in Italy showing a multistrain synbiotic formula prevented a decrease in gut microbiota diversity and prevented decreases in lymphocyte count and hemoglobin levels compared to placebo. The probiotic group also had enrichment of beneficial bacteria and fewer neurological/neurocognitive symptoms at 6 months, although not statistically significant. Authors suggest modulating gut microbiota in acute COVID-19 through probiotics could be a useful supportive strategy.
Jul 2024, Microorganisms, https://www.mdpi.com/2076-2607/12/7/1443, https://c19p.org/giancola
696. Budhiraja et al., Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience
976 patient HCQ late treatment study: 65% lower mortality (p<0.0001).Retrospective 976 hospitalized patients with 834 treated with HCQ+AZ showing HCQ mortality relative risk RR 0.35, p < 0.0001. Note that in this case HCQ was recommended for mild/moderate cases, so more severe cases may not have received HCQ (which may also be why they became severe cases). We note that this is opposite to a common bias in HCQ studies - in many cases HCQ was more likely to be given to more severe cases.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.16.20232223v1, https://c19p.org/budhiraja
697. Águila-Gordo et al., Mortality and associated prognostic factors in elderly and very elderly hospitalized patients with respiratory disease COVID-19
416 patient HCQ late treatment study: 67% lower mortality (p=0.1).67% lower mortality with HCQ. Retrospective 416 elderly patients in Spain showing adjusted HCQ mortality hazard ratio HR 0.33, p = 0.1.
Nov 2020, Revista Española de Geriatría y Gerontología, https://www.sciencedirect.com/science/article/pii/S0211139X20301748, https://c19p.org/aguilagordo
698. Blanc et al., Interest of Proton Pump Inhibitors in Reducing the Occurrence of COVID-19: A Case-Control Study
179 patient proton pump inhibitor prophylaxis study: 56% fewer cases (p=0.005).Retrospective 179 elderly patients in France, showing higher risk of COVID-19 cases with acetaminophen use, without statistical significance.
May 2020, Preprints, https://www.preprints.org/manuscript/202005.0016/v1, https://c19p.org/blanc2ppi
699. Nachega et al., Clinical Characteristics and Outcomes of Patients Hospitalized for COVID-19 in Africa: Early Insights from the Democratic Republic of the Congo
766 patient HCQ late treatment study: 28% lower mortality (p=0.17) and 26% greater improvement (p=0.13).Retrospective 766 hospitalized patients in DRC showing mortality reduced from 29% to 11%, and improvement at 30 days increased from 65% to 84%. Mortality cox regression adjusted hazard ratio aHR 0.26, p < 0.001 Risk of no improvement adjusted odds ratio aOR 0.28, p < 0.001 Using marginal structural model analysis these risks became: Mortality MSM adjusted odds ratio aOR 0.65, p = 0.166 Risk of no improvement MSM adjusted odds ratio aOR = 0.65, p = 0.132 Median age 46, 630 treated with CQ+AZ.
Oct 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/content/journals/10.4269/ajtmh.20-1240, https://c19p.org/nachega
700. Chechter et al., Evaluation of patients treated by telemedicine in the beginning of the COVID-19 pandemic in São Paulo, Brazil: A non-randomized clinical trial preliminary study
72 patient HCQ early treatment study: 95% lower hospitalization (p=0.004).Prospective study of 187 telemedicine patients in Brazil. 74 presenting with moderate symptoms were offered treatment with HCQ+AZ, 12 did not accept HCQ (taking AZ only), forming a control group. There was lower hospitalization and improved recovery with treatment.
Nov 2021, Heliyon, https://www.sciencedirect.com/science/article/pii/S2405844023025446, https://c19p.org/chechter
701. Delen et al., Effects of Hydroxychloroquine Plus Favipiravir Treatment on the Clinical Course and Biomarkers in Hospitalized COVID-19 Patients with Pneumonia
69 patient favipiravir late treatment study: 88% improved recovery (p=0.02), 2% longer hospitalization (p=0.74), and 3% lower hospital discharge (p=1).Retrospective 69 COVID-19 patients in Turkey, showing improved fever recovery with the addition of favipiravir to HCQ, but no significant difference in discharge, ICU admission, or hospitalization time.
Dec 2022, Acta Clinica Croatica, https://hrcak.srce.hr/clanak/428402, https://c19p.org/delen
702. Sandhu et al., Outpatient medications associated with protection from COVID-19 hospitalization
3,974,272 patient metformin prophylaxis study: 3% lower hospitalization (p=0.004).Retrospective 3,974,272 COVID-19 patients in the USA, showing 3% lower risk of hospitalization with pre-existing metformin use.
Mar 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0282961, https://c19p.org/sandhu2
703. Rosa et al., Ambulatory COVID-19 Patients Treated with Lactoferrin as a Supplementary Antiviral Agent: A Preliminary Study
121 patient lactoferrin early treatment study: 76% lower hospitalization (p=0.32), 40% slower recovery (p=0.5), and 39% faster viral clearance (p=0.02).Retrospective survey based study in Italy with 82 patients treated with lactoferrin, and 39 control patients, showing significantly faster viral clearance with treatment. There was no significant difference in recovery time overall, however the treatment group had significantly more moderate condition patients (39% versus 8%), and improved recovery was seen with treatment as age increased. Median dose for asymptomatic patients was 400mg/day, for paucisymptomatic patients 600mg/day, and for moderate condition patients 1000mg three times a day.
Sep 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/18/4276, https://c19p.org/rosa
704. Rogado et al., Covid-19 and lung cancer: A greater fatality rate?
17 patient HCQ late treatment study: 92% lower mortality (p=0.02).Retrospective 17 hospitalized lung cancer patients showing lower mortality with HCQ+AZ treatment.
May 2020, Lung Cancer, https://www.lungcancerjournal.info/article/S0169-5002(20)30468-2/fulltext, https://c19p.org/rogado
705. Coll et al., Covid-19 in transplant recipients: the spanish experience
635 patient HCQ late treatment study: 46% lower mortality (p<0.0001).Retrospective 652 transplant recipient patients in Spain showing 46% lower mortality for patients treated with HCQ, unadjusted relative risk RR 0.54, p<0.0001.
Oct 2020, American J. Transplantation, https://onlinelibrary.wiley.com/doi/abs/10.1111/ajt.16369, https://c19p.org/coll
706. Aghajani et al., Association between dietary antioxidant quality score and severity of coronavirus infection: a case–control study
295 patient diet study: 88% lower severe cases (p<0.0001).Case control study of 295 COVID-19 patients in Iran, showing lower risk of severe cases with higher dietary antioxidant quality scores, and with higher intake of vitamin D.
Jul 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1174113/full, https://c19p.org/aghajani2
707. Antunes et al., The influence of physical activity level on the length of stay in hospital in older men survivors of COVID-19
39 patient exercise study: 80% lower ICU admission (p=0.06), 40% improvement (p=0.48), and 43% shorter hospitalization (p=0.03).Retrospective 39 hospitalized COVID-19 survivors >60 years old, showing shorter hospitalization for patients with active lifestyles before COVID-19 symptoms.
Jun 2022, Sport Sciences for Health, https://link.springer.com/10.1007/s11332-022-00948-7, https://c19p.org/antunes
708. Izquierdo et al., Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19
19,208 patient N-acetylcysteine late treatment study: 26% lower mortality (p=0.0007).Retrospective 19,208 COVID+ hospitalized patients in Spain, 2,071 treated with high dose NAC, showing lower mortality with treatment. In multivariable analysis, authors adjust for corticosteroids, but do not adjust for HCQ use which was also significantly more common in the NAC group. NAC 600mg every 8 hours.
Jan 2022, Science Progress, https://journals.sagepub.com/doi/10.1177/00368504221074574, https://c19p.org/izquierdo
709. Tolouian et al., Effect of bromhexine in hospitalized patients with COVID-19
100 patient bromhexine late treatment RCT: 76% lower mortality (p=0.43), 76% greater improvement (p=0.43), and 75% worse viral clearance (p=0.02).Small RCT with 100 patients, 48 with bromhexine added to SOC, showing slower viral- conversion but lower mortality and greater clinical improvement with bromhexine (not statistically significant with few deaths and very high recovery). The very large difference between unadjusted and adjusted results is due to much higher risk for patients with renal disease and the much higher prevalence of renal disease in the bromhexine group. The study also shows 90% of patients in the control group had BMI>=30 compared to 0% in the treatment group, suggesting a possible problem with randomization. Due to the imbalance between groups, results were adjusted for BMI>30, smoking, and renal disease. 11 patients were lost to followup in the treatment group compared to zero in the control group, perhaps in part due to faster recovery in the treatment group. 9 patients were excluded from the treatment group because they did not want to take bromhexine after discharge. Therefore up to 29% of treatment..
Mar 2021, J. Investig. Med., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970656/, https://c19p.org/tolouian
710. Louca et al., Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app
372,720 patient vitamin D prophylaxis study: 8% fewer cases (p=0.0007).Survey analysis of dietary supplements showing vitamin D usage associated with lower incidence of COVID-19. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/louca
711. Delić et al., Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial
94 patient alkalinization ICU RCT: 23% lower mortality (p=0.13).RCT mechanically ventilated patients in Croatia, 42 treated with sodium bicarbonate inhalation, and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delicph
712. Delić et al., Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial
94 patient sodium bicarbonate ICU RCT: 23% lower mortality (p=0.13).RCT mechanically ventilated patients in Croatia, 42 treated with sodium bicarbonate inhalation, and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delicphsb
713. Delić et al., Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial
94 patient saline ICU RCT: 26% lower mortality (p=0.09).RCT mechanically ventilated patients in Croatia, showing no significant difference in mortality with saline inhalation. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delicnacl
714. Gaitán-Duarte et al., Effectiveness of rosuvastatin plus colchicine, emtricitabine/tenofovir and combinations thereof in hospitalized patients with COVID-19: a pragmatic, open-label randomized trial
314 patient colchicine late treatment RCT: 22% lower mortality (p=0.38).RCT 633 hospitalized patients in Colombia, 153 treated with colchicine + rosuvastatin, not showing statistically significant differences in outcomes. Improved results were seen with the combination of emtricitabine/tenofovir disoproxil + rosuvastatin + colchicine. NCT04359095.
Jul 2021, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00523-X/fulltext, https://c19p.org/gaitanduarte
715. Idris et al., Nigella sativa oil (NSO) as an adjuvant in the management of mild COVID-19 infection in Kaduna state
51 patient nigella sativa early treatment study: 39% faster recovery (p=0.003).Prospective study of 51 mild COVID-19 cases in Nigeria, showing faster recovery and improved viral clearance with nigella sativa oil (NSO) treatment. NSO patients received 5mL twice daily in addition to usual care (zinc, vitamin C and a multivitamin).
Jan 2024, The Nigerian Health J., https://tnhjph.com/index.php/tnhj/article/view/712, https://c19p.org/idris
716. Cordtz et al., Incidence of COVID-19 Hospitalisation in Patients with Systemic Lupus Erythematosus: A Nationwide Cohort Study from Denmark
2,533 patient HCQ prophylaxis study: 40% lower hospitalization (p=0.39).Retrospective 2,533 SLE patients in Denmark showing no significant difference in hospitalization risk for COVID-19 cases with HCQ treatment.
Aug 2021, J. Clinical Medicine, https://www.mdpi.com/2077-0383/10/17/3842, https://c19p.org/cordtz2
717. Lalau et al., Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19
1,090 patient metformin prophylaxis PSM study: 22% lower mortality (p=0.16), 18% lower combined mortality/intubation (p=0.21), and 7% lower ventilation (p=0.72).Retrospective 2,449 hospitalized COVID-19 diabetes patients in France, 1,496 with existing metformin use, showing lower mortality with treatment. Statistical significance was reached in model 1 but not in models 2-4 which also adjust for HbA1c, eGFR, and diabetes duration, but have a lower number of patients. CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes).
Dec 2020, Diabetes & Metabolism, https://www.sciencedirect.com/science/article/pii/S1262363620302731, https://c19p.org/lalau
718. Brito-Reia et al., Population-based virucidal phthalocyanine gargling/rinsing protocol to reduce the risk of coronavirus disease-2019: a community trial
5,040 patient phthalocyanine prophylaxis study: 54% fewer cases (p=0.08).Comparison of two similar communities in Brazil, with one using a phthalocyanine derivative mouthwash, suggesting efficacy of the treatment in lowering COVID-19 cases. There was 54% lower risk of confirmed cases during the intervention in the treatment community, compared with 15% higher and 8% lower risk before and after the intervention. Gargle/rinse with 5mL of mouthwash containing phthalocyanine derivative for 1 minute, 3 to 5 times per day.
Nov 2021, German Medical Science GMS Publishing House, https://www.egms.de/en/journals/dgkh/2022-17/dgkh000426.shtml, https://c19p.org/britoreia
719. Ozer et al., Effectiveness and Safety of Ivermectin in COVID-19 Patients: A Prospective Study at A Safety-Net Hospital
120 patient ivermectin late treatment study: 75% lower mortality (p=0.09), 13% lower ventilation (p=0.2), and 9% longer hospitalization (p=0.09).Small prospective PSM study in the USA, showing 75% lower mortality with ivermectin treatment, without reaching statistical significance, significantly shorter ventilation and ICU time, and longer hospitalization time. Authors leave the statistically significant improvements in ventilation and ICU time out of the abtract and conclusions, and incorrectly state that there were no differences in other outcomes (there were no statistically significant differences) [nature.com]. Authors are ambiguous on the primary outcome, referring to the primary mortality outcome in one case, and "clinical outcomes, measured by the rate of intubation, length of hospital stay, and mechanical ventilation duration" in another case. The longer hospitalization time may be partially due to the greater mortality in the control group.
Nov 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27469, https://c19p.org/ozer
720. Zargarzadeh et al., Higher Adherence to the Mediterranean Dietary Pattern Is Inversely Associated With Severity of COVID-19 and Related Symptoms: A Cross-Sectional Study
169 patient diet study: 77% lower severe cases (p=0.0002).Retrospective 250 COVID-19 patients in Iran, showing lower risk of severe disease with greater adherence to a Mediterranean diet.
Jul 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.911273/full, https://c19p.org/zargarzadeh
721. Johnston et al., Hydroxychloroquine with or Without Azithromycin for Treatment of Early SARS-CoV-2 Infection Among High-Risk Outpatient Adults: A Randomized Clinical Trial
231 patient HCQ late treatment RCT: 30% lower hospitalization (p=0.73), 2% improved recovery (p=0.95), and 29% faster viral clearance.Small early terminated late treatment RCT comparing vitamin C + folic acid, HCQ + folic acid, and HCQ+AZ, showing non-statistically significantly lower hospitalization with HCQ/HCQ+AZ, and faster viral clearance with HCQ. Enrollment was a median of 5.9 days after onset (6.2 and 6.3 in the treatment arms). The median time to viral clearance for vitamin C + folic acid was 8 days in the preprint but changed to 7 days in the published paper without explanation. Both vitamin C [c19early.org] and folic acid [Deschasaux-Tanguy, Farag] show efficacy in other trials, so the true effectiveness of HCQ(+AZ) may be higher than observed. Low risk patients, median age 37, no deaths (not matching the title which claims "high risk"). There was a post hoc addition of a new cycle threshold that obscures the statistically significant faster clearance. There was no analysis for time from symptom onset. Authors identify (relatively) low and high risk cohorts, but do not provide either viral..
Dec 2020, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00053-5/fulltext, https://c19p.org/johnston
722. Baguma et al., Characteristics of the COVID-19 patients treated at Gulu Regional Referral Hospital, Northern Uganda: A cross-sectional study
481 patient vitamin D late treatment study: 97% lower mortality (p=0.02).Retrospective COVID+ hospitalized patients in Uganda, 23 patients receiving vitamin D treatment, showing significantly lower mortality with treatment.
Dec 2021, Research Square, https://www.researchsquare.com/article/rs-1193578/v1, https://c19p.org/bagumad
723. Abu-Jamous et al., Associations of comorbidities and medications with COVID-19 outcome: A retrospective analysis of real-world evidence data
191 patient metformin late treatment study: 65% lower mortality (p=0.04).Retrospective diabetes patients in the UK, showing lower mortality for metformin treatment (administered within 21 days after a positive PCR test).
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.20.20174169, https://c19p.org/abujamous
724. Ahmadi et al., Oral nano-curcumin formulation efficacy in the management of mild to moderate outpatient COVID-19: A randomized triple-blind placebo-controlled clinical trial
60 patient curcumin early treatment RCT: 86% lower hospitalization (p=0.24) and 21% faster recovery (p=0.37).RCT 60 outpatients in Iran, 30 treated with nano-curcumin showing lower hospitalization and faster recovery with treatment.
Jun 2021, Food Science and Nutrition, https://onlinelibrary.wiley.com/doi/full/10.1002/fsn3.2226, https://c19p.org/ahmadi
1,150 patient HCQ late treatment study: 44% lower mortality (p=0.14).
Retrospective 1210 hospitalized patients in Turkey focused on chronic kidney disease, haemodialysis and renal transplant patients, but also showing lower mortality with HCQ. Subject to confounding by indication.
Dec 2020, Nephrology Dialysis Transplantation, https://academic.oup.com/ndt/article/35/12/2083/6020341, https://c19p.org/ozturk
726. Dian et al., Azvudine versus Paxlovid for oral treatment of COVID-19 in Chinese patients with pre-existing comorbidities
2,118 patient azvudine late treatment PSM study: 64% lower mortality (p=0.11), 67% lower ventilation (p=0.28), and 48% lower progression (p=0.03).Retrospective 2,118 hospitalized COVID-19 patients in China, showing improved results with azvudine vs. paxlovid.
Aug 2023, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445323002906, https://c19p.org/dian
727. Aparisi et al., Low-density lipoprotein cholesterol levels are associated with poor clinical outcomes in COVID-19
654 patient HCQ late treatment study: 63% lower mortality (p=0.008).Retrospective 654 hospitalized patients focused on low-density lipoprotein cholesterol levels, also showing results for HCQ with 605 HCQ patients, unadjusted 30 day mortality relative risk RR 0.37, p = 0.008.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20207092v1, https://c19p.org/aparisi
728. Ceccarelli et al., Oxygen Sparing Effect of Bacteriotherapy in COVID-19
69 patient probiotics late treatment study: 82% lower ICU admission (p=0.15).Prospective analysis of 69 severe COVID-19 patients requiring non-invasive oxygen therapy, 40 treated with probiotic formulation SLAB51, showing lower oxygen requirements and higher blood levels of pO2, O2Hb and SaO2 with treatment. Authors suggest that enzymes in SLAB51 could reduce oxygen requirements in intestinal cells, resulting in more oxygen available for other organs.
Aug 2021, Nutrients, https://www.mdpi.com/2072-6643/13/8/2898, https://c19p.org/ceccarelli2
729. Cavalcanti et al., Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
667 patient azithromycin late treatment RCT: 57% lower mortality (p=0.17), 54% higher ventilation (p=0.28), and 18% improved 7-point scale results (p=0.49).Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of the medications >24hrs. Analyzing these patients rather than excluding them may have revealed effectiveness with early use as shown in other studies. The..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2019014, https://c19p.org/cavalcantiazaz
730. Mareev et al., Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)
66 patient bromhexine late treatment RCT: 11% improved recovery (p=0.47), 8% shorter hospitalization (p=0.35), and 87% improved viral clearance (p=0.08).Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone, showing lower PCR+ at day 10 or hospitalization >10 days with treatment. Bromhexine 8mg 4 times daily, spironolactone 25-50 mg/day for 10 days.
Dec 2020, Кардиология, https://lib.ossn.ru/jour/article/view/1440, https://c19p.org/mareev
731. Mareev et al., Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)
66 patient spironolactone antiandrogen late treatment RCT: 11% improved recovery (p=0.47), 8% shorter hospitalization (p=0.35), and 87% improved viral clearance (p=0.08).Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone, showing lower PCR+ at day 10 or hospitalization >10 days with treatment. Bromhexine 8mg 4 times daily, spironolactone 25-50 mg/day for 10 days.
Dec 2020, Кардиология, https://lib.ossn.ru/jour/article/view/1440, https://c19p.org/mareevaa
732. Mareev et al., Results of Open-Label non-Randomized Comparative Clinical Trial: “BromhexIne and Spironolactone for CoronаvirUs Infection requiring hospiTalization (BISCUIT)
66 patient spironolactone late treatment RCT: 11% improved recovery (p=0.47), 8% shorter hospitalization (p=0.35), and 87% improved viral clearance (p=0.08).Prospective 103 PCR+ patients in Russia, 33 treated with bromexhine+spironolactone, showing lower PCR+ at day 10 or hospitalization >10 days with treatment. Bromhexine 8mg 4 times daily, spironolactone 25-50 mg/day for 10 days.
Dec 2020, Кардиология, https://lib.ossn.ru/jour/article/view/1440, https://c19p.org/mareevaasp
733. Tadbir Vajargah et al., Association of fruits, vegetables, and fiber intake with COVID-19 severity and symptoms in hospitalized patients: A cross-sectional study
166 patient diet study: 67% lower severe cases (p=0.003).Retrospective 250 hospitalized patients in Iran, showing higher consumption of fruits, vegetables, and fiber associated with lower COVID-19 severity.
Sep 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.934568/full, https://c19p.org/tadbirvajargah
734. van Helmond et al., Vitamin D3 Supplementation at 5000 IU Daily for the Prevention of Influenza-like Illness in Healthcare Workers: A Pragmatic Randomized Clinical Trial
3,082 patient vitamin D prophylaxis study: 98% fewer cases (p=0.07).Prospective prophylaxis trial with 255 healthcare workers taking vitamin D and 2,827 controls, showing significantly lower influenza-like illness with treatment, and lower COVID-19 cases, without statistical significance. While the intervention and control groups were initially randomized, exclusions were only processed in the treatment arm.
Sep 2022, Nutrients, https://www.mdpi.com/2072-6643/15/1/180, https://c19p.org/vanhelmond
735. Milan et al., Factors Associated with Adverse Outcomes among SARS-CoV-2 Positive Children in a Tertiary Government COVID-19 Referral Hospital in the Philippines
180 patient zinc late treatment study: 56% lower mortality (p=0.09), 13% lower ventilation (p=0.67), and 10% lower ICU admission (p=0.84).Retrospective 180 hospitalized pediatric COVID-19 patients in the Philippines showing lower mortality with vitamin D and zinc, and higher mortality with remdesivir, all without statistical significance. Remdesivir was given to few patients and authors do not provide information on the timing of treatment - confounding by indication may be significant.
Apr 2024, Acta Medica Philippina, https://actamedicaphilippina.upm.edu.ph/index.php/acta/article/view/8392, https://c19p.org/milan
736. Asadirad et al., Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial
60 patient curcumin late treatment RCT: 26% lower mortality (p=0.74), 50% lower progression (p=0.47), and 45% improved recovery (p=0.09).RCT 60 hospitalized patients in Iran, 30 treated with nano-curcumin, showing significant improvements in inflammatory cytokines, and improvements in clinical outcomes without statistical significance. 240 mg/day nano-curcumin for 7 days.
Jan 2022, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/10.1002/ptr.7375, https://c19p.org/asadirad
737. Meiser et al., Azelastine Nasal Spray in Non-Hospitalised Subjects with Mild COVID-19 Infection: A Randomized Placebo-Controlled, Parallel-Group, Multicentric, Phase II Clinical Trial
251 patient azelastine late treatment RCT: 13% improved recovery (p=0.42) and 6% improved viral clearance (p<0.0001).RCT 294 low-risk subjects with mild COVID-19 showing significantly greater reduction in viral load with azelastine 0.1% nasal spray vs. placebo. There was no COVID-19 related hospitalization in either group. The reduction in viral load was significantly higher in the azelastine group at day 3, 6 and 11. Authors report that treatment was associated with significant improvement in fever (p=0.0046), weakness (p=0.0012) and hypoxia (p<0.0001) compared to placebo, however detailed results are not provided for these and other symptoms. Treatment delay from symptom onset is not specified, however the baseline viral load, lack of progression, and recovery profile are consistent with relatively late treatment among low-risk patients. Time to recovery results are not clear, with an inconsistent HR and 95% CI reported 0.32 [0.83-2.32].
Oct 2024, MDPI AG, https://www.preprints.org/manuscript/202410.2532/v1, https://c19p.org/meiser
738. Meiser et al., Azelastine Nasal Spray in Non-Hospitalised Subjects with Mild COVID-19 Infection: A Randomized Placebo-Controlled, Parallel-Group, Multicentric, Phase II Clinical Trial
251 patient azelastine late treatment RCT: 13% improved recovery (p=0.42) and 6% improved viral clearance (p<0.0001).RCT 294 low-risk subjects with mild COVID-19 showing significantly greater reduction in viral load with azelastine 0.1% nasal spray vs. placebo. There was no COVID-19 related hospitalization in either group. The reduction in viral load was significantly higher in the azelastine group at day 3, 6 and 11. Authors report that treatment was associated with significant improvement in fever (p=0.0046), weakness (p=0.0012) and hypoxia (p<0.0001) compared to placebo, however detailed results are not provided for these and other symptoms. Treatment delay from symptom onset is not specified, however the baseline viral load, lack of progression, and recovery profile are consistent with relatively late treatment among low-risk patients. Time to recovery results are not clear, with an inconsistent HR and 95% CI reported 0.32 [0.83-2.32].
Oct 2024, MDPI AG, https://www.preprints.org/manuscript/202410.2532/v1, https://c19p.org/meiserazl
739. Falcone et al., Role of low-molecular weight heparin in hospitalized patients with SARS-CoV-2 pneumonia: a prospective observational study
315 patient HCQ late treatment PSM study: 65% lower mortality (p=0.2).Prospective observational study of 315 hospitalized patients in Italy showing 65% lower mortality with HCQ. The median treatment delay was 6 days for survivors and 6.5 days for non-survivors. Mortality relative risk: RR 0.35, p = 0.2, propensity score matched RR 0.75, p = 0.36, multivariate Cox regression RR 0.43, p < 0.001, univariate Cox regression
Nov 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa563/5992463, https://c19p.org/falcone
740. Mousavi et al., Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial
96 patient melatonin late treatment RCT: 67% lower mortality (p=0.62) and 40% lower ICU admission (p=0.41).RCT 96 hospitalized patients in Iran, 48 treated with melatonin, showing improved sleep quality and SpO2 with treatment. 3mg oral melatonin daily. Authors recommend studies with a higher dose. IRCT20200411047030N1.
Aug 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.27312, https://c19p.org/mousavi
741. Frontera et al., Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study
3,473 patient HCQ late treatment PSM study: 37% lower mortality (p=0.02).Retrospective 3,473 hospitalized patients showing lower mortality with HCQ+zinc.
Oct 2020, Research Square, https://www.researchsquare.com/article/rs-94509/v1, https://c19p.org/frontera
742. Frontera et al., Treatment with Zinc is Associated with Reduced In-Hospital Mortality Among COVID-19 Patients: A Multi-Center Cohort Study
3,473 patient zinc late treatment PSM study: 37% lower mortality (p=0.02).Retrospective 3,473 hospitalized patients showing 37% lower mortality with HCQ+zinc. PSM aHR 0.63, p=0.015 regression aHR 0.76, p = 0.023
Oct 2020, Research Square, https://www.researchsquare.com/article/rs-94509/v1, https://c19p.org/frontera2
743. Alshamrani et al., Comprehensive evaluation of six interventions for hospitalized patients with COVID-19: A propensity score matching study
814 patient HCQ late treatment PSM study: 50% lower mortality (p=0.18), 37% lower progression (p=0.21), 9% shorter ICU admission (p=0.66), and 3% longer hospitalization (p=0.7).PSM retrospective 29 hospitals in Saudi Arabia, finding lower mortality with HCQ, without reaching statistical significance (described by authors as "no impact").
Feb 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000348, https://c19p.org/alshamrani
744. Hamidi-Alamdari et al., Methylene blue for treatment of hospitalized COVID-19 patients: a randomized, controlled, open-label clinical trial, phase 2
80 patient vitamin C late treatment RCT: 44% lower mortality (p=0.38) and 38% shorter hospitalization (p=0.004).RCT 80 hospitalized patients with severe COVID-19, 40 treated with methylene blue + vitamin C + N-acetylcysteine, showing lower mortality, shorter hospitalization, and significantly improved SpO2 and respiratory distress with treatment.
Mar 2021, Clinical and Translational Investigation, https://www.clinicalandtranslationalinvestigation.com/frame_esp.php?id=375, https://c19p.org/hamidialamdari
745. Azaña Gómez et al., Mortality risk factors in patients with SARS-CoV-2 infection and atrial fibrillation: Data from the SEMI-COVID-19 registry
1,799 patient HCQ late treatment study: 36% lower mortality (p<0.0001).Retrospective 1,816 COVID-19 patients with atrial fibrillation in Spain, showing lower mortality with HCQ treatment.
Mar 2022, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775322000549, https://c19p.org/azanagomez
746. Sánchez-González et al., What if melatonin could help COVID-19 severe patients?
448 patient melatonin late treatment study: 54% lower mortality (p=0.0009).Retrospective 2,463 hospitalized patients in Spain, 265 treated with melatonin, showing lower mortality with treatment in PSM analysis, however these results are subject to immortal time bias. Authors excluded from the sample patients that died during the first 72 hours of admission without taking melatonin, and patients that started on melatonin in the last 7 days of their admittance, having completed 75% of their stay.
Jul 2021, Sánchez-González, https://jcsm.aasm.org/doi/10.5664/jcsm.9554, https://c19p.org/sanchezgonzalez
747. Usman et al., Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes
75 patient metformin prophylaxis study: 60% lower mortality (p=0.21), 76% lower ventilation (p=0.05), and 34% shorter hospitalization (p=0.13).Retrospective 75 diabetes patients, 34 on metformin, showing improved clinical outcomes with treatment, without statistical significance.
Jan 2022, J. Thrombosis and Thrombolysis, https://link.springer.com/article/10.1007%2Fs11239-022-02631-7, https://c19p.org/usman
748. Hosseini et al., PRevention of COVID-19 with Oral Vitamin D supplemental Therapy in Essential healthCare Teams (PROTECT): Ancillary study of a randomised controlled trial
34 patient vitamin D prophylaxis RCT: 82% fewer cases (p=0.19).Early terminated prophylaxis RCT for healthcare workers in Canada, showing 0/19 cases with vitamin D prophylaxis vs. 2/15 for control. 100,000IU cholecalciferol at baseline, 10,000IU weekly for 16 weeks.
Jul 2022, Research Square, https://www.researchsquare.com/article/rs-1588325/v1, https://c19p.org/hosseini4
749. Boari et al., Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study
258 patient HCQ late treatment study: 55% lower mortality (p=0.001).Retrospective 258 hospitalized patients in Italy showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.455, p<0.001. Data is in the supplementary appendix.
Nov 2020, Bioscience Reports, https://portlandpress.com/bioscirep/article/doi/10.1042/BSR20203455/226985, https://c19p.org/boari
750. Vaisi et al., The association between nutrients and occurrence of COVID-19 outcomes in the population of Western Iran: A cohort study
3,955 patient vitamin A prophylaxis study: 17% lower hospitalization (p=0.04) and 11% fewer symptomatic cases (p=0.03).Analysis of nutrient intake and COVID-19 outcomes for 3,996 people in Iran, showing lower risk of COVID-19 hospitalization with sufficient vitamin A, vitamin C, and selenium intake, with statistical significance for vitamin A and selenium.
May 2023, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13632, https://c19p.org/vaisi
751. Yang et al., Traditional Chinese medicine together with high-dose vitamin C improves the therapeutic effect of western medicine against COVID-19
20 patient vitamin C late treatment RCT: 33% faster recovery (p<0.0001) and 36% faster viral clearance (p<0.0001).Prospective study of 60 patients in China with three arms: SOC, SOC+TCM, and SOC+TCM+high dose vitamin C, showing successively faster recovery with the addition of TCM and the addition of high dose vitamin C. TCM included inhaled vitamin C 10g, 3-7 times per day. IV vitamin C 10g/60kg twice a day, and oral vitamin C 3g three times a day. Group C vs. group A includes combined treatment with TCM, while group C vs. group B both include vitamin C (high vs. low dose).
Jan 2022, American J. Translational Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8829592/, https://c19p.org/yang2
752. Satti et al., Characteristics and Obstetric Outcomes in Women With Autoimmune Rheumatic Disease During the COVID-19 Pandemic in Qatar
80 patient HCQ prophylaxis study: 61% fewer cases (p=0.04).Retrospective 80 consecutive pregnant patients with autoimmune rheumatic diseases in Qatar, showing lower risk of COVID-19 cases with HCQ prophylaxis.
Apr 2022, Cureus, https://www.cureus.com/articles/91696-characteristics-and-obstetric-outcomes-in-women-with-autoimmune-rheumatic-disease-during-the-covid-19-pandemic-in-qatar, https://c19p.org/satti
753. Said et al., The effect of Nigella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 patients: A randomized controlled clinical trial
60 patient vitamin D early treatment RCT: 42% improved recovery (p=0.57) and 49% improved viral clearance (p=0.2).120 patient RCT comparing vitamin D, nigella sativa, and combined vitamin D+nigella sativa, showing improved symptom recovery and viral clearance with both vitamin D and nigella sativa, and further improvements with the combination of both. All patients received vitamin C, zinc, and lactoferrin.
Nov 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.1011522/full, https://c19p.org/said
754. Jang et al., Clinical course of COVID-19 patients treated with ECMO: A multicenter study in Daegu, South Korea
19 patient vitamin B12 late treatment study: 78% improved recovery (p=0.04).Retrospective 19 COVID-19 ECMO patients in South Korea, showing a higher rate of weaning from ECMO with vitamin B12 treatment, without statistical significance. Authors perform multivariate analysis but do not provide full results, only reporting p > 0.05.
Dec 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S0147956320304027, https://c19p.org/jang2b12
755. Shadnoush et al., Effects of Spirulina platensis Supplementation on COVID-19 Severity in Critically Ill Patients: A Randomized Clinical Trial
126 patient spirulina ICU RCT: 3% higher mortality (p=0.93), 26% shorter ICU admission (p=0.007), 17% lower need for oxygen therapy (p=0.64), and 20% shorter hospitalization (p=0.001).RCT 192 critically ill COVID-19 ICU patients showing reduced SOFA score, hospital stay and ICU stay with spirulina supplementation (5g/day), but no significant difference in mortality, NEWS2 score, APACHE score, NUTRIC score, or respiratory support at discharge.
Sep 2024, J. Cellular and Molecular Anesthesia, https://brieflands.com/articles/jcma-149015, https://c19p.org/shadnoushspi
756. Baykal et al., Correlation of vitamin D level with the clinical-radiological severity of COVID-19 in geriatric patients
75 patient vitamin D late treatment study: 22% lower mortality (p=0.43) and 59% lower ICU admission (p=0.005).Retrospective 75 patients in Turkey showing lower ICU admission with vitamin D treatment in unadjusted results subject to confounding by time and indication (treatment was given to patients with low levels and only during a certain period). There was no significant difference in outcomes based on vitamin D levels.
May 2022, J. Health Sciences and Medicine, https://dergipark.org.tr/en/doi/10.32322/jhsm.1063405, https://c19p.org/baykal
757. Zarehoseinzade et al., Finasteride in hospitalized adult males with COVID-19: A risk factor for severity of the disease or an adjunct treatment: A randomized controlled clinical trial
80 patient finasteride antiandrogen late treatment RCT: 75% lower mortality (p=0.36) and no change in ICU admission (p=1).RCT 80 hospitalized COVID-19 patients in Iran, 40 treated with finasteride, showing no significant differences other than improved oxygen saturation on the 5th day with treatment. There was significantly more patients with diabetes in the control group. 5mg finasteride for 7 days. IRCT20200505047318N1.
Apr 2021, Medical J. The Islamic Republic of Iran, https://mjiri.iums.ac.ir/article-1-7160-en.html, https://c19p.org/zarehoseinzade
758. Karami et al., A Comparison of the Effects of Chlorhexidine and Sodium Bicarbonate Mouthwashes on COVID-19–Related Symptoms
80 patient alkalinization prophylaxis RCT: 45% lower progression (p=0.14) and 39% fewer cases (p=0.16).RCT 116 healthcare workers comparing 0.2% chlorhexidine mouthwash (n=36), 7.5% sodium bicarbonate mouthwash (n=40), and placebo (n=40) twice daily for 2 weeks, with symptoms followed for 4 weeks. There were lower symtoms and cases in both treatment groups, with statistical significance for chlorhexidine only. The treatments were stopped after two weeks, results may be better with continued use, more frequent use, and with the addition of nasal use.
Jan 2024, Iranian J. Nursing and Midwifery Research, https://journals.lww.com/jnmr/fulltext/2024/29010/a_comparison_of_the_effects_of_chlorhexidine_and.8.aspx, https://c19p.org/karamiph
759. Krishnan et al., Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study
2,431 patient HCQ late treatment study: 40% lower mortality (p=0.05).Case control study with 2,431 hospitalized COVID-19 patients in India, showing lower mortality with HCQ treatment, without statistical significance.
Apr 2023, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/view/journals/tpmd/108/4/article-p727.xml, https://c19p.org/krishnan2
760. Bernaola et al., Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid
1,645 patient HCQ late treatment study: 17% lower mortality (p<0.0001).HCQ HR 0.83 [0.77-0.89] based on propensity score matched retrospective analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88], 14 other medications showed either no signicant benefit or a negative effect.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.17.20155960v1, https://c19p.org/bernaola
761. Hess et al., High-dose intravenous vitamin C decreases rates of mechanical ventilation and cardiac arrest in severe COVID-19
100 patient vitamin C late treatment study: 20% lower mortality (p=0.54), 40% lower ventilation (p=0.05), and 27% lower ICU admission (p=0.11).Retrospective 100 severe condition hospitalized patients in the USA, 25 treated with high dose IV vitamin C, showing lower mechanical ventilation and cardiac arrest, and increased length of survival with treatment. 3g IV vitamin C every 6h for 7 days.
Mar 2022, Internal and Emergency Medicine, https://link.springer.com/article/10.1007/s11739-022-02954-6/fulltext.html, https://c19p.org/hess
762. Gao et al., Effect of Ursodeoxycholic Acid for Sars-Cov-2 Prevention in Hematological Malignancies: An Observational Real-World Study
393 patient ursodeoxycholic acid prophylaxis study: 12% fewer cases (p=0.03).Retrospective 393 hospitalized patients with hematologic disorders in China, showing lower risk of COVID-19 with UDCA use.
Nov 2023, Blood, https://ashpublications.org/blood/article/142/Supplement%201/7308/500982/Effect-of-Ursodeoxycholic-Acid-for-Sars-Cov-2, https://c19p.org/gao6
763. Izzo et al., Combining L-Arginine with Vitamin C Improves Long-COVID Symptoms: The Nationwide Multicenter LINCOLN Study
1,390 patient vitamin C long COVID study: 41% improved recovery (p<0.0001).Long COVID trial comparing L-arginine + vitamin C with multivitamin treatment (vitamin B1, B2, B6, B12, nicotinamide, folic acid, pantothenic acid), showing significant improvement in symptoms with L-arginine + vitamin C treatment.
Jul 2022, Pharmacological Research, https://www.sciencedirect.com/science/article/pii/S104366182200305X, https://c19p.org/izzo
764. Rohani et al., Evaluation and comparison of the effect of vitamin A supplementation with standard therapies in the treatment of patients with COVID-19
180 patient vitamin A early treatment RCT: 26% lower hospitalization (p=0.63) and 32% improved recovery (p=0.53).RCT 91 vitamin A and 91 control patients in Iran, showing improved recovery with treatment. All patients received HCQ. 25,000IU/day oral vitamin A for 10 days.
Aug 2022, Eastern Mediterranean Health J., http://www.emro.who.int/in-press/research/evaluation-and-comparison-of-the-effect-of-vitamin-a-supplementation-with-standard-therapies-in-the-treatment-of-patients-with-covid-19.html, https://c19p.org/rohani
765. Tehrani et al., Efficacy of Favipiravir in the Treatment of Moderate COVID-19 Patients: A Randomized, Open-label, Controlled Clinical Trial
78 patient favipiravir late treatment RCT: 34% lower hospitalization (p=0.24).RCT 78 patients in Iran, showing improved recovery with favipiravir treatment.
Jun 2022, Mediterranean J. Infection Microbes and Antimicrobials, https://mjima.org/pdf.php?&id=340, https://c19p.org/tehrani4
122 patient selenium late treatment RCT: 35% lower mortality (p=0.68), 81% lower need for oxygen therapy, and 22% improved recovery.
Randomized, double-blind, placebo-controlled trial of 122 moderate hospitalized COVID-19 patients in Iran, evaluating the addition of BCc1 iron chelator and Hep-S selenium nanomedicines to standard treatment. The nanomedicine group showed a significant 77% reduction in IL-6 levels by day 28 compared to an 18% increase in the placebo group, along with improvements in TNF-alpha and clinical scores for cough, fatigue, and oxygen need, without statistical significance.
Nov 2023, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07624-2, https://c19p.org/hafizi
767. Efird et al., The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2
16,338 patient vitamin D early treatment study: 49% lower mortality (p=0.1).Retrospective 26,508 COVID+ veterans in USA, showing lower mortality with vitamin D use after testing positive (defined as being administered ≥7 days or half of the survival time within 2 weeks after testing), with statistical significance for hospitalized patients.
Dec 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/19/1/447/html, https://c19p.org/efird
768. Mareev et al., Proactive anti-inflammatory therapy with colchicine in the treatment of advanced stages of new coronavirus infection. The first results of the COLORIT study
43 patient colchicine late treatment study: 50% improved recovery (p=0.06) and 26% shorter hospitalization (p=0.08).Small trial with 21 colchicine patients and 22 control patients in Russia, showing improved recovery with treatment. The trial was originally an RCT, however randomization to the control arm was stopped after 5 patients, and 17 retrospective patients were added for comparison.
Feb 2021, Kardiologiia, https://lib.ossn.ru/jour/article/view/1560/0?locale=en_US, https://c19p.org/mareev2
769. Taher et al., A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome
92 patient N-acetylcysteine late treatment RCT: 18% lower mortality (p=0.65), 14% lower ventilation (p=0.67), 20% shorter ICU admission (p=0.48), and 33% shorter hospitalization (p=0.31).RCT 92 hospitalized patients, 47 treated with NAC, showing non-significant improvements in outcomes. IRCT20120215009014N355. NAC 40mg/kg/day intravenous for 3 days.
Jun 2021, Pharmacological Reports, https://link.springer.com/article/10.1007%2Fs43440-021-00296-2, https://c19p.org/taher
456 patient favipiravir late treatment study: 56% higher mortality (p=0.26), 90% lower ventilation (p<0.0001), and 49% higher hospital discharge (p<0.0001).
Retrospective 234 favipiravir and 223 control patients in Saudi Arabia, showing shorter time to discharge and lower progression to ventilation, but no significant difference in mortality.
May 2021, Current Medical Research and Opinion, https://www.tandfonline.com/doi/full/10.1080/03007995.2021.1920900, https://c19p.org/alamer
771. Grau-Pujol et al., Pre-exposure prophylaxis with hydroxychloroquine for COVID-19: a double-blind, placebo-controlled randomized clinical trial
269 patient HCQ prophylaxis RCT: 11% fewer cases (p=1).Small PrEP RCT showing that PrEP with HCQ is safe at the dosage used. There were no deaths, hospitalizations, or serious adverse events. The paper states: "Among all trial participants at the end of the first month (n=253), only one participant from the placebo arm (1/116, 0.8%), tested positive for SARS-CoV-2 PCR and for a SARS-CoV-2 serology test". The abstract states: "only one participant in each group was diagnosed with COVID-19".
Sep 2020, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-021-05758-9, https://c19p.org/graupujol
772. Topless et al., Gout and the risk of COVID-19 diagnosis and death in the UK Biobank: a population-based study
341,398 patient colchicine prophylaxis study: 23% lower mortality (p=0.12).UK Biobank retrospective showing a higher risk of COVID-19 cases and mortality for patients with gout. Among patients with gout, mortality risk was lower for those on colchicine, OR 1.06 [0.60-1.89], compared to those without colchicine, OR 1.38 [1.08-1.76].
Jan 2022, The Lancet Rheumatology, https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(21)00401-X/fulltext, https://c19p.org/topless
773. Louca et al., Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app
372,720 patient probiotics prophylaxis study: 8% fewer cases (p=0.03).Survey analysis of dietary supplements showing probiotic usage associated with lower incidence of COVID-19. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucak
50 patient curcumin early treatment RCT: 33% improved recovery (p=0.15) and 50% improved viral clearance (p=0.009).
RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.
Apr 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.898062/full, https://c19p.org/khan4t
50 patient quercetin early treatment RCT: 33% improved recovery (p=0.15) and 50% improved viral clearance (p=0.009).
RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.
Apr 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.898062/full, https://c19p.org/khan4q
776. Zhang et al., Gut microbiota-derived synbiotic formula (SIM01) as a novel adjuvant therapy for COVID-19: An open-label pilot study
55 patient probiotics late treatment study: 67% improvement (p=0.06).Pilot study of probiotic SIM01 with 25 consecutive COVID-19 patients in Hong Kong and 30 control patients treated by a different team during the same time period, showing improved antibody formation, reduced viral load and pro-inflammatory responses, and improvements for gut dysbiosis. SIM01 contains bifidobacteria strains, galactooligosaccharides, xylooligosaccharide, and resistant dextrin (derived from metagenomic databases of COVID-19 patients and healthy patients).
Mar 2022, J. Gastroenterology and Hepatology, https://onlinelibrary.wiley.com/doi/10.1111/jgh.15796, https://c19p.org/zhang5
777. Siripongboonsitti et al., The Real-World Effectiveness of Fluvoxamine Therapy in Mild to Moderate COVID-19 Patients; a Historical Cohort Study (Fluvoxa Trial)
752 patient fluvoxamine early treatment study: 67% higher need for oxygen therapy (p=0.02), 42% lower progression (p=0.08), 34% improved recovery (p<0.0001), and 4% worse viral clearance (p=0.66).Retrospective 752 patients in Thailand showing mixed results with 50mg fluvoxamine bid. Authors note that trials showing benefit mostly used 100mg bid.
Oct 2023, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034123003374, https://c19p.org/siripongboonsitti5
778. Shahid et al., The effects of vitamin D therapy on outcomes for hispanic patients hospitalized for COVID-19
1,478 patient vitamin D late treatment study: 38% lower mortality (p=0.001).Retrospective 1,478 hospitalized Hispanic patients in the USA with 705 receiving vitamin D treatment, showing lower mortality with treatment in unadjusted results. Very minimal information is currently available.
Jun 2022, Abstracts from the 2022 Annual Meeting of the Society of General Internal Medicine, J. General Internal Medicine, https://link.springer.com/10.1007/s11606-022-07653-8, https://c19p.org/shahid
779. Fu et al., Prognostic Factors for COVID-19 Hospitalized Patients with Preexisting Type 2 Diabetes
80 patient metformin prophylaxis study: 72% improved recovery (p=0.03).Retrospective 108 T2D patients hospitalized with COVID-19, showing lower risk of unfavorable outcomes with metformin use vs. other diabetic medications.
Jan 2022, Int. J. Endocrinology, https://www.hindawi.com/journals/ije/2022/9322332/, https://c19p.org/fu
780. Navarro-López et al., Oral intake of Kluyveromyces marxianus B0399 plus lactobacillus rhamnosus CECT 30579 to mitigate symptoms in COVID-19 patients: A randomized open label clinical trial
39 patient probiotics early treatment RCT: 33% improved recovery (p=0.08).RCT with 24 probiotics and 15 control patients in Spain, showing lower overall symptoms and lower digestive symptoms with treatment. Kluyveromyces marxianus B0399 plus lactobacillus rhamnosus CECT 30579.
Aug 2022, Medicine in Microecology, https://www.sciencedirect.com/science/article/pii/S2590097822000118, https://c19p.org/navarrolopez
781. Rabe et al., Impact of SARS-CoV-2 infection on patients with systemic lupus erythematosus in England prior to vaccination: a retrospective observational cohort study
6,145 patient HCQ prophylaxis study: 29% fewer cases (p=0.22).Retrospective cohort of 6,145 SLE patients showing lower incidence of COVID-19 for patients receiving HCQ/CQ (antimalarials), without statistical significance. Groups were not matched and results may be influenced by factors such as disease severity. HCQ/antimalarials were used more in moderate/severe SLE patients, suggesting that the estimated protective effect will underestimate the real effect.
Nov 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-071072, https://c19p.org/rabe
782. Diaz et al., Effect of Colchicine vs Usual Care Alone on Intubation and 28-Day Mortality in Patients Hospitalized With COVID-19
1,279 patient colchicine late treatment RCT: 12% lower mortality (p=0.3) and 17% lower combined mortality/intubation (p=0.08).Very late stage RCT (O2 88%, 84% on oxygen) with 1,279 hospitalized patients in Argentina, showing lower mortality and lower combined mortality/ventilation, statistically significant only for the combined outcome and per-protocol analysis. NCT04328480. COLCOVID.
Dec 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2787585, https://c19p.org/diaz2
783. Halabchi et al., Regular Sports Participation as a Potential Predictor of Better Clinical Outcome in Adult Patients With COVID-19: A Large Cross-Sectional Study
4,694 patient exercise study: 89% lower mortality (p=0.08) and 28% lower hospitalization (p=0.04).Retrospective 4,694 COVID-19 patients in Iran, showing lower risk of hospitalization and mortality with regular sports participation.
Nov 2020, J. Physical Activity and Health, https://journals.humankinetics.com/view/journals/jpah/18/1/article-p8.xml, https://c19p.org/halabchi
784. Silva et al., Efficacy of Nitazoxanide in reducing the viral load in COVID-19 patients. Randomized, placebo-controlled, single-blinded, parallel group, pilot study
36 patient nitazoxanide early treatment RCT: 26% improved viral clearance (p=0.36).Small RCT with 23 nitazoxanide and 13 control patients showing significantly more patients achieved over 35% reduction in viral load from baseline. NCT04463264.
Mar 2021, Medical Research Archives, https://esmed.org/MRA/mra/article/view/3364, https://c19p.org/silva
785. Yeramaneni et al., Famotidine Use Is Not Associated With 30-day Mortality: A Coarsened Exact Match Study in 7158 Hospitalized Patients With Coronavirus Disease 2019 From a Large Healthcare System
7,158 patient famotidine prophylaxis study: 51% lower mortality (p=0.22).Retrospective 7,158 hospitalized COVID-19 patients in the USA, showing higher risk or mortality with in-hospital famotidine use, but lower risk when there was pre-existing at-home use, without statistical significance in both cases.
Feb 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)35249-5/fulltext, https://c19p.org/yeramaneni
786. Singh et al., Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial)
74 patient HCQ late treatment RCT: 48% lower mortality (p=0.45) and 14% improved recovery (p=0.76).Very small early terminated RCT in India, showing lower mortality but without statistical significance with the very small sample size. Time since symptom onset is not provided. The recovery percentage for non-severe group B (86.7%) does not match any number of recoveries, we have used the closest number (15/17).
Jun 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.06.06.21258091v1, https://c19p.org/singh2
787. Hafezi et al., Vitamin D enhances type I IFN signaling in COVID-19 patients
80 patient vitamin D ICU study: 63% lower mortality (p=0.04).Retrospective 80 ICU patients, and in vitro study with human airway epithelial cells, showing that vitamin D enhances host IFN-a/β signaling. Significantly lower mortality was seen with vitamin D treatment.
Oct 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-22307-9, https://c19p.org/hafezi
789. Mostafaie et al., Colchicine Plus Phenolic Monoterpenes to Treat COVID-19
120 patient colchicine late treatment RCT: 83% lower mortality (p=0.11) and 35% shorter hospitalization (p=0.0001).RCT with 60 patients treated with colchicine and phenolic monoterpenes and 60 control patients in Iran, showing lower mortality with treatment. NCT04392141.
Apr 2021, NCT04392141, https://clinicaltrials.gov/ct2/show/NCT04392141, https://c19p.org/mostafaie
790. Kontopoulou et al., Exercise Preferences and Benefits in Patients Hospitalized with COVID-19
66 patient exercise study: 66% faster recovery (p<0.0001).Retrospective 66 hospitalized COVID-19 patients in Greece, showing significantly improved recovery with a history of exercise in unadjusted results. Exercise after hospitalization was also associated with lower levels of dyspnea one month post hospitalization.
Apr 2022, J. Personalized Medicine, https://www.mdpi.com/2075-4426/12/4/645, https://c19p.org/kontopoulou
33 patient HCQ late treatment RCT: 24% improved viral clearance (p=0.71).
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76, p = 0.71. Small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR 1.29, p = 0.7. The RCT and retrospective study are listed separately [Chen, Chen].
Jul 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242763, https://c19p.org/chen25
792. Zamanian et al., The association of dietary approach to stop hypertension (DASH) diet with hospitalization risk in patients with COVID-19
141 patient diet study: 81% lower hospitalization (p=0.002).Case control study with 53 inpatients and 88 outpatients in Iran, showing lower risk of hospitalization with increased adherence to the DASH (Dietary Approach to Stop Hypertension) diet. Increased intake of fruits, vegetables and low-fat dairy products, and lower intake of sodium and processed/red meat were significantly associated with reduced risk of hospitalization due to COVID-19.
Mar 2023, Clinical Nutrition Open Science, https://www.sciencedirect.com/science/article/pii/S2667268523000050, https://c19p.org/zamanian
793. Sahebari et al., Influence of biologic and conventional disease-modifying antirheumatic drugs on COVID-19 incidence among rheumatic patients during the first and second wave of the pandemic in Iran
512 patient HCQ prophylaxis study: 56% fewer cases (p=0.02).Retrospective 512 rheumatic disease patients in Iran, showing lower risk of COVID-19 with HCQ use.
Sep 2022, Reumatologia/Rheumatology, https://www.termedia.pl/doi/10.5114/reum.2022.119039, https://c19p.org/sahebari
794. Tahmasebi et al., Nanocurcumin improves Treg cell responses in patients with mild and severe SARS-CoV2
80 patient curcumin late treatment RCT: 83% lower mortality (p=0.11).RCT 40 hospitalized, 40 ICU, and 40 control patients in Iran, showing lower mortality and improved regulatory T cell responses with nanocurcumin treatment (SinaCurcumin).
Mar 2021, Life Sciences, https://www.sciencedirect.com/science/article/abs/pii/S0024320521004227, https://c19p.org/tahmasebi
795. Zhao et al., High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study
110 patient vitamin C early treatment PSM study: 72% lower progression (p=0.03) and 8% slower viral clearance (p=0.79).PSM retrospective 110 patients, 55 treated with high-dose IV vitamin C, showing lower progression to severe disease with treatment. Patients in each group were in different time periods, time based confounding is likely due to SOC improving over time. ChiCTR2000033050.
Apr 2021, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2021.638556/full, https://c19p.org/zhao4
796. Nimer et al., Effect of natural products use prior to infection with COVID-19 on disease severity and hospitalization: A self-reported cross-sectional survey study
2,148 patient curcumin prophylaxis study: 31% lower hospitalization (p=0.08) and 13% lower severe cases (p=0.47).Survey 2,148 COVID-19 recovered patients in Jordan, showing lower hospitalization with turmeric prophylaxis, not reaching statistical significance.
Jun 2022, F1000Research, https://f1000research.com/articles/11-639/v1, https://c19p.org/nimer2
797. Panda et al., Antiviral Combination Clinically Better Than Standard Therapy in Severe but Not in Non-Severe COVID-19
41 patient HCQ late treatment RCT: 48% lower mortality (p=0.45).RCT 111 patients in India in 5 groups: severe patients: a) standard treatment, b) hydroxychloroquine + ribavirin + standard treatment, or c) lopinavir + ritonavir + ribavirin + standard treatment, and non-severe: a) standard treatment or b) hydroxychloroquine + ribavirin. Non-severe patients were transferred to the severe group on progression.
Sep 2021, Clinical Pharmacology: Advances and Applications, https://www.dovepress.com/antiviral-combination-clinically-better-than-standard-therapy-in-sever-peer-reviewed-fulltext-article-CPAA, https://c19p.org/panda2
798. Valsecchi et al., High-Dose Inhaled Nitric Oxide for the Treatment of Spontaneously Breathing Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) Pneumonia
71 patient nitric oxide late treatment study: 68% lower ventilation (p=0.08) and 39% lower ICU admission (p=0.28).Retrospective 71 hospitalized patients in Israel, 20 treated with inhaled nitric oxide, showing no significant differences.
Jul 2022, Obstetrics & Gynecology, https://journals.lww.com/10.1097/AOG.0000000000004847, https://c19p.org/valsecchi
799. Smith et al., Evaluating the Efficacy of Hydroxychloroquine and Azithromycin to Prevent Hospitalization or Death in Persons With COVID-19
16 patient HCQ early treatment RCT: 64% lower hospitalization (p=1) and 10% slower recovery.Early terminated NIAID RCT for HCQ. Patients >60 were only in the HCQ arm. 57% of patients were high risk in the HCQ arm vs. 22% for control. Treatment started up to 20 days after symptoms.
Jul 2020, NCT04358068, https://clinicaltrials.gov/study/NCT04358068, https://c19p.org/smith2
800. Damayanti et al., The Effectiveness and Safety of Favipiravir in COVID-19 Hospitalized Patients in Bali, Indonesia
192 patient favipiravir late treatment study: 54% improved recovery (p=0.03).Retrospective 192 hospitalized patients in Indonesia, 96 patients treated with favipiravir, showing improved recovery with treatment. Only the abstract is currently available.
Oct 2021, Kesmas: National Public Health J., https://journal.fkm.ui.ac.id/kesmas/article/view/5433, https://c19p.org/damayanti
801. Tare et al., The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice
36 patient camostat early treatment RCT: 33% improved recovery (p=0.7).Small early terminated RCT showing better recovery with camostat treatment, without statistical significance.
Nov 2023, BJGP Open, http://bjgpopen.org/lookup/doi/10.3399/BJGPO.2023.0109, https://c19p.org/tarecm
802. Amoah et al., Further observations on hydrogen peroxide antisepsis and COVID-19 cases among healthcare workers and inpatients
466 patient hydrogen peroxide prophylaxis study: 93% fewer cases (p=0.06).Retrospective 458 healthcare workers in Ghana, showing lower COVID-19 cases with hydrogen peroxide prophylaxis (oral and nasal rinse), without statistical significance.
Aug 2022, J. Hospital Infection, https://www.sciencedirect.com/science/article/pii/S0195670122001499, https://c19p.org/amoah
803. Valecha et al., The Effect of Vitamin B12, Magnesium and Vitamin D in COVID-19 among Geriatric Patients
55 patient vitamin D early treatment study: 87% lower ICU admission (p=0.09) and 38% shorter hospitalization (p<0.0001).Prospective study of 30 patients treated with vitamin D, magnesium, and vitamin B12, and 25 control patients, showing shorter hospitalization and lower oxygen and ICU requirements with treatment. Cholecalciferol 1000IU, magnesium oxide 150mg, vitamin B12 500μg.
Apr 2022, Int. J. Pharmaceutical and Clinical Research, http://impactfactor.org/PDF/IJPCR/14/IJPCR,Vol14,Issue5,Article113.pdf, https://c19p.org/valecha
208 patient HCQ late treatment study: 44% lower mortality (p=0.14) and 3% improved recovery (p=0.91).
Retrospective 208 hospitalized COVID-19 patients in Burkina Faso showing lower mortality with HCQ/CQ+AZ treatment, without statistical significance. There was no difference for recovery.
Feb 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-192.php?jid=jide, https://c19p.org/baguiya
805. Tehrani et al., An investigation into the Effects of Intravenous Vitamin C on Pulmonary CT Findings and Clinical Outcomes of Patients with COVID 19 Pneumonia A Randomized Clinical Trial
44 patient vitamin C late treatment RCT: 87% lower mortality (p=0.13) and 18% shorter hospitalization (p=0.23).RCT 54 late stage patients, 18 treated with IV vitamin C (2g every 6h for 5 days), showing significant relative improvements in oxygen saturation and respiratory rate.
Nov 2021, Urology J., https://journals.sbmu.ac.ir/urolj/index.php/uj/article/view/6863, https://c19p.org/tehrani3
806. Lyon et al., 5α-Reductase Inhibitors Are Associated with Reduced Risk of SARS-CoV-2 Infection: A Matched-Pair, Registry-Based Analysis
1,938 patient various antiandrogen prophylaxis study: 17% lower mortality (p=0.61) and 7% fewer cases (p=0.04).Retrospective 944 5ARI users in the USA and 944 matched controls, showing lower risk of COVID-19 cases with treatment.
Jan 2022, J. Urology, https://www.auajournals.org/doi/10.1097/JU.0000000000002180, https://c19p.org/lyon
807. Khurana et al., Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital
181 patient HCQ prophylaxis study: 51% fewer cases (p=0.02).Study of hospital health care workers showing HCQ prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis was important in this study which used a low dose of 400mg/week HCQ (800mg for week 1), so it may take longer to reach therapeutic levels. Actual benefit of HCQ may be larger because severity of symptoms are not considered here but HCQ may also reduce severity.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.21.20159301v1, https://c19p.org/khurana
808. Charif et al., Predictive Factors of Death and the Clinical Profile of Hospitalized Covid-19 Patients in Morocco: A One-Year Mixed Cohort Study
615 patient HCQ late treatment study: 27% lower mortality (p=0.0005).Retrospective 615 hospitalized COVID-19 patients in Morocco, showing lower mortality with HCQ in unadjusted results.
Dec 2022, Cureus, https://www.cureus.com/articles/122896-predictive-factors-of-death-and-the-clinical-profile-of-hospitalized-covid-19-patients-in-morocco-a-one-year-mixed-cohort-study, https://c19p.org/charif
809. Reis et al., The Association between Lifestyle Risk Factors and COVID-19 Hospitalization in a Healthcare Institution
546 patient exercise study: 41% lower hospitalization (p=0.18).Retrospective 546 COVID+ patients in the USA, showing lower risk of hospitalization with higher frequency of strength training, without statistical significance.
Oct 2022, American J. Lifestyle Medicine, http://journals.sagepub.com/doi/10.1177/15598276221135541, https://c19p.org/reis6ex
810. Ibrahim Alhajjaji et al., Effect of zinc supplementation on symptom reduction and length of hospital stay among pediatric patients with Coronavirus Disease 2019 (COVID-19)
101 patient zinc late treatment study: 88% lower mortality (p=0.13), 26% lower ventilation (p=0.75), 3% lower ICU admission (p=1), and 73% lower progression (p=0.004).Retrospective 101 hospitalized pediatric patients in Saudi Arabia, showing zinc treatment associated with lower respiratory failure and shorter hospitalization in unadjusted results. Patients receiving zinc were older. Authors note elevated serum creatinine and the possibility of kidney injury.
Mar 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000415, https://c19p.org/ibrahimalhajjaji
811. Pitanga et al., Leisure Time Physical Activity and SARS-CoV-2 Infection among ELSA-Brasil Participants
4,476 patient exercise study: 33% fewer cases (p=0.05).Retrospective 4,476 participants in Brazil, showing lower risk of COVID-19 cases with a history of physical activity, statistically significant only for those following specific practices to protect against COVID-19.
Oct 2022, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/19/21/14155, https://c19p.org/pitanga
812. Haji Aghajani et al., Decreased in-hospital mortality associated with aspirin administration in hospitalized patients due to severe COVID-19
991 patient aspirin late treatment study: 25% lower mortality (p=0.04).Retrospective 991 hospitalized patients in Iran, showing lower mortality with aspirin treatment.
Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27053, https://c19p.org/hajiaghajanie
813. Afaghi et al., N-acetylcysteine as adjuvant therapy for hospitalized Covid-19 patients: A single-center prospective cohort study
462 patient N-acetylcysteine late treatment study: 29% lower mortality (p=0.42), 41% lower ventilation (p=0.16), 20% lower ICU admission (p=0.36), and 14% shorter hospitalization (p=0.002).Prospective study of 217 patients treated with NAC and 245 matched controls, showing improved recovery with treatment. 1500mg intravenous NAC daily.
May 2023, Caspian J Intern Med, https://caspjim.com/article-1-3389-fa.html, https://c19p.org/afaghi2
60 patient N-acetylcysteine late treatment RCT: 67% lower mortality (p=0.61).
RCT 60 hospitalized COVID-19 patients evaluating the efficacy and safety of adding oral N-acetylcysteine (NAC) at 600mg three times daily to standard antiviral treatment regimens. The NAC group showed significantly greater reduction in C-reactive protein levels, indicating reduced inflammation. Authors conclude that oral NAC may provide benefits through reducing inflammation, increasing oxygen saturation, and potentially reducing mortality when combined with certain antiviral medications in hospitalized COVID-19 patients.
Nov 2023, Immunity, Inflammation and Disease, https://onlinelibrary.wiley.com/doi/10.1002/iid3.1083, https://c19p.org/atefi
815. Rana et al., Effects of mega dose vitamin C in critically ill COVID-19 patients: a randomized control trial
278 patient vitamin C ICU RCT: 55% lower mortality (p=0.2), 44% lower ventilation (p=0.41), and 37% shorter hospitalization (p=0.91).RCT 278 COVID-19 ICU patients in Pakistan, showing lower mortality and ventilation, and shorter length of stay with high dose vitamin C treatment, without statistical significance. 30 grams IV vitamin C for four days.
Jun 2023, Biological and Clinical Sciences Research J., http://bcsrj.com/ojs/index.php/bcsrj/article/view/343, https://c19p.org/rana2
816. Rezai et al., Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials
609 patient ivermectin late treatment RCT: 31% lower mortality (p=0.36), 50% lower ventilation (p=0.07), 16% lower ICU admission (p=0.47), and 11% longer hospitalization (p=0.009).RCT 609 inpatients in Iran. Reported outcomes are very different from the pre-specified outcomes [irct.ir]. The outpatient trial is listed separately. From the pre-specified outcomes, all are either positive or not reported. Pre-specified outcomes: - Reduction in persistent cough - RR 0.36 p = 0.06 - Negative RT-PCR - not reported - Main complaints recovery time - not reported - Mortality - RR 0.69 p = 0.36 - Side effects - reported as none (anomalous) - Reduction in tachypnea - RR 0.24 p = 0.38 - Oxygen saturation >94% - not reported All negative outcomes are protocol violations and are not listed in the protocol, including the novel "relative recovery" outcome. Authors include a researcher caught on video admitting that conclusions on ivermectin research were influenced by a funder [c19ivm.org]. Severe cases were more frequent in the ivermectin group, 49% vs. 43%. Dose was limited at a maximum of 30mg for 75+kg, resulting in underdosing for patients at higher risk. Almost..
Jun 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.919708/full, https://c19p.org/rezai2
817. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
2,148 patient vitamin B12 prophylaxis study: 24% lower hospitalization (p=0.15) and 27% lower severe cases (p=0.06).Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin B12 prophylaxis, without statistical significance.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerb12
818. Gamarra-Morales et al., Response to Intravenous N-Acetylcysteine Supplementation in Critically Ill Patients with COVID-19
140 patient N-acetylcysteine ICU RCT: 16% lower mortality (p=0.49).RCT 140 ICU patients in Spain, 72 treated with N-acetylcysteine (NAC). NAC patients showed improved PaO2/FiO2, CRP, D-dimer, and LDH, and there were associations between glutathione and clinical outcomes and severity biomarkers in NAC-treated patients. There was no significant difference in mortality.
May 2023, Nutrients, https://www.mdpi.com/2072-6643/15/9/2235, https://c19p.org/gamarramorales
819. Tan et al., Efficacy of diammonium glycyrrhizinate combined with vitamin C for treating hospitalized COVID-19 patients: a retrospective, observational study
161 patient vitamin C late treatment study: 25% lower combined mortality/intubation (p=0.74) and 73% lower progression (p=0.002).PSM retrospective 207 hospitalized patients in China, 46 treated with diammonium glycyrrhizinate and vitamin C, showing lower risk of ARDS with treatment.
Jul 2021, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcab184/6329274, https://c19p.org/tan3
820. Ochoa-Jaramillo et al., Clinical efficacy and safety of ivermectin (400 μg/kg, single dose) in patients with severe COVID-19: a randomized clinical trial
75 patient ivermectin late treatment RCT: 57% lower mortality (p=0.35), 34% higher ventilation (p=0.62), and 37% higher ICU admission (p=0.52).RCT 75 very late stage patients in Colombia, showing no significant difference in outcomes with a single dose of 400μg/kg ivermectin.
Oct 2022, Revista Infectio, http://revistainfectio.org/P_OJS/index.php/infectio/article/view/1105, https://c19p.org/ochoajaramillo
821. Malik et al., Effect of low dose acetylsalicylic acid and anticoagulant on clinical outcomes in COVID-19, analytical cross-sectional study
310 patient aspirin prophylaxis study: 14% lower mortality (p=0.72), 28% lower ICU admission (p=0.17), 25% lower ARDS (p=0.39), and 2% lower hospitalization (p=0.94).Retrospective 539 patients in the USA, showing lower mortality, ICU admission, and ARDS with aspirin treatment, without statistical significance.
Jul 2022, Health Science Reports, https://onlinelibrary.wiley.com/doi/10.1002/hsr2.699, https://c19p.org/malik
822. Johnson et al., Prevalent Metformin Use in Adults With Diabetes and the Incidence of Long COVID: An EHR-Based Cohort Study From the RECOVER Program
48,988 patient metformin prophylaxis study: 11% lower progression (p=0.11).N3C/PCORnet retrospective adults with type 2 diabetes in the USA showing lower incidence of mortality or long COVID with metformin use.
Sep 2024, Diabetes Care, https://diabetesjournals.org/care/article/doi/10.2337/DCa24-0032/157171/Prevalent-Metformin-Use-in-Adults-With-Diabetes, https://c19p.org/johnson
823. Patel et al., A pilot double-blind safety and feasibility randomized controlled trial of high-dose intravenous zinc in hospitalized COVID-19 patients
33 patient zinc late treatment RCT: 20% lower mortality (p=1).Small early terminated RCT with 33 hospitalized patients in Australia, 15 treated with zinc, showing no significant difference in clinical outcomes. Treatment increased zinc levels above the deficiency cutoff. Intravenous zinc 0.5mg/kg/day (elemental zinc concentration 0.24mg/kg/day) for up to 7 days. ACTRN12620000454976.
Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26895, https://c19p.org/patel2
824. Rodriguez-Gonzalez et al., COVID-19 in hospitalized patients in Spain: a cohort study in Madrid
1,208 patient HCQ late treatment study: 23% lower mortality (p=0.26).Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication.
Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304696, https://c19p.org/rodriguezgonzalez
825. Tret'yakov et al., COVID-19 in individuals adapted to aerobic exercise
293 patient exercise study: 98% lower severe cases (p=0.007).Retrospective 293 COVID+ patients in Russia, showing lower risk of severe COVID-19 for individuals who regularly practice aerobic training in unadjusted results.
Oct 2020, Pulmonologiya, https://journal.pulmonology.ru/pulm/article/view/1376, https://c19p.org/tretyakov
144 patient vitamin C late treatment study: 63% lower mortality (p=0.22).
Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing lower mortality with vitamin C treatment.
Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocy
827. Husain et al., Beneficial effect of low dose aspirin (Acetyl salicylic acid) in adult Covid-19 patients: a retrospective observational study in Bangladesh
42 patient aspirin late treatment study: 96% lower progression (p=0.001).Retrospective 42 patients in Bangladesh, 11 treated with aspirin, showing fewer complications with treatment.
Oct 2020, ResearchGate, https://www.researchgate.net/publication/344567523_Beneficial_effect_of_low_dose_aspirin_Acetyl_salicylic_acid_in_adult_Covid-19_patients_a_retrospective_observational_study_in_Bangladesh, https://c19p.org/husain
828. Scirocco et al., COVID-19 prognosis in systemic lupus erythematosus compared with rheumatoid arthritis and spondyloarthritis: results from the CONTROL-19 Study by the Italian Society for Rheumatology
627 patient HCQ prophylaxis study: 41% lower combined mortality/intubation (p=0.38).Retrospective 103 SLE and 524 RA patients in Italy, showing significantly lower mortality/ventilation with HCQ use for SLE patients, and no significant difference for RA patients in unadjusted results. Authors did not include HCQ in multivariable analysis, only including four variables "chosen among the most clinically relevant". Multivariable analysis may significantly improve results for RA patients because HCQ use may correlate with more severe disease due to use for patients that failed or do not tolerate first-line therapies. It is not clear how the patients were selected - the very high ~25% ventilation/mortality suggests that most were hospitalized COVID-19 patients, in which case any benefit of HCQ in reducing hospitalizations will not be reflected in the results. Authors falsely state that "subsequent studies have definitely proved that [HCQ] is not linked to COVID-19 prognosis", suggesting significant bias, and possibily indicating why HCQ..
Oct 2023, Lupus Science & Medicine, https://lupus.bmj.com/lookup/doi/10.1136/lupus-2023-000945, https://c19p.org/scirocco
829. Alzahrani et al., Clinical characteristics and outcome of COVID-19 in patients with rheumatic diseases
47 patient HCQ prophylaxis study: 59% lower mortality (p=1), 81% lower ventilation (p=0.54), and 33% lower severe cases (p=0.7).Retrospective 47 rheumatic disease patients not finding significant differences with HCQ.
Apr 2021, Rheumatology Int. , https://link.springer.com/article/10.1007/s00296-021-04857-9, https://c19p.org/alzahrani
830. Khan et al., Montelukast in hospitalized patients diagnosed with COVID-19
92 patient montelukast late treatment study: 64% lower progression (p=0.09) and 12% shorter hospitalization (p=0.33).Retrospective 92 hospitalized patients showing lower clinical deterioration with montelukast treatment, without statistical significance in multivariable analysis. The treatment group was older.
Mar 2021, J. Asthma, https://www.tandfonline.com/doi/full/10.1080/02770903.2021.1881967, https://c19p.org/khan7
831. Omma et al., Hydroxychloroquine shortened hospital stay and reduced intensive care unit admissions in hospitalized COVID-19 patients
393 patient HCQ late treatment study: 28% lower mortality (p=0.3), 50% lower ICU admission (p=0.004), and 17% shorter hospitalization (p=0.007).Retrospective 393 hospitalized COVID-19 patients in Turkey, showing lower ICU admission and shorter hospitalization time with HCQ. There was no significant difference for mortality. Severity was higher in the HCQ group with greater baseline ventilation, high flow oxygen, fever, and dyspnea.
Jan 2022, The J. Infection in Developing Countries, https://jidc.org/index.php/journal/article/view/14933, https://c19p.org/omma
100 patient probiotics early treatment RCT: 80% lower hospitalization (p=0.2) and 18% improved recovery (p=0.42).
RCT 150 patients in Egypt showing no significant difference in outcomes with probiotic lactobacillus acidophilus, although hospitalization was 2% versus 10% for control. SOC included vitamin C, D, and zinc.
Jun 2023, Research Square, https://www.researchsquare.com/article/rs-3049708/v1, https://c19p.org/hassan
833. Bryce et al., RECOVER: Phase 2 Randomized, Double-Blind Trial TREating Hospitalized Patients With COVID-19 With Camostat MesilatE, a TMPRSS2 Inhibitor
100 patient camostat late treatment RCT: 25% lower mortality (p=1).RCT 100 patients showing no significant difference with camostat. Results are currently unclear—different mortality numbers were provided for all-cause mortality and mortality rate (2/50 vs. 3/46 for the treatment group at 28 days, with the 28 day all-cause mortality result removed in an updated submission). The main outcome measures appear to be different due to only including patients that submitted day 28 outcome data.
Mar 2024, NCT04470544, https://clinicaltrials.gov/study/NCT04470544, https://c19p.org/bryce
834. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
2,148 patient vitamin C prophylaxis study: 25% lower hospitalization (p=0.08) and 17% lower severe cases (p=0.18).Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin C prophylaxis, without statistical significance.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerc
835. Elzein et al., In vivo evaluation of the virucidal efficacy of chlorhexidine and povidone-iodine mouthwashes against salivary SARS-CoV-2. A randomized-controlled clinical trial
34 patient povidone-iodine early treatment RCT: 89% improved viral clearance (p=0.05).Small RCT comparing mouthwashing with PVP-I, chlorhexidine, and water, showing significant efficacy for both PVP-I and chlorhexidine, with PVP-I increasing Ct by a mean of 4.45 (p < 0.0001) and chlorhexidine by a mean of 5.69 (p < 0.0001), compared to no significant difference for water.
Mar 2021, J. Evidence Based Dental Practice, https://www.sciencedirect.com/science/article/abs/pii/S1532338221000592, https://c19p.org/elzein
836. Simsek et al., Effects of high dose vitamin C administration in Covid-19 patients
139 patient vitamin C late treatment study: 44% lower mortality (p=0.19) and 10% lower ICU admission (p=0.66).Retrospective 139 hospitalized patients in Turkey, 58 treated with high dose vitamin C, showing improved kidney functioning with treatment. Mortality was lower with treatment, but not reaching statistical significance with the small sample size.
Sep 2021, Annals of Medical Research, https://www.annalsmedres.org/index.php/aomr/article/view/3910, https://c19p.org/simsekc
837. Magaña et al., Influence of mediterranean diet on survival from covid-19 disease
89 patient diet study: 53% lower mortality (p=0.05).Retrospective 89 COVID-19 patients in Spain, showing lower mortality with adherence to the Mediterranean diet.
Dec 2021, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457721009293, https://c19p.org/magana
421 patient metformin early treatment RCT: 27% lower mortality (p=0.53), 6% lower hospitalization (p=0.88), 14% more combined hospitalization/ER visits (p=0.58), and 31% lower progression (p=0.48).
Data for the primary outcome in this trial appears to be impossible [doyourownresearch.substack.com]. For example, considering the metformin arm and the ITT population: 24 were hospitalized and 8 had an ER visit (tables S2/S3), therefore the number for combined ER or hospitalization must be between 24 and 32. However, authors report 34 events for ER/hospitalization. RCT with 215 patients treated with metformin and 203 controls, showing no significant difference with treatment. For multiple major issues with this trial see [doyourownresearch.substack.com, doyourownresearch.substack.com]. An expression of concern was posted in 2024 [thelancet.com]. The hospitalization risk for off-protocol patients was several times higher in both arms, resulting in Simpson's paradox when combining per-protocol and off-protocol patients [web.archive.org]. 750mg twice daily for 10 days.
Aug 2021, The Lancet Regional Health - Americas, https://www.sciencedirect.com/science/article/pii/S2667193X21001381, https://c19p.org/reis3
839. Arroyo-Díaz et al., Previous Vitamin D Supplementation and Morbidity and Mortality Outcomes in People Hospitalised for COVID19: A Cross-Sectional Study
1,267 patient vitamin D prophylaxis study: 12% higher mortality (p=0.59), 43% lower ventilation (p=0.22), 44% lower ICU admission (p=0.03), and 12% shorter hospitalization (p=0.2).Retrospective 1,267 hospitalized patients in Spain, 189 on vitamin D supplementation before admission, showing lower ICU admission with supplementation, and no statistically significant difference for mortality or ventilation.
Sep 2021, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2021.758347/full, https://c19p.org/arroyodiaz
840. Matangila et al., Clinical characteristics of COVID-19 patients hospitalized at Clinique Ngaliema, a public hospital in Kinshasa, in the Democratic Republic of Congo: A retrospective cohort study
160 patient HCQ late treatment study: 55% lower mortality (p=0.21).55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showing adjusted OR 0.24 [0.03-2.2].
Dec 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244272, https://c19p.org/matangila
841. Meisel et al., Folate Levels in Patients Hospitalized with Coronavirus Disease 2019
334 patient vitamin B9 prophylaxis study: 27% lower mortality (p=0.54) and 6% lower combined mortality/intubation (p=0.88).Retrospective 333 hospitalized patients in Israel, showing no significant difference in outcomes with low folate levels or with folic acid supplementation.
Mar 2021, Nutrients, https://www.mdpi.com/2072-6643/13/3/812, https://c19p.org/meisel
842. Cariou et al., Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study
1,317 patient metformin prophylaxis study: 20% lower mortality (p=0.46).Analysis of 1,317 hospitalized COVID-19 patients with diabetes showing lower mortality with metformin use, without statistical significance.
May 2020, Diabetologia, https://link.springer.com/10.1007/s00125-020-05180-x, https://c19p.org/cariou
843. Bae et al., Recent Hydroxychloroquine Use Is Not Significantly Associated with Positive PCR Results for SARS-CoV-2: A Nationwide Observational Study in South Korea
3,441 patient HCQ prophylaxis PSM study: 30% fewer cases (p=0.18).Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment.
Feb 2021, Viruses 2021, https://www.mdpi.com/1999-4915/13/2/329, https://c19p.org/bae
844. Balouch et al., Role of Famotidine and Other Acid Reflux Medications for SARS-CoV-2: A Pilot Study
307 patient famotidine prophylaxis study: 22% fewer symptomatic cases (p=0.49) and 37% faster recovery (p=0.32).Survey of 307 patients in the USA, showing no significant difference in COVID-19 cases with famotidine use.
Jan 2021, J. Voice, https://www.sciencedirect.com/science/article/pii/S0892199721000321, https://c19p.org/balouch
845. Pellegrini et al., A Retrospective Analysis of Outcomes Amongst COVID-19 Infected Patients with Acute Hepatitis Receiving N-Acetylcysteine Therapy in a Safety Net Hospital
864 patient N-acetylcysteine late treatment study: 52% lower mortality (p=0.0001).Retrospective 864 hospitalized late stage COVID-19 patients in the USA, 138 receiving NAC treatment for acute hepatitis, showing lower mortality with treatment. Results are adjusted for confounders, however details are not provided.
May 2021, Gastroenterology, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8108159/, https://c19p.org/pellegrini
846. Calderón et al., Treatment with hydroxychloroquine vs nitazoxanide in patients with COVID-19: brief report
44 patient nitazoxanide late treatment study: 68% lower mortality (p=0.38), 87% lower ventilation (p=0.15), 59% lower ICU admission (p<0.0001), and 52% shorter hospitalization (p=0.007).Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.
Nov 2021, PAMJ - Clinical Medicine, https://www.clinical-medicine.panafrican-med-journal.com/content/article/7/15/full/, https://c19p.org/calderon2
38 patient colchicine early treatment RCT: 67% lower hospitalization (p=0.55) and 24% improved recovery (p=0.72).
RCT 38 low risk outpatients in Japan, showing no significant differences for colchicine and low-dose aspirin compared to loxoprofen. Hospitalization was lower, without statistical significance (4.3% vs. 13.3%, p=0.34). There were no critical cases, deaths, or severe adverse events in either group. Colchicine: 1.0mg loading dose, followed approximately half a day later by 0.5mg twice daily for 10 doses, and then 0.5 mg once daily for four doses. Aspirin: 100mg daily for 10 days. Both groups received probiotics and acetaminophen.
Mar 2024, The Kurume Medical J., https://www.jstage.jst.go.jp/article/kurumemedj/advpub/0/advpub_MS7012003/_article, https://c19p.org/inokuchi
848. Sainz-Amo et al., COVID-19 in Parkinson’s disease: what holds the key?
211 patient vitamin D prophylaxis study: 33% lower severe cases (p=0.45) and 44% fewer cases (p=0.23).Case control study with 39 COVID+ and 172 COVID- Parkinson's disease patients in Spain, showing positive and severe cases being less likely to use vitamin D supplementation compared to negative or mild/negative cases respectively. These differences were not statistically significant.
Oct 2020, J. Neurology, https://link.springer.com/article/10.1007/s00415-020-10272-0, https://c19p.org/sainzamo
849. Su et al., Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China
HCQ early treatment study: 85% lower progression (p=0.006), 24% faster improvement (p=0.02), and 36% improved viral clearance (p=0.001).85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, p = 0.006.
Dec 2020, BioScience Trends, https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.03340/_article/-char/ja/, https://c19p.org/su
850. Kumar et al., Efficacy of intravenous vitamin C in management of moderate and severe COVID-19: A double blind randomized placebo controlled trial
60 patient vitamin C ICU RCT: 23% lower mortality (p=0.6) and 21% lower ventilation (p=0.6).RCT 60 ICU patients in India, showing no significant difference in outcomes with vitamin C. Mortality was lower in the vitamin C arm despite having more severe cases at baseline (87% vs. 67%). 1 gram intravenous vitamin C 8 hourly for four days.
Aug 2022, J. Family Medicine and Primary Care, https://journals.lww.com/10.4103/jfmpc.jfmpc_2437_21, https://c19p.org/kumar5
851. Elalfy et al., Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1
113 patient nitazoxanide early treatment study: 87% improved viral clearance (p<0.0001).Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.
Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26880, https://c19p.org/elalfyn
852. Shah et al., Potential of the Combination of a Systemic Enzyme Complex and Probiotics administration to Combat COVID-19: A Randomized Open Label Prospective Analysis
60 patient probiotics late treatment RCT: 11% faster recovery (p=0.19) and 11% shorter hospitalization (p=0.18).Small RCT 60 patients in India, 30 treated with ImmunoSEB and ProbioSEB CSC3, showing faster recovery with treatment. CTRI/2020/09/027685, CTRI/2020/08/027168.
Feb 2021, Advances in Clinical Toxicology, https://advancedenzymesdirect.com/wp-content/uploads/2021/05/Covid-Published-paper.pdf, https://c19p.org/shah
853. Vinod et al., Effect of Aspirin Use on the Adverse Outcomes in Patients Hospitalized for COVID-19
376 patient aspirin late treatment study: 14% lower mortality (p=0.61), 30% lower ventilation (p=0.24), 40% lower progression (p=0.05), and 6% worse results (p=0.88).Retrospective 376 hospitalized COVID-19 patients in the United States showing no significant differences with aspirin. Mortality, mechanical ventilation, and hypoxia were lower with treatment, without statistical significance.
Jun 2024, Cardiology Research, http://www.cardiologyres.org/index.php/Cardiologyres/article/view/1645, https://c19p.org/vinod
854. Jung et al., Effect of hydroxychloroquine pre-exposure on infection with SARS-CoV-2 in rheumatic disease patients: A population-based cohort study
2,066 patient HCQ prophylaxis study: 59% lower mortality (p=1) and 13% more cases (p=0.86).Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information on severity is provided. 33% of the control group used HCQ within the last year. Remaining confounding by differences in the nature and severity of rheumatic disease is likely.
Dec 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20307527, https://c19p.org/jung
855. Guldemir et al., Clinical characteristics of bus drivers and field officers infected with COVID-19: A cross-sectional study from Istanbul
477 patient vitamin C prophylaxis study: 31% lower hospitalization (p=0.05).Retrospective 477 COVID+ public transportation workers in Turkey, showing lower risk of hospitalization with vitamin C use in unadjusted results.
Nov 2022, Work, https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-220292, https://c19p.org/guldemir
856. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
2,148 patient vitamin B9 prophylaxis study: 28% lower hospitalization (p=0.23) and 28% lower severe cases (p=0.16).Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin B9 prophylaxis, without statistical significance.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerb9
857. Yamamoto et al., Flight attendant occupational nutrition and lifestyle factors associated with COVID-19 incidence
52 patient diet study: 66% fewer cases (p=0.009).Retrospective 84 flight attendants, 52 reporting COVID-19 status and diet quality, showing higher risk of COVID-19 with lower self-reported diet quality.
Dec 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-04350-0, https://c19p.org/yamamoto
858. Shaw et al., COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients
144 patient HCQ prophylaxis PSM study: 13% fewer cases (p=0.006).PSM retrospective 144 alopecia patients in the USA, showing lower risk of COVID-19 with HCQ prophylaxis. The supplemental appendix is not available.
Jun 2021, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961621P0914X, https://c19p.org/shaw
859. Samajdar et al., Ivermectin and Hydroxychloroquine for Chemo-Prophylaxis of COVID-19: A Questionnaire Survey of Perception and Prescribing Practice of Physicians vis-a-vis Outcomes
309 patient ivermectin prophylaxis study: 80% fewer cases (p<0.0001).Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases are not provided, and the results are subject to survey bias. Authors also report on community prophylaxis but present only combined ivermectin/HCQ results.
Nov 2021, J. the Association of Physicians India, https://www.researchgate.net/publication/356294136_Ivermectin_and_Hydroxychloroquine_for_Chemo-Prophylaxis_of_COVID-19_A_Questionnaire_Survey_of_Perception_and_Prescribing_Practice_of_Physicians_vis-a-vis_Outcomes, https://c19p.org/samajdar
860. Espitia-Hernandez et al., Effects of Ivermectin-azithromycin-cholecalciferol combined therapy on COVID-19 infected patients: A proof of concept study
35 patient ivermectin early treatment study: 70% faster recovery (p=0.0001) and 97% improved viral clearance (p<0.0001).Small study with 28 patients treated with ivermectin + AZ + cholecalciferol and 7 control patients. All treated patients were PCR- at day 10 while all control patients remained PCR+. The mean duration of symptoms was 3 days in the treatment group and 10 days in the control group.
Aug 2020, Biomedical Research, https://www.biomedres.info/biomedical-research/effects-of-ivermectinazithromycincholecalciferol-combined-therapy-on-covid19-infected-patients-a-proof-of-concept-study-14435.html, https://c19p.org/espitiahernandez
861. Rubio-Sánchez et al., Prognostic factors for the severity of SARS-CoV-2 infection
197 patient HCQ late treatment study: 40% lower severe cases (p=0.02).Retrospective 197 hospitalized COVID-19 patients in Spain, showing lower progression to pneumonia with HCQ in unadjusted results.
Mar 2021, Advances in Laboratory Medicine / Avances en Medicina de Laboratorio, https://www.degruyter.com/document/doi/10.1515/almed-2021-0017/html, https://c19p.org/rubiosanchez
862. Chevalier et al., CovAID: Identification of factors associated with severe COVID-19 in patients with inflammatory rheumatism or autoimmune diseases
1,213 patient HCQ prophylaxis study: 35% lower mortality (p=0.19) and 19% lower hospitalization (p=0.36).Retrospective 1,213 rheumatic disease patients in France, showing lower risk of mortality and severe cases with HCQ use in univariate analysis, without statistical significance.
Mar 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1152587/full, https://c19p.org/chevalier
863. Hou et al., COVID-19 Illness Severity in the Elderly in Relation to Vegetarian and Non-vegetarian Diets: A Single-Center Experience
509 patient diet study: 72% lower severe cases (p=0.23) and 11% fewer moderate/severe cases (p=0.66).Retrospective 509 COVID-19 patients in Taiwan, showing higher risk of critical COVID-19 cases with non-vegetarian diets.
Apr 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.837458/full, https://c19p.org/hou
864. Gonzalez et al., The Prognostic Value of Eosinophil Recovery in COVID-19: A Multicentre, Retrospective Cohort Study on Patients Hospitalised in Spanish Hospitals
9,644 patient HCQ late treatment study: 27% lower mortality (p=0.06).Retrospective study focused on eosinophil recovery with 9,644 hospitalized patients in Spain, showing lower mortality for HCQ (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model including potential confounding factors, HCQ and AZ are associated with lower mortality, HCQ OR 0.662, p=0.057.
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.18.20172874v1, https://c19p.org/gonzalez2
607 patient HCQ late treatment study: 20% lower mortality (p=0.36).
Retrospective 607 patients reporting results for early outpatient HCQ use with mortality odds ratio OR 0.092 [0.022-0.381], p = 0.001 (65 patients), and for hospital use, mortality odds ratio OR 0.737 [0.38-1.41], p = 0.36 (558 patients). Median age 69.
Oct 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303357, https://c19p.org/guisadovasco
866. Farahani et al., Effect of fluvoxamine on preventing neuropsychiatric symptoms of post COVID syndrome in mild to moderate patients, a randomized placebo-controlled double-blind clinical trial
100 patient fluvoxamine long COVID RCT: 51% lower PASC (p=0.06).RCT 100 mild/moderate COVID-19 outpatients in Iran, showing lower post COVID symptoms 12 weeks after infection, statistically significant only for fatigue with the small sample size. All symptoms may occur for non-COVID-19 reasons, smell/taste disorder may be the most likely to be related to COVID-19 infection. Fluvoxamine 100mg daily for 10 days.
Mar 2023, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08172-5, https://c19p.org/farahani
867. Raabe et al., Hydroxychloroquine pre-exposure prophylaxis to prevent SARS-CoV-2 among health care workers at risk for SARS-CoV-2 exposure: A nonrandomized controlled trial
130 patient HCQ prophylaxis study: 82% fewer symptomatic cases (p=0.17).Small prophylaxis study with 130 healthcare workers in the USA, showing lower symptomatic cases with HCQ prophylaxis, without statistical significance. HCQ participants were significantly older. The only symptomatic HCQ patient reported headache only as a potential COVID-19 symptom.
Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277058, https://c19p.org/raabe
868. Pływaczewska-Jakubowska et al., Lifestyle, course of COVID-19, and risk of Long-COVID in non-hospitalized patients
1,847 patient exercise study: 11% fewer moderate/severe cases (p=0.3) and 14% lower PASC (p=0.24).Retrospective 1,847 COVID+ patients in Poland, showing no significant difference in moderate/severe cases with physical activity. Hospitalized patients were excluded.
Oct 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.1036556/full, https://c19p.org/plywaczewska
869. Delić et al., Effects of Different Inhalation Therapy on Ventilator-Associated Pneumonia in Ventilated COVID-19 Patients: A Randomized Controlled Trial
91 patient N-acetylcysteine ICU RCT: 14% lower mortality (p=0.37).RCT mechanically ventilated patients in Croatia, 39 treated with N-acetylcysteine and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from [repozitorij.mefst.unist.hr].
May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delic
870. Ali et al., Cardiovascular complications are the primary drivers of mortality in hospitalized patients with SARS-CoV-2 community-acquired pneumonia
1,645 patient aspirin prophylaxis study: 28% lower mortality (p=0.07).Retrospective 1,645 hospitalized patients in the USA, showing lower mortality with aspirin use, without statistical significance.
Nov 2022, Chest, https://www.sciencedirect.com/science/article/pii/S0012369222041617, https://c19p.org/ali7
871. Guglielmetti et al., Treatment for COVID-19—a cohort study from Northern Italy
600 patient HCQ late treatment study: 28% lower mortality (p=0.1).Retrospective 600 hospitalized patients in Italy, showing lower mortality with HCQ treatment, without reaching statistical significance (p = 0.1).
Oct 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-00243-4/, https://c19p.org/guglielmetti2
872. Arfijanto et al., Duration of SARS-CoV-2 RNA Shedding Is Significantly Influenced by Disease Severity, Bilateral Pulmonary Infiltrates, Antibiotic Treatment, and Diabetic Status: Consideration for Isolation Period
162 patient favipiravir late treatment study: 51% improved viral clearance (p=0.02).Retrospective 162 hospitalized COVID-19 patients in Indonesia, showing lower incidence of delayed viral clearance with favipiravir treatment in unadjusted results.
May 2023, Pathophysiology, https://www.mdpi.com/1873-149X/30/2/16, https://c19p.org/arfijanto
873. Valerio Pascua et al., A multi-mechanism approach reduces length of stay in the ICU for severe COVID-19 patients
65 patient colchicine ICU study: 23% lower mortality (p=0.6) and 40% shorter ICU admission (p=0.03).Retrospective 65 ICU patients in the USA and Honduras, showing shorter ICU stay with combined treatment including colchicine, LMWH, tocilizumab, dexamethasone, and methylprednisolone.
Jan 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245025, https://c19p.org/valeriopascua
874. Lano et al., Risk factors for severity of COVID-19 in chronic dialysis patients from a multicentre French cohort
122 patient HCQ late treatment study: 33% lower mortality (p=0.28) and 39% lower combined mortality/ICU admission (p=0.23).33% lower mortality with HCQ+AZ, p=0.28. Retrospective 122 French dialysis patients. 69% lower combined mortality/ICU, p=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment).
Oct 2020, Clinical Kidney J., October 2020, 878–888, https://academic.oup.com/ckj/article/13/5/878/5934808, https://c19p.org/lano
875. Yip et al., Metformin Does Not Reduce Hospitalisation for COVID-19
12,331 patient metformin prophylaxis PSM study: 7% lower combined mortality/hospitalization (p=0.61) and 15% lower progression (p=0.16).Retrospective 12,331 diabetes patients in Hong Kong, showing no significant difference in outcomes with metformin use.
Sep 2022, SSRN Electronic J., https://www.ssrn.com/abstract=4225660, https://c19p.org/yip2
876. Graves et al., A Cetylpyridinium Chloride Oral Rinse Reduces Salivary Viral Load in Randomized Controlled Trials
32 patient povidone-iodine late treatment RCT: 85% improved viral clearance (p=0.65).Two RCTs with a total of 247 recently diagnosed COVID-19 patients showing a significant reduction in salivary SARS-CoV-2 viral load 30 minutes after rinsing with a cetylpyridinium chloride (CPC) mouthwash compared to rinsing with saline or water. No significant difference was seen 60 minutes post-rinse or with other mouthwashes. Supplementary tables 9 and 10 show that viral load was lower for all treatments at 60 minutes (including saline and water), without statistical significance. Authors only report short-term viral load, no clinical or longer term results are reported. Patients were late stage, 6-7 days post symptoms, when there has likely been significant viral spread to other tissues.
Dec 2024, JDR Clinical & Translational Research, https://journals.sagepub.com/doi/10.1177/23800844241296840, https://c19p.org/gravesp
877. Al-kuraishy et al., The potential therapeutic effect of metformin in type 2 diabetic patients with severe COVID-19
100 patient metformin prophylaxis study: 78% lower mortality (p=0.01) and 41% improved recovery (p=0.0002).Prospective study of 60 hospitalized type 2 diabetes patients with COVID-19 on metformin monotherapy compared to 40 patients on other diabetes treatments, showing significantly lower inflammatory biomarkers, oxidative stress, and mortality, and improvements in radiological and clinical outcomes with metformin. Confounding due to differences in baseline characteristics may be significant.
Nov 2023, European Review for Medical and Pharmacological Sciences, https://doi.org/10.26355/eurrev_202312_34583, https://c19p.org/alkuraishy3
878. Schmidt et al., Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19
477 patient various antiandrogen prophylaxis PSM study: 20% lower mortality (p=0.41) and 2% lower severe cases (p=0.94).Retrospective 1,106 prostate cancer patients, showing no significant differences in COVID-19 outcomes with ADT.
Nov 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786026, https://c19p.org/schmidt
879. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
2,148 patient vitamin A prophylaxis study: 21% lower hospitalization (p=0.4) and 21% lower severe cases (p=0.36).Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with vitamin A prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimera
880. Faíco-Filho et al., No benefit of hydroxychloroquine on SARS-CoV-2 viral load reduction in non-critical hospitalized patients with COVID-19
66 patient HCQ late treatment study: 81% improved viral reduction rate (p=0.4).Viral load comparison for 34 HCQ and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for beneficial effects. While not achieving statistical significance, results show faster recovery with HCQ. The greatest benefit is seen mid-recovery as expected for an effective treatment: Δt7-12: 81% improvement with HCQ Δt<7: 24% improvement with HCQ For Δt>12, everyone has recovered so there is no room for improvement. Since the HCQ group started slightly higher the improvement is slightly less. Most participants have also dropped out by this test, with only 6 HCQ and 9 control remaining (also suggesting HCQ patients recovered faster).
Jun 2020, Braz J Microbiol, https://link.springer.com/article/10.1007/s42770-020-00395-x, https://c19p.org/faicofilho
881. Mamari et al., The effect of Chronic treatments of Type 2-diabetes mellitus on COVID-19 Morbidity and Symptoms Severity
109 patient metformin prophylaxis study: 50% lower mortality (p=0.01).Retrospective 109 hospitalized COVID-19 patients in Syria, 68 with diabetes, showing significantly lower mortality with metformin vs. sulfonylureas, and significantly higher mortality with discontinuation of metformin.
Nov 2023, Research J. Pharmacy and Technology, https://www.rjptonline.org/HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmacy%20and%20Technology;PID=2023-16-11-25, https://c19p.org/mamari
882. Darand et al., The association between adherence to unhealthy plant-based diet and risk of COVID-19: a cross-sectional study
8,157 patient diet study: 37% fewer cases (p=0.03).Analysis of 8,157 adults showing significantly higher risk of COVID-19 with higher adherence to an unhealthy diet, characterized by higher intake of less healthy foods such as fruit juices, refined grains, potatoes, and sugar-sweetened beverages. The association was independent of socio-demographic status and BMI.
Nov 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10115-7, https://c19p.org/darand2
883. Pływaczewska-Jakubowska et al., Lifestyle, course of COVID-19, and risk of Long-COVID in non-hospitalized patients
1,847 patient sleep study: 17% fewer moderate/severe cases (p=0.06) and 7% lower PASC (p=0.51).Retrospective 1,847 COVID+ patients in Poland, showing lower moderate/severe cases with improved sleep, without statistical significance. Hospitalized patients were excluded.
Oct 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.1036556/full, https://c19p.org/plywaczewskasl
884. Bejan et al., DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
9,267 patient zinc prophylaxis study: 18% lower ventilation (p=0.78) and 30% lower ICU admission (p=0.6).Retrospective 9,748 COVID-19 patients in the USA showing lower ventilation and ICU admission with zinc prophylaxis, without statistical significance.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanz
885. Byakika-Kibwika et al., Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial
105 patient HCQ late treatment RCT: no change in recovery (p=0.91) and 29% improved viral clearance (p=0.47).Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatment to make improvements. Time since symptom onset is not specified, but the distribution of symptoms at baseline suggests that the enrollment is relatively late within a cohort of low risk patients.
Jun 2021, Research Square, https://www.researchsquare.com/article/rs-506195/v1, https://c19p.org/byakikakibwika
886. Shinada et al., Longitudinal Analysis of Neutralizing Potency against SARS-CoV-2 in the Recovered Patients after Treatment with or without Favipiravir
34 patient favipiravir late treatment study: 7% shorter hospitalization (p=0.84) and 55% faster viral clearance (p=0.04).Retrospective 17 COVID+ patients treated with favipiravir and 17 matched controls in Japan, showing faster viral clearance with treatment. Favipiravir 3600mg day one, 1600mg per day for up to 14 days.
Mar 2022, Viruses, https://www.mdpi.com/1999-4915/14/4/670, https://c19p.org/shinada
887. Hassaniazad et al., Efficacy and safety of favipiravir plus interferon-beta versus lopinavir/ritonavir plus interferon-beta in moderately ill patients with COVID-19: A randomized clinical trial
63 patient favipiravir late treatment RCT: 68% lower mortality (p=0.15), 35% lower ICU admission (p=0.51), 25% shorter hospitalization (p=0.14), and 18% improved viral clearance (p=0.24).RCT comparing favipiravir and lopinavir/ritonavir, showing no significant differences. All patients received interferon-beta. Favipiravir 1600mg bid for the first day and 600mg bid for the following 4 days.
Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27724, https://c19p.org/hassaniazad2
888. Fogleman et al., A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19
66 patient melatonin late treatment RCT: 17% improved recovery (p=0.38).Early terminated low-risk patient RCT with 32 low-dose vitamin C, 32 melatonin, and 34 placebo patients, showing faster resolution of symptoms with melatonin in spline regression analysis, and no significant difference for vitamin C. All patients recovered with no serious outcomes reported. Baseline symptoms scores were higher in the melatonin and vitamin C arms (median 27 and 24 vs. 18 for placebo).
Jul 2022, The J. the American Board of Family Medicine, http://www.jabfm.org/lookup/doi/10.3122/jabfm.2022.04.210529, https://c19p.org/fogleman
889. Micek et al., Association of dietary intake of polyphenols, lignans, and phytosterols with immune-stimulating microbiota and COVID-19 risk in a group of Polish men and women
95 patient diet study: 70% fewer cases (p=0.09).Dietary analysis of 95 adults in Poland, showing lower risk of COVID-19 with higher intake of polyphenols, lignans, and phytosterols. Results were statistically significant for total phytosterols, secoisolariciresinol, β-sitosterol, matairesinol, and stigmasterol. Authors suggest that beneficial effects on gut microbiota and immune function may contribute to the lower risk.
Aug 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1241016/full, https://c19p.org/micek
890. Aldwihi et al., Patients’ Behavior Regarding Dietary or Herbal Supplements before and during COVID-19 in Saudi Arabia
738 patient nigella sativa early treatment study: 24% lower hospitalization (p=0.09).Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihins
891. Rothman et al., Time to Sustained Recovery Among Outpatients With COVID-19 Receiving Montelukast vs Placebo
1,250 patient montelukast late treatment RCT: 1% fewer combined hospitalization/ER visits (p=1), 48% higher progression (p=0.29), and 2% improved recovery (p=0.72).RCT 1,250 outpatients with mild to moderate COVID-19 showing no significant difference in time to sustained recovery with montelukast treatment. There were no deaths and only 2 hospitalizations in each group. Notably, results were better with patients that had mild COVID-19 at baseline compared to moderate/severe cases, and overall efficacy is reduced by poor results with extremely late treatment 9 days after onset, and with patients that had no symptoms at baseline. Authors note the treatment drug was voluntarily recalled and replaced from another source but do not report why the drug was recalled. Authors describe previous research testing 10mg and 20mg doses, noting that only 20mg showed improved pulmonary function testing, however authors do not indicate why they chose to test the lower dose for COVID-19. It is unclear why authors only report all-cause hospitalization and urgent care and do not report COVID-19 specific outcomes. Given the low rate of urgent care visits and..
May 2024, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825081, https://c19p.org/rothman
892. El-Badrawy et al., Role of Sodium Bicarbonate as Adjuvant Treatment of Nonsevere Computed Tomography-identified COVID-19 Pneumonia: A Preliminary Report
182 patient alkalinization late treatment study: 57% lower mortality (p=0.37), 39% lower progression (p=0.52), and 19% improved recovery (p=0.03).Prospective study of 182 COVID-19 pneumonia patients, 127 treated with sodium bicarbonate inhalation and nasal drops, showing significantly faster recovery and improved CT scores with treatment. Authors note that contacts of index cases also received sodium bicarbonate treatment, with none reporting COVID-19. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Jun 2022, Indian J. Respiratory Care, https://www.ijrc.in/abstractArticleContentBrowse/IJRC/98/10/3/30725/abstractArticle/Article, https://c19p.org/elbadrawy2
893. El-Badrawy et al., Role of Sodium Bicarbonate as Adjuvant Treatment of Nonsevere Computed Tomography-identified COVID-19 Pneumonia: A Preliminary Report
182 patient sodium bicarbonate late treatment study: 57% lower mortality (p=0.37), 39% lower progression (p=0.52), and 19% improved recovery (p=0.03).Prospective study of 182 COVID-19 pneumonia patients, 127 treated with sodium bicarbonate inhalation and nasal drops, showing significantly faster recovery and improved CT scores with treatment. Authors note that contacts of index cases also received sodium bicarbonate treatment, with none reporting COVID-19. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).
Jun 2022, Indian J. Respiratory Care, https://www.ijrc.in/abstractArticleContentBrowse/IJRC/98/10/3/30725/abstractArticle/Article, https://c19p.org/elbadrawy2sb
894. Samimagham et al., The Efficacy of Famotidine in improvement of outcomes in Hospitalized COVID-19 Patients: A phase III randomised clinical trial
20 patient famotidine late treatment RCT: 33% shorter hospitalization (p=0.04) and no change in recovery (p=1).Very small RCT with 20 patients in Iran, showing shorter hospitalization time with famotidine treatment. There was no mortality or ICU admission. Famotidine 160mg four times a day. IRCT20200509047364N2.
Apr 2021, Research Square, https://www.researchsquare.com/article/rs-462937/v1, https://c19p.org/samimagham
895. Dulcey et al., Long-Term Hydroxychloroquine and Its Association with Covid-19 Infection, a Cohort Study from a South American Hospital
967 patient HCQ prophylaxis study: 21% fewer cases (p=0.27).PSM retrospective 322 rheumatological patients on HCQ and 645 matched controls, showing lower risk of COVID-19 with treatment, without statistical significance. Authors mention lower mortality with HCQ but do not provide details. Only an abstract is available.
May 2023, J. Clinical Rheumatology, https://journals.lww.com/10.1097/RHU.0000000000001986, https://c19p.org/dulcey
896. Alizadeh et al., A Pilot Study on Controlling Coronavirus Disease 2019 (COVID-19) Inflammation Using Melatonin Supplement
31 patient melatonin early treatment RCT: 73% improved recovery (p=0.06).Small RCT 31 mild/moderate COVID-19 outpatients in Iran, 14 treated with melatonin, showing improved recovery with treatment.
May 2021, Iranian J. Allergy, Asthma and Immunology, https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3086, https://c19p.org/alizadeh
897. Tan et al., A retrospective comparison of drugs against COVID-19
285 patient HCQ late treatment study: 35% shorter hospitalization (p=0.04).Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ.
Dec 2020, Virus Research, https://www.sciencedirect.com/science/article/abs/pii/S0168170220311692, https://c19p.org/tan2
898. Becetti et al., Prevalence of coronavirus disease 2019 in a multiethnic cohort of patients with autoimmune rheumatic diseases in Qatar
700 patient HCQ prophylaxis study: 37% fewer cases (p=0.17).Retrospective 700 patients with autoimmune rheumatic disease in Qatar, showing lower risk of COVID-19 with HCQ use, without statistical significance. For patients having close contact with COVID-19 cases, there was a statistically significant association with HCQ use and lower risk of COVID-19 in unadjusted results.
Aug 2022, Qatar Medical J., https://www.qscience.com/content/journals/10.5339/qmj.2022.37, https://c19p.org/becetti
899. Olawore et al., Risk of Post-Acute Sequelae of SARS-CoV-2 Infection (PASC) Among Patients with Type 2 Diabetes Mellitus on Anti-Hyperglycemic Medications
7,047 patient metformin prophylaxis study: 19% lower PASC (p=0.29).Retrospective 7,047 outpatients with type 2 diabetes showing a lower risk of PASC (long COVID) with metformin compared to sulfonylurea or DPP-4 inhibitor use, without statistical significance.
May 2024, Clinical Epidemiology, https://www.dovepress.com/risk-of-post-acute-sequelae-of-sars-cov-2-infection-pasc-among-patient-peer-reviewed-fulltext-article-CLEP, https://c19p.org/olawore
900. Alberici et al., A report from the Brescia Renal COVID Task Force on the clinical characteristics and short-term outcome of hemodialysis patients with SARS-CoV-2 infection
94 patient HCQ late treatment study: 43% lower mortality (p=0.12).Analysis of 94 hemodialysis COVID-19 positive patients, showing lower mortality with HCQ treatment, not reaching statistical significance.
May 2020, Kidney Int., 20-26, July 1, 2020, https://www.kidney-international.org/article/S0085-2538(20)30508-1/fulltext, https://c19p.org/alberici
901. Belmont et al., COVID-19 PrEP HCW HCQ Study
80 patient HCQ prophylaxis study: 79% fewer symptomatic cases (p=0.21).Prospective study of HCQ prophylaxis in the USA, with 56 HCQ patients and 24 control patients, showing no significant differences. NCT04354870
Oct 2021, ClinicalTrials.gov, NCT04354870, https://clinicaltrials.gov/ct2/show/results/NCT04354870, https://c19p.org/belmont
902. Jalal et al., Effectiveness of colchicine among patients with COVID-19 infection: A randomized, open-labeled, clinical trial
80 patient colchicine late treatment RCT: 24% shorter hospitalization (p=0.009).Open label RCT of colchicine showing improved recovery with treatment. Only the abstract is currently available. Colchicine 0.5mg bid for 14 days.
May 2022, Indian J. Rheumatology, http://www.indianjrheumatol.com/preprintarticle.asp?id=344591;type=0, https://c19p.org/jalal
90 patient metformin prophylaxis study: 45% lower mortality (p=0.1).
Retrospective 90 hospitalized COVID-19 patients with diabetes in Italy, showing lower mortality with metformin use, without statistical significance.
Oct 2020, Diabetes Care, https://diabetesjournals.org/care/article/43/12/3042/30894/Impact-of-Comorbidities-and-Glycemia-at-Admission, https://c19p.org/mirani
904. Wang et al., Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study
249 patient azvudine early treatment study: 20% lower mortality (p=0.44) and 3% lower progression (p=0.91).Retrospective 249 elderly patients with severe COVID-19, 128 treated with azvudine, 66 treated with paxlovid, and 55 receiving neither treatment, showing no significant differences for Ct value changes, progression, or survival for either treatment. Early viral decline was faster with paxlovid, without statistical significance.
Feb 2024, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537024000476, https://c19p.org/wang25
905. Mohamed et al., Early viral clearance among COVID-19 patients when gargling with povidone-iodine and essential oils: a pilot clinical trial
10 patient povidone-iodine early treatment RCT: 86% improved viral clearance (p=0.17).Tiny RCT with 5 PVP-I patients, gargling 30 seconds, 3x per day, and 5 control patients (essential oils and tap water were also tested), showing improved viral clearance with PVP-I.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.07.20180448v1, https://c19p.org/mohamed
906. Din Ujjan et al., The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19—Results from a pragmatic randomized clinical trial
50 patient curcumin early treatment RCT: 29% improved recovery (p=0.11) and 91% improved viral clearance (p=0.05).Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.
Jan 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full, https://c19p.org/dinujjant
907. Din Ujjan et al., The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19—Results from a pragmatic randomized clinical trial
50 patient quercetin early treatment RCT: 29% improved recovery (p=0.11) and 91% improved viral clearance (p=0.05).Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.
Jan 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full, https://c19p.org/dinujjanq
908. Opdam et al., Identification of Risk Factors for COVID-19 Hospitalization in Patients with Anti-Rheumatic Drugs: Results from a Multicenter Nested Case Control Study
477 patient HCQ prophylaxis study: 45% lower hospitalization (p=0.18).Retrospective 81 cases and 396 controls among rheumatic disease patients in the Netherlands, showing lower risk of hospitalization with HCQ prophylaxis, without statistical significance.
Feb 2022, Clinical Pharmacology & Therapeutics, https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2551, https://c19p.org/opdam
910. Zhang et al., Pilot Trial of High-dose vitamin C in critically ill COVID-19 patients (preprint 8/10/2020)
56 patient vitamin C ICU RCT: 50% lower mortality (p=0.2).Small RCT for high dose vitamin C for ICU patients showing reduced (but not statistically significant) mortality. Dosage was 12g of vitamin C/50ml every 12 hours for 7 days at a rate of 12ml/hour.
Aug 2020, Annals of Intensive Care, https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00792-3, https://c19p.org/zhang
911. Seneviratne et al., Efficacy of commercial mouth-rinses on SARS-CoV-2 viral load in saliva: randomized control trial in Singapore
6 patient povidone-iodine late treatment RCT: 33% improved viral load (p=0.01).Small mouthwash RCT with 4 PVP-I patients and 2 water patients concluding that PVP-I may have a sustained effect on reducing the salivary SARS-CoV-2 level in COVID-19 patients. ISRCTN95933274.
Dec 2020, Infection, https://link.springer.com/article/10.1007/s15010-020-01563-9, https://c19p.org/seneviratne
912. Beigmohammadi et al., The effect of supplementation with vitamins A, B, C, D, and E on disease severity and inflammatory responses in patients with COVID-19: a randomized clinical trial
60 patient vitamin D ICU RCT: 89% lower mortality (p=0.11), 41% lower hospitalization (p=0.25), and 45% improved recovery (p=0.001).Small RCT 60 ICU patients in Iran, 30 treated with vitamins A, B, C, D, and E, showing significant improvement in SOFA score and several inflammatory markers at day 7 with treatment. 5,000 IU vitamin A daily, 600,000 IU vitamin D once, 300 IU of vitamin E twice a day, 500 mg vitamin C four times a day, and one ampule daily of B vitamins [thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg].
Nov 2021, Trials, https://link.springer.com/article/10.1186/s13063-021-05795-4/fulltext.html, https://c19p.org/beigmohammadi2
913. Oku et al., Risk factors for hospitalization or mortality for COVID-19 in patients with rheumatic diseases: Results of a nation-wide JCR COVID-19 registry in Japan
220 patient HCQ prophylaxis study: 92% lower mortality (p=1) and 12% lower hospitalization (p=0.34).Retrospecttive 220 COVID-19 patients with rheumatic disease in Japan, showing lower mortality and hospitalization with HCQ prophylaxis, without statistical significance.
Sep 2022, Modern Rheumatology, https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roac104/6692611, https://c19p.org/oku
914. Huvemek et al., Kovid-19 - Huvemek® Phase 2 clinical trial
100 patient ivermectin late treatment RCT: 32% greater improvement (p=0.28).Multicenter double-blind RCT with 100 hospitalized patients in Bulgaria showing faster viral clearance, greater clinical improvement, and improved biomarkers with treatment. Limited data has been reported currently. No serious adverse events were observed.
Mar 2021, Huvemek, Press Release, https://huvemec.bg/covid-19-huvemec-klinichno-izpitanie/za-isledvaneto/, https://c19p.org/petkov
915. Krishnan et al., Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia
152 patient vitamin C late treatment study: 31% lower mortality (p=0.04).Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnanc
916. Hernandez-Cardenas et al., Hydroxychloroquine for the treatment of severe respiratory infection by COVID-19: a randomized controlled trial
214 patient HCQ late treatment RCT: 12% lower mortality (p=0.66).Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no significant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43 [0.09-2.03]. Table 4 shows different results to the abstract - table 4 adjusted HR 0.80 [0.51-1.23], abstract HR 0.88 [0.51-1.53]. There was no significant difference in severe adverse events.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.01.21250371v1, https://c19p.org/hernandezcardenas
917. Mohsin et al., Lifestyle and Comorbidity-Related Risk Factors of Severe and Critical COVID-19 Infection: A Comparative Study Among Survived COVID-19 Patients in Bangladesh
1,500 patient exercise study: 19% lower severe cases (p=0.04).Retrospective 1,500 COVID+ patients in Bangladesh, showing lower risk of severe cases with regular exercise in unadjusted results.
Sep 2021, Infection and Drug Resistance, https://www.dovepress.com/lifestyle-and-comorbidity-related-risk-factors-of-severe-and-critical--peer-reviewed-fulltext-article-IDR, https://c19p.org/mohsinex
918. Núñez-Gil et al., Mortality risk assessment in Spain and Italy, insights of the HOPE COVID-19 registry
954 patient HCQ late treatment study: 8% lower mortality (p=0.005).Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, p=0.005.
Nov 2020, Internal and Emergency Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649104/, https://c19p.org/nunezgil
919. Gordon et al., Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms
206 patient indomethacin late treatment PSM study: 67% lower hospitalization (p=0.34) and 57% lower progression (p=0.21).Analysis of interactions between viral and human proteins for SARS-CoV-2, SARS-CoV-1, and MERS-CoV and genetic screening to identify host factors that enhance or inhibit viral infection. Authors predict indomethacin will have antiviral activity for SARS-CoV-2 and perform a retrospective study of patients in the USA that started treatment within 21 days after COVID-19 infection - 103 with indomethacin, and 103 using a celecoxib, a clinically similar drug without predicted antiviral activity. There were fewer hospital visits and hospitalizations with indomethacin, without statistical significance.
Dec 2020, Science, https://www.science.org/doi/10.1126/science.abe9403, https://c19p.org/gordon3
920. Lambermont et al., Predictors of Mortality and Effect of Drug Therapies in Mechanically Ventilated Patients With Coronavirus Disease 2019: A Multicenter Cohort Study
247 patient HCQ late treatment study: 32% lower mortality (p=0.46).Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox regression. The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but does not specify the adjusted risk values.
Nov 2020, Critical Care Explorations, https://journals.lww.com/ccejournal/Fulltext/2020/12000/Predictors_of_Mortality_and_Effect_of_Drug.10.aspx, https://c19p.org/lambermont
921. Silverii et al., Is Metformin Use Associated with a More Favorable COVID-19 Course in People with Diabetes?
524 patient metformin prophylaxis study: 29% lower mortality (p=0.5).Retrospective 524 hospitalized COVID-19 patients with diabetes in Italy, showing lower risk of mortality with metformin use, without statistical significance. The results adjusted only for COVID-19 MRS differ between the text and Figure 2.
Mar 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/7/1874, https://c19p.org/silverii
922. Klebanov et al., Antimalarials are not Effective as Pre-Exposure Prophylaxis for COVID-19: A Retrospective Matched Control Study
62,069 patient HCQ prophylaxis study: 31% lower mortality (p=0.8) and 6% more cases (p=0.7).Retrospective 3,074 patients with antimalarial prescriptions and 58,955 matched controls, showing no significant differences with antimalarial prophylaxis for PCR+ cases (99% HCQ). Authors provide only PCR+ and mortality outcomes, and do not provide intermediate clinical outcomes that may show a statistically significant benefit. Authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri] (for symptomatic disease).
Jun 2023, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961623P0840X, https://c19p.org/klebanov
923. Llenas-García et al., Ivermectin Effect on In-Hospital Mortality and Need for Respiratory Support in COVID-19 Pneumonia: Propensity Score-Matched Retrospective Study
192 patient ivermectin late treatment study: 17% lower mortality (p=0.82), 18% lower need for oxygen therapy (p=0.37), 23% lower progression (p=0.52), and 4% higher ICU admission (p=0.92).Retrospective 96 late stage patients receiving a single dose of 200 μg/kg ivermectin for strongyloides and 96 matched controls, showing no significant difference in outcomes. Authors note that this may be due to the low dose used.
May 2023, Viruses, https://www.mdpi.com/1999-4915/15/5/1138, https://c19p.org/llenasgarcia
924. Onal et al., Treatment of COVID-19 patients with quercetin: a prospective, single center, randomized, controlled trial
429 patient quercetin late treatment RCT: 94% lower ICU admission (p=0.39) and 78% higher hospital discharge (p=0.1).RCT 447 moderate-to-severe hospitalized patients in Turkey, 52 treated with quercetin, bromelain, and vitamin C, showing no statistically significant difference in clinical outcomes.
Jan 2021, Turk. J. Biol.-529, https://journals.tubitak.gov.tr/biology/vol45/iss7/13/, https://c19p.org/onal
925. Cloosterman et al., Running behavior and symptoms of respiratory tract infection during the COVID-19 pandemic
2,586 patient sleep study: 32% fewer symptomatic cases (p=0.09).Analysis of 2,586 participants of a running injury prevention RCT in the Netherlands, showing higher risk of COVID-19 symptoms with sleep disturbance.
Oct 2020, J. Science and Medicine in Sport, https://www.sciencedirect.com/science/article/pii/S144024402030788X, https://c19p.org/cloostermansl
926. Aldwihi et al., Patients’ Behavior Regarding Dietary or Herbal Supplements before and during COVID-19 in Saudi Arabia
738 patient zinc early treatment study: 24% lower hospitalization (p=0.16).Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihiz
927. Salmasi et al., Efficacy of oral indomethacin in the treatment of COVID-19 infection; a randomized clinical trial
45 patient indomethacin late treatment RCT: 66% lower ventilation (p=1) and 40% slower recovery (p=0.52).Very small RCT with 22 indomethacin and 23 control patients, showing no significant difference in outcomes. All patients were treated with HCQ.
Jan 2022, Immunopathologia Persa, https://immunopathol.com/Inpress/ipp-29284.pdf, https://c19p.org/salmasi
928. Tabarsi et al., Favipiravir Effects on the Control of Clinical Symptoms of Hospitalized COVID-19 Cases: An Experience with Iranian Formulated Dosage Form
62 patient favipiravir late treatment RCT: 41% lower ICU admission (p=0.36), 6% improved recovery (p=0.76), and 25% shorter hospitalization (p=0.03).Small 62 patient late stage RCT in Iran comparing favipiravir and lopinavir/ritonavir, showing significant improvement in fever, cough, and dyspnea with favipiravir on day 5. There was no significant difference in mortality, ICU admission, or chest CT improvement. IRCT20151227025726N14.
Sep 2021, Iranian J. Pharmaceutical Research, http://ijpr.sbmu.ac.ir/article_1101552.html, https://c19p.org/tabarsi
929. D'Arminio Monforte et al., Effectiveness of Hydroxychloroquine in COVID-19 disease: A done and dusted situation?
539 patient HCQ late treatment study: 34% lower mortality (p=0.12).Retrospective 539 COVID-19 hospitalized patients in Milan, with treatment a median of 1 day after admission, showing lower mortality with HCQ and with HCQ+AZ, with statistical significance only for HCQ+AZ.
Jul 2020, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(20)30600-7/fulltext, https://c19p.org/darminiomonforte
242 patient zinc late treatment study: 34% lower mortality (p=0.09).
Retrospective 242 hospitalized patients in the USA showing adjusted hazard ratio for zinc treatment, aHR 0.66 [0.41-1.07]. [ncbi.nlm.nih.gov] notes that the study would be more informative if baseline serum zinc levels were known.
Jul 2020, Chest, https://journal.chestnet.org/article/S0012-3692(20)31961-9/fulltext, https://c19p.org/yao2
931. Hussein et al., The Proportion and Associated Factors for Mortality among COVID-19 Infection with Diabetes in Iraq
545 patient metformin prophylaxis study: 64% lower mortality (p=0.05).Retrospective 545 hospitalized COVID-19 patients with diabetes showing high mortality (33%). Metformin, SGLT inhibitors, and DPP4 inhibitors were associated with lower mortality compared with insulin.
Jun 2024, The Review of Diabetic Studies, https://diabeticstudies.org/menuscript/index.php/RDS/article/view/393, https://c19p.org/hussein3
70 patient camostat early treatment RCT: 37% improved recovery (p=0.15).
RCT 70 outpatients showing significantly lower symptom scores at day 6, faster recovery, and improved taste/smell, and fatigue with camostat treatment. There was no significant difference for viral load. The recovery result is from [bmcinfectdis.biomedcentral.com].
Jan 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.01.28.22270035, https://c19p.org/chupp
933. Guglielmetti et al., Severe COVID-19 pneumonia in Piacenza, Italy – a cohort study of the first pandemic wave
218 patient HCQ late treatment study: 35% lower mortality (p=0.22).Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard ratio aHR 0.65 [0.33–1.30].
Dec 2020, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034120307516, https://c19p.org/guglielmetti
934. Elalfy et al., Effect of a combination of Nitazoxanide, Ribavirin and Ivermectin plus zinc supplement (MANS.NRIZ study) on the clearance of mild COVID-1
113 patient ivermectin early treatment study: 87% improved viral clearance (p<0.0001).Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.
Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26880, https://c19p.org/elalfy
7,019 patient budesonide prophylaxis study: 33% fewer cases (p=0.1).
Retrospective 44,968 patients in South Korea, 7,019 on inhaled corticosteroids, showing no statistically significant differences in COVID-19 cases.
Sep 2021, Research Square, https://www.researchsquare.com/article/rs-72221/v1, https://c19p.org/lee2
936. Hakamifard et al., The effect of vitamin E and vitamin C in patients with COVID-19 pneumonia; a randomized controlled clinical trial
72 patient vitamin C late treatment RCT: 46% lower ICU admission (p=0.46) and 1% shorter hospitalization (p=0.82).RCT with 38 patients treated with vitamin C and vitamin E, and 34 control patients, showing lower ICU admission with treatment, but not statistically significant.
Apr 2021, Immunopathologia Persa, https://immunopathol.com/Article/ipp-22230, https://c19p.org/hakamifard
937. Mathew et al., Predictors of COVID-19 severity and outcomes in Indian patients with rheumatic diseases: a prospective cohort study
64 patient HCQ prophylaxis study: 20% lower mortality (p=0.8), no change in hospitalization (p=0.94), and 40% lower severe cases (p=0.37).Prospective study of 64 rheumatic disease patients with COVID-19, showing no significant difference in outcomes with HCQ use.
Feb 2023, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkad025/7059537, https://c19p.org/mathew
938. Bramante et al., Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis
6,256 patient metformin prophylaxis study: 12% lower mortality (p=0.65).Retrospective 6,256 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment, statistically significant only for women.
Dec 2020, The Lancet Healthy Longevity, https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(20)30033-7/fulltext, https://c19p.org/bramante
939. Greco et al., The Impact of GLP-1 RAs and DPP-4is on Hospitalisation and Mortality in the COVID-19 Era: A Two-Year Observational Study
44,977 patient metformin prophylaxis study: 22% lower hospitalization (p=0.11).Retrospective 76,764 diabetes patients in Italy, showing that patients on metformin had lower rates of COVID-19 hospitalization compared to those on insulin/insulin secretagogues, GLP-1 receptor agonists, and DPP-4 inhibitors. Metformin vs. no metformin results are not provided. The most relevant result for COVID-19 and metformin may be the DPP-4i comparison, based on the DPP-4i group being the most similar to the metformin group in terms of baseline COVID-19 risk and confounders. Patients on insulin/secretagogues may have more severe or advanced diabetes.
Aug 2023, Biomedicines, https://www.mdpi.com/2227-9059/11/8/2292, https://c19p.org/greco
940. Valizadeh et al., Nano-curcumin therapy, a promising method in modulating inflammatory cytokines in COVID-19 patients
40 patient curcumin late treatment RCT: 50% lower mortality (p=0.3).Small RCT with 40 nano-curcumin patients and 40 control patients showing lower mortality with treatment. Authors conclude that nano-curcumin may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may improve clinical outcomes.
Oct 2020, Int. Immunopharmacol., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574843/, https://c19p.org/valizadeh
941. Hosseini et al., Evaluation of Th1 and Th2 mediated cellular and humoral immunity in patients with COVID-19 following the use of melatonin as an adjunctive treatment
40 patient melatonin late treatment study: 48% faster recovery (p=0.001).40 hospitalized patients in Iran, 20 treated with melatonin, showing faster recovery and attenuated inflammatory cytokines with treatment.
May 2021, European J. Pharmacology, https://www.sciencedirect.com/science/article/abs/pii/S0014299921003460#, https://c19p.org/hosseini
942. Kirenga et al., Characteristics and outcomes of admitted patients infected with SARS-CoV-2 in Uganda
56 patient HCQ early treatment study: 26% faster recovery (p=0.2).Prospective 56 patients in Uganda, 29 HCQ and 27 control, showing 25.6% faster recovery with HCQ, 6.4 vs. 8.6 days (p = 0.20). There was no ICU admission, mechanical ventilation, or death. Treatment delay is not specified but at least a portion of patients appear to have been treated early.
Sep 2020, BMJ Open Respiratory Research, https://bmjopenrespres.bmj.com/content/7/1/e000646, https://c19p.org/kirenga
943. Domazet Bugarin et al., Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients—Randomized Controlled Trial
152 patient vitamin D ICU RCT: 21% lower mortality (p=0.2), no change in recovery (p=0.71), and 6% longer hospitalization (p=0.76).Very late stage RCT 155 ICU patients in Croatia with low vitamin D levels, showing no significant differences with 10,000IU cholecalciferol daily. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage. The baseline mean age and median WHO scores for the treatment and control groups are both higher than the respective values reported for all patients combined, which is not possible. The trial was registered after completion in May 2022.
Feb 2023, Nutrients, https://www.mdpi.com/2072-6643/15/5/1234, https://c19p.org/domazetbugarin
944. Darcis et al., Long-term clinical follow-up of patients suffering from moderate-to-severe COVID-19 infection: a monocentric prospective observational cohort study
199 patient HCQ late treatment study: 32% lower PASC (p=0.58).Prospective observational study of 199 hospitalized COVID-19 patients in Belgium showing a high prevalence of persistent symptoms including dyspnea and fatigue at 6 months after discharge. Pulmonary function tests revealed reduced diffusion capacity, and CT scans showed a high prevalence of persistent lung abnormalities at 3 months, mainly ground glass opacities. Logistic regression shows lower risk of persistent symptoms with HCQ treatment, without statistical significance.
Aug 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221005725, https://c19p.org/darcis
945. Levy et al., Frail Older Adults with Presymptomatic SARS-CoV-2 Infection: Clinical Course and Prognosis
849 patient aspirin prophylaxis study: 26% lower combined mortality/hospitalization (p=0.13).Retrospective 849 COVID-19+ patients in skilled nursing homes, showing lower risk of combined hospitalization/death with aspirin prophylaxis, not reaching statistical significance.
Jan 2022, Gerontology, https://www.karger.com/Article/FullText/521412, https://c19p.org/levye
946. Oh et al., Metformin use and risk of COVID-19 among patients with type II diabetes mellitus: an NHIS-COVID-19 database cohort study
11,892 patient metformin prophylaxis study: 26% higher mortality (p=0.3) and 28% fewer cases (p<0.0001).Retrospective 27,493 type II diabetes patients in the USA, 7,204 on metformin, showing significantly lower COVID-19 cases, but no significant difference in mortality.
Feb 2021, Acta Diabetologica, https://link.springer.com/article/10.1007%2Fs00592-020-01666-7, https://c19p.org/oh
947. Alamdari et al., Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran
459 patient HCQ late treatment study: 55% lower mortality (p=0.03).Retrospective 459 patients in Iran with 93% treated with HCQ, showing HCQ mortality RR 0.45, p = 0.028. HCQ was the only antiviral that showed a significant difference. There was relatively few control patients and the result is subject to confounding by indication. Average admission delay 5.72 days.
Sep 2020, The Tohoku J. Experimental Medicine, https://www.jstage.jst.go.jp/article/tjem/252/1/252_73/_article/-char/ja/, https://c19p.org/alamdari
948. Arboleda et al., EAST framework to promote adherence to nutritional supplementation: a strategy to mitigate COVID-19 within health workers
823 patient vitamin D prophylaxis study: 36% fewer cases (p=0.03).Prospective study of 1,063 health workers in Colombia showing lower COVID-19 infection rates with adherence to a vitamin D and C supplementation plan, however very limited baseline information is provided for the adherent vs. non-adherent groups, and no adjusted results are provided. Higher risk patients had a much higher adherence rate, suggesting that the efficacy of treatment may be significantly higher than observed.
Mar 2024, Behavioural Public Policy, https://www.cambridge.org/core/product/identifier/S2398063X24000113/type/journal_article, https://c19p.org/arboleda
949. Campbell et al., Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19
20,730 patient aspirin prophylaxis study: 3% lower mortality (p=0.06).Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic aspirin use vs. sporadic NSAID use. Since aspirin is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2
950. Boulware et al., A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19
821 patient HCQ prophylaxis RCT: 17% fewer cases (p=0.35).Remote post-exposure prophylaxis RCT reporting that "[HCQ] did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure". However, this statement is incorrect - cases were reduced, just without statistical significance - it's not possible to conclude there was no efficacy. Additionally, treatment was not within 4 days - there was up to 68 hours shipping delay as below. Further, 6 independent analyses of the data in this study indicate efficacy: [arxiv.org, blog.philbirnbaum.com, drive.google.com, longdom.org, medrxiv.org, osf.io, researchgate.net]. COVID-19 cases were reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. For more detailed analysis, see [c19hcq.org]. See also: [nejm.org]. Authors compare with treatment with folic acid. [Kaur] et al. note that folic..
Jun 2020, NEJM, June 3 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2016638, https://c19p.org/boulwarepep
951. Datta et al., No Role of HCQ in COVID-19 Prophylaxis: A Survey amongst Indian Doctors
281 patient HCQ prophylaxis study: 22% fewer cases (p=0.47).Survey of Indian doctors not finding a significant effect of HCQ prophylaxis.
Nov 2020, J. Vaccines & Vaccination, S6:1000002, https://www.longdom.org/open-access/no-role-of-hcq-in-covid19-prophylaxis-a-survey-amongst-indian-doctors.pdf, https://c19p.org/datta
952. Aldwihi et al., Patients’ Behavior Regarding Dietary or Herbal Supplements before and during COVID-19 in Saudi Arabia
738 patient curcumin early treatment study: 31% lower hospitalization (p=0.1).Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihit
953. Shoaibi et al., Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients
29,451 patient HCQ late treatment study: 15% lower mortality (p=0.001).Retrospective database analysis focused on famotidine but also showing results for HCQ users, with unadjusted mortality RR 0.85, p<0.001 (13.6% vs. 16.1%).
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.23.20199463v1, https://c19p.org/shoaibi
954. Huang et al., Effect of traditional therapeutics on prevalence and clinical outcomes of coronavirus disease 2019 in Chinese patients with autoimmune diseases
432 patient HCQ prophylaxis study: 43% lower hospitalization (p=0.09) and 6% more cases (p=0.25).Retrospective 432 autoimmune disease patients in China showing lower hospitalization with HCQ without statistical significance (OR 0.566, p=0.085) in unadjusted results, slightly higher COVID-19 cases without statistical significance, and increased cough compared with CNI.
Dec 2023, J. Translational Autoimmunity, https://www.sciencedirect.com/science/article/pii/S2589909023000400, https://c19p.org/huang7
955. Erfani et al., Vitamin B12 effectiveness in the management of hospitalized COVID‐19 and its clinical outcomes and complications: A randomized clinical trial
34 patient vitamin B12 late treatment RCT: 75% lower ICU admission (p=0.34) and 1% longer hospitalization (p=0.97).Small RCT 34 hospitalized patients in Iran showing improved imflammatory markers and lower ICU admission with vitamin B12 treatment, without statistical significance. There was no mortality.
Sep 2023, Health Science Reports, https://onlinelibrary.wiley.com/doi/10.1002/hsr2.1509, https://c19p.org/erfani
956. Setayesh et al., Efficacy of a Persian herbal medicine compound on coronavirus disease 2019 (COVID-19): a randomized clinical trial
79 patient nigella sativa late treatment RCT: 27% lower need for oxygen therapy (p=0.007) and 29% shorter hospitalization (p<0.0001).Small RCT 41 patients treated with nigella sativa, glycyrrhiza glabra, punica granatum, and rheum palmatum, and 41 control patients, showing shorter hospitalization with treatment.
Jun 2022, Integrative Medicine Research, https://www.sciencedirect.com/science/article/pii/S2213422022000373, https://c19p.org/setayesh
957. Subramanian et al., Vitamin D, D-binding protein, free vitamin D and COVID-19 mortality in hospitalized patients
467 patient vitamin D prophylaxis study: 27% lower mortality (p=0.12).Retrospective 427 hospitalized COVID-19 patients in the United Kingdom, showing lower mortality with vitamin D supplementation (p=0.12), and higher mortality with both low and high vitamin D levels compared to a reference range of 50-74 nmol/L.
Jan 2022, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqac027/6518440, https://c19p.org/subramanian
83 patient N-acetylcysteine late treatment RCT: 2% lower mortality (p=1), 27% lower ventilation (p=0.57), 6% greater improvement (p=0.82), and 5% higher hospital discharge (p=0.8).
RCT 83 severe COVID-19 pnuemonia patients in Iran, 42 treated with acetylcysteine, showing no significant difference in clinical outcomes. All patients received remdesivir, famotidine, and vitamin C. More patients were at baseline category 4+ in the treatment group - 18 vs. 12. The trial focused on preventing liver injury in patients treated with remdesivir, showing improved AST/ALT levels with acetylcysteine.
Jun 2022, Gastroenterology and Hepatology from Bed to Bench, https://journals.sbmu.ac.ir/ghfbb/index.php/ghfbb/article/view/2565, https://c19p.org/mousapour
959. Liu et al., Clinical characteristics, outcomes, and risk factors of SARS-CoV-2 breakthrough infections among 572 fully vaccinated (BBIBP-CorV) hospitalized patients
572 patient azvudine late treatment study: 24% lower progression (p=0.44).Retrospective 572 fully vaccinated hospitalized patients in China, showing lower risk with azvudine treatment, without statistical significance. The composite outcome included intubation, non-invasive respiratory support, ICU admission, and all-cause death. Azvudine was not included in the multivariable analysis (only combined antiviral therapy was used without explanation).
Oct 2023, Heliyon, https://www.sciencedirect.com/science/article/pii/S240584402308595X, https://c19p.org/liu13azv
960. Cavalcanti et al., Hydroxychloroquine with or without Azithromycin in Mild-to-Moderate Covid-19
667 patient HCQ late treatment RCT: 16% lower mortality (p=0.77) and 28% higher hospitalization (p=0.3).Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Randomization resulted in 64.3% male patients (HCQ) vs. 54.2% (control) which may significantly affect results due to the much higher risk for male patients. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of..
Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2019014, https://c19p.org/cavalcanti
961. Abbas et al., The Effect of Ivermectin on Reducing Viral Symptoms in Patients with Mild COVID-19
202 patient ivermectin early treatment RCT: 41% lower progression (p=0.54) and 36% improved recovery (p=0.04).RCT 99 ivermectin and 103 control low risk patients in China, up to 7 days from symptom onset, showing statistically significant improvement in recovery with treatment, and non-statistically significant improvements in recovery time and deterioration. Authors selectively omitted the p-value for recovery which shows statistical significance. Very little information on the patients is provided (only age, gender, and insurance status). The table, text, and abstract show three different versions of recovery numbers. The table and abstract show two different versions of recovery time. The abstract contains a hazard ratio that is not in the text, and no statistical methods are reported. Given the selective omission of the statistically significant recovery p-value, three different sets of numbers for that outcome, and other inconsistencies, the data in this study does not appear to be very reliable. Patients >50 were excluded.
Dec 2021, Indian J. Pharmaceutical Sciences, https://www.ijpsonline.com/abstract/the-effect-of-ivermectin-on-reducing-viral-symptoms-in-patients-with-mild-covid19-4455.html, https://c19p.org/abbas2
962. Huang et al., Clinical characteristics of 17 patients with COVID-19 and systemic autoimmune diseases: a retrospective study
1,255 patient HCQ prophylaxis study: 80% lower hospitalization (p=0.001).Analysis of 1255 COVID-19 patients in Wuhan Tongji Hospital finding 0.61% with systemic autoimmune diseases, much lower than authors expected (3%-10%). Authors hypothesise that protective factors, such as CQ/HCQ use, reduce hospitalization.
Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/79/9/1163, https://c19p.org/huangard
963. Corrao et al., Safety of High-Dose Vitamin C in Non-Intensive Care Hospitalized Patients with COVID-19: An Open-Label Clinical Study
146 patient vitamin C late treatment study: 39% lower mortality (p=0.37), 19% lower combined mortality/ICU admission (p=0.24), 102% higher ICU admission (p=0.51), and 25% shorter hospitalization (p=0.16).Prospective study of 146 hospitalized COVID-19 patients showing shorter hospitalization with high-dose intravenous vitamin C. 104 patients received 10g of vitamin C intravenously daily for 3 days and 42 patients received only standard care. Mortality was lower with treatment (8.7% vs 14.3%) without statistical significance. Treatment was associated with significantly shorter hospitalization in multivariable analysis (−4.95, p=0.041). No adverse events were reported in the vitamin C group.
Jul 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/13/3987, https://c19p.org/corrao
964. Shover et al., Cannabis consumption is associated with lower COVID-19 severity among hospitalized patients: a retrospective cohort analysis
1,831 patient cannabidiol prophylaxis PSM study: 2% lower mortality (p=0.57), 5% lower ventilation (p=0.02), 9% lower ICU admission (p=0.02), and 3% lower need for oxygen therapy (p=0.27).Retrospective 1,831 hospitalized COVID-19 patients in the USA, showing lower mechanical ventilation and ICU admission, but no significant difference in mortality.
Aug 2022, J. Cannabis Research, https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00152-x, https://c19p.org/shover
965. Baldia et al., The association of prior paracetamol intake with outcome of very old intensive care patients with COVID-19: results from an international prospective multicentre trial
2,646 patient acetaminophen ICU study: 12% lower mortality (p=0.2).Prospective study of 2,646 ICU patients ≥70 years old, showing no significant difference in mortality with acetaminophen use in the 10 days prior to ICU admission.
Dec 2022, BMC Geriatrics, https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-022-03709-w, https://c19p.org/baldia
966. Regalia et al., Vitamin D Status and SARS-CoV-2 Infection in a Cohort of Kidney Transplanted Patients
179 patient vitamin D prophylaxis study: 33% fewer cases (p=0.21).Retrospective 61 COVID+ kidney transplant patients and 122 matched controls, showing significantly lower vitamin D levels in COVID+ patients, and lower cases with vitamin D supplementation, without statistical significance.
Jan 2022, Nutrients, https://www.mdpi.com/2072-6643/14/2/317/htm, https://c19p.org/regalia
967. Agarwal et al., Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective study
484 patient HCQ prophylaxis study: 27% lower progression (p=0.21) and 5% more cases (p=0.81).Small prophylaxis trial with 29 low dose HCQ and 455 control healthcare workers in India, showing no statistically significant differences.
Sep 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.09.13.21262971v1, https://c19p.org/agarwal2
968. Loue et al., Ivermectin and COVID-19 in Care Home: Case Report
25 patient ivermectin early treatment study: 70% lower mortality (p=0.34) and 55% lower severe cases (p=0.11).Small quasi-randomized (patient choice) study with 25 PCR+ patients in a nursing home offered ivermectin, of which 10 chose to be treated. The mean age was 83.5 in the treatment group and 81.8 in the control group. There was lower mortality and fewer serious cases with treatment.
Apr 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-202.php?jid=jide, https://c19p.org/loue
969. Lewandowski et al., Insulin and Metformin Administration: Unravelling the Multifaceted Association with Mortality across Various Clinical Settings Considering Type 2 Diabetes Mellitus and COVID-19
430 patient metformin prophylaxis study: 23% lower mortality (p=0.15).Retrospective 430 hospitalized COVID-19 patients with type 2 diabetes in Poland showing lower mortality with metformin and higher mortality with remdesivir, convalescent plasma, and aspirin in univariable analysis. These results were not statistically significant except for aspirin, and no baseline information per treatment is provided to assess confounding.
Mar 2024, Biomedicines, https://www.mdpi.com/2227-9059/12/3/605, https://c19p.org/lewandowski
970. Vaisi et al., The association between nutrients and occurrence of COVID-19 outcomes in the population of Western Iran: A cohort study
3,955 patient vitamin C prophylaxis study: 38% lower hospitalization (p=0.17) and 10% fewer symptomatic cases (p=0.71).Analysis of nutrient intake and COVID-19 outcomes for 3,996 people in Iran, showing lower risk of COVID-19 hospitalization with sufficient vitamin A, vitamin C, and selenium intake, with statistical significance for vitamin A and selenium.
May 2023, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13632, https://c19p.org/vaisic
971. Wada et al., Efficacy and safety of single-dose ivermectin in mild-to-moderate COVID-19: the double-blind, randomized, placebo-controlled CORVETTE-01 trial
214 patient ivermectin late treatment RCT: 19% lower progression (p=0.46), 14% higher need for oxygen therapy (p=0.46), 23% worse improvement (p=0.61), and 60% improved recovery (p=0.17).Late treatment (6.6 days after onset/PCR+) RCT with 221 low risk (no deaths) COVID-19 patients in Japan, showing no significant difference in viral clearance with a single dose of ivermectin under fasting. Authors note that a single 200 μg/kg dose under fasting was used as approved in Japan, and that the low dose, single day dosing, and fasting administration (~2.5 times lower plasma concentration according to [Guzzo]) limit applicability, and that studies with more favorable outcomes generally used a higher dose or multiday dosing. Details of PCR testing are not provided but the very slow clearance within the low risk population suggests a very high Ct value that may not accurately represent any reduction in replication-competent viral load. An erratum notes a conflict of interest for a reviewer that was a Merck employee: [frontiersin.org]
May 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1139046/full, https://c19p.org/wada
972. Ñamendys-Silva et al., Outcomes of patients with COVID-19 in the Intensive Care Unit in Mexico: A multicenter observational study
164 patient HCQ ICU study: 32% lower mortality (p=0.19).Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lower with CQ. HCQ+AZ vs. neither HCQ or CQ relative risk RR 0.68, p = 0.03 CQ vs. neither HCQ or CQ relative risk RR 0.63, p = 0.02 HCQ+AZ or CQ vs. neither relative risk RR 0.65, p = 0.006
Oct 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S014795632030412X, https://c19p.org/namendyssilva
973. Patel et al., The significance of oral ascorbic acid in patients with COVID-19
176 patient vitamin C late treatment study: 29% lower mortality (p=0.18).Retrospective 176 hospitalized patients, 96 treated with oral vitamin C (from 500mg to 1500mg daily), showing lower mortality with treatment.
Sep 2020, Chest Infections, https://journal.chestnet.org/article/S0012-3692(20)32508-3/fulltext, https://c19p.org/patel
974. Algahtani et al., The Prospect of Lactoferrin Use as Adjunctive Agent in Management of SARS-CoV-2 Patients: A Randomized Pilot Study
54 patient lactoferrin late treatment RCT: 25% improved recovery (p=1).RCT 54 hospitalized patients in Egypt, showing no significant differences in recovery with lactoferrin treatment. 200mg lactoferrin orally once daily (group 1) or 200mg lactoferrin orally twice daily (group 2).
Aug 2021, Medicina, https://www.mdpi.com/1648-9144/57/8/842, https://c19p.org/algahtani
975. Vasheghani et al., The relationship between serum 25-hydroxyvitamin D levels and the severity of COVID-19 disease and its mortality
508 patient vitamin D prophylaxis study: 30% lower mortality (p=0.45) and 64% lower ICU admission (p=0.009).Retrospective 508 hospitalized COVID-19 patients in Iran showing lower mortality with vitamin D supplementation (not reaching statistical significance), and an association between lower vitamin D levels and disease severity, ICU admission, and increased mortality. Details of supplementation are not provided. The multivariate result for vitamin D deficiency is in the preprint, the journal version only contains the multivariate result for serum level.
Jan 2021, Scientific Reports, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413335/, https://c19p.org/vasheghani
976. Ahmed et al., Factors Affecting the Incidence, Progression, and Severity of COVID-19 in Type 1 Diabetes Mellitus
100 patient HCQ prophylaxis study: 99% fewer cases (p=0.08).Retrospective type 1 diabetes patients in Saudi Arabia showing reduced risk of cases with HCQ prophylaxis.
Nov 2021, BioMed Research Int., https://www.hindawi.com/journals/bmri/2021/1676914/, https://c19p.org/ahmed2
977. Rahimi et al., Efficacy of N-acetyl Cysteine in Severe COVID-19 Patients: A Randomized Controlled Phase III Clinical Trial
40 patient N-acetylcysteine ICU RCT: 33% lower mortality (p=0.19) and 8% shorter hospitalization (p=0.63).RCT 40 ICU patients in Iran, showing lower mortality with NAC treatment, without statistical significance. Single dose intravenous NAC 300 mg/kg.
Oct 2022, Jundishapur J. Natural Pharmaceutical Products, https://brieflands.com/articles/jjnpp-129817.html, https://c19p.org/rahimi
978. Mura et al., Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients
176 patient antihistamine H1RA late treatment PSM study: 25% lower mortality (p=0.4).PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with H1RAs+H2RAs versus famotidine alone, without statistical significance.
Mar 2021, Signal Transduction and Targeted Therapy, https://www.nature.com/articles/s41392-021-00689-y, https://c19p.org/murah1
979. Dey et al., Hydroxy Chloroquine Prophylaxis Experience in Doctor Community with COVID-19 in West Bengal
117 patient HCQ prophylaxis study: 92% lower mortality (p=0.09), 27% fewer moderate/severe cases (p=0.39), and 16% lower hospitalization (p=0.55).Retrospective 117 COVID-19 positive doctors in India showing lower mortality and severity with HCQ prophylaxis, without statistical significance in unadjusted results without group details. Results do not include the risk of positive cases.
Jun 2024, J. College of Medical Sciences-Nepal, https://www.nepjol.info/index.php/JCMSN/article/view/43302, https://c19p.org/dey2
980. Park et al., Non-steroidal anti-inflammatory agent use may not be associated with mortality of coronavirus disease 19
794 patient acetaminophen prophylaxis PSM study: 25% lower mortality (p=0.46) and 38% lower ventilation (p=0.42).Retrospective 2,365 patients prescribed acetaminophen and 398 prescribed NSAIDs in South Korea, showing no significant differences.
Mar 2021, Scientific Reports, http://www.nature.com/articles/s41598-021-84539-5, https://c19p.org/park2
981. Bousquet et al., ADL-dependency, D-Dimers, LDH and absence of anticoagulation are independently associated with one-month mortality in older inpatients with Covid-19
108 patient HCQ late treatment study: 43% lower mortality (p=0.15).Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, p = 0.15.
Jun 2020, Aging, 11306-11313, https://www.aging-us.com/article/103583/text, https://c19p.org/bousquet
982. Kwon et al., Androgen-deprivation therapy and SARS-CoV-2 in men with prostate cancer: findings from the University of California Health System registry
5,211 patient various antiandrogen prophylaxis study: 21% lower mortality (p=1) and 18% more cases (p=0.54).Retrospective 5,211 prostate cancer patients, 799 on ADT, showing no significant differences in COVID-19 outcomes with treatment.
Jan 2021, Annals of Oncology, https://www.annalsofoncology.org/article/S0923-7534(21)00095-8/fulltext, https://c19p.org/kwon
983. Bielik et al., A Possible Preventive Role of Physically Active Lifestyle during the SARS-CoV-2 Pandemic; Might Regular Cold-Water Swimming and Exercise Reduce the Symptom Severity of COVID-19?
1,140 patient exercise study: 30% fewer moderate/severe cases (p=0.1) and 9% more cases (p=0.36).Retrospective 1,544 participants in Slovakia, showing a lower risk of more severe COVID-19 for physically active participants, without statistical significance.
Jul 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/13/7158, https://c19p.org/bielik
32,085 patient fluvoxamine prophylaxis PSM study: 27% lower mortality (p=0.41) and 37% higher hospitalization (p=0.5).
Retrospective COVID+ patients in Croatia, showing no significant difference in outcomes with fluvoxamine prophylaxis.
Nov 2022, European J. Clinical Pharmacology, https://link.springer.com/10.1007/s00228-023-03479-3, https://c19p.org/trkulja2
985. Schilling et al., Pharmacometrics of high dose ivermectin in early COVID-19: an open label, randomized, controlled adaptive platform trial (PLATCOV)
90 patient ivermectin early treatment RCT: 86% lower progression (p=0.24) and 9% worse viral clearance (p=0.36).Very high conflict of interest RCT with design optimized for a null result: very low risk patients, high existing immunity, post-hoc change to exclude patients more likely to benefit. There was no significant difference in viral clearance among low risk patients with high viral load at baseline. All 3 progression events occured in the control arm - one hospitalization and two cases of COVID-19 related rhabdomyolysis. Patients in both arms cleared the virus quickly with a viral clearance half-life of 21.1 hours vs. 19.2 hours, which may be in part due to prior immunity. With rapid viral clearance and very low risk patients, infection is less likely to spread to other tissues. Systemic treatment is less applicable, and has less time to reach therapeutic concentrations before self-recovery. Treatment administered directly to the respiratory tract, e.g. as in [ Albariqi , Albariqi (B) , Aref , Chaccour , Elkholy , Errecalde , Francés-Monerris , Mansour ] , may be more effective for COVID..
Jul 2022, eLife, https://elifesciences.org/articles/83201, https://c19p.org/schilling
986. Sourij et al., COVID‐19 fatality prediction in people with diabetes and prediabetes using a simple score upon hospital admission
247 patient metformin prophylaxis study: 37% lower mortality (p=0.13).Retrospective 247 hospitalized COVID-19 diabetes patients, showing lower mortality with metformin use in unadjusted results.
Dec 2020, Diabetes, Obesity and Metabolism, https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.14256, https://c19p.org/sourij
987. Rezk et al., miRNA-223-3p, miRNA- 2909 and Cytokines Expression in COVID-19 Patients Treated with Ivermectin
320 patient ivermectin late treatment study: 56% lower progression (p=0.06), 33% improved recovery (p=0.27), and 27% faster viral clearance (p=0.01).Prospective 320 hospitalized moderate COVID-19+ patients in Egypt, 160 treated with ivermectin, showing lower mortality, improved recovery, and decreased cytokine expression with treatment. All patients were treated with HCQ. 7890/26-8-2020.
Oct 2021, Zagazig University Medical J., https://journals.ekb.eg/article_202150_0.html, https://c19p.org/rezk
988. Cadegiani et al., An open-label prospective observational study of antiandrogen and non-antiandrogen early pharmacological approaches in females with mild-to-moderate COVID-19. The Pre-AndroCoV Female Trial
270 patient spironolactone antiandrogen early treatment study: 77% faster recovery (p=0.006) and 38% faster viral clearance (p=0.02).Prospective study of 270 female COVID-19 patients in Brazil, 75 with hyperandrogenism, of which 8 were on spironolactone. Results suggest that HA patients may be at increased risk, and that spironolactone use may reduce the risk compared to both other HA patients and non-HA patients. SOC included other treatments and there was no mortality or hospitalization.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.05.20206870v1, https://c19p.org/cadegiani9
989. Cadegiani et al., An open-label prospective observational study of antiandrogen and non-antiandrogen early pharmacological approaches in females with mild-to-moderate COVID-19. The Pre-AndroCoV Female Trial
270 patient spironolactone early treatment study: 77% faster recovery (p=0.006) and 38% faster viral clearance (p=0.02).Prospective study of 270 female COVID-19 patients in Brazil, 75 with hyperandrogenism, of which 8 were on spironolactone. Results suggest that HA patients may be at increased risk, and that spironolactone use may reduce the risk compared to both other HA patients and non-HA patients. SOC included other treatments and there was no mortality or hospitalization.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.05.20206870v1, https://c19p.org/cadegiani9sp
990. Ouchi et al., Antidiabetic treatment and COVID-19 Outcomes: A population-based cohort study in primary health care in Catalonia during the first wave of the pandemic
16,043 patient metformin prophylaxis study: 10% lower mortality (p=0.19) and 8% lower combined mortality/hospitalization (p=0.12).Retrospective 31,006 diabetic COVID-19 patients in Spain, showing lower mortality with metformin treatment, without statistical significance. Authors provide results for metformin compared with untreated patients rather than all non-metformin patients, which may increase confounding due to higher prevalence for treatment of patients with more severe disease.
Oct 2022, Primary Care Diabetes, https://www.sciencedirect.com/science/article/pii/S175199182200167X, https://c19p.org/ouchi
991. Akbar et al., The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank
10,000 patient vitamin C prophylaxis study: 14% fewer cases (p=0.29).Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with vitamin C supplementation, without statistical significance. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2c
60 patient melatonin early treatment study: 91% lower hospitalization (p=0.05).
Small study with 30 patients treated with melatonin, cannabidiol, and for 14 patients angiotensin 1-7, compared with an age/sex matched control group during the same period, showing lower hospitalization with treatment.
Dec 2020, J. Infectiology, https://www.infectiologyjournal.com/articles/covid-19-disease-as-an-acute-angiotensin-1-7-deficiency-a-preliminary-phase-2-study-with-angiotensin-1-7-in-association-with-melatonin-and-cannabidiol-in-symptomatic-covid19-infected-subjects, https://c19p.org/lissoni
993. Taheri et al., Therapeutic effects of olfactory training and systemic vitamin A in patients with COVID-19-related olfactory dysfunction: a double-blinded randomized controlled clinical trial
60 patient vitamin A late treatment RCT: 38% improved recovery (p=0.53).RCT 90 outpatients with post-COVID-19 anosmia showing significant improvements in smell alterations with olfactory training after 3 and 12 months. Adding oral vitamin A to olfactory training resulted in higher rates of improvement, but the difference was not statistically significant.
Jun 2024, Brazilian J. Otorhinolaryngology, https://www.sciencedirect.com/science/article/pii/S1808869424000661, https://c19p.org/taheri2
994. Salesi et al., Clinical signs, symptoms, and severity of COVID-19 in patients with rheumatic diseases during the COVID-19 epidemic
77 patient HCQ prophylaxis study: 85% lower severe cases (p=0.003) and 18% fewer moderate/severe cases (p=0.35).Retrospective study of 77 outpatients with rheumatic diseases diagnosed with COVID-19, showing lower risk of severe COVID-19 with HCQ use in unadjusted results.
Dec 2023, Immunopathologia Persa, https://immunopathol.com/Article/ipp-40568, https://c19p.org/salesi
215 patient HCQ ICU study: 29% lower mortality (p=0.07).
Retrospective 215 mechanically ventilated COVID-19 patients in Brazil, 71 treated with HCQ, showing lower mortality with treatment in unadjusted results, without statistical significance. Authors note HCQ was used more toward the start of the pandemic, which may introduce confounding due to overall protocols improving over time, suggesting that the actual benefit may be greater.
Jun 2022, The J. Critical Care Medicine, https://www.sciendo.com/article/10.2478/jccm-2022-0015, https://c19p.org/osawa
996. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
15,227 patient selenium prophylaxis study: 80% fewer cases (p=0.11).Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtse
997. Revollo et al., Hydroxychloroquine pre-exposure prophylaxis for COVID-19 in healthcare workers
487 patient HCQ prophylaxis PSM study: 23% fewer cases (p=0.52).Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ, and 418 control. Authors report PCR and IgG results, with no baseline results for either. Authors note they "identified 69 HCWs receiving HCQ" while providing no information as to why or when they started HCQ. No conclusions can be drawn from this study because many workers may have been positive before starting HCQ. Only 14% of workers chose to use HCQ and they may have been motivated to do so because they had an infection. Authors perform several different adjustments, finding very different results. No information on death, hospitalization, symptoms, or severity is provided. Details on timing of serology and baseline serology status is not provided. Potential bias due to self-selection for risk. 25% of infections were detected before 7 days, indicating that they actually happened earlier (PCR false positive is very high initially). It is likely that many infections were before HCQ could reach therapeutic..
Nov 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa477/5997449, https://c19p.org/revollo
998. Bejan et al., DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
9,267 patient vitamin B9 prophylaxis study: 9% lower mortality (p=0.87), 1% lower ventilation (p=0.99), and 17% lower ICU admission (p=0.7).Retrospective 9,748 COVID-19 patients in the USA showing no significant differences with vitamin B9 use, without statistical significance.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanb9
323 patient camostat early treatment RCT: 8% faster recovery (p=0.54).
Double-blind RCT with 342 mild to moderate COVID-19 outpatients in South Korea, showing no significant difference in time to clinical improvement with camostat mesylate. In a post-hoc subgroup analysis of high-risk patients, there were non-statistically significant trends towards faster improvement in ordinal scale scores and subjective symptom scores at day 7 with treatment. Viral cultures suggested faster viral clearance with treatment, without statistical significance.
Jan 2023, Antimicrobial Agents and Chemotherapy, https://journals.asm.org/doi/10.1128/aac.00452-22, https://c19p.org/kim19
1,000. Levitus et al., The Effect of Vitamin D Supplementation on Severe COVID-19 Outcomes in Patients With Vitamin D Insufficiency
129 patient vitamin D prophylaxis study: 31% lower severe cases (p=0.25).Retrospective 129 hospitalized patients with vitamin D levels measured within 90 days prior to admission, showing lower, but not statistically significant, risk of severe cases with vitamin D supplementation among patients with levels <20ng/mL or <12ng/mL. For <30ng/mL, lower (but not statistically significant) risk was seen overall but not for ≥50,000IU (the sample size is not given, it may be extremely small for this case). Only minimal details for <30ng/mL are provided, and no details for <20ng/mL or <12ng/mL are provided. The potential effect of supplementation on the risk of a case severe enough for hospitalization is not included.
May 2021, J. the Endocrine Society, https://academic.oup.com/jes/article/5/Supplement_1/A279/6240740, https://c19p.org/levitus
1,001. Al Sulaiman et al., The Role of Inhaled Corticosteroids (ICS) in Critically Ill Patients With COVID-19: A Multicenter, Cohort Study
130 patient budesonide ICU PSM study: 32% lower mortality (p=0.13).Combined retrospective (Mar-Jun 2020) and prospective (until Mar 2021) study of 954 COVID+ ICU patients in Saudi Arabia, 68 treated with ICS (80% budesonide or budesonide/formoterol, 20% fluticasone/salmeterol), showing lower mortality with treatment, statistically significant for 30-day but not in-hospital mortality.
Nov 2021, J. Intensive Care Medicine, https://journals.sagepub.com/doi/full/10.1177/08850666211053548, https://c19p.org/alsulaiman3
1,002. Miguel et al., Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney
132 patient metformin prophylaxis study: 37% lower ICU admission (p=0.24).Mouse models showing reduced lung and kidney injury with metformin. Metformin minimized lung damage and fibrosis in a mouse model of LPS-induced ARDS, and reduced UUO and FAN-induced kidney fibrosis. In Vitro study showing that metformin increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis, and inflammation markers in lung epithelial cells. Authors also include a retrospective study showing lower ICU admission with metformin without statistical significance.
Nov 2023, Redox Biology, https://www.sciencedirect.com/science/article/pii/S2213231723003580, https://c19p.org/miguel
1,003. Budhiraja et al., Clinical Profile of First 1000 COVID-19 Cases Admitted at Tertiary Care Hospitals and the Correlates of their Mortality: An Indian Experience
976 patient ivermectin late treatment study: 99% lower mortality (p=0.04).Retrospective 976 hospitalized patients with 34 treated with ivermectin showing lower mortality with ivermectin in unadjusted results.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.16.20232223v1, https://c19p.org/budhirajai
1,004. Mura et al., Real-world evidence for improved outcomes with histamine antagonists and aspirin in 22,560 COVID-19 patients
1,054 patient aspirin late treatment PSM study: 15% lower mortality (p=0.08).PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with aspirin (not reaching statistical significance) and famotidine, and improved results from the combination of both.
Mar 2021, Signal Transduction and Targeted Therapy, https://www.nature.com/articles/s41392-021-00689-y, https://c19p.org/mura
1,005. Yadollahzadeh et al., Colchicine with Infliximab Compared to Infliximab in Hospitalized Patients with COVID-19 Pneumonia: An Open-label Randomized Trial
52 patient colchicine late treatment RCT: 33% lower mortality (p=0.54).Open-label RCT with 52 severe COVID-19 pneumonia patients showing no significant differences in mortality with colchicine. All patients received infliximab and remdesivir.
Feb 2024, Coronaviruses, https://www.eurekaselect.com/223567/article, https://c19p.org/yadollahzadeh
1,006. Bagheri et al., Supplement Usage Pattern in a Group of COVID-19 Patients in Tehran
510 patient zinc prophylaxis study: 60% lower severe cases (p=0.41) and 41% lower hospitalization (p=0.37).Retrospective 510 patients in Iran, showing lower risk of severity with vitamin D (statistically significant) and zinc (not statistically significant) supplementation. IR.TUMS.VCR.REC.1398.1063.
Aug 2021, J. Family & Reproductive Health, https://europepmc.org/article/PMC/PMC7868648, https://c19p.org/bagheriz
1,007. Ahmadi et al., Lifestyle risk factors and infectious disease mortality, including COVID-19, among middle aged and older adults: Evidence from a community-based cohort study in the United Kingdom
468,569 patient sleep study: 3% lower mortality (p=0.91).Retrospective 468,569 adults in the UK, showing no significant difference in COVID-19 mortality based on sleep quality.
Aug 2021, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912100180X, https://c19p.org/ahmadi2sl
1,008. Alqatari et al., COVID-19 in patients with rheumatological diseases in the Eastern Province of Saudi Arabia
34 patient HCQ prophylaxis study: 89% lower ventilation (p=0.13), 64% lower ICU admission (p=0.14), and 64% lower severe cases (p=0.14).Retrospective 34 rheumatological disease patients with COVID-19 in Saudi Arabia, showing lower risk of severe cases with HCQ use in unadjusted results, without statistical significance.
May 2023, J. Medicine and Life, https://europepmc.org/article/PMC/PMC10478665, https://c19p.org/alqatari
50 patient vitamin D early treatment RCT: 33% improved recovery (p=0.15) and 50% improved viral clearance (p=0.009).
RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.
Apr 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.898062/full, https://c19p.org/khan4
1,010. Bai et al., COPD patients with high blood eosinophil counts exhibit a lower rate of omicron infection and milder post‐infection symptoms
315 patient budesonide prophylaxis study: 31% lower hospitalization (p=0.18) and 24% fewer cases (p=0.0001).Retrospective 315 COPD patients in China showing significantly lower COVID-19 cases with budesonide/formoterol or budesonide/glycopyrronium/formoterol use. Note that Table 4 includes only infected patients, we show the COVID-19 hospitalization risk among all patients with known medication status. Minimal details are provided for the groups on these medications.
May 2024, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13790, https://c19p.org/bai
1,011. Dudley et al., Revisiting vitamin D status and supplementation for in-patients with intellectual and developmental disability in the North of England, UK
64 patient vitamin D prophylaxis study: 22% fewer symptomatic cases (p=0.65).Retrospective 64 patients with intellectual and developmental disability in the UK, showing no significant difference in COVID-19 status with vitamin D supplementation. Only 6 patients were not on vitamin D supplementation.
May 2021, BJPsych Bulletin, https://www.cambridge.org/core/journals/bjpsych-bulletin/article/revisiting-vitamin-d-status-and-supplementation-for-inpatients-with-intellectual-and-developmental-disability-in-the-north-of-england-uk/9ABB85B839DD2343107CCD98B10A81EA, https://c19p.org/dudley
1,012. Peng et al., Early versus late acute kidney injury among patients with COVID-19—a multicenter study from Wuhan, China
4,020 patient HCQ late treatment study: 11% lower progression (p=0.63).Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with HCQ.
Dec 2020, Nephrology Dialysis Transplantation, https://academic.oup.com/ndt/article/35/12/2095/6020340, https://c19p.org/peng
1,013. Labbani-Motlagh et al., High-dose intravenous Vitamin C in early stages of severe acute respiratory syndrome coronavirus 2 infection: A double-blind, randomized, controlled clinical trial
74 patient vitamin C late treatment RCT: 33% lower mortality (p=0.74), 13% longer hospitalization (p=0.49), and 16% lower progression (p=0.12).RCT 74 patients in Iran, showing no significant differences in outcomes with high dose vitamin C treatment. Tables 1b and 2a show conflicting baseline SOFA scores. The percentages of patients receiving antiviral treatments and corticosteroids are switched between the text and Table 1b. Authors indicate ICU admission was an outcome, but the result is not provided. AKI was lower with treatment, though not reaching statistical significance.
Dec 2022, J. Research in Pharmacy Practice, http://www.jrpp.net/text.asp?2022/11/2/64/363550, https://c19p.org/labbanimotlagh
1,014. Samajdar et al., Ivermectin and Hydroxychloroquine for Chemo-Prophylaxis of COVID-19: A Questionnaire Survey of Perception and Prescribing Practice of Physicians vis-a-vis Outcomes
309 patient HCQ prophylaxis study: 75% fewer cases (p<0.0001).Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases are not provided, and the results are subject to survey bias. Authors also report on community prophylaxis but present only combined ivermectin/HCQ results.
Nov 2021, J. the Association of Physicians India, https://www.researchgate.net/publication/356294136_Ivermectin_and_Hydroxychloroquine_for_Chemo-Prophylaxis_of_COVID-19_A_Questionnaire_Survey_of_Perception_and_Prescribing_Practice_of_Physicians_vis-a-vis_Outcomes, https://c19p.org/samajdarh
1,015. Ignatova et al., Therapeutic possibilities of using an expectorant mucolytic agent with antioxidant properties in COVID-19 infection
111 patient N-acetylcysteine early treatment study: 20% shorter hospitalization (p=0.05).Retrospective 111 patients with moderate COVID-19 pneumonia, 56 treated with NAC, showing shorter hospitalization time with treatment. NAC 1200mg daily intravenous, divided into two doses.
Nov 2021, Russian Medical Inquiry, https://www.rusmedreview.com/upload/iblock/b14/473-478.pdf, https://c19p.org/ignatova
1,016. Rodriguez-Blanque et al., Evaluation of the effect of Loigolactobacillus coryniformis K8 CECT 5711 consumption in health care workers exposed to COVID-19
255 patient probiotics prophylaxis RCT: 9% fewer cases (p=0.92).Prophylaxis RCT with 127 probiotics and 128 control healthcare workers in Spain, showing no significant difference in cases. There were only 4 cases. Severity information by arm is not provided. L. coryniformis K8 CECT 5711. Treatment may help sustain the immune response to vaccination - in the subgroup of subjects for whom more than 81 days had passed since they received the first dose, IgG levels were significantly higher in the treatment group. Patients that started probiotic consumption before the first vaccine dose also reported significantly fewer side effects.
Aug 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.962566/full, https://c19p.org/rodriguezblanque
1,017. Liu et al., Factors affecting different COVID-19 outcomes in patients with systemic lupus erythematosus during the second pandemic wave of COVID-19 in China
301 patient HCQ prophylaxis study: 39% lower severe cases (p=0.26).Retrospective 301 consecutive SLE patients with COVID-19, showing lower risk of severe outcomes with HCQ use, with statistical significance in multivariable adjusted model 1 but not model 2.
Feb 2024, Lupus, http://journals.sagepub.com/doi/10.1177/09612033241230736, https://c19p.org/liu18
1,018. Spoorthi et al., Utility of Ivermectin and Doxycycline combination for the treatment of SARSCoV-2
100 patient ivermectin late treatment study: 21% faster recovery (p=0.03) and 16% shorter hospitalization (p=0.01).100 patient prospective trial of ivermectin + doxycycline showing reduced time to symptom resolution and shorter hospital stay with treatment.
Nov 2020, IAIM, 2020, 177-182, http://iaimjournal.com/wp-content/uploads/2020/10/iaim_2020_0710_23.pdf, https://c19p.org/spoorthi
1,019. Cegolon et al., Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial
108 patient xylitol late treatment study: 32% improved viral clearance (p=0.05).108 patient prospective study showing improved viral clearance with Panthexyl nasal spray (a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid).
Nov 2022, Pharmaceutics, https://www.mdpi.com/1999-4923/14/11/2502, https://c19p.org/cegolon
725 patient azvudine late treatment study: no change in mortality (p=1), 28% lower ventilation (p=0.04), 55% lower ICU admission (p=0.05), and 22% lower progression (p=0.07).
PSM retrospective 725 hospitalized COVID-19 patients in China compared the effectiveness and safety of the oral antivirals azvudine and paxlovid. There was no significant difference in the risk of disease progression between groups, but azvudine was associated with lower ICU admission and invasive ventilation use.
Oct 2023, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2023.1274294/full, https://c19p.org/wei2
1,021. Thairu et al., A Comparison of Ivermectin and Non Ivermectin Based Regimen for COVID-19 in Abuja: Effects on Virus Clearance, Days-to-discharge and Mortality
87 patient ivermectin late treatment PSM study: 88% lower mortality (p=0.12), 55% higher hospital discharge (p=0.0001), and 95% improved viral clearance (p=0.001).PSM retrospective 87 patients in Nigeria, 61 treated with ivermectin, showing lower mortality, faster recovery, and faster viral clearance with ivermectin treatment. All patients received zinc and vitamin C. A synergistic effect was seen for viral clearance when ivermectin and remdesivir were combined, as predicted by In Vitro research [Jeffreys]. Subject to confounding by time, with ivermectin patients from April-June 2021, and non-ivermectin patients from September-November 2021.
Feb 2022, J. Pharmaceutical Research Int., https://journaljpri.com/index.php/JPRI/article/view/36328, https://c19p.org/thairu
1,022. Morán Blanco et al., Antihistamines and azithromycin as a treatment for COVID-19 on primary health care – A retrospective observational study in elderly patients
84 patient proton pump inhibitor prophylaxis study: 31% fewer symptomatic cases (p=0.34).Retrospective 84 elderly nursing home residents in Spain showing no mortality, hospitalization, or ICU admission with early treatment with antihistamines alone or in combination with azithromycin.
Apr 2021, Pulmonary Pharmacology & Therapeutics, https://www.sciencedirect.com/science/article/pii/S1094553921000018, https://c19p.org/moranblancoppi
1,023. Qadeer et al., Ivermectin A Potential Treatment In Covid-19, Related to Critical Illness
210 patient ivermectin late treatment study: 58% improved viral clearance (p<0.0001).Prospective convenience sampling study of 210 hospitalized age-matched COVID-19 patients, showing faster viral clearance with ivermectin. Baseline information per group is not provided.
Aug 2022, Pakistan J. Medical and Health Sciences, https://pjmhsonline.com/index.php/pjmhs/article/view/2153, https://c19p.org/qadeer
1,024. Israel et al., Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
20,859 patient zinc prophylaxis study: 100% lower hospitalization (p=0.04).Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with calcium + zinc supplements (defined as being picked up within 35 days prior to PCR+), however only 10 patients took the supplements. Other patients may have acquired supplements outside of the healthcare system.
Jul 2021, Epidemiology and Global Health Microbiology and Infectious Disease, https://elifesciences.org/articles/68165, https://c19p.org/israel2z
1,025. Saheb Sharif-Askari et al., Vitamin D modulates systemic inflammation in patients with severe COVID-19
45 patient vitamin D ICU study: 36% shorter ICU admission (p=0.01).Retrospective 20 ICU patients treated with vitamin D in the UAE, and 25 matched controls, showing significantly shorter ICU stay with treatment. Lower proinflammatory cytokines were associated with lower severity markers. Authors also perform a PBMC In Vitro study, with both the clinical and in vitro studies showing vitamin D attenuated major proinflammatory signaling pathways.
Aug 2022, Life Sciences, https://www.sciencedirect.com/science/article/pii/S0024320522006099, https://c19p.org/sahebsharifaskari
1,026. Kurniyanto et al., Factors Associated with Death and ICU Referral among COVID-19 Patients Hospitalized in the Secondary Referral Academic Hospital in East Jakarta, Indonesia
477 patient favipiravir late treatment study: 48% lower mortality (p=0.21).Retrospective 477 hospitalized patients in Indonesia, showing lower mortality with favipiravir in unadjusted results, not reaching statistical significance.
Feb 2022, J. Clinical Virology Plus, https://www.sciencedirect.com/science/article/pii/S2667038022000084, https://c19p.org/kurniyanto
1,027. Blanc et al., Therapeutic prevention of COVID-19 in elderly: a case–control study
179 patient metformin prophylaxis study: 79% lower mortality (p=0.06) and 44% more cases (p=0.12).Retrospective 179 patients in France exposed to COVID-19 showing, without statistical significance, a higher risk of cases, and a lower risk of mortality among cases with existing metformin treatment.
Jul 2021, GeroScience, https://link.springer.com/article/10.1007/s11357-021-00397-z, https://c19p.org/blanc
1,028. Sherkawy et al., Impact of N-Acetylcysteine on Modulating Inflammation in Patients Hospitalized with Moderate COVID-19 Infections: A Prospective Randomized Trial
60 patient N-acetylcysteine late treatment RCT: 15% lower need for oxygen therapy (p=0.6) and 12% shorter hospitalization (p=0.45).RCT 60 hospitalized patients showing that oral N-acetylcysteine (NAC) at 1800mg daily significantly decreased plasma TNF-α levels and increased glutathione peroxidase levels. The NAC group had a shorter duration of oxygen support, while there were no significant difference for length of hospital stay, need for oxygen support, or mortality. Overall, the addition of high-dose NAC reduced inflammatory markers and oxidative stress in moderate COVID-19. Limitations include the small sample size, late treatment, lack of blinding, potential overlap of treatment effect with SOC, clinical significance of biomarker results, and limited adverse event reporting.
May 2023, Archives of Pharmaceutical Sciences Ain Shams University, https://aps.journals.ekb.eg/article_306468.html, https://c19p.org/sherkawy
1,029. Ashraf et al., COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes
100 patient HCQ early treatment study: 68% lower mortality (p=0.15).Small limited trial with 100 patients concluding that HCQ improved clinical outcome, OR 0.016 [0.002-0.11] in regression analysis.
Apr 2020, medRxiv doi:10.1101/2020.04.20.20072421, https://www.researchgate.net/publication/341197843_COVID-19_in_Iran_a_comprehensive_investigation_from_exposure_to_treatment_outcomes, https://c19p.org/ashraf
1,030. Soto-Becerra et al., Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru
3,322 patient HCQ late treatment study: 18% lower mortality (p<0.0001).Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More..
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v1, https://c19p.org/sotobecerra
1,031. Behboodikhah et al., Evaluation of the Costs and Outcomes of COVID-19 Therapeutic Regimens in Hospitalized Patients in Shiraz
2,174 patient favipiravir late treatment study: 68% lower mortality (p=0.2).Retrospective 2,174 hospitalized patients showing significantly shorter length of stay with favipiravir treatment.
Sep 2022, Iranian J. Science and Technology, Transactions A: Science, https://link.springer.com/10.1007/s40995-022-01351-0, https://c19p.org/behboodikhah
1,032. Chen et al., Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication
120 patient metformin prophylaxis study: 33% lower mortality (p=0.46).Retrospective 120 COVID-19 diabetes patients, showing non-statistically significantly lower mortality with existing metformin treatment.
Jul 2020, Diabetes Care, https://care.diabetesjournals.org/content/43/7/1399, https://c19p.org/chen3
1,033. Di Pierro et al., Clinical Effects of Streptococcus salivarius K12 in Hospitalized COVID-19 Patients: Results of a Preliminary Study
50 patient probiotics late treatment RCT: 62% lower mortality (p=0.17) and no change in ICU admission (p=1).RCT 50 hospitalized patients in Pakistan, 25 treated with S. salivarius K12, showing lower mortality with treatment, without statistical significance. There were more patients with higher oxygen requirements at baseline in the control group - 18 vs. 6 with O2 ≥ 8 L/min.
Sep 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/10/1926, https://c19p.org/dipierro6
1,034. Sánchez-Rico et al., Melatonin does not reduce mortality in adult hospitalized patients with COVID-19: a multicenter retrospective observational study
58,562 patient melatonin late treatment study: 19% lower mortality (p=0.15).Retrospective database analysis in France with 272 patients treated with melatonin, showing 19% lower mortality after adjustments, without statistical significance. Risk was lower for higher dosage (not statistically significant). Age was only in three age ranges and severe COVID was binary, likely leading to substantial residual confounding. Unadjusted differences were extreme with 60% >80 years old for melatonin compared to 15% for control. Mean daily dose 2.61mg. The title of the paper is incorrect, the most adjusted results show melatonin did reduce mortality (without reaching statistical significance).
Feb 2022, J. Travel Medicine, https://academic.oup.com/jtm/advance-article/doi/10.1093/jtm/taab195/6523003, https://c19p.org/sanchezrico
1,035. Li et al., Evaluation of the efficacy and safety of hydroxychloroquine in comparison with chloroquine in moderate and severe patients with COVID-19
28 patient HCQ late treatment study: 50% higher hospital discharge (p=0.09).Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note that HCQ may have more promising efficacy in immune system modulation, indicated by ferritin reduction in the moderate cases and improvement of CT scores and lymphocyte counts in the severe cases. HCQ and CQ were well tolerated. Authors also compare RCT patients to a matched sample of non-RCT patients in the same hospital, showing shorter time to discharge with CQ/HCQ, but not statistically significant due to the small size.
Jan 2021, Science China Life Sciences, https://link.springer.com/article/10.1007/s11427-020-1871-4, https://c19p.org/li3
1,036. Serrano et al., COVID-19 and lung cancer: What do we know?
22 patient HCQ late treatment study: 43% lower mortality (p=0.15).Small retrospective study of 22 lung cancer patients, 14 treated with HCQ+AZ, showing HCQ+AZ mortality relative risk RR 0.57, p = 0.145.
Sep 2020, Ann. Oncol., 2020, Sep, 31, S1026, https://www.annalsofoncology.org/article/S0923-7534(20)41826-5/fulltext, https://c19p.org/serrano
1,037. Mahto et al., Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India
689 patient zinc prophylaxis study: 37% lower IgG positivity (p=0.35).Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with zinc prophylaxis.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtoz
1,038. Fariña-González et al., Hourly Analysis of Mechanical Ventilation Parameters in Critically Ill Adult Covid-19 Patients: Association with Mortality
140 patient N-acetylcysteine ICU study: 39% lower mortality (p=0.08).Retrospective 140 mechanically ventilated patients in Spain, showing lower mortality with acetylcysteine treatment in unadjusted results, not reaching statistical significance.
May 2022, J. Intensive Care Medicine, http://journals.sagepub.com/doi/10.1177/08850666221105423, https://c19p.org/farinagonzalez
1,039. Sahai et al., Effect of aspirin on short-term outcomes in hospitalized patients with COVID-19
496 patient aspirin late treatment PSM study: 13% lower mortality (p=0.53).PSM retrospective 1,994 PCR+ patients in the USA, not showing a significant difference in mortality with aspirin treatment.
May 2021, Vascular Medicine, https://journals.sagepub.com/doi/10.1177/1358863X211012754, https://c19p.org/sahai
1,040. Alotaibi et al., Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study
437 patient favipiravir late treatment study: 57% lower mortality (p=0.05).Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subject to significant confounding by indication and confounding by time.
Sep 2021, Int. J. General Medicine, https://www.dovepress.com/getfile.php?fileID=73585, https://c19p.org/alotaibia
1,041. Majidi et al., The Effect of Vitamin C on Pathological Parameters and Survival Duration of Critically Ill Coronavirus Disease 2019 Patients: A Randomized Clinical Trial
100 patient vitamin C ICU RCT: 14% lower mortality (p=0.03).RCT 100 ICU patients in Iran, 31 treated with vitamin C, showing lower mortality with treatment.
Dec 2021, Frontiers in Immunology, https://www.frontiersin.org/articles/10.3389/fimmu.2021.717816/full, https://c19p.org/majidi
1,042. Giannini et al., Effectiveness of In-Hospital Cholecalciferol Use on Clinical Outcomes in Comorbid COVID-19 Patients: A Hypothesis-Generating Study
91 patient vitamin D late treatment study: 37% lower combined mortality/ICU admission (p=0.13).Retrospective 91 hospitalized patients, 36 treated with high-dose cholecalciferol, showing lower combined death/ICU admission with treatment. Authors also analyze the relationship with comorbidity burden, finding that the positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden.
Jan 2021, Nutrients , https://www.mdpi.com/2072-6643/13/1/219/htm, https://c19p.org/giannini
1,043. López-Medina et al., Effect of Ivermectin on Time to Resolution of Symptoms Among Adults With Mild COVID-19: A Randomized Clinical Trial
398 patient ivermectin early treatment RCT: 61% lower progression (p=0.11) and 15% improved recovery (p=0.53).Phone survey based RCT with low risk patients, 200 ivermectin and 198 control, showing lower mortality, lower disease progression, lower treatment escalation, and faster resolution of symptoms with treatment, without reaching statistical significance. Authors find the results of this trial alone do not support the use of ivermectin. However the effects are all positive, especially for serious outcomes which are unable to reach statistical significance with the very small number of events in the low risk population. An open letter, signed by >100 physicians, concluding this study is fatally flawed can be found at [ jamaletter.com ] . With the low risk patient population, there is little room for improvement with an effective treatment - 59/57% (IVM/control) recovered within the first 2 days to either "no symptoms" or "not hospitalized and no limitation of activities"; 73/69% within 5 days. Less than 3% of all patients ever deteriorated. The primary outcome was changed mid-trial, it..
Mar 2021, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2777389, https://c19p.org/lopezmedina
1,044. Assad et al., Pharmacotherapy prescribing pattern and outcome for hospitalized patients with severe and critical COVID-19
291 patient HCQ late treatment study: 60% lower mortality (p=0.002).Retrospective 346 hospitalized patients in Iraq, showing lower mortality with HCQ in unadjusted results. HCQ results are only provided within the 93% of patients treated with enoxaparin.
Oct 2022, Current Issues in Pharmacy and Medical Sciences, https://www.sciendo.com/article/10.2478/cipms-2022-0020, https://c19p.org/assad
1,045. Rivera-Izquierdo et al., Agentes terapéuticos utilizados en 238 pacientes hospitalizados por COVID-19 y su relación con la mortalidad
238 patient HCQ late treatment study: 19% lower mortality (p=0.75).Retrospective 238 hospitalized patients in Spain showing lower mortality with HCQ, adjusted hazard ratio aHR 0.81 [0.24-2.76].
Jul 2020, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775320304486, https://c19p.org/riveraizquierdo
1,046. Louca et al., Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app
372,720 patient vitamin C prophylaxis study: no change in cases (p=1).Survey analysis of dietary supplements showing no significant difference in PCR+ cases with vitamin C usage in the UK, however significant reductions were found in the US and Sweden. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucac
1,047. Magagnoli et al., Outcomes of hydroxychloroquine usage in United States veterans hospitalized with Covid-19
807 patient HCQ late treatment study: 11% lower mortality (p=0.74).Retrospective 807 hospitalized patients, no statistically significant reduction in mortality or the need for mechanical ventilation with HCQ or HCQ+AZ, or for death with HCQ+AZ, HR 1.83, p=0.009 for HCQ mortality. The preprint notes that HCQ was more likely to be prescribed to patients with more severe disease, however this was deleted in the published version. 425 patients had dispositions of death or discharge by the end of the study period and thus did not encounter the issue of length-biased sampling and differential rates of right-censored observations among the groups. Also see: [mediterranee-infection.com]
Apr 2020, Med, https://www.sciencedirect.com/science/article/pii/S2666634020300064, https://c19p.org/magagnoli
1,048. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient famotidine prophylaxis study: 18% lower mortality (p=0.25).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3fm
1,049. Fontana et al., SARS-CoV-2 infection in dialysis patients in northern Italy: a single-centre experience
15 patient HCQ late treatment study: 50% lower mortality (p=0.53).Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, p = 0.53.
Jun 2020, Clinical Kidney J., 334–339, https://academic.oup.com/ckj/article/13/3/334/5860798, https://c19p.org/fontana
1,050. Goren et al., Anti-androgens may protect against severe COVID-19 outcomes: results from a prospective cohort study of 77 hospitalized men
77 patient various antiandrogen late treatment study: 81% lower ICU admission (p=0.08).Prospective study of 77 men hospitalized with COVID-19, 12 taking antiandrogens (9 dutasteride, 2 finasteride, 1 spironolactone), showing lower ICU admission with treatment (statistically significant with age-matched controls only when excluding the spironolactone patient). NCT04368897.
Sep 2020, J. the European Academy of Dermatology and Venereology, https://onlinelibrary.wiley.com/doi/10.1111/jdv.16953, https://c19p.org/goren
1,051. Coskun et al., The Effect of High-dose Vitamin C Treatment for Acute Respiratory Failure due to Coronavirus Disease Pneumonia on Mortality and Length of Intensive Care Stay: A Retrospective Cohort Study
78 patient vitamin C ICU study: 25% lower mortality (p=0.26), 2% lower ventilation (p=1), no change in ICU admission, and 28% improved recovery (p=0.005).Retrospective 78 ICU patients in Turkey, showing lower mortality with high-dose vitamin C treatment, without statistical significance. The SOFA score was significantly better with treatment at day 4. Authors incorrectly state that "HDVC treatment did not reduce the short-term mortality...". Mortality was lower with treatment, although not statistically significant given the sample size. 6g of vitamin C daily in 4 equal doses every 6h, for a total of 96h.
Mar 2023, SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital, https://sislietfaltip.org/jvi.aspx?un=SETB-66742&volume=, https://c19p.org/coskun
1,052. Usanma Koban et al., The factors affecting the prolonged PCR positivity in COVID-19 patients
126 patient vitamin C early treatment study: 33% improved viral clearance (p=0.73).Retrospective 126 patients in Turkey, showing no significant difference in PCR+ at day 14 with vitamin C treatment.
Jun 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7706&category_id=179&option=com_virtuemart, https://c19p.org/usanmakobanc
1,053. Mazziotti et al., Vitamin D deficiency, secondary hyperparathyroidism and respiratory insufficiency in hospitalized patients with COVID-19
348 patient vitamin D late treatment study: 19% lower mortality (p=0.49) and 67% higher ventilation (p=0.08).Retrospective 348 hospitalized patients in Italy showing vitamin D deficiency associated with acute hypoxemic respiratory failure. Vitamin D supplementation during hospitalization was not significantly associated with mortality or ventilation.
Mar 2021, J. Endocrinological Investigation, https://link.springer.com/article/10.1007/s40618-021-01535-2, https://c19p.org/mazziotti
1,054. Pinzón et al., Clinical Outcome of Patients with COVID-19 Pneumonia Treated with Corticosteroids and Colchicine in Colombia
301 patient colchicine late treatment study: 35% lower mortality (p=0.18).Retrospective 301 pneumonia patients in Colombia showing lower mortality with colchicine treatment.
Oct 2020, Research Square, https://www.researchsquare.com/article/rs-94922/v1, https://c19p.org/pinzon
1,055. Abella et al., Efficacy and Safety of Hydroxychloroquine vs Placebo for Pre-exposure SARS-CoV-2 Prophylaxis Among Health Care Workers
125 patient HCQ prophylaxis RCT: 5% fewer cases (p=1).Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 [0.25 - 3.64]. There was no hospitalization or death, no significant difference in QTc, no severe adverse events, no cardiac events (e.g., syncope and arrhythmias) observed. Medication adherence was 81%. Therapeutic levels of HCQ may not have been reached by the time of the infection in the first week. 2 infections were reported to be after discontinuation of the medication, but the authors do not specify which arm these were in. Hypothetically, if these were both in the HCQ arm, the resulting RR for treatment would be much lower.
Sep 2020, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771265, https://c19p.org/abella
1,056. Tavakol et al., Relationship between physical activity, healthy lifestyle and COVID-19 disease severity; a cross-sectional study
188 patient exercise study: 69% lower severe cases (p=0.05).Retrospective 206 patients in Iran, showing COVID-19 disease severity associated with lower physical activity.
Feb 2021, J. Public Health, http://link.springer.com/article/10.1007/s10389-020-01468-9/fulltext.html, https://c19p.org/tavakol
1,057. Capsoni et al., CPAP Treatment In COVID-19 Patients: A Retrospective Observational Study In The Emergency Department
52 patient HCQ late treatment study: 40% lower ventilation (p=0.3).Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ.
Nov 2020, Research Square, https://www.researchsquare.com/article/rs-113418/v1, https://c19p.org/capsoni
1,058. Tsuzuki et al., Effectiveness of Favipiravir on Nonsevere, Early-Stage COVID-19 in Japan: A Large Observational Study Using the COVID-19 Registry Japan
7,654 patient favipiravir early treatment study: 13% lower mortality (p=0.59), 2% higher ventilation (p=0.93), and 18% lower progression (p=0.1).Retrospective database analysis of 7,654 hospitalized patients in Japan, showing no significant differences with favipiravir treatment. NCGM-G-003494-0.
Mar 2022, Infectious Diseases and Therapy, https://link.springer.com/article/10.1007/s40121-022-00617-9/fulltext.html, https://c19p.org/tsuzuki2
1,059. Barry et al., Clinical Characteristics and Outcomes of Hospitalized COVID-19 Patients in a MERS-CoV Referral Hospital during the Peak of the Pandemic
605 patient HCQ late treatment study: 99% lower mortality (p=0.6).605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ).
Mar 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221002769, https://c19p.org/barry
1,060. Özden et al., Effects of Famotidine on COVID-19 Patients in Intensive Care Unit: A Retrospective Clinical Trial
59 patient famotidine ICU study: 29% lower mortality (p=0.19), 1% higher ventilation (p=1), and 26% shorter ICU admission (p=0.6).Retrospective 59 ICU patients in Turkey, showing no significant difference in 30-day mortality or invasive mechanical ventilation with 160mg/day famotidine treatment. However, the famotidine group had lower fibrinogen and procalcitonin, suggesting possible benefits for coagulation, inflammation, and secondary infections. Limitations include the small sample size, lack of randomization, and other confounding treatments.
Feb 2023, Boğazi̇çi̇ Tip Dergi̇si̇, https://jag.journalagent.com/bmj/pdfs/BMJ-77044-ORIGINAL_RESEARCH-OZDEN.pdf, https://c19p.org/ozden
1,061. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
15,227 patient probiotics prophylaxis study: 30% fewer cases (p=0.11).Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtk
1,062. Askari et al., The efficacy of curcumin-piperine co-supplementation on clinical symptoms, duration, severity, and inflammatory factors in COVID-19 outpatients: a randomized double-blind, placebo-controlled trial
26 patient curcumin early treatment RCT: 26% improved recovery (p=0.26).Small RCT 46 outpatients in Iran, 23 treated with curcimin-piperine, showing no significant difference in recovery. 1000mg curcumin and 10mg piperine/day for 14 days.
Jun 2022, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06375-w, https://c19p.org/askari
1,063. Duarte et al., Impact of androgen deprivation therapy on mortality of prostate cancer patients with COVID-19: a propensity score-based analysis
199 patient various antiandrogen prophylaxis study: 11% lower mortality (p=0.37).Retrospective 199 prostate cancer patients hospitalized with COVID-19 in Brazil, showing no significant difference in mortality with active ADT.
Nov 2021, Infectious Agents and Cancer, https://link.springer.com/article/10.1186/s13027-021-00406-y/fulltext.html, https://c19p.org/duarte
1,064. Taşdemir et al., Famotidine in COVID-19 treatment
179 patient famotidine late treatment study: 45% lower mortality (p=0.29), 37% lower ICU admission (p=0.36), 18% shorter hospitalization (p=0.003), and 20% faster recovery (p=0.04).Retrospective 179 hospitalized patients in Turkey, 85 treated with famotidine and 94 treated with pantoprazole, showing faster recovery with famotidine in unadjusted results.
Jul 2021, Konuralp Tıp Dergisi, https://dergipark.org.tr/en/pub/ktd/article/935888, https://c19p.org/tasdemir
1,065. Li et al., Modifiable lifestyle factors and severe COVID-19 risk: a Mendelian randomisation study
exercise study: 81% lower severe cases (p=0.02) and 56% lower hospitalization (p=0.07).Mendelian randomization study showing lower risk of severe COVID-19 with physical activity.
Feb 2021, BMC Medical Genomics, https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-021-00887-1, https://c19p.org/li17
1,066. Miao et al., Metformin use and mortality and length of stay among hospitalized patients with type 2 diabetes and COVID-19: A multiracial, multiethnic, urban observational study
4,462 patient metformin prophylaxis PSM study: 1% lower mortality (p=0.91) and 5% shorter hospitalization (p=0.23).Retrospective 4,462 COVID+ diabetes patients in the USA, showing no significant difference in outcomes with metformin use.
Nov 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.1002834/full, https://c19p.org/miao
1,067. Gönenli et al., Analysis of the Prophylactic use of Hydroxychloroquine at the Beginning of the COVID-19 Pandemic Among Physicians
564 patient HCQ prophylaxis study: 30% lower progression (p=0.77) and 19% more cases (p=0.58).Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, p = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, p = 0.58, which may be due to survey bias, treatment self-selection, and inconsistent regimens. Improvement on severity may be related to the higher HCQ concentration in lung tissue, and also reflect that binary PCR does not distinguish replication-competence. Details of the pneumonia numbers for treatment/control are from the author, it's unclear why the lower progression to pneumonia was not reported in the paper.
Dec 2020, Infectious Diseases and Clinical Microbiology, https://www.idcmjournal.org/hqn-use-among-physicians-during-the-pandemic, https://c19p.org/gonenli
1,068. Louca et al., Modest effects of dietary supplements during the COVID-19 pandemic: insights from 445 850 users of the COVID-19 Symptom Study app
372,720 patient zinc prophylaxis study: 1% fewer cases (p=0.8).Survey analysis of dietary supplements showing no significant difference in PCR+ cases with zinc usage. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.
Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucaz
1,069. Değirmenci et al., Is vitamin D level important in pregnant women with COVID-19?
125 patient HCQ late treatment study: 43% lower hospitalization (p=0.76).Retrospective 125 pregnant women hospitalized with COVID-19 in Turkey, showing no significant difference in hospitalization length with HCQ, and longer hospitalization with lopinavir/ritonavir use.
Jul 2024, J. Controversies in Obstetrics & Gynecology and Pediatrics, http://journal-jcogp.com/Publication/DisplayArticle/27358, https://c19p.org/degirmencih
1,070. Chen et al., Favipiravir Versus Arbidol for Clinical Recovery Rate in Moderate and Severe Adult COVID-19 Patients: A Prospective, Multicenter, Open-Label, Randomized Controlled Clinical Trial
236 patient favipiravir late treatment RCT: 74% lower progression (p=0.37), 20% lower need for oxygen therapy (p=0.42), and 20% improved recovery (p=0.15).Very late stage (9 days from symptom onset) RCT with 116 favipiravir patients and 120 arbidol patients in China, showing no significant difference in clinical recovery (relief of fever and cough, respiratory frequency ≤24 times/min, and oxygen saturation ≥98%), however the time to resolution of fever and cough was significantly lower with favipiravir. ChiCTR2000030254.
Sep 2021, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2021.683296/full, https://c19p.org/chen4
1,071. Sukumar et al., The Frontline War: A Case-control study of risk factors for COVID-19 among health care workers
116 patient HCQ prophylaxis study: 38% fewer cases (p=0.3).Case control study of healthcare workers in India, showing lower risk of cases with HCQ prophylaxis, without statistical significance. While authors comment negatively, as may be required for publication, and this study alone is not statistically significant, the result is consistent with the positive results in all studies to date.
Nov 2022, F1000Research, https://f1000research.com/articles/11-1298/v1, https://c19p.org/sukumar
1,072. Hegazy et al., Beneficial role of healthy eating Index-2015 score & physical activity on COVID-19 outcomes
73 patient exercise study: 54% fewer moderate/severe cases (p=0.01).Retrospective 68 COVID-19 patients showing physical activity and healthier nutrition associated with lower COVID-19 severity.
Oct 2023, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-023-00727-8, https://c19p.org/hegazy
1,073. Kim et al., One-year mortality and associated factors in older hospitalized COVID-19 survivors: a Nationwide Cohort Study in Korea
63,369 patient HCQ late treatment study: 15% lower mortality (p=0.62).Retrospective 63,369 hospitalized COVID-19 survivors aged 60 years or older in Korea, showing lower 1-year mortality with macrolides (including azithromycin), higher 1-year mortality with corticosteroids (including dexamethasone and methylprednisolone), and no significant difference with HCQ (only used for 0.2% of patients).
Oct 2024, Scientific Reports, https://www.nature.com/articles/s41598-024-76871-3, https://c19p.org/kim21h
1,074. Sevinç Gül et al., Effect of oral antiseptics on the viral load of SARS-CoV-2: A randomized controlled trial
41 patient povidone-iodine early treatment RCT: 99% improved viral load (p=0.37).RCT with 21 PVP-I and 20 saline patients gargling for 30 seconds and testing PCR Ct after 30 minutes, showing greater improvement with PVP-I, without statistical significance. Ct values differ across testing platforms, however the reported Ct value difference can represent a large difference in viral load. For example, using the calibration included with the ct2vl converter, the reported difference in mean Ct values corresponds to a reduction in viral load of over 3x for PVP-I.
Jul 2022, Dental and Medical Problems, https://dmp.umw.edu.pl/en/ahead-of-print/150831/, https://c19p.org/sevincgul
1,075. Hamdan et al., Risk factors associated with hospitalization owing to COVID-19: a cross-sectional study in Palestine
300 patient exercise study: 16% lower hospitalization (p=0.53).Retrospective 300 participants in Palestine, showing lower risk of hospitalization with physical activity, without statistical significance.
Dec 2021, J. Int. Medical Research, http://journals.sagepub.com/doi/10.1177/03000605211064405, https://c19p.org/hamdan
1,076. Shaw et al., COVID-19 in Individuals Treated With Long-Term Hydroxychloroquine: A Propensity Score-Matched Analysis of Cicatricial Alopecia Patients
144 patient antiandrogen prophylaxis PSM study: 6% fewer cases (p=0.006).PSM retrospective 144 alopecia patients in the USA, showing no significant difference in COVID-19 cases with anti-androgen use. The supplemental appendix is not available.
Jun 2021, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961621P0914X, https://c19p.org/shawaa
1,077. Okushin et al., Ursodeoxycholic acid for coronavirus disease 2019 prevention
94 patient ursodeoxycholic acid prophylaxis PSM study: 17% fewer symptomatic cases (p=0.81) and no change in cases (p=1).Retrospective 94 outpatients attending a university hospital gastroenterology clinic in Japan showing no significant difference in SARS-CoV-2 infection rates between ursodeoxycholic acid (UDCA)-treated patients and control groups without UDCA treatment. However, UDCA-treated patients tended to have higher rates of subclinical infection based on serology, suggesting UDCA may reduce COVID-19 severity.
Jul 2023, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13704, https://c19p.org/okushin
1,078. Dhaliwal et al., A Randomised Phase II Trial in Early COVID-19, Assessing Use of Camostat by Blocking SARS-CoV-2 Spike Protein-initiated Membrane Fusion
34 patient camostat early treatment RCT: 14% lower hospitalization (p=1).Early terminated RCT with 34 patients showing no significant differences with camostat treatment.
Mar 2022, NCT04455815, https://clinicaltrials.gov/study/NCT04455815, https://c19p.org/dhaliwal
1,079. Sisinni et al., Pre-admission acetylsalicylic acid therapy and impact on in-hospital outcome in COVID-19 patients: The ASA-CARE study
984 patient aspirin prophylaxis study: 7% higher mortality (p=0.65) and 30% lower combined mortality/intubation (p=0.01).Retrospective 984 COVID-19 patients, 253 taking aspirin prior to admission, showing lower risk of respiratory support upgrade with treatment.
Oct 2021, Int. J. Cardiology, https://www.sciencedirect.com/science/article/abs/pii/S0167527321014996, https://c19p.org/sisinni
1,080. Synolaki et al., The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality
312 patient HCQ late treatment study: 24% lower mortality (p=0.27).Retrospective 117 patients showing lower mortality for HCQ patients, without statistical significance. Version 1 of this paper stated: "HCQ, AZ, [and ...] were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores <3". FACTCLINYCoD scores predict mortality risk based on severity markers and comorbidities.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.05.20184655v2, https://c19p.org/synolaki
1,081. Smith et al., Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic
255 patient HCQ late treatment study: 27% lower mortality (p=0.002).Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level. Although authors mention immortal time bias, full details on the timing of HCQ administration is not provided and this is not fully addressed. Survival curves indicate immortal time bias will significantly change results, although the observed benefit appears to exceed the potential bias.
May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.05.28.21258012v1, https://c19p.org/smith
1,082. Aweimer et al., Mortality rates of severe COVID-19-related respiratory failure with and without extracorporeal membrane oxygenation in the Middle Ruhr Region of Germany
149 patient HCQ ICU study: 40% lower mortality (p=0.12).Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with HCQ in unadjusted results.
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimerh
1,083. Wang et al., A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward
58 patient aspirin prophylaxis study: 58% lower mortality (p=0.43).Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing no significant difference with aspirin treatment.
Jul 2020, J. Hematology & Oncology, https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00934-x, https://c19p.org/wang3e
1,084. Wang et al., A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward
58 patient metformin prophylaxis study: 58% lower mortality (p=0.43).Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing non-statistically significant lower mortality with metformin treatment.
Jul 2020, J. Hematology & Oncology, https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00934-x, https://c19p.org/wang3
1,085. Yeh et al., Hospitalization and mortality in patients with COVID-19 with or at risk of type 2 diabetes: data from five health systems in Pennsylvania and Maryland
metformin prophylaxis study: 44% lower progression (p<0.0001) and 37% lower hospitalization (p<0.0001).Retrospective 4,944 COVID-19 patients with type 2 diabetes in the USA, showing lower risk of hospitalization and combined ICU/intubation/death with metformin use.
Jun 2022, BMJ Open Diabetes Research & Care, https://drc.bmj.com/content/10/3/e002774.long, https://c19p.org/yeh2
46,535 patient sleep study: 43% lower mortality (p=0.02) and 36% lower hospitalization (p=0.008).
UK Biobank retrospective, 46,535 participants with sleep behavior assessed between 2006 and 2010, showing higher risk of hospitalization and mortality with poor sleep.
Jun 2021, Sleep, https://academic.oup.com/sleep/article/doi/10.1093/sleep/zsab138/6304657, https://c19p.org/li13
1,087. Lecronier et al., Comparison of hydroxychloroquine, lopinavir/ritonavir, and standard of care in critically ill patients with SARS-CoV-2 pneumonia: an opportunistic retrospective analysis
80 patient HCQ ICU study: 42% lower mortality (p=0.24), 6% lower treatment escalation (p=0.73), and 15% improved viral clearance (p=0.61).Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences found for treatment escalation, ventilator-free days, viral load, or mortality. Authors consider treatment escalation more important than mortality, for unknown reasons.
Jul 2020, Critical Care, 2020, https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03117-9, https://c19p.org/lecronier
1,088. Alhmoud et al., Characteristics and outcomes of adult patients with asthma presenting with COVID-19: A comparative cohort study
616 patient montelukast prophylaxis study: 13% lower hospitalization (p=0.61).Retrospective 616 COVID-19 patients with asthma in Qatar showing no significant difference in hospitalization risk with montelukast use.
Sep 2023, Qatar Medical J., https://www.qscience.com/content/journals/10.5339/qmj.2023.15, https://c19p.org/alhmoud
1,089. Carvallo et al., Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel
1,195 patient ivermectin prophylaxis study: 100% fewer cases (p<0.0001).Prophylaxis study using ivermectin and iota-carrageenan showing 0 of 788 cases from treated healthcare workers, compared to 237 of 407 control. See [doyourownresearch.substack.com] for discussion of issues with this trial.
Nov 2020, J. Biomedical Research and Clinical Investigation, https://medicalpressopenaccess.com/upload/1605709669_1007.pdf, https://c19p.org/carvalloprep
1,090. Abd-Elsalam et al., Clinical Study Evaluating the Efficacy of Ivermectin in COVID-19 Treatment: A Randomized Controlled Study
164 patient ivermectin late treatment RCT: 20% shorter hospitalization (p=0.09).RCT 164 hospitalized patients in Egypt showing lower mortality and shorter hospitalization, but without statistical significance. There were no serious adverse effects. Authors suggest the low dosage may have resulted in lower efficacy than other trials, and recommend increased dosage in future trials. Time from symptom onset is not specified. The trial was retrospectively registered and the recruitment start date in the trial registration (June 2020) differs from the paper (March 2020) [osf.io]. For other concerns see [onlinelibrary.wiley.com].
Jun 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27122, https://c19p.org/abdelsalam3
1,091. Siripongboonsitti et al., A Randomized Trial to Assess the Acceleration of Viral Clearance by the Combination Favipiravir/Ivermectin/Niclosamide in Mild-to-Moderate COVID-19 Adult Patients (FINCOV)
60 patient ivermectin early treatment RCT: 39% improved recovery (p=0.19) and 6% improved viral clearance (p=0.75).RCT 60 low-risk outpatients, median age 31, with mild to moderate COVID-19 showing no significant differences with combined favipiravir/ivermectin/niclosamide treatment compared to favipiravir alone. There was limited room for improvement with almost no progression and no hospitalization, ICU admission, supplemental oxygen, or mortality. The combined group showed significantly improved visual analog scale (VAS) scores for cough, runny nose, and diarrhea from day 3. Authors note that "the WHO-CPS were significantly decreased among FPV/IVM/NCL vs FPV alone on day 10", however the degree of improvement cannot be determined based on the values reported. Authors state that "All data generated or analyzed during this study are included in this published article", which is incorrect - only summary statistics are published. The trial registration states that data will not be made available. This raises concerns, especially given many inconsistencies in the published data:..
Mar 2024, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034124001060, https://c19p.org/siripongboonsitti6
1,092. Ghauri et al., Ivermectin Use Associated with Reduced Duration of Covid-19 Febrile Illness in a Community Setting
90 patient ivermectin early treatment study: 92% improved recovery (p=0.04).Retrospective 95 outpatients in Pakistan with strong clinical suspicion of COVID-19 (testing was not widely available), with 40 patients treated with ivermectin, showing significantly shorter duration of febrile illness with treatment. Most patients also received HCQ, AZ, zinc, and aspirin. Authors note that there was a treatment delay-response relationship.
Dec 2020, Int. J. Clinical Studies & Medical Case Reports, https://ijclinmedcasereports.com/pdf/IJCMCR-RA-00320.pdf, https://c19p.org/ghauri
1,093. Behera et al., Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
372 patient HCQ prophylaxis study: 28% fewer cases (p=0.29).Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/behera
1,094. Luo et al., Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis
283 patient HCQ late treatment study: 32% lower mortality (p=0.72).Retrospective 283 COVID-19+ diabetes patients in China, showing non-statistically significant lower mortality with HCQ/CQ treatment.
May 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/configurable/content/journals$002ftpmd$002f103$002f1$002farticle-p69.xml?t:ac=journals%24002ftpmd%24002f103%24002f1%24002farticle-p69.xml, https://c19p.org/luo3h
1,095. Munir et al., Clinical Disease Characteristics and Treatment Trajectories Associated with Mortality among COVID-19 Patients in Punjab, Pakistan
1,000 patient ivermectin late treatment study: 48% lower mortality (p=0.13).Retrospective 1,000 hospitalized COVID-19 patients in Pakistan, showing lower mortality with ivermectin without statistical significance.
Apr 2023, Healthcare, https://www.mdpi.com/2227-9032/11/8/1192, https://c19p.org/munir
1,096. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
15,227 patient vitamin A prophylaxis study: 56% fewer cases (p=0.41).Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holta
1,097. Vishnuram et al., Role of high dose oral liposomal vitamin C in reducing mortality in patients with COVID-19
8,875 patient vitamin C late treatment study: 54% lower mortality (p=0.03).Retrospective 8,634 hospitalized patients in India, showing lower mortality with high-dose vitamin C in unadjusted results. No group details are provided, the text and table appear to show different results, and some numbers do not match.
Jun 2021, Indian J. Basic and Applied Medical Research, https://www.ijbamr.com/assets/images/issues/pdf/FuXsaN_e2u6D7_ZY1348_LzacYt_766641.pdf, https://c19p.org/vishnuram
1,098. Shehab et al., Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection
253 patient vitamin D prophylaxis study: 46% lower severe cases (p=0.2).Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehab
1,099. Al-Sumiadai et al., Therapeutic effect of vitamin A on COVID-19 patients and its prophylactic effect on contacts
209 patient vitamin A prophylaxis study: 64% fewer cases (p<0.0001) and 32% faster recovery.Treatment and prophylaxis studies of vitamin A in Iraq. The prophylaxis study contained 209 contacts of COVID-19 patients, 97 treated with vitamin A, showing significantly lower cases with treatment, and shorter duration of symptoms. The treatment study is listed separately [Al-Sumiadai].
Jan 2021, Systematic Reviews in Pharmacy, https://www.researchgate.net/publication/351637178_THERAPEUTIC_EFFECT_OF_VITAMIN_A_ON_COVID-19_PATIENTS_AND_ITS_PROPHYLACTIC_EFFECT_ON_CONTACTS, https://c19p.org/alsumiadaip
1,100. Ferrer et al., Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2
21 patient povidone-iodine late treatment RCT: 34% improved viral load (p=0.82).Small very late (>50% 7+ days from symptom onset, 9 PVP-I patients) RCT testing mouthwashing with cetylpyridinium chloride, chlorhexidine, povidone-iodine, hydrogen peroxide, and distilled water, showing no significant differences. Over 30% of patients show >90% decrease in viral load @2 hrs with all 5. Authors note that a trend was observed for viral load decrease with PVP-I @2h for patients <6 days from onset (p=0.06, Wilcox test).
Dec 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-03461-y, https://c19p.org/ferrer2
1,101. Tylicki et al., Predictors of Mortality in Hemodialyzed Patients after SARS-CoV-2 Infection
133 patient vitamin D prophylaxis study: 14% lower mortality (p=0.61).Retrospective 133 COVID+ hemodialysis patients in Poland, showing lower mortality with existing vitamin D use, without statistical significance.
Jan 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/2/285, https://c19p.org/tylicki
1,102. Rangel et al., Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis
153 patient HCQ prophylaxis study: 25% lower mortality (p=0.77) and 22% lower hospitalization (p=0.29).Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically significant due to the small number of events. The actual benefit for HCQ could be much larger. The study does not address the risk of being sick enough to visit the hospital. HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Jan 2021, J. the American Academy of Dermatology, https://www.sciencedirect.com/science/article/pii/S0190962221001109, https://c19p.org/rangel
1,103. Hegazy et al., Beyond probiotic legend: ESSAP gut microbiota health score to delineate SARS-COV-2 infection severity
200 patient exercise study: 46% fewer moderate/severe cases (p=0.11).Analysis of 200 mild and moderate COVID-19 outpatients showing an association between higher ESSAP scores (measuring exercise, sugar and prebiotic consumption, sleep, and antibiotic use) and milder COVID-19 disease. Authors find increased risk with daily yogurt containing probiotics. Probiotic intake based on yogurt only may be inaccurate. Authors hypothesize that commercial yogurt products may not contain sufficient beneficial bacteria or may be contaminated. Other research shows that probiotic food labels are often misleading—of 26 probiotic foods tested, only 5 contained Bifidobacterium in sufficient concentration for exhibiting a therapeutic effect [Hazan]. For sleep, authors compare <8 hours and ≥8 hours, while sleep for less than or longer than a recommended range may indicate increased risk.
Jun 2021, British J. Nutrition, https://www.cambridge.org/core/product/identifier/S0007114521001926/type/journal_article, https://c19p.org/hegazy2
1,104. Mas Romero et al., COVID-19 outbreak in long-term care facilities from Spain. Many lessons to learn
198 patient proton pump inhibitor prophylaxis study: 26% lower mortality (p=0.44) and 8% more symptomatic cases (p=0.54).Retrospective 1,084 residents from 6 long-term care facilities in Spain showing no signficant difference in cases and mortality with PPI use in unadjusted results.
Oct 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241030, https://c19p.org/masromero
1,105. Trullàs et al., High in-hospital mortality due to COVID-19 in a community hospital in Spain: a prospective observational study
100 patient HCQ late treatment study: 36% lower mortality (p=0.12).Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ.
Jul 2020, Research Square, https://www.researchsquare.com/article/rs-39421/v1, https://c19p.org/trullas
1,106. Abd-Elsalam et al., Do Zinc Supplements Enhance the Clinical Efficacy of Hydroxychloroquine?: a Randomized, Multicenter Trial
191 patient zinc late treatment RCT: 1% lower mortality (p=0.99), 34% lower ventilation (p=0.54), 6% improved recovery (p=0.97), and 4% shorter hospitalization (p=0.55).191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. No information on baseline zinc values was recorded. Egypt has a low rate of zinc deficiency so supplementation may be less likely to be helpful [ncbi.nlm.nih.gov, ncbi.nlm.nih.gov]. For several issues with this trial, see [osf.io]. See also [link.springer.com]. The primary outcome was changed from viral clearance to "improvement or mortality" in the last month of the trial. The pre-specified outcome was not reported.
Nov 2020, Biological Trace Element Research, https://link.springer.com/article/10.1007/s12011-020-02512-1, https://c19p.org/abdelsalam2z
1,107. Fogleman et al., A Pilot of a Randomized Control Trial of Melatonin and Vitamin C for Mild-to-Moderate COVID-19
66 patient vitamin C late treatment RCT: 4% improved recovery (p=0.83).Early terminated low-risk patient RCT with 32 low-dose vitamin C, 32 melatonin, and 34 placebo patients, showing faster resolution of symptoms with melatonin in spline regression analysis, and no significant difference for vitamin C. All patients recovered with no serious outcomes reported. Baseline symptoms scores were higher in the melatonin and vitamin C arms (median 27 and 24 vs. 18 for placebo).
Jul 2022, The J. the American Board of Family Medicine, http://www.jabfm.org/lookup/doi/10.3122/jabfm.2022.04.210529, https://c19p.org/foglemanc
1,108. Mohajeri et al., Adherence to the Mediterranean Diet Association with Serum Inflammatory Factors Stress Oxidative and Appetite in COVID-19 Patients
600 patient diet study: 25% lower progression (p<0.0001).Retrospective 600 COVID-19 patients in Iran with moderate/severe CT scans, showing lower prevalence of dyspnea, fever, taste/smell abnormalities, and cough with high adherence to the Mediterranean diet in unadjusted results.
Jan 2023, Medicina, https://www.mdpi.com/1648-9144/59/2/227, https://c19p.org/mohajeri2
107 patient ursodeoxycholic acid prophylaxis study: 38% improved recovery (p=0.05).
Retrospective 115 COVID-19 patients hospitalized during an Omicron outbreak in China, of which 65 received ursodeoxycholic acid (UDCA) treatment and 50 received standard care. It found that UDCA was associated with faster body temperature recovery, with a hazard ratio of 1.62 (95% CI 0.99-2.60, p=0.053) compared to standard care after adjusting for covariates. Patients receiving higher UDCA doses (≥300mg daily) had significantly faster recovery than the standard care group, with a hazard ratio of 1.82 (95% CI 1.07-3.10, p=0.028). To further analyze the exposure-response relationship, the authors developed an AI model called VirtualBody that accurately predicted individualized UDCA pharmacokinetic profiles. Additional analysis using VirtualBody-generated data found UDCA AUC, indicating total exposure over time, had a stronger correlation with clinical outcome than cumulative dose. Overall, the study suggests UDCA may shorten recovery time from COVID-19, especially at higher doses,..
May 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.05.02.23289410, https://c19p.org/yu5
1,110. Hartantri et al., Clinical and treatment factors associated with the mortality of COVID-19 patients admitted to a referral hospital in Indonesia
favipiravir late treatment study: 76% lower mortality (p=0.0005).Retrospective 689 hospitalized patients in Indonesia, showing lower mortality with favipiravir treatment.
Feb 2023, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368223000276, https://c19p.org/hartantri
1,111. Sawanpanyalert et al., Assessment of outcomes following implementation of antiviral treatment guidelines for COVID-19 during the first wave in Thailand
favipiravir early treatment study: 68% lower progression (p=0.003).Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided.
Sep 2021, Southeast Asian J. Tropical Medicine and Public Health, https://journal.seameotropmednetwork.org/index.php/jtropmed/article/view/490, https://c19p.org/sawanpanyalerta
1,112. Monserrat Villatoro et al., A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis
colchicine prophylaxis PSM study: 80% lower mortality (p=0.02).PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoroo
1,113. Tse et al., Aspirin is associated with lower risks of severe covid-19 disease: a population-based study
2,664 patient aspirin prophylaxis PSM study: 67% lower combined mortality/intubation (p=0.0003).PSM retrospective 2,664 COVID-19 hospitalized patients receiving steroids/antiviral therapy in Hong Kong, showing lower risk of combined death/intubation with aspirin use.
Jun 2023, Heart, https://heart.bmj.com/content/109/Suppl_3/A244.2, https://c19p.org/tse
1,114. He et al., Clinical characteristics and risk factors for in-hospital mortality of COVID-19 patients in Hubei Province: A multicenter retrospective study
53,030 patient metformin late treatment study: 74% lower mortality (p<0.0001).Retrospective 53,030 COVID-19 patients from 138 hospitals in Hubei, China showing lower mortality with metformin.
Nov 2024, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906724002409, https://c19p.org/he2
1,115. Baynouna AlKetbi et al., Risk Factors for SARS-CoV-2 Infection Severity in Abu Dhabi
exercise study: 98% lower mortality (p=0.05).Retrospective 234 COVID-19 cases in the United Arab Emirates, showing lower risk of mortality with increased physical activity.
Aug 2021, J. Epidemiology and Global Health, https://link.springer.com/article/10.1007/s44197-021-00006-4/fulltext.html, https://c19p.org/baynounaalketbi
1,116. Brawner et al., Inverse Relationship of Maximal Exercise Capacity to Hospitalization Secondary to Coronavirus Disease 2019
exercise study: 74% lower hospitalization (p=0.001).Retrospective 246 COVID-19 patients in the USA, showing the risk of hospitalization inversely associated with maximal exercise capacity. Adjusted results are only provided for MET as a continuous variable.
Oct 2020, Mayo Clinic Proceedings, https://www.mayoclinicproceedings.org/article/S0025-6196(20)31130-7/fulltext, https://c19p.org/brawner
1,117. Monserrat Villatoro et al., A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis
loratadine prophylaxis PSM study: 80% lower mortality (p=0.05).PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of loratadine.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoroh1
70 patient HCQ prophylaxis study: 50% lower mortality (p=0.67).
Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.26.20219154v1, https://c19p.org/arleo
1,119. Din Ujjan et al., The possible therapeutic role of curcumin and quercetin in the early-stage of COVID-19—Results from a pragmatic randomized clinical trial
50 patient vitamin D early treatment RCT: 29% improved recovery (p=0.11) and 91% improved viral clearance (p=0.05).Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.
Jan 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full, https://c19p.org/dinujjan
1,120. Behera et al., Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study
215 patient vitamin C prophylaxis study: 18% fewer cases (p=0.58).Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/beherac
1,121. Razjouyan et al., Smoking Status and Factors associated with COVID-19 In-Hospital Mortality among US Veterans
7,846 patient smoking prophylaxis study: 3% lower mortality (p=0.8).Retrospective 10,074 hospitalized veterans with COVID-19 in the USA, showing higher risk of mortality for former smokers and no significant difference for current smokers.
Oct 2021, Nicotine & Tobacco Research, https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntab223/6409756?login=false, https://c19p.org/razjouyansm
1,122. Shehab et al., Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection
253 patient zinc prophylaxis study: 47% lower severe cases (p=0.24).Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabz
1,123. Jones et al., Public health impact of poor sleep on COVID-19, influenza and upper respiratory infections
sleep study: 39% lower mortality (p=0.001), 32% lower hospitalization (p<0.0001), and 7% fewer cases (p=0.04).FinnGen Mendelian randomization study showing higher risk of COVID-19 mortality, hospitalization, and infection with insomnia.
Jul 2022, Sleep Medicine, https://www.sciencedirect.com/science/article/pii/S1389945722005536, https://c19p.org/jones
1,125. Salvucci et al., Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation
27 patient antihistamine H1RA long COVID study: 29% lower PASC (p=0.1).Retrospective 14 patients with long-COVID symptoms attributed to mast cell activation treated with H1 and H2 antihistamines compared to 13 control patients, showing significant improvements in several symptoms in the treatment group compared to controls after 20 days. 29% of treated patients had complete resolution of long-COVID symptoms, compared with none in the control group.
Jul 2023, Frontiers in Cardiovascular Medicine, https://www.frontiersin.org/articles/10.3389/fcvm.2023.1202696/full, https://c19p.org/salvucci
1,126. Yeramaneni et al., Famotidine Use Is Not Associated With 30-day Mortality: A Coarsened Exact Match Study in 7158 Hospitalized Patients With Coronavirus Disease 2019 From a Large Healthcare System
7,158 patient azithromycin late treatment study: 7% lower mortality (p=0.84).Retrospective 7,158 hospitalized COVID-19 patients in the USA analyzing famotidine treatment, showing no significant difference in mortality with associated azithromycin treatment.
Feb 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)35249-5/fulltext, https://c19p.org/yeramaneniazaz
24 patient povidone-iodine early treatment RCT: 74% improved viral load (p=0.27).
60 patient RCT comparing chlorhexidine, PVP-I, and saline in Saudi Arabia with a single mouth rinse treatment and PCR testing 5 minutes later, showing statistically significant improvement in Ct value for PVP-I. PVP-I showed greater improvement than saline, without statistical significance.
Jul 2022, Medicine, https://journals.lww.com/md-journal/Fulltext/2022/07290/The_short_term_effect_of_different_chlorhexidine.78.aspx, https://c19p.org/natto
1,128. Darban et al., Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial
20 patient zinc ICU RCT: 33% lower progression (p=1) and 6% shorter ICU admission (p=0.3).Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.
Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darbanz
1,129. Darban et al., Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial
20 patient melatonin ICU RCT: 33% lower progression (p=1) and 6% shorter ICU admission (p=0.3).Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.
Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darban
1,130. Bliden et al., Metformin Use in Patients Hospitalized With COVID-19: Lower Inflammation, Oxidative Stress, and Thrombotic Risk Markers and Better Clinical Outcomes
75 patient metformin prophylaxis study: 60% lower mortality (p=0.21) and 76% lower ventilation (p=0.05).Retrospective 75 diabetes patients, 34 on metformin, showing lower mortality with treatment in unadjusted results with minimal group details.
Nov 2021, Circulation, 144:A12228, https://www.ahajournals.org/doi/abs/10.1161/circ.144.suppl_1.12228, https://c19p.org/bliden
1,131. Hofmann-Winkler et al., Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation
11 patient camostat ICU study: 58% lower mortality (p=0.55), 61% shorter ICU admission, and 56% improved recovery.Retrospective 11 critically ill COVID-19 ICU patients with organ failure treated with camostat mesylate (6 patients) or HCQ (5 patients). Over an 8 day period, the severity of COVID-19 decreased in the camostat group as measured by a decline in the SOFA score, inflammatory markers, and improvement in oxygenation. A similar effect was not seen in the HCQ group.
Nov 2020, Critical Care Explorations, https://journals.lww.com/10.1097/CCE.0000000000000284, https://c19p.org/hofmannwinkler
1,132. Akbar et al., The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank
10,000 patient exercise study: 7% fewer cases (p=0.4).Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with increased leisure time physical activity, without statistical significance. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2ex
1,133. Orioli et al., Clinical characteristics and short-term prognosis of in-patients with diabetes and COVID-19: A retrospective study from an academic center in Belgium
73 patient HCQ late treatment study: 13% lower mortality (p=1).Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, p = 1.0.
Dec 2020, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://www.sciencedirect.com/science/article/pii/S1871402120305154, https://c19p.org/orioli
1,134. Mahto et al., Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India
689 patient diet study: 20% lower IgG positivity (p=0.32).Retrospective 689 healthcare workers in India, showing non-statistically significant lower risk of IgG positivity with a vegetarian diet in unadjusted results.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtodt
1,135. Kasiri et al., The effects of colchicine on hospitalized COVID-19 patients: A randomized, double-blind, placebo-controlled clinical trial
110 patient colchicine late treatment RCT: 7% lower mortality (p=1), 7% lower ventilation (p=1), 24% higher ICU admission (p=0.63), and 28% improved recovery (p=0.59).Very late treatment (10 days from onset) RCT 110 patients in Iran, showing no significant difference in outcomes with colchicine. Colchicine 2mg loading dose followed by 0.5mg bid for 7 days.
Jan 2023, J. Investigative Medicine, http://journals.sagepub.com/doi/10.1177/10815589221141815, https://c19p.org/kasiri
1,136. Menardi et al., A retrospective analysis on pharmacological approaches to COVID-19 patients in an Italian hub hospital during the early phase of the pandemic
277 patient HCQ late treatment study: 35% lower mortality (p=0.12).Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication.
Sep 2021, PharmAdvances, http://www.pharmadvances.com/a-retrospective-analysis-on-pharmacological-approaches-to-covid-19-patients-in-an-italian-hub-hospital-during-the-early-phase-of-the-pandemic-2/, https://c19p.org/menardi
1,137. Reis et al., Effect of Early Treatment with Ivermectin among Patients with Covid-19
1,358 patient ivermectin early treatment RCT: while presented as negative, the co-principal investigator privately reported that "there is a clear signal that IVM works in COVID patients".Together Trial Ivermectin: impossible data, critical issues, blinding broken, randomization failure, data pledge violation, protocol violations.
Aug 2021, New England J. Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2115869, https://c19p.org/togetherivm
1,138. Fantozzi et al., Efficacy of antiseptic mouthrinses against SARS-CoV-2: A prospective randomized placebo-controlled pilot study
38 patient povidone-iodine late treatment RCT: 57% improved viral load and 31% improved viral clearance (p=0.26).Mouthrinse RCT in Italy comparing short-term viral load after a single 60 second treatment with povidone-iodine, hydrogen peroxide, chlorhexidine, and saline. The greatest efficacy was seen with povidone-iodine, especially for patients with low viral load at baseline.
Jul 2022, American J. Otolaryngology, https://www.sciencedirect.com/science/article/pii/S0196070922001764, https://c19p.org/fantozzi
1,139. Karruli et al., Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience
32 patient aspirin ICU study: 46% lower mortality (p=0.63).Retrospective 32 ICU patients showing lower mortality with aspirin treatment, without statistical significance.
Aug 2021, Microbial Drug Resistance, https://www.liebertpub.com/doi/full-xml/10.1089/mdr.2020.0489, https://c19p.org/karruli
1,140. Jabeen et al., Protective Effect of Vitamin-D Supplementation in Patients of Acute Coronary Syndrome During COVID-19 Pandemic
40 patient vitamin D prophylaxis study: 89% fewer symptomatic cases (p=0.11).Prospective study of 40 acute coronary syndrome patients in Pakistan, 20 given a single dose of 200,000IU vitamin D, showing lower incidence of COVID-19 in the following 2 months.
May 2022, Pakistan J. Medical and Health Sciences, https://pjmhsonline.com/index.php/pjmhs/article/view/773, https://c19p.org/jabeen
1,141. Baguma et al., Characteristics of the COVID-19 patients treated at Gulu Regional Referral Hospital, Northern Uganda: A cross-sectional study
481 patient ivermectin late treatment study: 97% lower mortality (p=0.31).Retrospective COVID+ hospitalized patients in Uganda, showing no statistically significant difference in mortality with ivermectin, however there were only 7 patients receiving ivermectin.
Dec 2021, Research Square, https://www.researchsquare.com/article/rs-1193578/v1, https://c19p.org/baguma
1,142. Pinchera et al., Diabetes and SARS-CoV-2 Infection: The Potential Role of Antidiabetic Therapy in the Evolution of COVID-19
43 patient metformin prophylaxis study: 15% lower severe cases (p=0.05).Retrospective 43 diabetes patients hospitalized for COVID-19 in Italy, showing lower risk of severe cases with metformin vs. insulin.
Jan 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/1/145, https://c19p.org/pinchera
1,143. Cárdenas-Jaén et al., Gastrointestinal symptoms and complications in patients hospitalized due to COVID-19, an international multicentre prospective cohort study (TIVURON project)
829 patient HCQ late treatment study: 56% lower severe cases (p=0.13).Retrospective 829 hospitalized COVID-19 patients in Spain focused on gastrointestinal symptoms, showing lower risk of severe COVID-19 with HCQ treatment in bivariate analysis, without statistical significance.
Jun 2023, Gastroenterología y Hepatología, https://www.sciencedirect.com/science/article/pii/S2444382423001104, https://c19p.org/cardenasjaen
1,144. Ip et al., Hydroxychloroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study
2,512 patient HCQ late treatment study: 1% lower mortality (p=0.93).Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), HCQ alone (HR, 1.02 [95% CI, 0.83-1.27]), or HCQ+AZ (HR, 0.98 [95% CI, 0.75-1.28]). Misclassification is possible due to manual abstraction of EHR data. They observed a change in the prescribing patterns of HCQ during the study timeframe. Confounding by indication.
May 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237693, https://c19p.org/ip2
1,145. Bejan et al., DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing
9,229 patient aspirin prophylaxis study: 1% lower ventilation (p=0.97).Retrospective 9,748 COVID-19 patients in the USA showing no signficant difference with aspirin use.
Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejane
1,146. Martinez-Lopez et al., Multiple Myeloma and SARS-CoV-2 Infection: Clinical Characteristics and Prognostic Factors of Inpatient Mortality
167 patient HCQ late treatment study: 33% lower mortality (p=0.2).Retrospective 167 multiple myeloma patients in Spain, showing no significant difference in mortality with HCQ treatment in unadjusted results without group details.
Jun 2020, Blood Cancer J., https://www.nature.com/articles/s41408-020-00372-5, https://c19p.org/martinezlopez
1,147. Campbell et al., Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19
22,125 patient ibuprofen prophylaxis study: no change in mortality (p=0.54).Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic ibuprofen use vs. sporadic NSAID use. Since ibuprofen is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2ib
1,148. Murai et al., Effect of a Single High Dose of Vitamin D3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19: A Randomized Clinical Trial
237 patient vitamin D late treatment RCT: 49% higher mortality (p=0.43), 48% lower ventilation (p=0.09), 25% lower ICU admission (p=0.3), and 7% higher hospital discharge (p=0.63).Very late stage (mean 10 days from symptom onset, 90% on oxygen at baseline) vitamin D supplementation RCT not showing significant differences. Ethnicity was poorly matched between arms, and diabetes was 41% in the treatment arm vs. 29% in the control arm. Baseline ventilation was 15% in the treatment arm vs. 12% control. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage. Treatment was dissolved in 10mL of peanut oil.
Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2776738, https://c19p.org/murai
60 patient azithromycin late treatment study: 85% lower mortality (p=0.31).
RCT 60 hospitalized COVID-19 patients evaluating the efficacy and safety of adding oral N-acetylcysteine (NAC) at 600mg three times daily to standard antiviral treatment regimens. There was lower mortality for patients that received azithromycin, without statistical significance.
Nov 2023, Immunity, Inflammation and Disease, https://onlinelibrary.wiley.com/doi/10.1002/iid3.1083, https://c19p.org/atefiazaz
1,150. Krishnan et al., Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia
152 patient HCQ late treatment study: 20% lower mortality (p=0.48).Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnan
1,151. Hafez et al., Antiviral Used among Non-Severe COVID-19 Cases in Relation to Time till Viral Clearance: A Retrospective Cohort Study
1,486 patient HCQ late treatment study: 12% faster viral clearance (p=0.59).Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir.
Apr 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/4/498, https://c19p.org/hafez
1,152. Rodriguez et al., Severe infection due to the SARS-CoV-2 coronavirus: Experience of a tertiary hospital with COVID-19 patients during the 2020 pandemic
43 patient HCQ late treatment study: 59% lower mortality (p=0.23).Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, p=0.23.
Nov 2020, Medicina Intensiva, https://www.sciencedirect.com/science/article/pii/S2173572720301739, https://c19p.org/rodriguez
1,153. Beaumont et al., Factors associated with hospital admission and adverse outcome for COVID-19: role of social factors and medical care
296 patient HCQ late treatment study: 14% lower combined mortality/intubation (p=0.55).Retrospective 296 hospitalized patients in France, showing no significant difference with HCQ treatment.
Feb 2022, Infectious Diseases Now, https://www.sciencedirect.com/science/article/pii/S266699192200032X, https://c19p.org/beaumont
1,154. Paccoud et al., Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital
89 patient HCQ late treatment study: 11% lower mortality (p=0.88).Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered.
Jun 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa791/5859555, https://c19p.org/paccoud
1,155. Kuno et al., The association between famotidine and in-hospital mortality of patients with COVID-19
9,565 patient famotidine late treatment PSM study: no change in mortality (p=0.97).PSM retrospective 9,565 COVID-19 hospitalized patients in the USA, 1,593 receiving famotidine, showing no significant difference in mortality.
Oct 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.27375, https://c19p.org/kuno2
1,156. Zhou et al., Secondary pulmonary infection and co-infection in elderly COVID-19 patients during the pandemics in a tertiary general hospital in Beijing, China
322 patient azvudine late treatment study: 22% lower mortality (p=0.15).Retrospective 322 hospitalized patients ≥65 in China, showing lower mortality with azvudine treatment, without statistical significance.
Oct 2023, Frontiers in Microbiology, https://www.frontiersin.org/articles/10.3389/fmicb.2023.1280026/full, https://c19p.org/zhou13azv
1,157. Mittra et al., Resveratrol and Copper for treatment of severe COVID-19: an observational study (RESCU 002)
230 patient resveratrol late treatment study: 44% lower mortality (p=0.06).Retrospective 230 severe COVID-19 patients in India, showing lower mortality with resveratrol + copper, without statistical significance. This study followed preclinical data showing that sepsis-related cytokine storm and fatality in mice could be prevented with oral administration of resveratrol and copper.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.21.20151423, https://c19p.org/mittra
1,158. Khoubnasabjafari et al., Prevalence of COVID-19 in patients with rheumatoid arthritis (RA) already treated with hydroxychloroquine (HCQ) compared with HCQ-naive patients with RA: a multicentre cross-sectional study
1,858 patient HCQ prophylaxis study: 17% fewer cases (p=0.59).Survey analysis of 1,858 RA patients in Iran, showing no significant difference in cases with HCQ prophylaxis.
Jan 2021, Postgraduate Medical J., https://pmj.bmj.com/content/early/2021/01/13/postgradmedj-2020-139561, https://c19p.org/khoubnasabjafari
1,159. Blanch-Rubió et al., Influence of anti-osteoporosis treatments on the incidence of COVID-19 in patients with non-inflammatory rheumatic conditions
2,102 patient vitamin D prophylaxis study: 8% fewer cases (p=0.68).Retrospective 2,102 rheumatology patients in Spain showing no significant difference in cases with vitamin D supplementation. Details of vitamin D supplementation are not providied - other patients may have also independently taken vitamin D.
Oct 2020, Aging, https://www.aging-us.com/article/104117/text, https://c19p.org/blanchrubio
1,160. Güven et al., The effect of high-dose parenteral vitamin D3 on COVID-19-related inhospital mortality in critical COVID-19 patients during intensive care unit admission: an observational cohort study
175 patient vitamin D ICU study: 25% lower mortality (p=0.32).Retrospective 175 ICU patients, 113 treated with a single dose of 300,000IU intramuscular cholecalciferol, showing lower mortality with treatment, but not reaching statistical significance. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage.
Jul 2021, European J. Clinical Nutrition, https://www.nature.com/articles/s41430-021-00984-5, https://c19p.org/guven
30 patient povidone-iodine early treatment RCT: 6% improved viral clearance (p=0.74).
Small mouth rinsing and gargling RCT with 15 1% PVP-I, 12 0.5% PVP-I, 15 3% hydrogen peroxide, 12 1.5% hydrogen peroxide, and 15 water patients, showing rapid improvement in Ct value in all groups, and no significant differences between groups.
Mar 2022, F1000Research, https://f1000research.com/articles/11-1238/v1, https://c19p.org/sulistyani
1,162. Goldman et al., Remdesivir for 5 or 10 Days in Patients with Severe Covid-19
397 patient HCQ late treatment study: 22% lower mortality (p=0.46).Study focused on remdesivir but with results for HCQ in the supplementary appendix, showing 9% death with HCQ versus 12% control, unadjusted relative risk uRR 0.78, p = 0.46.
May 2020, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2015301, https://c19p.org/goldmanh
1,163. Podder et al., Outcome of ivermectin treated mild to moderate COVID-19 cases: a single-centre, open-label, randomised controlled study
62 patient ivermectin late treatment RCT: 16% faster recovery (p=0.34).Small RCT with 32 ivermectin patients and 30 control patients. The mean recovery time after enrolment in the intervention arm was 5.31 ± 2.48 days vs. 6.33 ± 4.23 days in the control arm, p > 0.05. Negative PCR results were not significantly different between control and intervention arms, p>0.05. We are not sure what the results were because the abstract and Table 5 have switched the results.
Sep 2020, IMC J. Med. Science, http://imcjms.com/registration/journal_abstract/353, https://c19p.org/podder
1,164. Shehab et al., Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection
253 patient curcumin prophylaxis study: 42% lower severe cases (p=0.55).Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabt
1,165. Karimpour-razkenari et al., Melatonin as adjunctive therapy in patients admitted to the Covid-19
31 patient melatonin ICU study: 39% lower mortality (p=0.37), 43% shorter ventilation (p=0.13), and 2% shorter ICU admission (p=0.85).Retrospective 31 ICU patients, 12 treated with melatonin, showing lower mortality with treatment, without statistical significance. Melatonin 15mg daily.
Mar 2022, Annals of Medicine and Surgery, https://www.sciencedirect.com/science/article/pii/S2049080122002527, https://c19p.org/karimpourrazkenari
1,166. Mahale et al., A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital
134 patient HCQ late treatment study: 29% lower mortality (p=0.36).Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with HCQ treatment in unadjusted results.
Dec 2020, Indian J. Critical Care Medicine, https://www.ijccm.org/doi/pdf/10.5005/jp-journals-10071-23599, https://c19p.org/mahaleh
1,167. Al Sulaiman et al., Ascorbic Acid as an Adjunctive Therapy in Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study
284 patient vitamin C late treatment PSM study: 15% lower mortality (p=0.27).Retrospective 158 critically ill patients receiving vitamin C and propensity matched controls, showing mortality OR 0.77 [0.48-1.23], and statistically significantly lower thrombosis, OR 0.42 [0.18-0.94]. 1000mg of vitamin C was given daily.
Apr 2021, Research Square, https://www.researchsquare.com/article/rs-354711/v1, https://c19p.org/alsulaiman2
1,168. He et al., Clinical characteristics and risk factors for in-hospital mortality of COVID-19 patients in Hubei Province: A multicenter retrospective study
53,030 patient HCQ late treatment study: 53% lower mortality (p<0.0001).Retrospective 53,030 COVID-19 patients from 138 hospitals in Hubei, China showing lower mortality with metformin.
Nov 2024, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906724002409, https://c19p.org/he2h
1,169. Madamombe et al., Factors associated with COVID-19 fatality among patients admitted in Mashonaland West Province, Zimbabwe 2020-2022: a secondary data analysis
672 patient vitamin C early treatment study: 53% lower mortality (p=0.0004).Retrospective 672 COVID-19 patients in Zimbabwe, showing lower mortality with vitamin C treatment.
Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombe
1,170. Sharif et al., Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study
vitamin C prophylaxis study: 46% lower severe cases (p=0.001).Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharifc
1,171. Sharif et al., Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study
zinc prophylaxis study: 40% lower severe cases (p=0.0001).Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharifz
1,172. Monserrat Villatoro et al., A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis
budesonide prophylaxis PSM study: 49% lower mortality (p=0.01).PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoro
1,173. Servais et al., Mortality-related risk factors of inpatients with diabetes and COVID-19: a multicenter retrospective study in Belgium
metformin prophylaxis study: 49% lower mortality (p=0.002).Retrospective 375 hospitalized diabetes patients in Belgium, showing lower risk of COVID-19 mortality with metformin use.
Dec 2022, Annals of Endocrinology, https://pubmed.ncbi.nlm.nih.gov/37574109/, https://c19p.org/servais
1,174. Sanchez et al., Influence of Physical Exercise on the Severity of COVID-19
exercise study: 54% fewer symptomatic cases (p<0.0001).Retrospective 29,875 university staff and students in Spain, 3,662 with data, showing lower risk of COVID-19 symptoms for people that exercise. Exercise more than 5 days/week was the most protective, and intense exercise was more effective than moderate exercise.
Apr 2023, Fisioterapia, https://www.sciencedirect.com/science/article/pii/S0211563823002006, https://c19p.org/sanchez
1,175. Ekblom-Bak et al., Cardiorespiratory fitness and lifestyle on severe COVID-19 risk in 279,455 adults: a case control study
exercise study: 48% lower severe cases (p=0.02).Retrospective 857 severe COVID-19 cases and matched controls in Sweden, showing lower risk of severe COVID-19 with higher cardiorespiratory fitness.
Oct 2021, Int. J. Behavioral Nutrition and Physical Activity, https://link.springer.com/article/10.1186/s12966-021-01198-5/fulltext.html, https://c19p.org/ekblombak
1,176. Maltagliati et al., Muscle strength explains the protective effect of physical activity against COVID-19 hospitalization among adults aged 50 years and older
exercise study: 52% lower hospitalization (p=0.02).Retrospective 3,139 adults >50 in Europe, with 66 COVID-19 hospitalizations, showing lower risk of hospitalization with higher physical activity and with higher muscle strength. Note that model 2 includes muscle strength which is correlated with physical activity [eurapa.biomedcentral.com].
Aug 2021, J. Sports Sciences, https://www.tandfonline.com/doi/pdf/10.1080/02640414.2021.1964721, https://c19p.org/maltagliati
1,177. Naushin et al., Insights from a Pan India Sero-Epidemiological survey (Phenome-India Cohort) for SARS-CoV2
diet study: 40% lower seropositivity (p<0.0001).Retrospective 10,427 volunteers in India, 1,058 anti-nucleocapsid antibody positive, showing lower risk of seropositivity with a vegetarian diet.
Apr 2021, eLife, https://elifesciences.org/articles/66537, https://c19p.org/naushin
1,178. Reznikov et al., Identification of antiviral antihistamines for COVID-19 repurposing
azelastine prophylaxis study: 45% fewer cases (p=0.03).Retrospective 219,000 patients showing lower risk of COVID-19 with antihistamine H1RA use. In Vitro study showing these drugs exhibit direct antiviral activity against SARS-CoV-2. Molecular docking suggests hydroxyzine and azelastine may exert antiviral effects by binding ACE2 and the sigma-1 receptor.
Jan 2021, Biochemical and Biophysical Research Communications, https://www.sciencedirect.com/science/article/pii/S0006291X20321409, https://c19p.org/reznikovazl
1,179. Madamombe et al., Factors associated with COVID-19 fatality among patients admitted in Mashonaland West Province, Zimbabwe 2020-2022: a secondary data analysis
672 patient azithromycin early treatment study: 40% lower mortality (p=0.03).Retrospective 672 COVID-19 patients in Zimbabwe, showing lower mortality with azithromycin treatment.
Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombeazaz
1,180. Piñana et al., Risk factors and outcome of COVID-19 in patients with hematological malignancies
azithromycin prophylaxis study: 58% lower mortality (p=0.02).Retrospective study of 367 hematology patients with COVID-19 in Spain. Among 216 patients with very severe COVID-19, there was significantly lower mortality with azithromycin treatment. Mortality was also lower with HCQ, but without statistical significance.
Aug 2020, Experimental Hematology & Oncology, https://ehoonline.biomedcentral.com/articles/10.1186/s40164-020-00177-z, https://c19p.org/pinanaazaz
1,181. Doocy et al., Clinical progression and outcomes of patients hospitalized with COVID-19 in humanitarian settings: A prospective cohort study in South Sudan and Eastern Democratic Republic of the Congo
144 patient zinc late treatment study: 41% lower mortality (p=0.41).Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing lower mortality with zinc treatment, without statistical significance.
Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocyz
1,182. Bielza et al., Clinical characteristics, frailty and mortality of residents with COVID-19 in nursing homes of a region of Madrid
630 patient HCQ late treatment study: 22% lower mortality (p=0.09).Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, p = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Median age 87.
Dec 2020, J. the American Medical Directors Association, https://www.sciencedirect.com/science/article/pii/S1525861020310525, https://c19p.org/bielza
1,183. Hashmi et al., Ivermectin for patients admitted to an ICU with COVID-19: REMAP-CAP randomized controlled trial
150 patient ivermectin ICU RCT: 15% lower mortality (p=0.64) and 24% improvement (p=0.57).Early terminated REMAP-CAP results delayed >600 days, showing no significant differences with very low dose, poor administration, very late treatment of ICU patients. Results trend towards benefit for non-critical patients, with 32% lower mortality in unadjusted results, despite higher baseline severity in the treatment group. Results are currently only available in a CCR24 presentation. There are many critical issues as below. Authors appear to have post-hoc removed adjustment for severity to favor the control group. Preliminary analysis, please report errors or other issues. Severity Issue CRITICAL 1. Severity adjustment deleted in second post-hoc SAP CRITICAL 2. Baseline severity favors control CRITICAL 3. 32% lower mortality for non-critical patients CRITICAL 4. Expected failure based on design CRITICAL 5. Inclusion change to ICU only CRITICAL 6. >600 days delay in reporting CRITICAL 7. Adjustment direction different from expected CRITICAL 8. Remdesivir use CRITICAL 9. Bias in..
Jun 2024, Critical Care Reviews, CCR24, https://criticalcarereviews.com/meetings/ccr24#1, https://c19p.org/hashmi
1,184. Mahto et al., Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India
689 patient HCQ prophylaxis study: 27% lower IgG positivity (p=0.38).Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with HCQ prophylaxis in unadjusted results.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahto
1,185. Kyagambiddwa et al., Thirty-Day Outcomes of Young and Middle-Aged Adults Admitted with Severe COVID-19 in Uganda: A Retrospective Cohort Study
246 patient zinc late treatment study: 25% lower mortality (p=0.28).Retrospective 246 severe COVID-19 patients in Uganda, showing lower mortality with zinc treatment in unadjusted results, without statistical significance.
May 2023, Infection and Drug Resistance, https://www.dovepress.com/thirty-day-outcomes-of-young-and-middle-aged-adults-admitted-with-seve-peer-reviewed-fulltext-article-IDR, https://c19p.org/kyagambiddwaz
1,186. Bennani et al., Androgen deprivation therapy may constitute a more effective COVID-19 prophylactic than therapeutic strategy
118 patient various antiandrogen prophylaxis study: 95% lower mortality (p=1), 119% higher ICU admission (p=0.4), 25% lower hospitalization (p=0.6), and 8% lower severe cases (p=1).Retrospective 118 prostate cancer patients, 4 on androgren deprivation therapy, not showing significant differences (as expected with only 4 patients in the treatment group).
Aug 2020, Annals of Oncology, https://www.annalsofoncology.org/article/S0923-7534(20)42103-9/fulltext, https://c19p.org/bennani
1,187. Alizadeh et al., High dose melatonin as an adjuvant therapy in intubated patients with COVID-19: A randomized clinical trial
67 patient melatonin ICU RCT: 4% lower mortality (p=0.73), 14% improved recovery (p=0.19), and 27% shorter ventilation (p=0.09).RCT 67 extremely late stage intubated patients in Iran, showing lower CRP with melatonin treatment, but no significant difference in outcomes.
May 2022, J. Taibah University Medical Sciences, https://www.sciencedirect.com/science/article/pii/S1658361222000877, https://c19p.org/alizadeh2
1,188. Bychinin et al., Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU
106 patient vitamin D ICU RCT: 27% lower mortality (p=0.18), 7% lower ventilation (p=0.68), 94% longer ICU admission (p=0.001), and 41% longer hospitalization (p=0.007).RCT ICU patients in Russia, showing significantly increased lymphocyte counts with treatment. Mortality was lower but without statistical significance. 40% of patients were on mechanical ventilation at baseline in the treatment group, compared to 30% in the placebo group. Authors state that there has been 6 RCTs for COVID-19 and vitamin D, however there was at least 23 at the time of publication: [c19early.org].
Nov 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-22045-y, https://c19p.org/bychinin2
1,189. Yüksel et al., Effects of high dose vitamin c on patient outcomes in ARDS patients admitted to intensive care with COVID-19; multi-center retrospective study
86 patient vitamin C ICU PSM study: 19% lower mortality (p=0.04).PSM retrospective 86 ICU patients on mechanical ventilation in Turkey, showing lower mortality with high dose vitamin C treatment (≥200mg/kg for 4 days).
Sep 2020, Intensive Care Medicine Experimental, 9:S1, 001458, https://icm-experimental.springeropen.com/track/pdf/10.1186/s40635-021-00413-8.pdf, https://c19p.org/yuksel
1,190. Hong et al., Use of combined treatment of 3rd-generation cephalosporin, azithromycin and antiviral agents on moderate SARs-CoV-2 patients in South Korea: A retrospective cohort study
30 patient HCQ late treatment PSM study: 25% faster recovery (p=0.45), 13% longer hospitalization (p=0.75), and no change in viral clearance (p=0.99).Retrospective 25 hospitalized patients treated with cephalosporin, azithromycin, and HCQ, and 217 SOC patients in South Korea, reporting no significant differences. 5 patients receiving lopinavir/ritonavir and HCQ >5 days were excluded for unknown reasons. HCQ was typically initiated based on progression or side effects from another treatment. Conflicting results are reported. Table 2 indicates 15 CA/HCQ patients after matching, while Table S2 shows 25, and the Table 3 count is blank. S2 appears to incorrectly show before matching results, and the after matching results are missing in Table 3. 200mg HCQ bid.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267645, https://c19p.org/hong2
1,191. Niwas et al., Clinical outcome, viral response and safety profile of chloroquine in COVID-19 patients — initial experience
29 patient HCQ late treatment study: 29% faster recovery (p=0.008).Retrospective 12 hospitalized patients in India treated with CQ and 17 controls, showing faster recovery with treatment. There was no significant difference in viral clearance. The CQ group mean age was 41.3 vs. 47.6 for controls.
Oct 2020, Advances in Respiratory Medicine, https://journals.viamedica.pl/advances_in_respiratory_medicine/article/view/69692, https://c19p.org/niwas
1,192. Hafez et al., Factors Influencing Disease Stability and Response to Tocilizumab Therapy in Severe COVID-19: A Retrospective Cohort Study
42 patient vitamin D late treatment study: 94% lower mortality (p=0.07).Retrospective 49 severe COVID-19 patients treated with tocilizumab, showing lower mortality with vitamin D treatment and a dose-dependent response.
Aug 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/8/1078, https://c19p.org/hafez2
1,193. Chachar et al., Effectiveness of Ivermectin in SARS-CoV-2/COVID-19 Patients
50 patient ivermectin late treatment RCT: 10% improved recovery (p=0.5).Small RCT with 25 ivermectin and 25 control patients, not finding a significant difference in recovery at day 7.
Sep 2020, Int. J. Sciences-35, https://www.ijsciences.com/pub/article/2378, https://c19p.org/chachar
1,194. Kumar et al., Role of Zinc and Clinicopathological Factors for COVID-19-Associated Mucormycosis (CAM) in a Rural Hospital of Central India: A Case-Control Study
105 patient zinc prophylaxis study: 20% lower mortality (p=0.71).Case control study of 105 COVID-19 patients in India, 55 with mucormycosis and 50 without, showing zinc prophylaxis and diabetes both associated with mucormycosis in unadjusted results. This is likely confounded because zinc supplementation is commonly used with diabetes [academic.oup.com], and Arora et al. show lower risk of mucormycosis with zinc prophylaxis, aOR 0.05 [0.01–0.19] [Arora]. There was no significant difference in mortality based on zinc prophylaxis in unadjusted results.
Feb 2022, Cureus, https://www.cureus.com/articles/87998-role-of-zinc-and-clinicopathological-factors-for-covid-19-associated-mucormycosis-cam-in-a-rural-hospital-of-central-india-a-case-control-study, https://c19p.org/kumar4
1,195. Citu et al., Calcium, Magnesium, and Zinc Supplementation during Pregnancy: The Additive Value of Micronutrients on Maternal Immune Response after SARS-CoV-2 Infection
135 patient zinc prophylaxis study: 18% lower severe cases (p=1).Retrospective 448 pregnant women with COVID-19. Patients with calcium, zinc, and magnesium supplementation, or magnesium only, had a significantly higher titer of SARS-CoV-2 anti-RBD antibodies. There was no statistically significant difference in severe cases based on supplementation.
Mar 2022, Nutrients, https://www.mdpi.com/2072-6643/14/7/1445, https://c19p.org/citu
1,196. Ebrahimzadeh et al., Major dietary patterns in relation to disease severity, symptoms, and inflammatory markers in patients recovered from COVID-19
diet study: 69% lower severe cases (p=0.004), 56% lower hospitalization (p=0.07), and 68% improved recovery (p=0.003).Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases and shorter recovery and hospitalization times with a healthy diet. Notably, all individual symptoms show lower incidence with a healthy diet with the exception of fever and chills. Fever and chills help the immune system fight infections (shivering helps to raise the body temperature).
Aug 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.929384/full, https://c19p.org/ebrahimzadeh
1,197. Loucera et al., Real-world evidence with a retrospective cohort of 15,968 COVID-19 hospitalized patients suggests 21 new effective treatments
15,968 patient vitamin B9 prophylaxis study: 1% lower mortality (p=0.88).Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing no significant difference in mortality with existing use of folic acid. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.
Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3b9
1,198. Ozcifci et al., The incidence, clinical characteristics, and outcome of COVID-19 in a prospectively followed cohort of patients with Behçet’s syndrome
1,047 patient colchicine prophylaxis study: 4% fewer cases (p=0.72).Prospective analysis of 1,047 Behçet’s syndrome patients in Turkey, showing no significant difference in cases with colchicine use.
Nov 2021, Rheumatology Int., https://link.springer.com/10.1007/s00296-021-05056-2, https://c19p.org/ozcifci
1,199. Maldonado et al., COVID-19 incidence and outcomes in a home dialysis unit in Madrid (Spain) at the height of the pandemic
12 patient HCQ late treatment study: 91% lower mortality (p=0.17).Very small retrospective of 12 dialysis patients showing 1/11 deaths with HCQ and 1/1 without HCQ.
Nov 2020, Nefrología, https://www.sciencedirect.com/science/article/pii/S0211699520301661, https://c19p.org/maldonado
1,200. Martin-Vicente et al., Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients
92 patient HCQ ICU study: 59% lower mortality (p=0.41).Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21253121v1, https://c19p.org/martinvicente
1,201. Haji Aghajani et al., Decreased in-hospital mortality associated with aspirin administration in hospitalized patients due to severe COVID-19
991 patient HCQ late treatment study: 19% lower mortality (p=0.09).Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.
Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27053, https://c19p.org/hajiaghajani
1,202. Donida et al., First COVID-19 wave in the province of Bergamo, Italy: epidemiological and clinical characteristics, outcome and management of the first hospitalized patients
723 patient azithromycin late treatment study: 7% lower mortality (p=0.79).Retrospective 723 hospitalized COVID-19 patients in Italy showing no significant difference with azithromycin treatment.
Jan 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09034-4, https://c19p.org/donidaazaz
1,203. Chen et al., Oral Azvudine (FNC) Tablets in Patients infected with SARS-CoV-2 Omicron Variant: A Retrospective Cohort Study
207 patient azvudine early treatment study: 12% slower recovery (p=0.95) and 32% improved viral clearance (p=0.04).Retrospective 207 COVID-19 patients in China, showing azvudine associated with faster viral clearance, with azvudine-treated patients obtaining a negative PCR test result 1.7 days faster on average compared to supportive care alone after adjusting for age and sex.
Jan 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.01.05.23284180, https://c19p.org/chen13
1,204. Fernández-Cruz et al., Higher mortality of hospitalized haematologic patients with COVID-19 compared to non-haematologic is driven by thrombotic complications and development of ARDS: An age-matched cohorts study
71 patient HCQ late treatment study: 27% lower mortality (p=0.47).Retrospective 71 hospitalized haematologic patients in Spain, showing lower mortality with HCQ treatment in unadjusted results and without statistical significance.
Jan 2022, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S259017022200005X, https://c19p.org/fernandezcruz
1,205. Chaccour et al., The effect of early treatment with ivermectin on viral load, symptoms and humoral response in patients with non-severe COVID-19: A pilot, double-blind, placebo-controlled, randomized clinical trial
24 patient ivermectin early treatment RCT: 96% improved symptoms (p=0.05), 95% improved viral load (p=0.01), and 8% improved viral clearance (p=1).Tiny RCT for early treatment of mild COVID-19 in low risk patients, with 12 400mcg/kg single dose ivermectin patients and 12 control patients, showing significantly faster viral load reduction and symptom improvement with ivermectin. Average median viral load for gene E and gene N mid-viral recovery at day 7: Ivermectin: 1637, control: 30175 (supplementary appendix).
Dec 2020, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30464-8/fulltext, https://c19p.org/chaccour
1,206. Shupp et al., Proton pump inhibitor therapy usage and associated hospitalization rates and critical care outcomes of COVID-19 patients
2,496 patient proton pump inhibitor prophylaxis study: 19% lower mortality (p=0.32) and 10% higher hospitalization (p=0.51).Retrospective 2,594 COVID-19 patients in the United States showing no significant association between proton pump inhibitor (PPI) use and COVID-19 severity, including need for hospitalization or 30-day mortality. There was increasing mortality with increasing PPI use with 14%, 20%, and 27% mortality for low, standard, and high use, without statistical significance.
May 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-11680-0, https://c19p.org/shupp
1,207. Paul et al., Health behaviours the month prior to COVID-19 infection and the development of self-reported long COVID and specific long COVID symptoms: A longitudinal analysis of 1,811 UK adults
1,811 patient sleep study: 67% lower PASC (p<0.0001).Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with good sleep quality in the month before infection.
Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paul
1,208. Elmunzer et al., Association Between Preadmission Acid Suppressive Medication Exposure and Severity of Illness in Patients Hospitalized With COVID-19
1,846 patient proton pump inhibitor prophylaxis study: 13% lower mortality (p=0.31) and 2% higher ventilation (p=0.89).Retrospective 1,846 hospitalized COVID-19 patients in North America showing no significant association between preadmission proton pump inhibitor (PPI) use and mechanical ventilation or mortality. Results do not account for the risk of hospitalization based on PPI use.
Mar 2021, Gastroenterology, https://www.sciencedirect.com/science/article/pii/S0016508520353956, https://c19p.org/elmunzer
1,209. Ravindra et al., Retrospective Assessment of Treatments of Hospitalized Covid-19 Patients
366 patient metformin prophylaxis study: 30% lower mortality (p=0.42).Retrospective 1,035 hospitalized patients in India. Of 366 diabetic patients, there was lower mortality for the 53 that were on metformin.
May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.20.21255792v2, https://c19p.org/ravindra
1,210. Lokanuwatsatien et al., Prevalence and associating factors of long COVID in pediatric patients during the Delta and the Omicron variants
802 patient favipiravir early treatment study: 14% lower PASC (p=0.34).Prospective analysis of 802 COVID-19 pediatric patients in Thailand, showing no significant difference in long COVID with favipiravir treatment in unadjusted results.
May 2023, Frontiers in Pediatrics, https://www.frontiersin.org/articles/10.3389/fped.2023.1127582/full, https://c19p.org/lokanuwatsatien
1,211. Alieva et al., Factors influencing the severity of COVID-19 course for patients with diabetes mellitus in tashkent: a retrospective cohort study
763 patient metformin prophylaxis study: 15% lower hospitalization (p=0.56).Retrospective 763 COVID-19 patients with type 2 diabetes in Uzbekistan, showing lower hospitalization with metformin use in unadjusted results, without statistical significance.
Jun 2023, Obesity and metabolism, https://www.omet-endojournals.ru/jour/article/view/12801, https://c19p.org/alieva
1,212. Al Sulaiman et al., Evaluation of Zinc Sulfate as an Adjunctive Therapy in COVID-19 Critically Ill Patients: a Two Center Propensity-score Matched Study
164 patient zinc ICU PSM study: 36% lower mortality (p=0.11), 25% longer ICU admission (p=0.28), and 6% longer hospitalization (p=0.61).Retrospective 266 ICU patients showing lower mortality with zinc treatment, reaching statistical significance only for 30 day mortality, and lower odds of acute kidney injury, without statistical significance. NRC21R/287/07.
Jun 2021, Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-021-03785-1, https://c19p.org/alsulaiman
1,213. Saadeh et al., Associations of pre-pandemic levels of physical function and physical activity with COVID-19-like symptoms during the outbreak
587 patient exercise study: 9% fewer symptomatic cases (p=0.71).Retrospective 904 patients in Sweden, showing higher risk of COVID-19-like symptoms with poor muscle strength. Risk was slightly higher for physical inactivity, without statistical significance.
Oct 2021, Aging Clinical and Experimental Research, https://link.springer.com/article/10.1007/s40520-021-02006-7/fulltext.html, https://c19p.org/saadeh
1,214. Mannucci et al., Infection Rates and Impact of Glucose Lowering Medications on the Clinical Course of COVID-19 in People with Type 2 Diabetes: A Retrospective Observational Study
metformin prophylaxis study: 38% lower mortality (p=0.02) and 15% lower hospitalization (p=0.25).Retrospective 54,009 diabetes patients in Italy, showing lower mortality with metformin use.
Oct 2022, Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, https://www.dovepress.com/infection-rates-and-impact-of-glucose-lowering-medications-on-the-clin-peer-reviewed-fulltext-article-DMSOhttps://www.dovepress.com/getfile.php?fileID=84551, https://c19p.org/mannucci
1,215. Hraiech et al., Lack of viral clearance by the combination of hydroxychloroquine and azithromycin or lopinavir and ritonavir in SARS-CoV-2-related acute respiratory distress syndrome
32 patient HCQ ICU study: 65% lower mortality (p=0.21) and 3% worse viral clearance (p=1).Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6 days from ARDS.
May 2020, Ann. Intensive Care, https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00678-4, https://c19p.org/hraiech
1,216. Dominguez-Nicolas et al., Low-field thoracic magnetic stimulation increases peripheral oxygen saturation levels in coronavirus disease (COVID-19) patients
22 patient thermotherapy late treatment study: 53% greater improvement (p=0.05).Single-blind, sham-controlled, crossover study of 17 COVID-19 outpatients showing significantly increased peripheral oxygen saturation (SpO2) levels correlated with hyperthermia (up to 44°C) produced by 30 minutes of low-field thoracic magnetic stimulation (LF-ThMS) applied to the dorsal thorax. The safety and lack of adverse events supports future research into mechanisms and potential therapeutic use of localized heat therapy for improving respiratory function in COVID-19 patients.
May 2021, Medicine, https://journals.lww.com/10.1097/MD.0000000000027444, https://c19p.org/domingueznicolas
1,217. Alqassieh et al., Clinical characteristics and predictors of the duration of hospital stay in COVID-19 patients in Jordan
131 patient HCQ late treatment study: 18% shorter hospitalization (p=0.11).Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, p = 0.11.
Dec 2020, F1000Research, https://f1000research.com/articles/9-1439, https://c19p.org/alqassieh
1,218. Vahedian-Azimi et al., Association of In-hospital Use of Statins, Aspirin, and Renin-Angiotensin-Aldosterone Inhibitors with Mortality and ICU Admission Due to COVID-19
587 patient aspirin late treatment study: 22% lower mortality (p=0.56) and 10% higher ICU admission (p=0.67).Retrospective 587 COVID+ hospitalized patients in Iran, showing no significant differences in outcomes with aspirin treatment.
Jul 2021, Identification of Biomarkers, New Treatments, and Vaccines for COVID-19, https://link.springer.com/chapter/10.1007%2F978-3-030-71697-4_17, https://c19p.org/vahedianazimi2
1,219. Jayaraman et al., Povidone iodine, hydrogen peroxide and chlorhexidine mouthwashes reduce SARS-CoV2 burden in whole mouth fluid and respiratory droplets
12 patient hydrogen peroxide early treatment study: 50% improved viral clearance (p=0.18).Study of SARS-CoV-2 burden in whole mouth fluid and respiratory droplets with povidone iodine, hydrogen peroxide, and chlorhexidine mouthwashes in 36 hospitalized COVID-19 patients using PCR and rapid antigen testing. There were significant reductions in SARS-CoV-2 burden with all treatments in both respiratory droplets and whole mouth fluid. . Authors perform antigen testing for 6 hydrogen peroxide patients, showing that 50% became negative after treatment.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.25.21252488v1, https://c19p.org/jayaramanhp
1,220. Qin et al., Low molecular weight heparin and 28-day mortality among patients with coronavirus disease 2019: A cohort study in the early epidemic era
749 patient HCQ late treatment study: 34% lower mortality (p=0.61).Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, p = 0.61.
Nov 2020, Thrombosis Research, https://www.sciencedirect.com/science/article/pii/S0049384820306277, https://c19p.org/qin
1,221. Uygen et al., Effect of Hydroxychloroquine Use on the Length Of Hospital Stay in Children Diagnosed With Covid 19
40 patient HCQ late treatment study: 12% faster viral clearance (p=0.05).Retrospective 40 pediatric hospitalized patients, 15 treated with HCQ, showing 7.2 vs. 8.2 days until PCR-, not quite reaching statistical significance.
Sep 2021, Northern Clinics of Istanbul, https://northclinist.com/jvi.aspx?pdir=nci&plng=eng&un=NCI-65471&look4=, https://c19p.org/uygen
1,222. Yegerov et al., Epidemiological and Clinical Characteristics, and Virologic Features of COVID-19 Patients in Kazakhstan: a Nation-Wide, Retrospective, Cohort Study
1,072 patient HCQ late treatment study: 95% lower mortality (p=1).Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.01.06.20249091v1, https://c19p.org/yegerov
1,223. Karakaş et al., Reducing length of hospital stay with colchicine
336 patient colchicine late treatment study: 13% lower mortality (p=0.72), 16% lower ICU admission (p=0.5), and 25% shorter hospitalization (p=0.0001).Retrospective 356 hospitalized COVID-19 patients, shorter hospitalization time with colchicine treatment. There were no statistically significant differences for mortality or ICU admission. Significantly lower mortality was seen with higher dosage (1mg/day vs 0.5mg/day). More control patients were on oxygen at baseline (65% vs. 54%).
Jan 2022, The J. Infection in Developing Countries, https://jidc.org/index.php/journal/article/view/14924, https://c19p.org/karakas
1,224. Salvador et al., Clinical Features and Prognostic Factors of 245 Portuguese Patients Hospitalized With COVID-19
245 patient HCQ late treatment study: 33% lower mortality (p=0.1), 448% higher ventilation (p=0.003), and 17% lower combined mortality/intubation (p=0.21).Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely.
Mar 2021, Cureus, https://www.cureus.com/articles/53247-clinical-features-and-prognostic-factors-of-245-portuguese-patients-hospitalized-with-covid-19, https://c19p.org/salvador
1,225. Haji Aghajani et al., Decreased In-Hospital Mortality Associated with Aspirin Administration in Hospitalized Patients Due to Severe COVID-19
991 patient favipiravir late treatment study: 26% lower mortality (p=0.28).Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.
Apr 2021, J. Medical Virology, https://europepmc.org/article/med/33913549, https://c19p.org/hajiaghajania
1,226. Rutskaya-Moroshan et al., Clinical Characteristics, Prognostic Factors, and Outcomes of COVID-19 in Autoimmune Rheumatic Disease Patients: A Retrospective Case–Control Study from Astana, Kazakhstan
140 patient HCQ prophylaxis study: 38% lower severe cases (p=1) and 24% lower hospitalization (p=1).Retrospective case-control study of 140 COVID-19 patients with autoimmune rheumatic diseases (AIRDs) and 140 matched controls showing higher rates of hospitalization, oxygen therapy, and mechanical ventilation with AIRDs. For the AIRD patients, there was no significant difference in outcomes based on HCQ use (only 10 patients).
Aug 2024, Medicina, https://www.mdpi.com/1648-9144/60/9/1377, https://c19p.org/rutskayamoroshan
1,227. Kragholm et al., Association Between Prescribed Ibuprofen and Severe COVID-19 Infection: A Nationwide Register-Based Cohort Study
4,002 patient ibuprofen prophylaxis study: 4% lower progression (p=0.78).Retrospective 4,002 COVID-19 patients in Denmark, 264 with ibuprofen prescriptions, showing no significant difference for COVID-19 severity.
Oct 2020, Clinical and Translational Science, https://onlinelibrary.wiley.com/doi/10.1111/cts.12904, https://c19p.org/kragholm
1,228. Santos et al., Determinants of COVID-19 disease severity in patients with underlying rheumatic disease
38 patient HCQ prophylaxis study: 92% lower mortality (p=0.19).Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].
Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos
1,229. Davidsson et al., Androgen deprivation therapy in men with prostate cancer is not associated with COVID‐2019 infection
655 patient antiandrogen prophylaxis study: 2% lower IgG positivity (p=0.95).Retrospective 655 prostate cancer patients in Sweden, showing no significant difference in seropositivity with ADT.
Jan 2023, The Prostate, https://onlinelibrary.wiley.com/doi/10.1002/pros.24485, https://c19p.org/davidsson
1,230. Mustafa et al., Pattern of medication utilization in hospitalized patients with COVID-19 in three District Headquarters Hospitals in the Punjab province of Pakistan
444 patient ivermectin late treatment study: 64% lower mortality (p=0.09).Retrospective 444 hospitalized patients in Pakistan, showing lower mortality with ivermectin treatment in unadjusted results, not reaching statistical significance. Ivermectin was mostly used with patients in severe condition. Dose ranged from 12mg to 36mg for up to seven days.
Dec 2021, Exploratory Research in Clinical and Social Pharmacy, https://www.sciencedirect.com/science/article/pii/S2667276621001013, https://c19p.org/mustafa
1,231. Shabrawishi et al., Negative nasopharyngeal SARS-CoV-2 PCR conversion in response to different therapeutic interventions
93 patient HCQ late treatment study: 15% improved viral clearance (p=0.66).Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, p = 0.65. The treatment group had significantly more severe illness and significantly more male patients.
May 2020, medRxix, https://www.medrxiv.org/content/10.1101/2020.05.08.20095679v1, https://c19p.org/shabrawishi
1,232. Cheung et al., Association Between Famotidine Use and COVID-19 Severity in Hong Kong: A Territory-wide Study
952 patient proton pump inhibitor prophylaxis study: 25% lower severe cases (p=0.8).Retrospective 952 COVID-19 patients in Hong Kong, showing no significant difference in severe disease with famotidine use or PPI use.
Apr 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34940-4/fulltext, https://c19p.org/cheungppi
1,233. Goodall et al., Risk factors for severe disease in patients admitted with COVID-19 to a hospital in London, England: a retrospective cohort study
981 patient metformin prophylaxis study: 3% lower mortality (p=0.81).Retrospective 981 hospitalized patients in the UK, showing no significant difference with metformin use.
Oct 2020, Epidemiology and Infection, https://www.cambridge.org/core/journals/epidemiology-and-infection/article/risk-factors-for-severe-disease-in-patients-admitted-with-covid19-to-a-hospital-in-london-england-a-retrospective-cohort-study/9B704FF68359D8413E194D7123E49123, https://c19p.org/goodall
1,234. Al-Sumiadai et al., Therapeutic effect of Vitamin A on severe COVID-19 patients
140 patient vitamin A early treatment study: 86% lower mortality (p=0.002).Retrospective 70 severe condition patients treated with vitamin A (200,000IU for two days), salbutamol, and budesonide, and 70 patients not treated with vitamin A, showing significantly lower mortality with the addition of vitamin A.
Dec 2020, EurAsian J. Biosciences-7350, http://ejobios.org/article/therapeutic-effect-of-vitamin-a-on-severe-covid-19-patients-8517, https://c19p.org/alsumiadai2
1,235. de Gonzalo-Calvo et al., A blood microRNA classifier for the prediction of ICU mortality in COVID-19 patients: a multicenter validation study
491 patient HCQ ICU study: 38% lower mortality (p=0.23).Retrospective 491 ICU patients in Spain showing lower mortality with HCQ without statistical significance in unadjusted results.
Jun 2023, Respiratory Research, https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02462-x, https://c19p.org/degonzalocalvo
1,236. Jang et al., Clinical course of COVID-19 patients treated with ECMO: A multicenter study in Daegu, South Korea
19 patient vitamin C late treatment study: 51% improved recovery (p=0.15).Retrospective 19 COVID-19 ECMO patients in South Korea, showing a higher rate of weaning from ECMO with vitamin C treatment, without statistical significance. Authors perform multivariate analysis but do not provide full results, only reporting p > 0.05.
Dec 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S0147956320304027, https://c19p.org/jang2
1,237. Pott-Junior et al., Use of ivermectin in the treatment of Covid-19: a pilot trial
31 patient ivermectin late treatment RCT: 85% lower ventilation (p=0.25), 85% lower ICU admission (p=0.25), and 1% improved viral clearance (p=1).Very small RCT with 4 control patients and 28 ivermectin patients split across 3 different dosage levels, showing lower (non-statistically significant) ICU admission with treatment. Authors suggest that ivermectin for SARS-CoV-2 is safe and reduces symptoms and viral load, and that the antiviral effect appears to be dose-dependent. NCT04431466. Retraction/censorship: this paper appears to have been censored at the request of the journal's founding editor [pubmed.ncbi.nlm.nih.gov]. An external review is mentioned but is not provided, and there is no reply from the authors, or indication that the authors were notified. Conclusions in this study are limited due to the small size, however we should consider all information in the context of the full body of research.
Mar 2021, Toxicology Reports, https://www.sciencedirect.com/science/article/pii/S2214750021000445, https://c19p.org/pottjunior
1,238. Santos et al., Determinants of COVID-19 disease severity in patients with underlying rheumatic disease
38 patient HCQ late treatment study: 26% lower mortality (p=0.6).Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].
Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos2
1,239. Pablo-Marcos et al., Utility of mouth rinses with povidone-iodine and hydrogen peroxide in patients with COVID-19
71 patient povidone-iodine early treatment study: 29% improved viral clearance (p=0.4).Small prospective study with 31 patients gargling povidone-iodine, 17 hydrogen peroxide, and 40 control patients, showing lower viral load mid-recovery with povidone-iodine, without reaching statistical significance. Oropharyngeal only, and only every 8 hours for two days. Results may be better with the addition of nasopharyngeal use, more frequent use, and without the two day limit. Authors report only one of the 7 previous trials for PVP-I and COVID-19. Non-randomized study with no adjustments or group details. Some results in Figure 1 appear to be switched compared to the text and the labels in the figure. The viral clearance figures do not match the group sizes - for example authors report 62% PCR- for PVP-I at the 3rd test, however there is no number of 31 patients that rounds to 62%.
Oct 2021, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/pii/S0213005X21002950, https://c19p.org/pablomarcos
1,240. Bubenek-Turconi et al., Clinical characteristics and factors associated with ICU mortality during the first year of the SARS-Cov-2 pandemic in Romania
HCQ ICU study: 22% lower mortality (p=0.01).Prospective study of 9,058 COVID-19 ICU patients in Romania, showing lower mortality with HCQ treatment.
Nov 2022, European J. Anaesthesiology, https://journals.lww.com/10.1097/EJA.0000000000001776, https://c19p.org/bubenekturconi
1,241. Go et al., Hydroxychloroquine, azithromycin and methylprednisolone and in hospital survival in severe COVID-19 pneumonia
HCQ late treatment study: 55% lower mortality (p=0.03).Retrospective 759 hospitalized patients in the USA, showing lower mortality with combined HCQ+AZ+methylprednisolone treatment compared to methylprednisolone monotherapy.
Sep 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.935370/full, https://c19p.org/go2
1,242. Sharif et al., Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study
vitamin D prophylaxis study: 28% lower severe cases (p=0.001).Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharif
1,243. Hamer et al., Lifestyle risk factors, inflammatory mechanisms, and COVID-19 hospitalization: A community-based cohort study of 387,109 adults in UK
exercise study: 28% lower hospitalization (p=0.0004).UK Biobank retrospective analysis of 387,109 people, showing lower risk of COVID-19 hospitalization with physical activity.
Jul 2020, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912030996X?via%3Dihub, https://c19p.org/hamer
1,244. Kim et al., COVID-19 illness in relation to sleep and burnout
2,884 patient sleep study: 17% fewer moderate/severe cases (p=0.03) and 11% fewer cases (p=0.003).Retrospective 2,884 high-risk healthcare workers in France, Germany, Italy, Spain, UK, and the USA, showing shorter sleep duration associated with increased risk of COVID-19 cases and severity.
Mar 2021, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/132.info, https://c19p.org/kim5
1,245. Cherrie et al., Ultraviolet A radiation and COVID-19 deaths in the USA with replication studies in England and Italy
sunlight study: 32% lower mortality (p=0.004).Analysis of UVA exposure and COVID-19 mortality in the USA, England, and Italy, showing increased UVA exposure associated with lower mortality.
Apr 2021, British J. Dermatology, https://onlinelibrary.wiley.com/doi/10.1111/bjd.20093, https://c19p.org/cherrie
1,246. Reznikov et al., Identification of antiviral antihistamines for COVID-19 repurposing
antihistamine H1RA prophylaxis study: 34% fewer cases (p<0.0001).Retrospective 219,000 patients showing lower risk of COVID-19 with antihistamine H1RA use. In Vitro study showing these drugs exhibit direct antiviral activity against SARS-CoV-2. Molecular docking suggests hydroxyzine and azelastine may exert antiviral effects by binding ACE2 and the sigma-1 receptor.
Jan 2021, Biochemical and Biophysical Research Communications, https://www.sciencedirect.com/science/article/pii/S0006291X20321409, https://c19p.org/reznikov
1,247. Lounnas et al., An Independent Analysis of a Retrospective Cohort of 30,423 Covid-19 Patients Treated at IHU-Mediterranean in Marseille, France: Part 1, Efficacy of early Treatment with Hydroxychloroquine and Azithromycin
azithromycin early treatment PSM study: 27% lower combined mortality/ICU admission (p=0.0005).Independent analysis of the IHU-Mediterranean data [Brouqui] with 30,423 COVID-19 patients showing significantly lower risk of ICU admission or death with early treatment of hydroxychloroquine plus azithromycin (HCQ-AZ), and with azithromycin, both compared to no treatment.
Feb 2024, Archives of Microbiology & Immunology, https://www.fortunejournals.com/articles/an-independent-analysis-of-a-retrospective-cohort-of-30423-covid19-patients-treated-at-ihumediterranean-in-marseille-france-part-1.html, https://c19p.org/lounnas2azaz
1,248. Chari et al., Clinical features associated with COVID-19 outcome in multiple myeloma: first results from the International Myeloma Society data set
502 patient HCQ late treatment study: 33% lower mortality (p=0.17).Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, p = 0.17 (data is in the supplementary material).
Dec 2020, Blood, https://www.sciencedirect.com/science/article/pii/S0006497120839044, https://c19p.org/chari
1,249. Turrini et al., Clinical Course and Risk Factors for In-Hospital Mortality of 205 Patients with SARS-CoV-2 Pneumonia in Como, Lombardy Region, Italy
205 patient HCQ late treatment study: 10% lower mortality (p=0.15).Retrospective 205 patients in Italy, 160 treated with HCQ, showing lower mortality with treatment in multivariate analysis, but not reaching statistical significance.
Jun 2021, Vaccines, https://www.mdpi.com/2076-393X/9/6/640, https://c19p.org/turrini
1,250. Suna et al., Effect of high-dose intravenous vitamin C on prognosis in patients with SARS-CoV-2 pneumonia
323 patient vitamin C late treatment study: 21% lower mortality (p=0.52) and 2% higher ICU admission (p=1).Retrospective 323 hospitalized patients, 153 treated with vitamin C, showing no significant differences. Patients in each group were in different time periods, with the vitamin C group first. Time based confounding is possible due to improvements in SOC.
May 2021, Med. Clin., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112281/, https://c19p.org/suna
1,251. Azimi Pirsaraei et al., Anticoagulant Use in COVID-19 Patients: A Longitudinal Study From Zanjan, Iran
831 patient HCQ late treatment study: 39% lower mortality (p=0.16).Retrospective 831 hospitalized COVID-19 patients showing lower mortality with HCQ in unadjusted results, without statistical significance.
Aug 2024, Cureus, https://www.cureus.com/articles/263779-anticoagulant-use-in-covid-19-patients-a-longitudinal-study-from-zanjan-iran, https://c19p.org/azimipirsaraeih
1,252. Gavrielatou et al., Effect of Vitamin C on Clinical Outcomes of Critically Ill Patients With COVID-19: An Observational Study and Subsequent Meta-Analysis
113 patient vitamin C ICU study: 58% lower mortality (p=0.11).Retrospective 113 consecutive mechanically ventilated COVID+ ICU patients in Greece, 10 receiving high dose IV vitamin C, showing lower mortality with treatment, without statistical significance (p=0.11). The associated meta analysis includes only 11 studies, while there are currently studies, with mortality results. Authors only include critical patients, however not all studies with critical patients are included, for example [Hamidi-Alamdari, Majidi, Yüksel, Özgünay]. The meta analysis also uses unadjusted results, while PSM, Cox proportional hazards, or KM results are reported by [Al Sulaiman, Gao, Zhang, Zheng]. For [Zhang] authors use 28 day mortality, while the study reports longer term in-hospital mortality.
Feb 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.814587/full, https://c19p.org/gavrielatou
1,253. Gogtay et al., Retrospective analysis of aspirin's role in the severity of COVID-19 pneumonia
125 patient aspirin prophylaxis study: 6% higher mortality (p=0.87), 50% lower ventilation (p=0.16), and 49% lower ICU admission (p=0.41).Retrospective 125 COVID+ hospitalized patients in the USA, showing no significant differences with aspirin prophylaxis.
Mar 2022, World J. Critical Care Medicine, https://www.wjgnet.com/2220-3141/full/v11/i2/92.htm, https://c19p.org/gogtay
1,254. Kamran et al., Clearing the fog: Is HCQ effective in reducing COVID-19 progression: A randomized controlled trial
500 patient HCQ late treatment study: 5% lower progression (p=1) and 26% improved viral clearance (p=0.001).Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ treatment, 52.1% (HCQ) versus 35.7% (control), p=0.001, but no statistically significant difference at day 14, or in progression. Patients were relatively young and there was no mortality. Only 3% of patients had any disease progression and all patients recovered, so there is little if any room for treatment benefit. Progression among higher-risk patients with comorbidities was lower with treatment (12.9% versus 28.6%, p=0.3, very few cases). Despite the title, this is not an RCT since patients self-selected the arm, or were chosen based on allergies/contraindications. The treatment group had about twice the number of patients with comorbidities. Treatment delay is unknown - it was recorded but not reported in the paper. Viral load was not measured...
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.30.20165365v1, https://c19p.org/kamran
1,255. Sarhan et al., Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients
108 patient HCQ late treatment RCT: 26% lower mortality (p=0.39), 26% higher hospital discharge (p=0.39), and 25% longer hospitalization (p=0.06).Small 108 patient RCT comparing HCQ vs. remdesivir in very late stage treatment. All patients received tocilizumab. There were significant unadjusted baseline differences in ventilation and ICU admission. NCT04779047. REC-H-PhBSU-21011.
Nov 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121003452, https://c19p.org/sarhan
1,256. Abdulateef et al., COVID-19 severity in relation to sociodemographics and vitamin D use
427 patient vitamin D prophylaxis study: 41% lower hospitalization (p=0.3).Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.
Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateef
1,257. Merino et al., Ivermectin and the odds of hospitalization due to COVID-19: evidence from a quasi-experimental analysis based on a public intervention in Mexico City
77,381 patient ivermectin early treatment study: 74% lower hospitalization (p=0.001).Analysis of Mexico City's use of an ivermectin-based medical kit, showing significantly lower hospitalization with use. Authors use logistic-regression models with matched observations, including adjustments for age, sex, COVID severity, and comorbidities. This preprint was censored by the original preprint host. Censors claim that the government treatment program, which used approved medications and saved over 500 people from hospitalization, was unethical. In part they also indicate that studies of "the effects of a medication on a disease outcome" are outside the scope of their site, however retroactively censoring a paper for this reason is not appropriate. The author's response (not provided by the censors) can be found here: [twitter.com]. Author's provide the data and code for the study, and the results have been independently verified. See also: [doyourownresearch.substack.com]. This study was censored.
May 2021, Preprint, http://web.archive.org/web/20211218011849/https://files.osf.io/v1/resources/r93g4/providers/osfstorage/609085945533b4031ee1c789?action=download&direct&version=1, https://c19p.org/merino
1,258. Wang et al., Retinol and retinol binding protein 4 levels and COVID-19: a Mendelian randomization study
vitamin A prophylaxis study: 35% lower severe cases (p=0.28), 24% lower hospitalization (p=0.29), and 31% fewer cases (p=0.006).Mendelian randomization study suggesting a causal association between retinol and related proteins (RBP4, RDH16, CRABP1) and COVID-19. The study found that genetically-predicted higher retinol levels were associated with lower COVID-19 susceptibility. There was a lower risk of hospitalization and severity without statistical significance. Authors conclude that the results support a potential protective effect of vitamin A treatment for COVID-19. Given the lack of clear evidence for pleiotropy, and the lower precision of the MR-Egger estimates, the IVW estimates are likely more reliable in this case when the IVW and MR-Egger estimates differ.
Apr 2024, BMC Pulmonary Medicine, https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-024-03013-w, https://c19p.org/wang31
1,259. Beltran Gonzalez et al., Efficacy and Safety of Ivermectin and Hydroxychloroquine in Patients with Severe COVID-19: A Randomized Controlled Trial
73 patient ivermectin late treatment RCT: 14% lower mortality (p=1), 9% lower progression (p=1), 37% lower hospital discharge (p=0.71), and 20% longer hospitalization (p=0.43).RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 36 low dose ivermectin and 37 control patients not finding significant differences. NCT04391127. Another study reports results on a larger group of patients in the same hospital, showing ivermectin mortality RR 0.81 [0.53-1.24] [ Guzman ] . Questions have been raised about this study and the early termination of the study and discontinuation of treatments, because the hospital statistics show a dramatically lower (~75%) case fatality rate during the period of the study [ web.archive.org ] (data from [ gob.mx ] ). Date Cases Deaths CFR 3/2020 2 1 50% 4/2020 4 1 25% 5/2020 13 1 8% 6/2020 37 2 5% 7/2020 65 5 8% 8/2020 79 23 29% 9/2020 54 12 22% 10/2020 62 21 34% 11/2020 80 26 33% 12/2020 41 13 32% Several other inconsistencies have been reported [ Chamie ] . Although the data from this study is reported to be available and has been shared with an anti-treatment group,..
Feb 2021, Infectious Disease Reports, https://www.mdpi.com/2036-7449/14/2/20, https://c19p.org/beltrangonzalez
1,260. Shousha et al., Hepatic and gastrointestinal disturbances in Egyptian patients infected with coronavirus disease 2019: A multicentre cohort study
547 patient lactoferrin late treatment study: 79% lower mortality (p=0.11).Retrospective 547 hospitalized COVID+ patients in Egypt, showing lower mortality with lactoferrin treatment (without statistical significance).
Oct 2021, World J. Gastroenterology, https://www.wjgnet.com/1007-9327/full/v27/i40/6951.htm, https://c19p.org/shoushalf
1,261. Cilli et al., Characteristics and outcomes of COVID-19 patients with IPF: A multi-center retrospective study
46 patient favipiravir late treatment study: 38% lower mortality (p=0.51).Retrospective 46 idiopathic pulmonary fibrosis patients with COVID-19 in Turkey, showing lower mortality with favipiravir in unadjusted results, without statistical significance.
Mar 2022, Respiratory Medicine and Research, https://www.sciencedirect.com/science/article/pii/S2590041222000174?via%3Dihub, https://c19p.org/cilli
1,262. Carvallo et al., Usefulness of Topic Ivermectin and Carrageenan to Prevent Contagion of Covid 19 (IVERCAR)
229 patient ivermectin prophylaxis study: 96% fewer cases (p<0.0001).Prophylaxis study using ivermectin and carrageenan showing 0 of 131 cases from treated healthcare workers, compared to 11 of 98 control. The effect is likely to be primarily due to ivermectin - the author has later reported that carrageenan is not necessary [youtube.com]. See [doyourownresearch.substack.com] for discussion of issues with this trial.
Oct 2020, NCT04425850, https://clinicaltrials.gov/ct2/show/results/NCT04425850, https://c19p.org/carvalloprep2
1,263. Singh et al., Outcomes of Hydroxychloroquine Treatment Among Hospitalized COVID-19 Patients in the United States- Real-World Evidence From a Federated Electronic Medical Record Network
1,820 patient HCQ late treatment study: 5% lower mortality (p=0.72) and 19% lower ventilation (p=0.26).EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indication is likely.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.12.20099028v1, https://c19p.org/singh
1,264. Gorial et al., Effectiveness of Ivermectin as add-on Therapy in COVID-19 Management (Pilot Trial)
87 patient ivermectin late treatment study: 42% shorter hospitalization (p<0.0001).Small trial of hospitalized patients with 16 of 87 patients being treated with ivermectin, showing a significantly lower mean hospital stay with ivermectin: 7.62 vs. 13.22 days, p=0.00005. 0 of 16 ivermectin patients died vs. 2 of 71 control patients.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.07.20145979v1, https://c19p.org/gorial
1,265. Desbois et al., Prevalence and clinical features of COVID-19 in a large cohort of 199 patients with sarcoidosis
199 patient HCQ prophylaxis study: 17% fewer cases (p=1).Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, p=1.0.
Jul 2020, Research Square, https://www.researchsquare.com/article/rs-41653/v1, https://c19p.org/desbois
1,266. Camprubí et al., Lack of efficacy of standard doses of ivermectin in severe COVID-19 patients
26 patient ivermectin late treatment study: 40% lower ventilation (p=0.67), 33% lower ICU admission (p=1), 33% worse improvement (p=1), and 25% worse viral clearance (p=1).Tiny 26 patient retrospective study of very late treatment with ivermectin 200 μg/kg, median 12 days after symptoms, not showing significant differences. Authors suggest the dose is too low and recommend evaluation of higher doses. All patients received HCQ which may reduce the potential benefit for adding ivermectin.
Nov 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242184, https://c19p.org/camprubi
1,267. Chen et al., All-cause mortality in moderate and severe COVID-19 patients with myocardial injury receiving versus not receiving azvudine: a propensity score-matched analysis
198 patient azvudine late treatment PSM study: 6% lower mortality (p=0.88).PSM retrospective 332 hospitalized moderate to critically ill COVID-19 patients with myocardial injury in China, showing improved 14 day mortality but no difference in overall in-hospital mortality with azvudine treatment.
Apr 2023, Cardiology Plus, https://journals.lww.com/10.1097/CP9.0000000000000049, https://c19p.org/chen16
1,268. Naseem et al., Predicting mortality in SARS-COV-2 (COVID-19) positive patients in the inpatient setting using a Novel Deep Neural Network
1,214 patient HCQ late treatment study: 33% lower mortality (p=0.34).Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR 0.67, p = 0.34.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.13.20247254v1, https://c19p.org/naseem
1,269. Bassets-Bosch et al., Negativización de PCR a SARS-CoV-2 en muestra respiratoria en pacientes con necesidad de asistencia recurrente
15 patient HCQ late treatment study: 29% faster viral clearance (p=0.45).Retrospective 15 pediatric patients in Spain, showing faster viral clearance with HCQ+AZ, without statistical significance. Treatment time and details are not provided.
Apr 2022, Anales de Pediatría, https://www.sciencedirect.com/science/article/pii/S1695403321000126, https://c19p.org/bassetsbosch
1,270. Shukla et al., An observational multi-centric COVID-19 sequelae study among health care workers
679 patient HCQ prophylaxis study: 5% lower PASC (p=0.78).Retrospective 679 healthcare workers post COVID-19 discharge, 76 using HCQ prophylaxis, showing no significant difference in PASC.
Dec 2022, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368222001469, https://c19p.org/shukla
1,271. Asoudeh et al., The association between dietary intakes of zinc, vitamin C and COVID-19 severity and related symptoms: A cross-sectional study
250 patient vitamin C prophylaxis study: 69% lower severe cases (p=0.003).Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases with higher vitamin C intake.
Mar 2023, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457723000803, https://c19p.org/asoudeh
1,272. Firoozi et al., The Association between Energy-Adjusted Dietary Inflammatory Index, Body Composition, and Anthropometric Indices in COVID-19-Infected Patients: A Case-Control Study in Shiraz, Iran
diet study: 65% fewer cases (p<0.0001).Retrospective 133 COVID-19 patients and 322 controls, showing higher risk of COVID-19 for diets that have a higher inflammatory index (E-DII).
Mar 2022, Int. J. Clinical Practice, https://www.hindawi.com/journals/ijclp/2022/5452488/, https://c19p.org/firoozi
1,273. Moludi et al., The relationship between Dietary Inflammatory Index and disease severity and inflammatory status: a case–control study of COVID-19 patients
diet study: 92% fewer cases (p<0.0001).Retrospective 60 COVID-19 hospitalized patients and 60 controls in Iran, showing pro-inflammatory diets associated with COVID-19 cases and severity. IR.KUMS.REC.1399·444, IR.TBZMED.REC.1399·225.
Aug 2021, British J. Nutrition, https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0007114521003214, https://c19p.org/moludi
1,274. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
15,227 patient vitamin D prophylaxis study: 7% fewer cases (p=0.53).Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtd
1,275. Almansour et al., The Influence of Physical Activity on COVID-19 Prevention Among Quarantined Individuals: A Case–Control Study
142 patient exercise study: 6% fewer cases (p=0.85).Retrospective 142 patients in Saudi Arabia, showing no significant difference in cases with physical activity.
Feb 2022, J. Multidisciplinary Healthcare, https://www.dovepress.com/the-influence-of-physical-activity-on-covid-19-prevention-among-quaran-peer-reviewed-fulltext-article-JMDH, https://c19p.org/almansour
1,276. Elhadi et al., Epidemiology, outcomes, and utilization of intensive care unit resources for critically ill COVID-19 patients in Libya: A prospective multi-center cohort study
465 patient vitamin D ICU study: 23% lower mortality (p=0.29).Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.
Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadi
1,277. Roig et al., Clinical and pharmacological data in COVID-19 hospitalized nonagenarian patients
79 patient HCQ late treatment study: 16% lower mortality (p=0.76).Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76.
Jan 2021, Revista Espanola de Quimioterapia, https://europepmc.org/article/med/33522213, https://c19p.org/roig
1,278. Ramos-Rincón et al., Association between prior cardiometabolic therapy and in-hospital mortality in very old patients with type 2 diabetes mellitus hospitalized due to COVID-19. A nationwide observational study in Spain
790 patient metformin prophylaxis study: 1% lower mortality (p=0.78).Retrospective 790 hospitalized type 2 diabetes patients ≥80 years old in Spain, showing no significant difference in mortality with existing metformin use.
Dec 2020, Research Square, https://www.researchsquare.com/article/rs-133358/v1, https://c19p.org/ramosrincon
1,279. Mustafa et al., Pattern of medication utilization in hospitalized patients with COVID-19 in three District Headquarters Hospitals in the Punjab province of Pakistan
444 patient aspirin late treatment study: 44% lower mortality (p=0.28).Retrospective 444 hospitalized patients in Pakistan, showing lower mortality with aspirin treatment in unadjusted results, not reaching statistical significance.
Dec 2021, Exploratory Research in Clinical and Social Pharmacy, https://www.sciencedirect.com/science/article/pii/S2667276621001013, https://c19p.org/mustafae
1,280. Shamsi et al., Survival and Mortality in Hospitalized Children with COVID-19: A Referral Center Experience in Yazd, Iran
183 patient famotidine late treatment study: 75% lower mortality (p=0.21).Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsifm
1,281. Tehrani et al., Risk factors for mortality in adult COVID-19 patients: frailty predicts fatal outcome in older patients
255 patient HCQ late treatment study: 13% lower mortality (p=0.63).Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, p=0.63. Confounding by indication is likely.
Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322761, https://c19p.org/tehrani
1,282. Krishnan et al., Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia
152 patient zinc late treatment study: 18% lower mortality (p=0.18).Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnanz
1,283. Oh et al., Musculoskeletal Disorders, Pain Medication, and in-Hospital Mortality among Patients with COVID-19 in South Korea: A Population-Based Cohort Study
7,713 patient acetaminophen prophylaxis study: 2% lower mortality (p=0.97).Retrospective 7,713 COVID-19 patients in Korea, showing no significant difference in mortality with paracetamol use.
Jun 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/13/6804, https://c19p.org/oh3
1,284. Darban et al., Efficacy of High Dose Vitamin C, Melatonin and Zinc in Iranian Patients with Acute Respiratory Syndrome due to Coronavirus Infection: A Pilot Randomized Trial
20 patient vitamin C ICU RCT: 33% lower progression (p=1) and 6% shorter ICU admission (p=0.3).Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.
Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darbanc
1,285. Hall et al., Multi-institutional Analysis of 505 COVID-19 Patients Supported with ECMO: Predictors of Survival
505 patient HCQ ICU study: 11% lower mortality (p=0.31).Retrospective 505 ECMO patients showing no significant difference in mortality in unadjusted results.
Feb 2022, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/abs/pii/S0003497522001989, https://c19p.org/hall
1,286. Wijewickrema et al., Efficacy and safety of oral ivermectin in the treatment of mild to moderate Covid-19 patients: a multi-centre double-blind randomized controlled clinical trial
249 patient ivermectin early treatment RCT: 51% improved viral clearance (p=0.03).RCT 249 hospitalized patients with mild to moderate COVID-19 in Sri Lanka, showing statistically significant lower viral load. There was no significant difference in clinical outcomes. Only one patient had a serious outcome. Mid-recovery 11/15 symptoms showed lower scores with treatment on day 5 and on day 10. On day 10, 19% of treatment patients were asymptomatic vs. 13% of placebo patients. WHO score analysis is limited by the large percentage of missing data. Authors report that ivermectin blood levels taken before or with meals were not significantly different, however authors note that most patients consumed low fat meals. [Guzzo] show that absorption of ivermectin was significantly higher when administered following a high-fat meal.
Jul 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09563-y, https://c19p.org/wijewickrema
1,287. Pourhoseingholi et al., Case Characteristics, Clinical Data, And Outcomes of Hospitalized COVID-19 Patients In Qom Province, Iran: A Prospective Cohort Study
2,468 patient N-acetylcysteine late treatment study: 11% lower mortality (p=0.43).Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with NAC treatment. IR.MUQ.REC.1399.013.
May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholina
1,288. Yuan et al., Mortality and pre-hospitalization use of low-dose aspirin in COVID-19 patients with coronary artery disease
183 patient aspirin prophylaxis study: 4% lower mortality (p=0.89).Retrospective 183 hospitalized patients in China, 52 taking low-dose aspirin prior to hospitalization, showing no significant difference with treatment.
Dec 2020, J. Cellular and Molecular Medicine, https://onlinelibrary.wiley.com/doi/10.1111/jcmm.16198, https://c19p.org/yuan
1,289. Macias et al., Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxychloroquine therapy
722 patient HCQ prophylaxis study: 26% lower hospitalization (p=1) and 49% more cases (p=0.53).Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HCQ and 2 no-HCQ, confirmed+likely cases were 1 HCQ and 3 no-HCQ. 1 HCQ and 2 no-HCQ patients were admitted to hospital. We do not think a conclusion can be drawn based on these sample sizes. There are very significant differences between the groups, for example 30% of the HCQ group have SLE vs. 2.5% of the no-HCQ group. SLE patients have a 5.7 times relative risk of pneumonia according to [ncbi.nlm.nih.gov], whereas the relative risk with glucocorticoids and TNF-α inhibitors is significantly lower [academic.oup.com]. Two more recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.
May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.16.20104141v1, https://c19p.org/macias
1,290. Aweimer et al., Mortality rates of severe COVID-19-related respiratory failure with and without extracorporeal membrane oxygenation in the Middle Ruhr Region of Germany
149 patient vitamin D ICU study: 21% lower mortality (p=0.31).Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with vitamin D prophylaxis in unadjusted results.
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimer
1,291. Sbidian et al., Hydroxychloroquine with or without azithromycin and in-hospital mortality or discharge in patients hospitalized for COVID-19 infection: a cohort study of 4,642 in-patients in France
4,642 patient HCQ late treatment study: 5% higher mortality (p=0.74) and 20% higher hospital discharge (p=0.002).Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days. Other studies show faster resolution for HCQ, suggesting there will be a significant improvement when extending past 28 days. Hopefully authors will extend the analysis. Note that the median age is higher in the group not treated with HCQ or AZ. For other issues with the adjustments see [medrxiv.org]. Also see the analysis here [web.archive.org].
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.16.20132597v1, https://c19p.org/sbidian
1,292. Alwafi et al., Negative Nasopharyngeal SARS-CoV-2 PCR Conversion in Response to Different Therapeutic Interventions
93 patient HCQ late treatment study: 15% improved viral clearance (p=0.65).Retrospective 93 hospitalized patients in Saudi Arabia, 45 treated with CQ/HCQ, showing no significant difference in viral clearance. More patients treated with CQ/HCQ had severe cases at baseline (20% vs. 2%).
Jan 2022, Cureus, https://www.cureus.com/articles/82181-negative-nasopharyngeal-sars-cov-2-pcr-conversion-in-response-to-different-therapeutic-interventions, https://c19p.org/alwafi
1,293. Zhang et al., Physical activity and COVID-19: an observational and Mendelian randomisation study
exercise study: 26% lower mortality (p=0.17) and 18% fewer cases (p=0.01).UK Biobank retrospective showing significantly lower COVID-19 cases with objectively measured physical activity.
Dec 2020, J. Global Health, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719276/, https://c19p.org/zhang4
1,294. Shamsi et al., Survival and Mortality in Hospitalized Children with COVID-19: A Referral Center Experience in Yazd, Iran
183 patient favipiravir late treatment study: 96% lower mortality (p=0.14).Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsi
1,295. Poonam et al., Nitric oxide versus epoprostenol for refractory hypoxemia in Covid-19
103 patient nitric oxide ICU study: 14% lower mortality (p=0.1).Retrospective 103 mechanically ventilated patients, 41 treated with inhaled nitric oxide, and 62 with inhaled epoprostenol, showing no significant difference in outcomes.
Jun 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270646, https://c19p.org/poonam
1,296. Pourhoseingholi et al., Case Characteristics, Clinical Data, And Outcomes of Hospitalized COVID-19 Patients In Qom Province, Iran: A Prospective Cohort Study
2,468 patient vitamin C late treatment study: 13% lower mortality (p=0.38).Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with vitamin C treatment. IR.MUQ.REC.1399.013.
May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholi
1,297. Hazan et al., Effectiveness of ivermectin-based multidrug therapy in severely hypoxic, ambulatory COVID-19 patients
24 patient ivermectin late treatment study: 86% lower mortality (p=0.04) and 93% lower hospitalization (p=0.001).Small study of 24 consecutive patients in serious condition (9 days post symptoms, mean SpO2 87.4) using combined treatment with ivermectin, doxycycline, zinc, vitamin D, and vitamin C, showing no mortality or hospitalization with treatment. Two patients declined treatment and both died. This study uses a synthetic control arm.
Jul 2021, Future Microbiology, https://www.futuremedicine.com/doi/full/10.2217/fmb-2022-0014, https://c19p.org/hazan
1,298. Tu et al., Risk Factors for Severity and Mortality in Adult Patients Confirmed with COVID-19 in Sierra Leone: A Retrospective Study
180 patient HCQ late treatment study: 17% lower mortality (p=0.81).Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing no significant difference with HCQ treatment in unadjusted results, however HCQ was significantly more likely to be used for severe patients (33% vs. 12%).
Jan 2022, Infectious Diseases & Immunity, https://journals.lww.com/10.1097/ID9.0000000000000037, https://c19p.org/tu
1,299. Afşin et al., Factors affecting prognosis and mortality in severe COVID-19 pneumonia patients
80 patient HCQ late treatment study: 17% lower mortality (p=0.5).Retrospective 80 hospitalized severe COVID-19 patients in Turkey, showing no significant difference with HCQ treatment in unadjusted results. All patients received favipiravir.
Jul 2023, Acta Clinica Croatica, https://www.researchgate.net/publication/372951875_FACTORS_AFFECTING_PROGNOSIS_AND_MORTALITY_IN_SEVERE_COVID-19_PNEUMONIA_PATIENTS, https://c19p.org/afsin
1,300. Al-Sumiadai et al., Therapeutic effect of vitamin A on COVID-19 patients and its prophylactic effect on contacts
100 patient vitamin A early treatment study: 67% lower progression (p=0.27) and 38% faster recovery.Treatment and prophylaxis studies of vitamin A in Iraq. The treatment study contained 100 patients, 50 treated with 200,000IU vitamin A for two days, showing lower progression to severe disease, and shorter duration of symptoms. The prophylaxis study is listed separately [Al-Sumiadai].
Jan 2021, Systematic Reviews in Pharmacy, https://www.researchgate.net/publication/351637178_THERAPEUTIC_EFFECT_OF_VITAMIN_A_ON_COVID-19_PATIENTS_AND_ITS_PROPHYLACTIC_EFFECT_ON_CONTACTS, https://c19p.org/alsumiadai
1,301. Pasquini et al., Effectiveness of remdesivir in patients with COVID-19 under mechanical ventilation in an Italian ICU
51 patient HCQ ICU study: 16% lower mortality (p=0.34).Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment.
Aug 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/article/75/11/3359/5896161, https://c19p.org/pasquini
1,302. Chen et al., A pilot study of hydroxychloroquine in treatment of patients with common coronavirus disease-19 (COVID-19)
30 patient HCQ late treatment RCT: 29% lower progression (p=0.57) and 100% worse viral clearance (p=1).30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HCQ but not statistically significant. One HCQ patient developed to a severe case. Treatment group 4 years older and with higher incidence of hypertension.
Mar 2020, J. Zhejiang University, https://pubmed.ncbi.nlm.nih.gov/32391667/, https://c19p.org/chenmedsci
1,303. Ahsan et al., Clinical Variants, Characteristics, and Outcomes Among COVID-19 Patients: A Case Series Analysis at a Tertiary Care Hospital in Karachi, Pakistan
165 patient ivermectin late treatment study: 50% lower mortality (p=0.03).Retrospective 165 hospitalized patients in Pakistan showing unadjusted lower mortality with combined ivermectin and doxycycline treatment. Details of the ivermectin group compared to other patients are not provided, however ivermectin was given to a similar percentage of patients in the mild, moderate, and severe/critical groups (34.5%, 29.1%, and 36.4%), suggesting that ivermectin treatment was not based on severity.
Apr 2021, Cureus, https://www.cureus.com/articles/56545-clinical-variants-characteristics-and-outcomes-among-covid-19-patients-a-case-series-analysis-at-a-tertiary-care-hospital-in-karachi-pakistan, https://c19p.org/ahsan
1,304. Pablo-Marcos et al., Utility of mouth rinses with povidone-iodine and hydrogen peroxide in patients with COVID-19
71 patient hydrogen peroxide early treatment study: 12% improved viral clearance (p=0.67).Small prospective study with 31 patients gargling povidone-iodine, 17 hydrogen peroxide, and 40 control patients, showing lower viral load mid-recovery with povidone-iodine, without reaching statistical significance. Oropharyngeal only, and only every 8 hours for two days. Results may be better with the addition of nasopharyngeal use, more frequent use, and without the two day limit. Authors report only one of the 7 previous trials for PVP-I and COVID-19. Non-randomized study with no adjustments or group details. Some results in Figure 1 appear to be switched compared to the text and the labels in the figure. The viral clearance figures do not match the group sizes - for example authors report 62% PCR- for PVP-I at the 3rd test, however there is no number of 31 patients that rounds to 62%.
Oct 2021, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/pii/S0213005X21002950, https://c19p.org/pablomarcoshp
1,305. Uyaroğlu et al., Comparison of Favipiravir to Hydroxychloroquine Plus Azithromycin in the Treatment of Patients with Non-critical COVID-19: A Single-center, Retrospective, Propensity Score-matched Study
84 patient favipiravir late treatment PSM study: 67% lower mortality (p=1), 200% higher ICU admission (p=1), and 11% longer hospitalization (p=0.9).PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ.
Mar 2022, Acta Medica, https://actamedica.org/index.php/actamedica/article/view/719, https://c19p.org/uyaroglua
1,306. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
HCQ prophylaxis study: 12% fewer cases (p=0.01).Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of HCQ.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfadden
1,307. Asoudeh et al., The association between dietary intakes of zinc, vitamin C and COVID-19 severity and related symptoms: A cross-sectional study
250 patient zinc prophylaxis study: 57% lower severe cases (p=0.03).Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases with higher zinc intake.
Mar 2023, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457723000803, https://c19p.org/asoudehz
1,308. Yulia et al., Evaluation of Antibacterial and Antiviral Drug Effectiveness in COVID-19 Therapy: A Data-Driven Retrospective Approach
432 patient favipiravir late treatment study: 85% lower mortality (p=0.05).Retrospective hospitalized patients in Indonesia, showing lower mortality and shorter hospitalization with favipiravir.
Mar 2022, Pathophysiology, https://www.mdpi.com/1873-149X/29/1/9, https://c19p.org/yulia
1,309. Latorre-Román et al., Protective role of physical activity patterns prior to COVID-19 confinement with the severity/duration of respiratory pathologies consistent with COVID-19 symptoms in Spanish populations
exercise study: 76% lower hospitalization (p=0.05).Retrospective 420 people in Spain, showing lower risk of COVID-19 hospitalization with a history of physical activity.
Jun 2021, Research in Sports Medicine, https://www.tandfonline.com/doi/full/10.1080/15438627.2021.1937166, https://c19p.org/latorreroman
1,310. Yue et al., Long-term diet and risk of SARS -CoV-2 infection and Coronavirus Disease 2019 (COVID-19) severity
diet study: 19% fewer cases (p=0.008).Analysis of 42,935 participants showing lower risk of COVID-19 with healthier diets. Risk of severe cases was also lower with healthier diets, while not reaching statistical significance. Severity results are only provided with diet indices as a continuous variable.
Aug 2022, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqac219/6659183, https://c19p.org/yue
1,311. Marcus et al., Predictors of incident viral symptoms ascertained in the era of COVID-19
14,335 patient sleep study: 16% fewer symptomatic cases (p=0.0007).Prospective survey based study with 14,335 participants, showing risk of viral symptoms associated with shorter sleep duration.
Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253120, https://c19p.org/marcussl
1,312. Deschasaux-Tanguy et al., Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort
7,766 patient vitamin B9 prophylaxis study: 16% fewer cases (p=0.02).Analysis of 7,766 adults in France, showing higher intakes of vitamin C, folate, vitamin K, dietary fibre, and fruit and vegetables associated with lower seropositivity.
Nov 2021, BMC Medicine, https://link.springer.com/article/10.1186/s12916-021-02168-1/fulltext.html, https://c19p.org/deschasauxtanguyb9
1,313. Prempree et al., SARS-CoV-2 Clearance from Andrographis paniculata, Boesenbergia rotunda, and Favipiravir among Mild COVID-19 Cases in Klong Prem Central Prison during Mid-2021: a Retrospective Study
60 patient andrographolide late treatment study: 19% improved viral clearance (p=0.61).Retrospective 120 patients in Thailand, showing improved viral clearance with andrographis compared with favipiravir.
Dec 2022, OSIR, https://www.osirjournal.net/index.php/osir/article/download/311/251, https://c19p.org/prempree
1,314. Deschasaux-Tanguy et al., Nutritional risk factors for SARS-CoV-2 infection: a prospective study within the NutriNet-Santé cohort
7,766 patient vitamin K prophylaxis study: 14% fewer cases (p=0.04).Analysis of 7,766 adults in France, showing higher intakes of vitamin C, folate, vitamin K, dietary fibre, and fruit and vegetables associated with lower seropositivity.
Nov 2021, BMC Medicine, https://link.springer.com/article/10.1186/s12916-021-02168-1/fulltext.html, https://c19p.org/deschasauxtanguyvk
1,315. Doocy et al., Clinical progression and outcomes of patients hospitalized with COVID-19 in humanitarian settings: A prospective cohort study in South Sudan and Eastern Democratic Republic of the Congo
144 patient vitamin A late treatment study: 26% lower mortality (p=1).Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing no significant difference with vitamin A treatment in unadjusted results with only 8 patients receiving vitamin A.
Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocyva
1,316. Shamsi et al., Survival and Mortality in Hospitalized Children with COVID-19: A Referral Center Experience in Yazd, Iran
183 patient aspirin late treatment study: 96% lower mortality (p=0.22).Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsie
1,317. Alosaimi et al., Analyzing the Difference in the Length of Stay (LOS) in Moderate to Severe COVID-19 Patients Receiving Hydroxychloroquine or Favipiravir
74 patient favipiravir late treatment PSM study: 80% lower mortality (p=0.49), 75% longer hospitalization (p=0.63), and 40% lower hospital discharge (p=0.74).Retrospective 200 hospitalized COVID-19 patients in Saudi Arabia, showing no significant difference in outcomes between HCQ and favipiravir.
Nov 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/12/1456, https://c19p.org/alosaimia
1,318. Acar Sevinc et al., Favipiravir Experience in COVID-19 Patients at a Tertiary Center Intensive Care Unit
100 patient favipiravir ICU study: 16% lower mortality (p=0.38) and 10% lower ventilation (p=0.75).Retrospective 100 ICU patients in Turkey, showing improved survival with favipiravir vs. lopinavir/ritonavir.
Jun 2022, SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital, https://sislietfaltip.org/jvi.aspx?un=SETB-35902&volume=, https://c19p.org/acarsevinc
1,319. Akinosoglou et al., COVID-19 Outcomes and Diabetes Mellitus: A Comprehensive Multicenter Prospective Cohort Study
354 patient metformin prophylaxis study: 37% lower mortality (p=0.12), 39% higher ICU admission (p=0.26), and 3% higher ARDS (p=0.92).Prospective multicenter study of 354 hospitalized type 2 diabetes patients with COVID-19 in Greece showing increased risk with DPP4 inhibitor use as part of chronic diabetes treatment. There was no significant difference with metformin use in unadjusted results. Results do not account for differences in the risk of hospitalization.
May 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/6/1416, https://c19p.org/akinosoglou
1,320. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
15,227 patient zinc prophylaxis study: 7% fewer cases (p=0.77).Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtz
1,321. Ubaldo et al., COVID-19: A Single-Center ICU Experience of the First Wave in the Philippines
31 patient HCQ ICU study: 18% lower mortality (p=0.64).Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64.
Jan 2021, Critical Care Research and Practice, https://www.hindawi.com/journals/ccrp/2021/7510306/, https://c19p.org/ubaldo
1,322. Eikelboom et al., Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial
3,881 patient aspirin late treatment RCT: 9% higher mortality (p=0.84), 20% lower progression (p=0.21), and 17% lower hospitalization (p=0.31).Late (5.4 days) outpatient RCT showing no significant difference in outcomes with aspirin treatment.
Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002995, https://c19p.org/eikelboom2e
1,323. Ma et al., Sex Differences in Association Between Anti-Hypertensive Medications and Risk of COVID-19 in Middle-Aged and Older Adults
77,221 patient aspirin prophylaxis PSM study: 9% lower mortality (p=0.12), 2% lower hospitalization (p=0.47), 9% more symptomatic cases (p=0.18), and 7% more cases (p=0.09).UK Biobank retrospective 77,271 patients aged 50-86, showing no significant differences with aspirin use. Matching lead to different results for the gender vs. overall analysis, for example the overall result for cases was OR 1.07, however both gender results are lower OR 0.97 and 1.02.
Aug 2021, Drugs & Aging, https://link.springer.com/article/10.1007%2Fs40266-021-00886-y, https://c19p.org/ma3
1,324. Sawanpanyalert et al., Assessment of outcomes following implementation of antiviral treatment guidelines for COVID-19 during the first wave in Thailand
HCQ early treatment study: 42% lower progression (p=0.37).Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided.
Sep 2021, Southeast Asian J. Tropical Medicine and Public Health, https://journal.seameotropmednetwork.org/index.php/jtropmed/article/view/490, https://c19p.org/sawanpanyalert
1,325. Hirsch et al., Proton Pump Inhibitors and Risk of COVID-19 Infection in Children
116,209 patient proton pump inhibitor prophylaxis study: 15% lower hospitalization (p=0.27) and 15% fewer cases (p=0.002).Retrospective 116,209 pediatric patients showing lower risk of COVID-19 with PPI use. There was no significant difference for hospitalization.
Jun 2024, The J. Pediatrics, https://www.sciencedirect.com/science/article/pii/S0022347624002828, https://c19p.org/hirsch2
1,326. Annie et al., Hydroxychloroquine in hospitalized COVID-19 patients: Real world experience assessing mortality
734 patient HCQ late treatment study: 4% lower mortality (p=0.83).Retrospective database analysis with PSM not including COVID-19 severity, finding mortality OR 0.95 [0.62-1.46] for HCQ, and 1.24 [0.70-2.22] for HCQ+AZ. Confounding by indication likely.
Oct 2020, Pharmacotherapy, https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2467, https://c19p.org/annie
1,327. Park et al., Pre-pandemic physical activity as a predictor of infection and mortality associated with COVID-19: Evidence from the National Health Insurance Service
exercise study: 26% lower mortality (p=0.08) and 7% fewer cases (p=0.02).Retrospective 4,363 COVID-19 patients and 67,125 controls in South Korea, showing higher risk of mortality and cases with insufficient physical activity.
Feb 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1072198/full, https://c19p.org/park3
1,328. Shamsi et al., Survival and Mortality in Hospitalized Children with COVID-19: A Referral Center Experience in Yazd, Iran
183 patient vitamin D late treatment study: 58% lower mortality (p=0.7).Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsid
1,329. Mahmood et al., Coronavirus in HIP Fractures CHIP 2: Is Vitamin D Deficiency Associated with Increased Mortality from COVID-19 Infections in A Hip Fracture Population?
490 patient vitamin D prophylaxis study: 9% lower mortality (p=0.67).Retrospective 517 hip fracture patients in the UK with vitamin D levels measured during COVID-19 admission, not showing significant differences in mortality for supplementation in unadjusted analysis with no group details and subject to confounding by indication. There was also no significant effect based on deficiency.
Dec 2021, European J. Medical and Health Sciences, https://ej-med.org/index.php/ejmed/article/view/1159, https://c19p.org/mahmood
1,330. Krishnan et al., Clinical comorbidities, characteristics, and outcomes of mechanically ventilated patients in the State of Michigan with SARS-CoV-2 pneumonia
152 patient vitamin D late treatment study: 19% lower mortality (p=0.42).Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.
Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnand
200 patient probiotics late treatment RCT: 2% higher mortality (p=1), 18% lower ventilation (p=1), 27% lower ICU admission (p=0.77), and 5% faster recovery (p=0.47).
RCT 200 patients, 99 treated with a probiotic (Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301). There was no significant difference in mortality or recovery time, however benefits were seen for diarrhea. NCT04854941.
Oct 2021, Probiotics Antimicrob Proteins, https://pubmed.ncbi.nlm.nih.gov/34643888/, https://c19p.org/ivashkin
1,332. Roger et al., French Multicentre Observational Study on SARS-CoV-2 infections Intensive care initial management: the FRENCH CORONA Study
966 patient HCQ ICU study: no change in mortality (p=0.94).Prospective study of 966 ICU patients in France, 289 treated with HCQ, showing no significant difference with treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Jul 2021, Anaesthesia Critical Care & Pain Medicine, https://www.sciencedirect.com/science/article/pii/S2352556821001351, https://c19p.org/roger
1,333. Fowler et al., SAFEty Study of Early Infusion of Vitamin C for Treatment of Novel Coronavirus Acute Lung Injury (SAFE EVICT CORONA-ALI)
47 patient vitamin C ICU RCT: 19% lower mortality (p=0.75) and 2% worse results (p=0.28).RCT 47 ICU patients showing no significant differences with vitamin C treatment.
Apr 2024, NCT04344184, https://clinicaltrials.gov/study/NCT04344184, https://c19p.org/fowler
1,334. Sen et al., Post-COVID-19 condition in patients with autoimmune rheumatic diseases: the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study
HCQ long COVID study: 40% lower PASC (p=0.08).Retrospective 755 autoimmune rheumatic disease patients, showing lower risk of PASC (long COVID) with HCQ use, without statistical significance.
Apr 2023, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991323000668, https://c19p.org/sen2
1,335. Pham et al., Failure of chronic hydroxychloroquine in preventing severe complications of COVID-19 in patients with rheumatic diseases
42 patient HCQ prophylaxis study: 20% lower mortality (p=0.77) and 35% higher ICU admission (p=0.61).Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mentions differences favoring HCQ but ignores those favoring control (large differences in ethnicity, rheumatic conditions, hypertension, coronary artery disease, solid organ transplant recipients, immunosuppresive drugs). 61% of control patients also received HCQ. Adherence for chronic HCQ patients was not examined. Despite the very large differences between the groups, no adjustments are made. The study claims that HCQ did not prevent severe cases, but the study is among hospitalized patients, i.e., they already have cases severe enough for hospitalization - this study can not identify a protective effect of HCQ that reduces the probability of disease severe enough for hospitalization.
Mar 2021, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkab014/6156645, https://c19p.org/pham
1,336. Kyagambiddwa et al., Thirty-Day Outcomes of Young and Middle-Aged Adults Admitted with Severe COVID-19 in Uganda: A Retrospective Cohort Study
246 patient vitamin C late treatment study: 50% lower mortality (p=0.06).Retrospective 246 severe COVID-19 patients in Uganda, showing lower mortality with vitamin C treatment, without statistical significance (p = 0.06).
May 2023, Infection and Drug Resistance, https://www.dovepress.com/thirty-day-outcomes-of-young-and-middle-aged-adults-admitted-with-seve-peer-reviewed-fulltext-article-IDR, https://c19p.org/kyagambiddwa
1,337. Lin et al., Predictors of incident SARS-CoV-2 infections in an international prospective cohort study
exercise study: 47% fewer cases (p=0.4).Prospective survey analysis of 28,575 people in 99 countries, showing a lower risk of COVID-19 with a exercise, without statistical significance.
Sep 2021, BMJ Open, https://bmjopen.bmj.com/content/11/9/e052025, https://c19p.org/lin
1,338. Liu et al., Effectiveness of Azvudine and Nirmatrelvir-ritonavir in Kidney Transplant Recipients With COVID-19: A Retrospective Cohort Study
148 patient azvudine late treatment PSM study: 45% lower progression (p=0.36).Retrospective 148 hospitalized kidney transplant patients with COVID-19 in China showing lower risk of disease progression with azvudine treatment compared, and higher risk with paxlovid treatment.
Apr 2024, Infections in the immunosuppressed and immunocompromised host, https://www.atsjournals.org/doi/10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A2917, https://c19p.org/liu23
1,339. Sirijatuphat et al., A pilot study of 0.4% povidone-iodine nasal spray to eradicate SARS-CoV-2 in the nasopharynx
12 patient povidone-iodine early treatment study: 33% improved viral load (p=0.58).Small single-arm trial testing short-term viral load change after a single administration of three puffs of 0.4% PVP-I, showing lower viral titer at 3 minutes and 4 hours, not reaching statistical significance. Authors note that one reason for the lower change compared to in vitro results is that the spray administration may be less effective.
Aug 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.18.22278340, https://c19p.org/sirijatuphat3
1,340. Cadegiani et al., Early COVID-19 Therapy with azithromycin plus nitazoxanide, ivermectin or hydroxychloroquine in Outpatient Settings Significantly Improved COVID-19 outcomes compared to Known outcomes in untreated patients
247 patient ivermectin early treatment study: 94% lower ventilation (p=0.005) and 98% lower hospitalization (p<0.0001).Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.
Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297521000792, https://c19p.org/cadegianii
1,341. Albani et al., Impact of Azithromycin and/or Hydroxychloroquine on Hospital Mortality in COVID-19
816 patient HCQ late treatment study: 18% lower mortality (p=0.15) and 9% higher ICU admission (p=0.7).Retrospective 1376 hospitalized patients in Italy, 211 treated with HCQ and 166 with HCQ+AZ.
Aug 2020, J, Clinical Medicine, https://www.mdpi.com/2077-0383/9/9/2800, https://c19p.org/albani
1,342. Abdulrahman et al., Favipiravir efficacy and safety for the treatment of severe coronavirus 2019: a retrospective study
1,699 patient favipiravir ICU study: 3% lower mortality (p=0.81).Retrospective 1,699 ICU patients in Saudi Arabia, 193 treated with favipiravir, showing no significant difference in mortality.
Jun 2022, J. Ayub Medical College Abbottabad, https://jamc.ayubmed.edu.pk/jamc/index.php/jamc/article/view/10305, https://c19p.org/abdulrahman2
1,343. Wang et al., Comorbidity and Sociodemographic determinants in COVID-19 Mortality in an US Urban Healthcare System
7,592 patient HCQ late treatment study: 6% lower mortality (p=0.63).Database analysis of 7,592 patients in NYC, showing adjusted HCQ mortality odds ratio OR 0.96, p = 0.82, and HCQ+AZ OR 0.94, p = 0.63
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.11.20128926v1, https://c19p.org/wangrx
1,344. Mohseni et al., Do body mass index (BMI) and history of nutritional supplementation play a role in the severity of COVID-19? A retrospective study
603 patient vitamin D prophylaxis study: 12% fewer cases (p=0.09).Retrospective 603 patients in Iran, 192 taking vitamin D supplements, showing no significant difference in COVID-19 cases in unadjusted results. IR.SHOUSHTAR.REC.1399.015.
Aug 2021, Nutrition & Food Science, https://www.emerald.com/insight/content/doi/10.1108/NFS-11-2020-0421/full/html, https://c19p.org/mohseni
1,345. Zangeneh et al., Survival analysis based on body mass index in patients with Covid-19 admitted to the intensive care unit of Amir Al-Momenin Hospital in Arak – 2021
famotidine ICU study: 39% lower mortality (p=0.01).Retrospective 193 ICU patients in Iran, showing lower mortality with famotidine treatment.
May 2022, Obesity Medicine, https://www.sciencedirect.com/science/article/pii/S245184762200032Xhttps://www.sciencedirect.com/science/article/pii/S245184762200032X/pdf, https://c19p.org/zangeneh
1,346. Gendebien et al., Systematic analysis of COVID-19 infection and symptoms in a systemic lupus erythematosus population: correlation with disease characteristics, hydroxychloroquine use and immunosuppressive treatments
225 patient HCQ prophylaxis study: 4% fewer cases (p=0.93).Small study of SLE patients taking HCQ with a phone survey for COVID-19 suggestive symptoms. There was 2 hospitalizations (group not identified) and no ICU or death cases. A similar percentage of suspected infections were reported for HCQ users and non-HCQ users, RR 0.96, p = 0.93. There was no mortality and severity was not analyzed to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity of SLE. Only 5 cases were PCR confirmed.
Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/06/25/annrheumdis-2020-218244, https://c19p.org/gendebien
1,347. Shehab et al., Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection
253 patient vitamin C prophylaxis study: 4% lower severe cases (p=1).Retrospective survey-based analysis of 349 COVID-19 patients, showing no significant difference with vitamin C prophylaxis in unadjusted analysis. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabc
1,348. Abdulateef et al., COVID-19 severity in relation to sociodemographics and vitamin D use
427 patient vitamin C prophylaxis study: 19% lower hospitalization (p=0.69).Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.
Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateefc
1,349. An et al., Treatment Response to Hydroxychloroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea
226 patient HCQ late treatment study: 3% faster viral clearance (p=0.92).Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. "It is notable that HQ plus antibiotics group had worse baseline clinical profiles (i.e. higher percentage of moderate severity patients, more patients with fever >=37.5C, higher average body temperature) and prognostic indicators such as age, LDH, lymphocyte count, and CRP". We note that propensity score matching removed almost all of the male patients in the control group (40% -> 5%) but increased the percentage of male patients in the treatment group. This provides a large advantage to the control group because there is a very large difference in severity and mortality based on gender [ncbi.nlm.nih.gov]. In terms of viral RNA clearance we note that other research has found that "active viral replication drops quickly after the first week, and viable virus..
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.04.20146548v1, https://c19p.org/an
1,350. Fitzgerald et al., Risk Factors for Infection and Health Impacts of the COVID-19 Pandemic in People with Autoimmune Diseases
4,666 patient HCQ prophylaxis study: 9% fewer cases (p=0.54).Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 [0.68-1.23]. Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity of autoimmune or inflammatory condition.
Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.03.21251069v1, https://c19p.org/fitzgerald
1,351. Gianfrancesco et al., Characteristics associated with hospitalisation for COVID-19 in people with rheumatic disease: data from the COVID-19 Global Rheumatology Alliance physician-reported registry
600 patient HCQ prophylaxis study: 3% lower hospitalization (p=0.82).Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 [0.57-1.57], p=0.82 after adjustments.
May 2020, Annals of the Rheumatic Diseases, 859-866, https://europepmc.org/article/med/32471903, https://c19p.org/gianfrancesco
1,352. Oh et al., Incidence and Mortality Associated with Cardiovascular Medication among Hypertensive COVID-19 Patients in South Korea
aspirin prophylaxis study: 1% lower mortality (p=0.95) and 12% fewer cases (p=0.04).Retrospective database analysis of 328,374 adults in South Korea, showing lower risk of COVID-19 cases with aspirin use, but no difference in mortality for COVID-19 patients.
Jun 2021, Yonsei Medical J., https://eymj.org/DOIx.php?id=10.3349/ymj.2021.62.7.577, https://c19p.org/oh2
1,353. Abdulateef et al., COVID-19 severity in relation to sociodemographics and vitamin D use
428 patient zinc prophylaxis study: 13% lower hospitalization (p=0.83).Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.
Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateefz
1,354. Son et al., Effect of aspirin on coronavirus disease 2019
21,669 patient aspirin prophylaxis PSM study: 11% lower mortality (p=0.67), 7% higher progression (p=0.8), and 11% more cases (p=0.21).PSM retrospective case control study in South Korea, showing a trend towards lower mortality, but no significant differences with aspirin use.
Jul 2021, Medicine, https://journals.lww.com/10.1097/MD.0000000000026670, https://c19p.org/son
1,355. Çiyiltepe et al., The Effect of Pre-admission Hydroxychloroquine Treatment on COVID-19-Related Intensive Care Follow-up in Geriatric Patients
147 patient HCQ ICU study: 3% lower mortality (p=0.85).Retrospective 147 ICU patients in Turkey, showing no significant difference in outcomes based on HCQ treatment before ICU admission. This is not very informative, for example we do not know if HCQ treated patients were much less likely to be admitted to the ICU.
Apr 2021, South. Clin. Ist. Euras., https://jag.journalagent.com/scie/pdfs/SCIE-89847-RESEARCH_ARTICLE-CIYILTEPE.pdf, https://c19p.org/ciyiltep
1,356. Vernaz et al., Early experimental COVID-19 therapies: associations with length of hospital stay, mortality and related costs
198 patient HCQ late treatment PSM study: 15% lower mortality (p=0.71) and 49% longer hospitalization (p=0.002).Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity with a 16% higher mNEWS score for HCQ vs. SOC in the matched cohort. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse. Authors note: "overall, there was an indication bias, with the reason of prescription being associated with the outcome of interest. Indeed, patients with more severe COVID-19 were more likely to receive experimental therapies."
Dec 2020, Swiss Medical Weekly, https://smw.ch/article/doi/smw.2020.20446, https://c19p.org/vernaz
1,357. Elavarasi et al., Clinical features, demography, and predictors of outcomes of SARS-CoV-2 infection at a tertiary care hospital in India: A cohort study
1,758 patient ivermectin late treatment study: 20% lower mortality (p=0.12).Retrospective 2017 hospitalized patients in India, showing lower mortality with ivermectin treatment in unadjusted results. No group details are provided and this result is subject to confounding by indication.
Aug 2021, Lung India, https://journals.lww.com/lungindia/Fulltext/2022/01000/Clinical_features,_demography,_and_predictors_of.5.aspx, https://c19p.org/elavarasi
1,358. Rao et al., Hydroxychloroquine as pre-exposure prophylaxis against COVID-19 infection among healthcare workers: a prospective cohort study
1,294 patient HCQ prophylaxis study: 11% fewer cases (p=0.68).Prospective PrEP study with low risk healthcare workers in India showing RR=0.89 [0.53-1.52]. There were no significant adverse effects. Only mean age and gender distribution are provided for baseline characteristics, no severity information is provided, and no adjustments were made. Authors analyze HCQ use for <8 vs. ≥8 weeks, noting a lack of statistical significance, but not providing the results.
Dec 2021, Expert Review of Anti-infective Therapy, https://www.tandfonline.com/doi/abs/10.1080/14787210.2022.2015326, https://c19p.org/rao
1,359. Guldemir et al., Clinical characteristics of bus drivers and field officers infected with COVID-19: A cross-sectional study from Istanbul
477 patient vitamin D prophylaxis study: 5% lower hospitalization (p=0.89).Retrospective 477 COVID+ public transportation workers in Turkey, showing no significant difference in hospitalization with vitamin D use in unadjusted results.
Nov 2022, Work, https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-220292, https://c19p.org/guldemird
1,360. Bidari et al., Development of a Scoring Method Based on a Chest CT Scan to Determine the Outcomes of COVID-19 Patients
406 patient metformin prophylaxis study: 10% lower severe cases (p=0.53).Retrospective 406 COVID-19 patients in Iran, showing lower risk of severe cases with metformin use in unadjusted results, without statistical significance.
Oct 2023, Cureus, https://www.cureus.com/articles/194481-development-of-a-scoring-method-based-on-a-chest-ct-scan-to-determine-the-outcomes-of-covid-19-patients, https://c19p.org/bidari
1,361. Barra et al., COVID-19 in hospitalized patients in 4 hospitals in San Isidro, Buenos Aires, Argentina
668 patient HCQ late treatment study: 11% lower mortality (p=1).Retrospective 668 hospitalized patients in Argentina, 18 treated with HCQ, not showing a significant difference in unadjusted results.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.30.21261220v1, https://c19p.org/barra
1,362. Piñana et al., Risk factors and outcome of COVID-19 in patients with hematological malignancies
HCQ prophylaxis study: 36% lower mortality (p=0.11).Retrospective study of 367 hematology patients with COVID-19 in Spain. Among 216 patients with very severe COVID-19, there was significantly lower mortality with azithromycin treatment. Mortality was also lower with HCQ, but without statistical significance.
Aug 2020, Experimental Hematology & Oncology, https://ehoonline.biomedcentral.com/articles/10.1186/s40164-020-00177-z, https://c19p.org/pinana
1,363. Frontera et al., A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications
382 patient zinc late treatment study: 33% lower PASC (p=0.07).Prospective study of 382 hospitalized COVID-19 patients in New York City, showing significantly worse 6-month functional outcomes, activities of daily living, and return to work with neurological complications during initial hospitalization.
Jul 2021, J. the Neurological Sciences, https://www.sciencedirect.com/science/article/pii/S0022510X21001805, https://c19p.org/frontera3
1,364. Hinks et al., Azithromycin versus standard care in patients with mild-to-moderate COVID-19 (ATOMIC2): an open-label, randomised trial
298 patient azithromycin late treatment RCT: 1% lower combined mortality/hospitalization (p=0.99) and 80% lower progression (p=0.24).RCT 298 mild-to-moderate COVID-19 outpatients in the UK showing no significant difference in hospitalization or death with late azithromycin treatment. Treatment was delayed an average of 6 days from onset. 7 vs. 3 hospitalizations occurred by day 1 in the treatment vs. control groups in this open label trial (Figure 2).
Oct 2021, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260021002630, https://c19p.org/hinksaz
1,365. Elhadi et al., Epidemiology, outcomes, and utilization of intensive care unit resources for critically ill COVID-19 patients in Libya: A prospective multi-center cohort study
465 patient famotidine ICU study: 7% lower mortality (p=0.57).Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.
Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadifm
1,366. Rodriguez-Nava et al., Clinical characteristics and risk factors for mortality of hospitalized patients with COVID-19 in a community hospital: A retrospective cohort study
313 patient colchicine late treatment study: 6% lower mortality (p=0.87).Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support. Confounding by indication likely.
Nov 2020, Mayo Clinic Proceedings: Innovations, Quality & Outcomes, https://www.sciencedirect.com/science/article/pii/S2542454820302071, https://c19p.org/rodrigueznavao
1,367. Shabani et al., Evaluation of the Prophylactic Effect of Hydroxychloroquine on People in Close-Contact with Patients with Covid-19
113 patient HCQ prophylaxis study: 19% fewer symptomatic cases (p=1) and 6% more cases (p=1).Small PEP trial with 51 HCQ patients, not showing a significant difference in cases. IRCT20130917014693N10.
Aug 2021, Pulmonary Pharmacology & Therapeutics, https://www.sciencedirect.com/science/article/abs/pii/S109455392100081X, https://c19p.org/shabani
1,368. Jacobs et al., Multi-institutional Analysis of 200 COVID-19 Patients treated with ECMO:Outcomes and Trends
200 patient HCQ late treatment study: 7% lower mortality (p=0.74).Prospective study of 200 ECMO patients showing no significant difference in unadjusted results for HCQ treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (as shown in figure 4), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Jul 2021, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/pii/S0003497521011772, https://c19p.org/jacobs
1,369. Lázaro et al., Vitamin D deficit in type 2 diabetes patients during COVID-19 lockdown with and without supplementation
239 patient vitamin D prophylaxis study: 27% fewer cases (p=1).Analysis of 239 consecutive diabetic patients, 97 taking vitamin D supplements, showing significantly higher vitamin D levels in supplemented patients. There was no statistically significant difference in cases based on supplementation, with only 3 cases total.
Sep 2021, Endocrine Abstracts, https://www.endocrine-abstracts.org/ea/0070/ea0070ep552, https://c19p.org/lazaro
1,370. Elhadi et al., Epidemiology, outcomes, and utilization of intensive care unit resources for critically ill COVID-19 patients in Libya: A prospective multi-center cohort study
465 patient aspirin ICU study: 10% lower mortality (p=0.5).Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.
Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadie
1,371. Soto-Becerra et al., Real-World Effectiveness of hydroxychloroquine, azithromycin, and ivermectin among hospitalized COVID-19 patients: Results of a target trial emulation using observational data from a nationwide Healthcare System in Peru
2,833 patient ivermectin late treatment study: 17% lower mortality (p=0.01).Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More..
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v1, https://c19p.org/sotobecerrai
1,372. Shehab et al., Immune-boosting effect of natural remedies and supplements on progress of, and recovery from COVID-19 infection
253 patient nigella sativa prophylaxis study: no change in severe cases (p=1).Retrospective survey-based analysis of 349 COVID-19 patients, showing no significant difference with nigella sativa prophylaxis in unadjusted analysis. REC/UG/2020/03.
Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabns
1,373. Gendelman et al., Continuous Hydroxychloroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare Database Analysis
14,520 patient HCQ prophylaxis study: 8% fewer cases (p=0.88).Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HCQ patient cases. Only considers people tested at a time when primarily symptomatic cases were tested. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. Adjusting for the difference in baseline risk using the result in Ferri et al. shows substantial benefit for HCQ, RR 0.211, but with only 3 HCQ cases the result is inconclusive. More recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.
May 2020, Autoimmunity Reviews, July 2020, https://www.sciencedirect.com/science/article/pii/S1568997220301282, https://c19p.org/gendelman
1,374. Ravikirti et al., Association between Ivermectin treatment and mortality in Covid-19: A hospital-based case-control study
965 patient ivermectin late treatment study: 3% lower mortality (p=0.82).Retrospective 965 late stage (44% severe, 27% ICU) hospitalized patients in India, showing no significant difference with ivermectin treatment. Overall mortality was very high, suggesting very late treatment. The low non-weight-adjusted dose may not be very effective with such late stage patients. 210 patients were excluded due to early discharge, which may have been patients with earlier onset that are more likely to benefit with ivermectin. Age grouping is very unusual with no breakdown of ages for the 71% of patients >45. Numbers may be unreliable, e.g., cardiovascular disease counts and/or percentages for IVM appear incorrect. Details of adjustments are not provided, there may be extreme confounding by age within the >45 groups which contain the majority of the patients, in addition to confounding by indication.
Apr 2022, Research Square, https://www.researchsquare.com/article/rs-1522422/v1, https://c19p.org/ravikirti2
1,375. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
spironolactone antiandrogen prophylaxis study: 7% fewer cases (p=0.008).Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of spironolactone.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenaa
1,376. Leal et al., Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis
acetaminophen prophylaxis study: 7% fewer cases (p=0.004).UK Biobank retrospective showing lower cases with acetaminophen use.
Aug 2021, COVID, https://www.mdpi.com/2673-8112/1/1/18, https://c19p.org/leal
1,377. Leal et al., Paracetamol Is Associated with a Lower Risk of COVID-19 Infection and Decreased ACE2 Protein Expression: A Retrospective Analysis
ibuprofen prophylaxis study: 3% fewer cases (p=0.29).UK Biobank retrospective showing no significant difference in cases with ibuprofen use.
Aug 2021, COVID, https://www.mdpi.com/2673-8112/1/1/18, https://c19p.org/lealib
1,378. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
spironolactone prophylaxis study: 7% fewer cases (p=0.008).Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of spironolactone.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenaasp
1,379. Konig et al., Baseline use of hydroxychloroquine in systemic lupus erythematosus does not preclude SARS-CoV-2 infection and severe COVID-19
80 patient HCQ prophylaxis study: 3% lower hospitalization (p=0.88).Analysis of 80 SLE patients diagnosed with COVID-19, showing the frequency of hospitalisation did not differ between individuals using an antimalarial versus non-users (55% (16/29) vs 57% (29/51), p=ns. Authors suggest that the dosage used may be too low to reach therapeutic levels.
May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/20/annrheumdis-2020-217690, https://c19p.org/konig
1,380. Karruli et al., Multidrug-Resistant Infections and Outcome of Critically Ill Patients with Coronavirus Disease 2019: A Single Center Experience
32 patient HCQ ICU study: 5% lower mortality (p=1).Retrospective 32 ICU patients, showing no significant difference with HCQ treatment in unadjusted results.
Aug 2021, Microbial Drug Resistance, https://www.liebertpub.com/doi/full-xml/10.1089/mdr.2020.0489, https://c19p.org/karrulih
1,381. Veterini et al., Probiotics Intake as Adjunct Therapy for Infected Health-Care with SARS COV-2
30 patient probiotics early treatment study: 29% faster viral clearance (p=0.22).Small case control analysis with 15 probiotics patients and 15 contol patients, showing no significant differences. PCR tests were only done weekly. Dosage is unknown. 115/LOE/301.4.2/IX/2020.
Jun 2021, Indian J. Forensic Medicine & Toxicology, http://medicopublication.com/index.php/ijfmt/article/view/15003/13584, https://c19p.org/veterini
1,382. Jiménez-Alcaide et al., Influence of androgen deprivation therapy on the severity of COVID-19 in prostate cancer patients
1,349 patient various antiandrogen prophylaxis study: 33% lower mortality (p=0.41), 8% higher progression (p=0.77), and 68% more cases (p=0.15).Retrospective 1,349 prostate cancer patients in Spain, 156 on ADT, showing no significant differences in COVID-19 outcomes with treatment.
Sep 2021, The Prostate, https://onlinelibrary.wiley.com/doi/full/10.1002/pros.24232, https://c19p.org/jimenezalcaide
1,383. Lamback et al., Hydroxychloroquine with azithromycin in patients hospitalized for mild and moderate COVID-19
193 patient HCQ late treatment study: 9% lower mortality (p=0.83), 20% higher ICU admission (p=0.61), and 12% shorter hospitalization.Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became more controversial in Brazil over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients (those refusing HCQ) likely come later in the period when treatment protocols were greatly improved. The paper does not mention the word "confounding" or make any adjustments.
Feb 2021, The Brazilian J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S141386702100012X, https://c19p.org/lamback
1,384. Paul et al., Health behaviours the month prior to COVID-19 infection and the development of self-reported long COVID and specific long COVID symptoms: A longitudinal analysis of 1,811 UK adults
1,811 patient exercise study: 38% lower PASC (p=0.16).Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with 3+ hours of exercise per week in the month before infection, without statistical significance (p=0.16).
Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paulex
1,385. Paul et al., Health behaviours the month prior to COVID-19 infection and the development of self-reported long COVID and specific long COVID symptoms: A longitudinal analysis of 1,811 UK adults
1,811 patient smoking long COVID study: 37% lower PASC (p=0.14).Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with no smoking in the month before infection, not reaching statistical significance (p=0.14).
Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paulsm
1,386. Zadeh et al., Effect of aspirin in COVID-19 outcomes of older adults with a history of coronary artery disease
aspirin prophylaxis study: 37% lower mortality (p=0.28) and 1% higher ICU admission (p=0.79).Retrospective 4,017 coronary artery disease patients hospitalized for COVID-19 in the USA, showing no significant difference in outcomes with low dose aspirin use.
Dec 2022, Innovation in Aging, https://academic.oup.com/innovateage/article/6/Supplement_1/850/6939246, https://c19p.org/zadeh
1,387. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
15,227 patient exercise study: 17% fewer cases (p=0.18).Prospective survey-based study with 15,227 people in the UK, showing reduced risk of COVID-19 cases with lower impact physical activity. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtex
1,388. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
15,227 patient sleep study: 12% fewer cases (p=0.5).Prospective survey-based study with 15,227 people in the UK, showing reduced risk of COVID-19 cases with 8 hours sleep, with statistical significance when compared with ≥9 hours. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtsl
1,389. Drake et al., Non-steroidal anti-inflammatory drug use and outcomes of COVID-19 in the ISARIC Clinical Characterisation Protocol UK cohort: a matched, prospective cohort study
ibuprofen prophylaxis study: 10% lower mortality (p=0.36).Prospective study of 78,674 COVID-19 patients, showing no significant difference in mortality with ibuprofen use.
Jul 2021, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991321001041, https://c19p.org/drake
1,390. Carvallo et al., Safety and Efficacy of the Combined Use of Ivermectin, Dexamethasone, Enoxaparin and Aspirina against COVID-19 the I.D.E.A. Protocol
46 patient ivermectin early treatment study: 85% lower mortality (p=0.08).Prospective trial of ivermectin, dexamethasone, enoxaparin, and aspirin, showing no hospitalization for mild cases, and lower mortality for moderate/severe patients.
Sep 2020, J. Clinical Trials, https://www.longdom.org/open-access/safety-and-efficacy-of-the-combined-use-of-ivermectin-dexamethasone-enoxaparin-and-aspirina-against-covid19-the-idea-protocol-70290.html, https://c19p.org/carvallo
1,391. Cortez et al., Clinical characteristics and outcomes of COVID-19 patients in a tertiary hospital in Baguio City, Philippines
280 patient HCQ late treatment study: 15% lower mortality (p=1).Retrospective 280 hospitalized patients in the Philippines, 25 treated with HCQ, not showing any significant differences in unadjusted results.
Nov 2021, Western Pacific Surveillance and Response J., https://ojs.wpro.who.int/ojs/index.php/wpsar/article/view/852, https://c19p.org/cortez
1,392. Salehi et al., Risk factors of death in mechanically ventilated COVID-19 patients: a retrospective multi-center study
125 patient vitamin C ICU study: 10% lower mortality (p=0.56).Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with vitamin C treatment in unadjusted results.
Mar 2022, Research Square, https://www.researchsquare.com/article/rs-1362678/v1, https://c19p.org/salehic
1,393. Seifi et al., Dietary mineral intakes predict Coronavirus-disease 2019 (COVID-19) incidence and hospitalization in older adults
zinc prophylaxis study: 31% lower hospitalization (p=0.02).Analysis of 1,957 older adults showing lower risk of COVID-19 hospitalization with higher dietary zinc intake. Each unit increase in zinc intake was associated with a 31% reduction in the risk of COVID-19 hospitalization after adjustments. A dynamical system model showed that consumption of zinc < 9.7mg per day was associated with a 1.5 times greater risk of COVID-19 infection.
Mar 2024, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-024-00821-5, https://c19p.org/seifi
1,394. Azizi et al., A study on the effect of aspirin on clinical symptoms, laboratory indices, and outcomes in patients with COVID-19
262 patient aspirin prophylaxis study: no change in mortality (p=1).Retrospective 131 COVID-19 patients with aspirin use and 131 matched controls in Iran, showing no significant difference in outcomes, however age matching used only two categories, 40-60 and 60+, therefore matching may be very poor given the relationship between age and COVID-19 risk. The percentages given for the control group death/recovery outcomes do not match the reported counts.
Feb 2023, J. Nephropharmacology, https://www.jnephropharmacology.com/Inpress/npj-10506.pdf, https://c19p.org/azizi
1,395. Fung et al., Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients
HCQ prophylaxis study: 13% lower mortality (p=0.15), 3% lower hospitalization (p=0.63), and 9% fewer cases (p=0.02).Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri]. Authors compare with patients that never used HCQ and with patients that previously used HCQ. The comparison with patients previously using HCQ is more relevant because the matching of patients with systemic autoimmune disease is likely to be better.
Sep 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266922, https://c19p.org/fung
1,396. Ahmed et al., Causal Inference and COVID-19 Nursing Home Patients: Identifying Factors That Reduced Mortality Risk
vitamin D prophylaxis study: 10% lower mortality (p=0.28).Retrospective causal inference analysis of 4,091 COVID+ long-term care high risk patients in the USA, showing lower mortality with vitamin D, without statistical significance.
Nov 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.11.18.21266489, https://c19p.org/ahmed3
1,397. Drew et al., Aspirin and NSAID use and the risk of COVID-19
aspirin prophylaxis study: 22% lower progression (p=0.3) and 3% more cases (p=0.8).Retrospective 2,736,091 individuals in the U.S., U.K., and Sweden, showing lower risk of hospital/clinic visits with aspirin use.
May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.28.21256261, https://c19p.org/drew
1,398. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
metformin prophylaxis study: 1% fewer cases (p=0.45).Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of metformin.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenmf
1,399. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
famotidine prophylaxis study: 7% fewer cases (p=0.16).Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of famotidine.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenfm
1,400. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
vitamin B9 prophylaxis study: no change in cases (p=1).Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of vitamin B9.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenb9
1,401. Khamis et al., Randomized Controlled Open Label Trial on the Use of Favipiravir Combined with Inhaled Interferon beta-1b in Hospitalized Patients with Moderate to Severe COVID-19 Pneumonia
89 patient favipiravir late treatment RCT: 15% lower mortality (p=1), 2% higher ICU admission (p=1), and 10% worse recovery (p=0.82).Small 89 patient RCT comparing favipiravir and inhaled interferon with HCQ for moderate to severe COVID-19 pneumonia, not finding significant differences. There was no control group.
Nov 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220323195, https://c19p.org/khamisf
1,402. Roy et al., Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study
29 patient HCQ early treatment study: 2% faster recovery (p=0.96).Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21252883v1, https://c19p.org/royh
1,403. Fung et al., Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients
famotidine prophylaxis study: no change in mortality (p=1), 6% lower hospitalization (p=0.0002), and 12% more cases (p<0.0001).Retrospective database analysis of 374,229 patients in the USA, showing higher cases, lower hospitalizations, and no change in mortality with famotidine use.
Sep 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266922, https://c19p.org/fungfm
1,404. Alegiani et al., Risk of COVID-19 hospitalization and mortality in rheumatic patients treated with hydroxychloroquine or other conventional DMARDs in Italy
HCQ prophylaxis study: 8% higher mortality (p=0.64) and 18% lower hospitalization (p=0.03).Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ significantly from previous studies, for example showing mortality OR 0.94 [0.83-1.06] for patients with rheumatic disease and mortality OR 0.88 [0.74-1.05] for patients with RA/SLE. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall.
Apr 2021, Rheumatology, https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab348/6226505?searchresult=1, https://c19p.org/alegiani
1,405. Salvarani et al., Susceptibility to COVID-19 in Patients Treated With Antimalarials: A Population-Based Study in Emilia-Romagna, Northern Italy
HCQ prophylaxis study: 6% fewer cases (p=0.75).Comparison of CQ/HCQ users with the general population in a region of Italy, showing no significant difference in the probability of COVID-19. CQ/HCQ users were mostly systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Aug 2020, Arthritis & Rheumatology, https://onlinelibrary.wiley.com/doi/10.1002/art.41475, https://c19p.org/salvarani
1,406. Roy et al., Outcome of Different Therapeutic Interventions in Mild COVID-19 Patients in a Single OPD Clinic of West Bengal: A Retrospective study
29 patient ivermectin early treatment study: 6% faster recovery (p=0.87).Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups. Subject to the usual limitation of a database study, very small size, and limited evaluation of patients.
Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21252883v1, https://c19p.org/roy
1,407. Zangeneh et al., Survival analysis based on body mass index in patients with COVID-19 admitted to the intensive care unit of Amir Al-Momenin Hospital in Arak – 2021
vitamin C ICU study: 4% lower mortality (p=0.86).Retrospective 193 ICU patients in Iran, showing no significant difference with vitamin C treatment.
May 2022, Obesity Medicine, https://www.sciencedirect.com/science/article/pii/S245184762200032Xhttps://www.sciencedirect.com/science/article/pii/S245184762200032X/pdf, https://c19p.org/zangenehc
1,408. IVERCOR PREP et al., Ivermectina en agentes de salud e IVERCOR COVID19
875 patient ivermectin prophylaxis study: 73% fewer cases (p<0.0001).Report on ivermectin prophylaxis in a hospital in Argentina showing lower cases for healthcare workers taking ivermectin. Results have been published in the press [lanacion.com.ar] (interim results), and a presentation posted online: [web.archive.org], however there is no formal publication to date. These results would be expected to receive priority publication due to the predicted impact on the pandemic and confirmation of previous prophylaxis studies. The lack of formal publication suggests a negative publication bias that may be due to politicization in the authors' location. Note that this prophylaxis study is different to the Vallejos early treatment trial.
Dec 2020, IVERCOR PREP, Preliminary Results, https://web.archive.org/web/20210226215453/https://twitter.com/Covid19Crusher/status/1365420061859717124, https://c19p.org/vallejos
1,409. Borody et al., Combination Therapy For COVID-19 Based on Ivermectin in an Australian Population
600 patient ivermectin early treatment study: 92% lower mortality (p=0.03) and 93% lower hospitalization (p<0.0001).Retrospective 600 PCR+ outpatients in Australia treated with ivermectin, zinc, and doxycycline, showing significantly lower mortality and hospitalization with treatment. This trial uses a synthetic control group, and the preliminary report provides minimal details. For discussion of the use of a synthetic control group, see [doyourownresearch.substack.com]. Notably, advantages include less-biased recruitment (patients do not opt-out if they feel they need treatment and don't want to risk placebo), trials are cheaper, there is less delay in treatment, and trials can be run where it is not ethical to give patients placebo.
Oct 2021, TrialSite News, https://www.trialsitenews.com/a/combination-therapy-for-covid-19-based-on-ivermectin-in-an-australian-population, https://c19p.org/borody
25 patient HCQ late treatment study: 38% improved viral clearance (p=0.17).
Early results from a very small trial, reported within the application for a later trial. Very minimal details are provided, but we include this as the earliest published results. For COVID-19 patients with pneumonia the viral negative conversion rate was 50% (5/10) with CQ versus 20% (3/15) with lopinavir/ritonavir.
Feb 2020, ChiCTR2000029741, http://www.chictr.org.cn/showproj.aspx?proj=49263, https://c19p.org/xia
1,411. Özgünay et al., The use of vitamin C in the intensive care unit during the COVID-19 pandemic
160 patient vitamin C ICU study: 9% lower mortality (p=0.69) and 1% higher ventilation (p=1).Retrospective 160 ICU patients, 32 with raised neutrophil/lymphocyte ratio treated with vitamin C, showing no significant differences.
Jul 2021, The European Research J., https://dergipark.org.tr/en/download/article-file/1774154, https://c19p.org/ozgunay
1,412. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
2,148 patient aspirin prophylaxis study: 4% lower hospitalization (p=0.08) and 18% higher severe cases (p=0.28).Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with aspirin prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimere
1,413. Kodvanj et al., People exposed to proton‐pump inhibitors shortly preceding COVID‐19 diagnosis are not at an increased risk of subsequent hospitalizations and mortality: A nationwide matched cohort study
58,529 patient proton pump inhibitor prophylaxis study: 7% lower mortality (p=0.12) and 4% higher hospitalization (p=0.32).Retrospective 433,609 COVID-19 patients in Croatia showing no significant difference in mortality or hospitalization risk with proton-pump inhibitor (PPI) use before COVID-19 diagnosis compared to matched controls with PPI-requiring morbidities but no PPI prescriptions. There was significantly higher hospitalization for users with 1-3 prescriptions which authors do not comment on. The classification of users and possible users may introduce confounding. Users required a PPI prescription, while possible users includes those with ≥3 NSAID prescriptions. Possible users may be OTC PPI users, and may differ significantly in NSAID use. NSAID use per group is not reported, and was not used in adjustments.
Oct 2022, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15525, https://c19p.org/kodvanj
1,414. Argenziano et al., Characterization and clinical course of 1000 patients with coronavirus disease 2019 in New York: retrospective case series
1,000 patient proton pump inhibitor prophylaxis study: 1% lower ICU admission (p=1) and 9% higher hospitalization (p=0.01).Retrospective 1,000 hospitalized COVID-19 patients in New York City showing high rates of acute kidney injury, inpatient dialysis, prolonged intubation times, and length of stay compared to previous cohorts.
May 2020, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj.m1996, https://c19p.org/argenziano
1,415. Chalageri et al., Impact of steam inhalation, saline gargling, and povidone-iodine gargling on clinical outcome of COVID-19 patients in Bengaluru, Karnataka: A randomized control trial
40 patient saline early treatment RCT: 43% improved recovery (p=0.0004).RCT with 20 saline and 20 control low risk patients in India, showing faster recovery with saline gargling, but no significant difference in viral clearance.
Jul 2022, Indian J. Community Medicine, https://journals.lww.com/ijcm/Fulltext/2022/47020/Impact_of_Steam_Inhalation,_Saline_Gargling,_and.12.aspx, https://c19p.org/chalagerisa
1,416. Alhamlan et al., Epidemiology and Clinical Characteristics in Individuals with Confirmed SARS-CoV-2 Infection During the Early COVID-19 Pandemic in Saudi Arabia
HCQ late treatment study: 52% higher mortality (p=0.58).Retrospective hospitalized patients in Saudi Arabia showing higher mortality with most treatments although not reaching statistical significance. Confounding by indication, time, or other factors is likely (a 19x higher risk with lopinavir/ritonavir and 3.5x higher risk with azithromycin is not supported by other studies for example). The number of patients treated with HCQ is not provided.
Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.13.21260428v1, https://c19p.org/alhamlan
1,417. Zengin et al., The Effect of Montelukast Treatment on Elderly Patients Diagnosed with COVID-19
75 patient montelukast late treatment study: 14% lower mortality (p=1), 90% higher ICU admission (p=0.46), and 3% shorter hospitalization (p=0.81).Retrospective 75 hospitalized COVID-19 patients over 60 in Turkey showing no significant differences with montelukast treatment.
Aug 2024, Genel Tıp Dergisi, http://dergipark.org.tr/en/doi/10.54005/geneltip.1352153, https://c19p.org/zengin2
1,418. Küçükakkaş et al., The effect of hydroxychloroquine against SARS-CoV-2 infection in rheumatoid arthritis patients
17 patient HCQ prophylaxis study: 43% higher ICU admission (p=1).Retrospective 17 rheumatoid arthritis COVID-19+ patients, 7 on HCQ treatment, showing no significant differences. They study reports only including hospitalized patients, but the results include non-hospitalized patients. Results do not reflect potential difference in the probability that a case is serious enough to have been tested and identified. Few group details are provided (even the age of patients in each group is not specified).
Jul 2021, Research Square, https://www.researchsquare.com/article/rs-43812/v1, https://c19p.org/kucukakkas
1,419. Zangeneh et al., Survival analysis based on body mass index in patients with Covid-19 admitted to the intensive care unit of Amir Al-Momenin Hospital in Arak – 2021
vitamin D ICU study: 26% higher mortality (p=0.4).Retrospective 193 ICU patients in Iran, showing no significant difference with vitamin D treatment.
May 2022, Obesity Medicine, https://www.sciencedirect.com/science/article/pii/S245184762200032Xhttps://www.sciencedirect.com/science/article/pii/S245184762200032X/pdf, https://c19p.org/zangenehd
1,420. Prieto-Campo et al., Impact of prior use of antiplatelets on COVID-19 susceptibility, progression, and severity: a population-based study
aspirin prophylaxis study: 13% higher mortality (p=0.38), 3% lower hospitalization (p=0.64), no change in progression (p=0.98), and 8% fewer cases (p=0.02).Population-based case-control study of 86,602 people in Spain, shower lower risk of COVID-19 cases with low-dose aspirin, but no significant difference for severity, hospitalization, or mortality.
Jan 2024, Revista Española de Cardiología, https://www.sciencedirect.com/science/article/pii/S1885585724000148, https://c19p.org/prietocampo
1,421. Rosenthal et al., Risk Factors Associated With In-Hospital Mortality in a US National Sample of Patients With COVID-19
HCQ late treatment study: 8% higher mortality (p=0.13).Retrospective database analysis of 64,781 hospitalized patients in the USA, showing lower mortality with vitamin C or vitamin D (authors do not distinguish between the two), and higher mortality with zinc and HCQ, statistically significant for zinc. Authors excluded hospital-based outpatient visits, without explanation. Confounding by indication is likely, adjustments do not appear to include any information on COVID-19 severity at baseline.
Dec 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2773971, https://c19p.org/rosenthal
1,422. Zangeneh et al., Survival analysis based on body mass index in patients with Covid-19 admitted to the intensive care unit of Amir Al-Momenin Hospital in Arak – 2021
zinc ICU study: 21% higher mortality (p=0.66).Retrospective 193 ICU patients in Iran, showing no significant difference with zinc treatment.
May 2022, Obesity Medicine, https://www.sciencedirect.com/science/article/pii/S245184762200032Xhttps://www.sciencedirect.com/science/article/pii/S245184762200032X/pdf, https://c19p.org/zangenehz
1,423. Rosenthal et al., Risk Factors Associated With In-Hospital Mortality in a US National Sample of Patients With COVID-19
zinc late treatment study: 16% higher mortality (p=0.003).Retrospective database analysis of 64,781 hospitalized patients in the USA, showing lower mortality with vitamin C or vitamin D (authors do not distinguish between the two), and higher mortality with zinc and HCQ, statistically significant for zinc. Authors excluded hospital-based outpatient visits, without explanation. Confounding by indication is likely, adjustments do not appear to include any information on COVID-19 severity at baseline.
Dec 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2773971, https://c19p.org/rosenthalz
1,424. Jeong et al., Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study
acetaminophen early treatment study: 15% worse results (p=0.61).Retrospective 1,824 hospitalized COVID-19 patients in South Korea, showing higher progression to combined death, ICU, ventilation, or sepsis (4% versus 0%, group sizes not provided) with paracetamol vs. NSAIDs. Treatment time may vary - exposure was defined as 7 days before and including cohort entry in hospitalized COVID-19 patients.
Jul 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/73/11/e4179/5876905, https://c19p.org/jeong
1,425. Lazzeri et al., Impact of anti-androgen therapies on COVID-19 susceptibility: a case-control study in male population from two COVID-19 regional centers of Lombardy (Italy)
various antiandrogen prophylaxis study: 23% higher combined mortality/ICU admission (p=0.33).Retrospective case-control study in Italy with 943 male COVID-19 patients, 45 on chronic 5ARI treatment (finasteride/dutasteride). There was significantly fewer COVID-19 patients >55 on 5ARI treatment compared to age-matched controls (5.57 vs. 8.14%, p=0.0083). The difference was greater for men aged >65 (7.14 vs. 12.31%, p=0.0001). There was no significant difference for ICU admission or death.
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.04.20.20068056v2, https://c19p.org/lazzeri
1,426. Paul et al., Health behaviours the month prior to COVID-19 infection and the development of self-reported long COVID and specific long COVID symptoms: A longitudinal analysis of 1,811 UK adults
1,811 patient alcohol study: 28% higher PASC (p=0.4).Retrospective 1,811 COVID-19 patients in the UK, showing no significant difference in self-reported long COVID based on having ≤14 vs. >14 alcoholic drinks per week in the month before infection.
Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paulac
1,427. Mousaviasl et al., The Effect of a Low Dose of Vitamin C in Patients With COVID-19: A Double-Blind Randomized Controlled Trial
401 patient vitamin C late treatment RCT: 20% lower mortality (p=0.64), 200% higher ventilation (p=1), and 33% higher ICU admission (p=0.79).RCT 401 hospitalized COVID-19 patients showing no significant differences with low-dose oral vitamin C (1000mg daily for 5 days).
Jul 2023, Disease and Diagnosis, https://ddj.hums.ac.ir/Article/ddj-500, https://c19p.org/mousaviasl
1,428. Szente Fonseca et al., Risk of Hospitalization for Covid-19 Outpatients Treated with Various Drug Regimens in Brazil: Comparative Analysis
717 patient ivermectin early treatment study: 14% higher hospitalization (p=0.53).Retrospective 717 patients in Brazil showing OR 1.17 [0.72-1.90] for ivermectin. This paper focuses on HCQ, event counts for ivermectin are not provided. With significant correlation between the variables used, including overlap in the prescription of multiple treatments that show efficacy alone, and limited data for the model size, the model used here may be inaccurate due to multicollinearity [statisticsbyjim.com].
Oct 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/abs/pii/S1477893920304026, https://c19p.org/fonsecai
1,429. Monserrat Villatoro et al., A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis
aspirin prophylaxis PSM study: 31% higher mortality (p=0.04).PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoroe
1,430. Lehrer et al., Association of cannabis with chronic obstructive pulmonary disease and COVID-19 infection
cannabidiol prophylaxis study: 24% more cases (p=0.009).UK Biobank retrospective showing a higher risk of COVID-19 cases with a history of cannabis use.
Jun 2022, Chronic Diseases and Translational Medicine, https://onlinelibrary.wiley.com/doi/10.1002/cdt3.38, https://c19p.org/lehrer2
1,431. Lapi et al., To clarify the safety profile of paracetamol for home-care patients with COVID-19: a real-world cohort study, with nested case–control analysis, in primary care
acetaminophen early treatment study: 15% higher combined mortality/hospitalization (p=0.22).Retrospective paracetamol use with a primary care database in Italy, showing no significant difference in hospitalization/death for use 0-3 and 4-7 days from diagnosis, and significantly higher risk for use >7 days from diagnosis. Confounding by indication may have a greater effect on late usage.
Jul 2022, Internal and Emergency Medicine, https://link.springer.com/10.1007/s11739-022-03054-1, https://c19p.org/lapi
1,432. Lerner et al., Mining Electronic Health Records for Drugs Associated With 28-day Mortality in COVID-19: Pharmacopoeia-wide Association Study (PharmWAS)
5,783 patient acetaminophen late treatment study: 27% higher mortality (p=0.1).Retrospective 5,783 hospitalized patients in France, showing higher mortality with paracetamol use, without statistical significance.
Mar 2022, JMIR Medical Informatics, https://medinform.jmir.org/2022/3/e35190, https://c19p.org/lerner
1,433. MacFadden et al., Screening Large Population Health Databases for Potential COVID-19 Therapeutics: A Pharmacopeia-Wide Association Study (PWAS) of Commonly Prescribed Medications
acetaminophen prophylaxis study: 48% more cases (p<0.0001).Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing higher cases with chronic use of acetaminophen.
Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenace
1,434. Kolin et al., Clinical, regional, and genetic characteristics of Covid-19 patients from UK Biobank
397,064 patient acetaminophen prophylaxis study: 23% more cases (p=0.009).397,064 patient UK Biobank retrospective showing higher risk of COVID-19 with acetaminophen use.
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241264, https://c19p.org/kolin
1,435. Salehi et al., Risk factors of death in mechanically ventilated COVID-19 patients: a retrospective multi-center study
125 patient HCQ ICU study: 14% higher mortality (p=0.44).Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with HCQ treatment in unadjusted results.
Mar 2022, Research Square, https://www.researchsquare.com/article/rs-1362678/v1, https://c19p.org/salehih
1,436. Sarfaraz et al., Determinants of in-hospital mortality in COVID-19; a prospective cohort study from Pakistan
186 patient HCQ late treatment study: 45% higher mortality (p=0.07).Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, p = 0.07. Confounding by indication is likely.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.28.20248920v1, https://c19p.org/sarfaraz
1,437. Shamsi et al., Survival and Mortality in Hospitalized Children with COVID-19: A Referral Center Experience in Yazd, Iran
183 patient HCQ late treatment study: 39% higher mortality (p=0.51).Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.
Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsih
1,438. Al Mutair et al., Overview of Clinical Outcome and Therapeutic Effectiveness of Favipiravir in Patients with COVID-19 Admitted to Intensive Care Unit, Riyadh, Saudi Arabia
538 patient favipiravir ICU study: 7% lower mortality (p=0.49), 9% higher ARDS (p=0.63), 34% longer ICU admission (p=0.001), and 37% longer hospitalization (p=0.001).Retrospective 269 favipiravir ICU patients in Saudi Arabia and 269 matched controls receiving different treatments, showing no significant difference.
Feb 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034122000259, https://c19p.org/almutair
1,439. Nickols et al., Effect of Androgen Suppression on Clinical Outcomes in Hospitalized Men With COVID-19
96 patient degarelix antiandrogen late treatment RCT: 18% lower mortality (p=0.66), 19% higher ventilation (p=0.7), 17% worse results (p=0.7), and 20% longer hospitalization (p=0.94).Early terminated RCT with 62 very late stage (79% on oxygen) degarelix patients and 34 placebo patients, showing no significant differences with treatment. For discussion of many issues with this study see [twitter.com].
Apr 2022, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791293, https://c19p.org/nickols
1,440. Huang et al., Cannabis use is associated with lower COVID-19 susceptibility but poorer survival
13,099 patient cannabidiol prophylaxis study: 181% higher mortality (p=0.04) and 19% fewer cases (p=0.0001).UK Biobank retrospective with 13,099 cannabis users, showing a lower risk of COVID-19 infection, however regular users had a significantly higher risk of mortality.
Mar 2022, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2022.829715/abstract, https://c19p.org/huang2
1,441. Zhang et al., Analysis of the Effect of Proton-Pump Inhibitors on the Course of COVID-19
154 patient proton pump inhibitor prophylaxis PSM study: 11% longer hospitalization (p=0.29), 6% higher hospital discharge (p=0.82), and 37% improved viral clearance (p=0.05).Retrospective 154 hospitalized moderate COVID-19 patients in China showing no significant difference in viral clearance time or hospital stay duration with proton pump inhibitor (PPI) use. There was no association between PPI use and viral clearance or hospital stay duration in univariate or multivariate analysis. The same results were obtained after propensity score matching.
Feb 2021, J. Inflammation Research, https://www.dovepress.com/analysis-of-the-effect-of-proton-pump-inhibitors-on-the-course-of-covi-peer-reviewed-article-JIR, https://c19p.org/zhang30
1,442. Abdulrahman et al., The efficacy and safety of hydroxychloroquine in COVID19 patients : a multicenter national retrospective cohort
446 patient HCQ late treatment PSM study: 17% lower mortality (p=1) and 75% higher combined mortality/intubation (p=0.24).Retrospective analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity. 17.5% of HCQ patients required oxygen while only 12.6% of control patients did.
Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.25.20234914v1, https://c19p.org/abdulrahman
1,443. Mohseni et al., Do body mass index (BMI) and history of nutritional supplementation play a role in the severity of COVID-19? A retrospective study
603 patient vitamin C prophylaxis study: 44% more cases (p=0.002).Retrospective 603 patients in Iran, 34 taking vitamin C supplements, showing increased risk of COVID-19 cases in unadjusted results. IR.SHOUSHTAR.REC.1399.015.
Aug 2021, Nutrition & Food Science, https://www.emerald.com/insight/content/doi/10.1108/NFS-11-2020-0421/full/html, https://c19p.org/mohsenic
1,444. Gálvez-Barrón et al., COVID-19: Clinical Presentation and Prognostic Factors of Severe Disease and Mortality in the Oldest-Old Population: A Cohort Study
103 patient acetaminophen prophylaxis study: 47% higher mortality (p=0.42) and 23% lower severe cases (p=0.55).Analysis of 103 elderly hospitalized COVID-19 patients in Spain, showing higher mortality with acetaminophen, without statistical significance.
Apr 2021, Gerontology, https://www.karger.com/Article/FullText/515159, https://c19p.org/galvezbarron
1,445. Alamdari et al., Mortality Risk Factors among Hospitalized COVID-19 Patients in a Major Referral Center in Iran
459 patient aspirin late treatment study: 28% higher mortality (p=0.52).Retrospective 459 patients in Iran, 53 treated with aspirin, showing no significant difference with treatment.
Sep 2020, The Tohoku J. Experimental Medicine, https://www.jstage.jst.go.jp/article/tjem/252/1/252_73/_article/-char/ja/, https://c19p.org/alamdarie
1,446. JamaliMoghadamSiahkali et al., Safety and Effectiveness of High-Dose Vitamin C in Patients with COVID-19; A Randomized Controlled open-label Clinical Trial
60 patient vitamin C late treatment RCT: 25% higher ventilation (p=1) and 31% longer hospitalization (p=0.03).Small late stage RCT for the addition of vitamin C to HCQ and lopinavir/ritonavir, with 30 treatment and 30 control patients, finding a significant reduction in temperature and a significant improvement in oxygenation after 3 days in the vitamin C group. However, hospitalization time was longer and there was no significant difference in mortality.
Jan 2021, Research Square, https://www.researchsquare.com/article/rs-139942/v1, https://c19p.org/jamalimoghadamsiahkali
1,447. Fan et al., Effect of Acid Suppressants on the Risk of COVID-19: A Propensity Score-Matched Study Using UK Biobank
proton pump inhibitor prophylaxis PSM study: 17% higher mortality (p=0.69) and 22% more cases (p=0.15).PSM retrospective 9,469 UK Biobank participants tested for COVID-19, showing no significant association between proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H2RA) use and risk of SARS-CoV-2 infection or COVID-19 mortality. Omeprazole was associated with higher risk of cases in patients with upper gastrointestinal diseases. The results for patients with upper gastrointestinal diseases should be more accurate due to reduced confounding and more accurate ascertainment of current use.
Jan 2021, Gastroenterology, https://www.sciencedirect.com/science/article/pii/S0016508520352094, https://c19p.org/fan4
299 patient HCQ late treatment RCT: 15% higher mortality (p=0.7) and 24% improved viral clearance (p=0.68).
Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial. 4% more patients were on ventilation at baseline in the HCQ group. This preprint presents more recent results than the earlier journal article.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2022.02.16.22271064, https://c19p.org/discovery
1,449. Kishoria et al., Ivermectin as adjuvant to hydroxychloroquine in patients resistant to standard treatment for SARS-CoV-2: results of an open-label randomized clinical study
32 patient ivermectin late treatment RCT: 8% lower hospital discharge (p=1) and 8% worse viral clearance (p=1).Small RCT of hospitalized patients in India with 19 ivermectin patients and 13 control patients, with all receiving SOC including HCQ, showing no significant differences. The patient population is biased because the study recruited patients that did not respond to standard treatment. Authors do not specify the treatment delay but it is likely relatively late because the patients had already undergone standard treatment. Criteria for discharge are not provided. The time of discharge status is not specified and may not have been an equal time since treatment initiation for all patients. Authors indicate 19 treatment and 16 control patients, but the results only show 13 control patients. Authors do not indicate why the other 3 are missing. Randomization in this small sample resulted in very large differences in the groups, with over twice as many in the ivermectin group with age >40, and the only 2 patients with age >60 both in the ivermectin group. Authors did not adjust for these..
Aug 2020, Paripex - Indian J. Research, https://www.worldwidejournals.com/paripex/recent_issues_pdf/2020/August/ivermectin-as-adjuvant-to-hydroxycholoroquine-in-patients-resistant-to-standard-treatment-for-sarscov2-results-of-an-openlabel-randomized-clinical-study_August_2020_1597492974_4801859.pdf, https://c19p.org/kishoria
32 patient vitamin C ICU PSM study: 11% higher mortality (p=1).
PSM retrospective 8 ICU patients treated with vitamin C and 24 matched controls, showing no significant difference. Authors note that "it is possible for the delayed timing of IV vitamin C to have blunted the beneficial effects as these patients may have already progressed to the late fibroproliferative phase or ARDS". IV vitamin C 1.5 grams every 6 hours.
Jun 2021, J. Pharmacy Practice, https://journals.sagepub.com/doi/10.1177/08971900211015052, https://c19p.org/li7
1,451. Brandenburg et al., Does Higher Self-Reported Cardiorespiratory Fitness Reduce the Odds of Hospitalization From COVID-19?
211 patient exercise study: 6% higher hospitalization (p=0.6) and 35% lower severe cases (p=0.3).Retrospective 263 COVID+ patients, showing lower hospitalization with higher self-reported cardiorespiratory fitness, but no significant differences for physical activity. Participants in the study were healthier and more fit than the general population.
Jun 2021, J. Physical Activity and Health, https://journals.humankinetics.com/view/journals/jpah/18/7/article-p782.xml, https://c19p.org/brandenburg
1,452. Erden et al., COVID-19 outcomes in patients with antiphospholipid syndrome: a retrospective cohort study
9 patient HCQ prophylaxis study: 75% lower hospitalization (p=0.23).Retrospective 9 COVID-19 patients with antiphospholipid syndrome in Turkey, showing no significant differences based on existing HCQ treatment.
Jan 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7533&category_id=179&option=com_virtuemart&vmcchk=1&Itemid=1, https://c19p.org/erden
1,453. Bliek-Bueno et al., Baseline Drug Treatments as Indicators of Increased Risk of COVID-19 Mortality in Spain and Italy
8,570 patient vitamin B9 prophylaxis study: 87% higher mortality (p<0.0001).Retrospective 8,570 individuals in Spain and Italy, showing higher mortality with combined vitamin B9 and B12 supplementation. Adjustments only considered age.
Nov 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/22/11786, https://c19p.org/bliekbuenob9
1,454. Saleemi et al., Time to negative PCR from symptom onset in COVID-19 patients on Hydroxychloroquine and Azithromycin - A real world experience
85 patient HCQ late treatment study: 21% slower viral clearance (p=0.05).Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidities and symptoms in the HCQ+AZ group.
Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.05.20151027v1, https://c19p.org/saleemi
1,455. Madrid-García et al., Influence of colchicine prescription in COVID-19-related hospital admissions: a survival analysis
colchicine prophylaxis study: 37% higher mortality (p=0.57) and 137% higher hospitalization (p=0.2).Retrospective 9,379 patients attending a rheumatology outpatient clinic in Spain, showing higher mortality and hospitalization with colchicine use, without statistical significance.
Jan 2021, Therapeutic Advances in Musculoskeletal Disease, http://journals.sagepub.com/doi/10.1177/1759720X211002684, https://c19p.org/madridgarcia
1,456. Özgülteki̇n et al., The effect of high-dose vitamin C on renal functions in COVID–19 patients
43 patient vitamin C ICU study: 5% higher mortality (p=1).Retrospective 43 ICU patients in Turkey, 21 treated with vitamin C, showing no significant difference in mortality and increased renal failure. Treatment included stage 1 AKI patients. Vitamin C 45-50 g/day for 5 days.
Sep 2022, Kastamonu Medical J., https://www.kastamonumedicaljournal.com/index.php/kmj/article/view/59, https://c19p.org/ozgultekin
1,457. Hayward et al., Ivermectin for COVID-19 in adults in the community (PRINCIPLE): an open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes
5,413 patient ivermectin late treatment RCT: 36% lower long COVID and 16% faster recovery despite very late treatment, low-risk patients, and poor administration. Probability of superiority > 0.999.Significantly improved recovery and significantly lower risk of long COVID with ivermectin, despite very late treatment, low-risk patients, and poor administration. 36% lower ongoing persistent COVID-19 specific symptoms, p 0.999), missing from the abstract (details below). The p values for sustained recovery, early sustained recovery, alleviation of all symptoms, and sustained alleviation are all The efficacy seen for ivermectin here is despite the trial being the most clearly designed to fail trial, with major bias in design, operation, analysis, and reporting. This trial is a great example of bias in clinical trials which will be covered in detail in the future. c19 early .org Molnupiravir PANORAMIC [ Gbinigie , isrctn.com ] Ivermectin PRINCIPLE [ isrctn.com (B) ] Investigator Prof. Chris Butler Prof. Chris Butler Delay ≤5 days from onset median 2 days ≤14 days from onset median unknown Population 50+ or 18+ w/comorbidities 18+ (mid-trial change) Treatment 5 days, 2x per day 3..
Feb 2024, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445324000641, https://c19p.org/principleivm
1,458. Al-Muhsen et al., Favipiravir Effectiveness and Safety in Hospitalized Moderate-Severe COVID-19 Patients: Observational Prospective Multicenter Investigation in Saudi Arabia
598 patient favipiravir late treatment study: 263% higher mortality (p=0.04), 41% lower need for oxygen therapy (p<0.0001), and 40% longer hospitalization (p=0.03).Prospective observational study of 598 hospitalized patients in Saudi Arabia, showing higher risk of mortality and longer hospitalization time with favipiravir.
Mar 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.826247/full, https://c19p.org/almuhsen
1,459. Zubair et al., The effect of ivermectin on non-severe and severe COVID-19 disease and gender-based difference of its effectiveness
188 patient ivermectin late treatment study: 9% higher mortality (p=1) and 8% longer hospitalization (p=0.4).Retrospective 188 hospitalized patients in Pakistan, 90 treated with ivermectin, showing no significant differences with treatment. The ivermectin group had more severe disease (66% vs 58%, with 6x higher risk for severe disease patients), and more male patients (70% vs. 65%). Higher use of remdesivir and steroids in the ivermectin group also suggests that ivermectin was more likely to be given to patients in more severe condition. There were no side effects seen with ivermectin. Authors note that significantly improved ferritin levels were seen with treatment. Authors state that ivermectin patients received 2 12mg doses, 24 hours apart, but later state that the dosage was not standardized.
Jan 2022, Monaldi Archives for Chest Disease, https://monaldi-archives.org/index.php/macd/article/download/2062/1397, https://c19p.org/zubair
1,460. Bruminhent et al., Clinical Course and Outcomes among COVID-19 Patients at the Hospitel in Bangkok: A Retrospective Study
favipiravir early treatment study: 227% higher progression (p=0.005).Retrospective 514 patients in Thailand, showing higher risk of progression with favipiravir treatment.
Sep 2022, Tropical Medicine and Infectious Disease, https://www.mdpi.com/2414-6366/7/9/238, https://c19p.org/bruminhent
1,461. Alsultan et al., Efficacy of Colchicine and Budesonide in Improvement Outcomes of Patients with Coronavirus Infection 2019 in Damascus, Syria: A Randomized Control Trial
35 patient budesonide late treatment RCT: 7% higher mortality (p=1) and 20% shorter hospitalization.Small RCT 49 severe condition hospitalized patients in Syria, showing lower mortality with colchicine and shorter hospitalization time with both colchicine and budesonide (all of these are not statistically significant).
Dec 2021, Interdisciplinary Perspectives on Infectious Diseases, https://www.hindawi.com/journals/ipid/2021/2129006/, https://c19p.org/alsultan
1,462. Lewandowski et al., Insulin and Metformin Administration: Unravelling the Multifaceted Association with Mortality across Various Clinical Settings Considering Type 2 Diabetes Mellitus and COVID-19
430 patient aspirin late treatment study: 70% higher mortality (p=0.02).Retrospective 430 hospitalized COVID-19 patients with type 2 diabetes in Poland showing lower mortality with metformin and higher mortality with remdesivir, convalescent plasma, and aspirin in univariable analysis. These results were not statistically significant except for aspirin, and no baseline information per treatment is provided to assess confounding.
Mar 2024, Biomedicines, https://www.mdpi.com/2227-9059/12/3/605, https://c19p.org/lewandowski2e
1,463. Monserrat Villatoro et al., A Case-Control of Patients with COVID-19 to Explore the Association of Previous Hospitalisation Use of Medication on the Mortality of COVID-19 Disease: A Propensity Score Matching Analysis
vitamin B9 prophylaxis PSM study: 132% higher mortality (p=0.003).PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.
Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatorob9
1,464. Jimenez et al., Acid pH Increases SARS-CoV-2 Infection and the Risk of Death by COVID-19
1,357 patient proton pump inhibitor prophylaxis study: 124% higher mortality (p<0.0001).In Vitro study showing lower pH increased ACE2 expression and viral load on SARS-CoV-2 infection, and retrospective study showing proton pump inhibitor use, which is correlated with low gastric pH-related diseases, was associated with higher mortality.
Aug 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.637885/full, https://c19p.org/jimenez2ppi
1,465. Abdelwahab et al., Acetylsalicylic Acid Compared with Enoxaparin for the Prevention of Thrombosis and Mechanical Ventilation in COVID-19 Patients: A Retrospective Cohort Study
67 patient aspirin late treatment study: 8% higher ventilation (p=0.93).Retrospective 225 hospitalized patients in Egypt, showing significantly lower thromboembolic events with aspirin treatment, but no significant difference in the need for mechanical ventilation.
Jul 2021, Clinical Drug Investigation, https://link.springer.com/article/10.1007/s40261-021-01061-2, https://c19p.org/abdelwahab
1,466. Luo et al., COVID-19 in patients with lung cancer
48 patient HCQ late treatment study: 2% higher mortality (p=0.99).Analysis of hospitalized lung cancer patients with 35 of 48 taking HCQ, mortality OR 1.03, p = 0.99.
Jun 2020, Annals of Oncology, 1386-1396, https://www.annalsofoncology.org/article/S0923-7534(20)39894-X/fulltext, https://c19p.org/luo
1,467. Alosaimi et al., Analyzing the Difference in the Length of Stay (LOS) in Moderate to Severe COVID-19 Patients Receiving Hydroxychloroquine or Favipiravir
74 patient HCQ late treatment PSM study: 400% higher mortality (p=0.49), 43% shorter hospitalization (p=0.63), and 29% higher hospital discharge (p=0.74).Retrospective 200 hospitalized COVID-19 patients in Saudi Arabia, showing no significant difference in outcomes between HCQ and favipiravir.
Nov 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/12/1456, https://c19p.org/alosaimi
1,468. Sosa-García et al., Experience in the management of severe COVID-19 patients in an intensive care unit
56 patient HCQ ICU study: 11% higher mortality (p=1).Small retrospective study of 56 ICU patients in Mexico showing HCQ RR 1.1, p = 1.0.
Jun 2020, Cir Cir. 2020, 569-575, https://cirugiaycirujanos.com/frame_esp.php?id=358, https://c19p.org/sosagarcia
1,469. Mahale et al., A Retrospective Observational Study of Hypoxic COVID-19 Patients Treated with Immunomodulatory Drugs in a Tertiary Care Hospital
134 patient colchicine late treatment study: 7% higher mortality (p=0.83).Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with colchicine treatment in unadjusted results.
Dec 2020, Indian J. Critical Care Medicine, https://www.ijccm.org/doi/pdf/10.5005/jp-journals-10071-23599, https://c19p.org/mahale
1,470. Peng et al., Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer
166 patient azvudine late treatment study: 13% higher mortality (p=0.85).Retrospective 166 hospitalized NSCLC patients with COVID-19 showing no significant difference in mortality with paxlovid or azvudine in univariate analysis.
Jan 2024, Technology in Cancer Research & Treatment, https://journals.sagepub.com/doi/10.1177/15330338241248573, https://c19p.org/peng4azv
1,471. Cannata-Andía et al., A single-oral bolus of 100,000 IU of cholecalciferol at hospital admission did not improve outcomes in the COVID-19 disease: the COVID-VIT-D — a randomised multicentre international clinical trial
543 patient vitamin D late treatment RCT: 44% higher mortality (p=0.31), 5% higher ICU admission (p=0.82), and 5% longer hospitalization.RCT 274 very late stage (>80% pulmonary involvement at baseline) hospitalized COVID-19 patients treated with a single dose of cholecalciferol, and 269 control patients, showing no significant differences. High serum calcidiol levels at admission were associated with lower pulmonary involvement, shorter hospitalization, and lower ICU admission. Serum levels increased in the treatment group, however average levels were still insufficient at discharge. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage. 100,000IU cholecalciferol.
Feb 2022, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02290-8, https://c19p.org/cannataandia
1,472. Aweimer et al., Mortality rates of severe COVID-19-related respiratory failure with and without extracorporeal membrane oxygenation in the Middle Ruhr Region of Germany
149 patient aspirin ICU study: 10% higher mortality (p=0.43).Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with aspirin prophylaxis in unadjusted results.
Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimere
1,473. Solh et al., Clinical course and outcome of COVID-19 acute respiratory distress syndrome: data from a national repository
643 patient HCQ late treatment study: 18% higher mortality (p=0.17).Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients analyzing progression to ARDS and 30-day mortality from ARDS. Confounding by indication is likely. Chronological bias is likely, with HCQ more likely to be used earlier on, before significant improvements in overall treatment. No results are provided for HCQ for progression to ARDS.
Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.16.20214130v1, https://c19p.org/solh
1,474. Welén et al., A Phase 2 Trial of the Effect of Antiandrogen Therapy on COVID-19 Outcome: No Evidence of Benefit, Supported by Epidemiology and In Vitro Data
5,338 patient various antiandrogen prophylaxis study: 2% lower mortality (p=0.94), 28% higher ICU admission (p=0.28), and 23% higher hospitalization (p=0.09).Retrospective 7,894 COVID+ prostate cancer patients, analyzing patients on antiandrogen treatment, ADT, and ADT + abiraterone acetate or enzalutamide, showing mixed results and higher mortality for ADT + abiraterone acetate or enzalutamide. This paper also includes a small RCT which is listed separately, and an In Vitro HBEC study showing no significant differences (p = 0.084). The supplementary data is not currently available. NCT04475601. For discussion of issues with this study see [sciencedirect.com, sciencedirect.com, sciencedirect.com, sciencedirect.com].
Dec 2021, European Urology, https://www.europeanurology.com/article/S0302-2838(21)02224-7/fulltext, https://c19p.org/welen2
1,475. Pourhoseingholi et al., Case Characteristics, Clinical Data, And Outcomes of Hospitalized COVID-19 Patients In Qom Province, Iran: A Prospective Cohort Study
2,468 patient aspirin late treatment study: 32% higher mortality (p=0.04).Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing higher mortality with aspirin treatment. IR.MUQ.REC.1399.013.
May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholie
106 patient vitamin D prophylaxis study: 25% more cases (p=0.56).
Analysis of vitamin D and zinc levels in 53 PCR+ outpatients and 53 matched controls, showing lower zinc levels in COVID-19 patients, and increased risk of cases and symptoms with vitamin D deficiency. There was no significant difference in the use of supplements between cases and controls. IR.ABADANUMS.REC.1399.073.
Aug 2021, Nutrients, https://www.mdpi.com/2072-6643/13/10/3368, https://c19p.org/golabi2
1,477. Gadhiya et al., Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state
283 patient zinc late treatment study: 41% higher mortality (p=0.33).Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiyaz
1,478. Gadhiya et al., Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state
271 patient HCQ late treatment study: 5% higher mortality (p=0.89).Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (March 1 to May 31, 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiya
1,479. Gadhiya et al., Clinical characteristics of hospitalised patients with COVID-19 and the impact on mortality: a single-network, retrospective cohort study from Pennsylvania state
281 patient vitamin C late treatment study: 1% higher mortality (p=0.99).Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiyac
1,480. Uyaroğlu et al., Comparison of Favipiravir to Hydroxychloroquine Plus Azithromycin in the Treatment of Patients with Non-critical COVID-19: A Single-center, Retrospective, Propensity Score-matched Study
84 patient HCQ late treatment PSM study: 200% higher mortality (p=1), 67% lower ICU admission (p=1), and 10% shorter hospitalization (p=0.9).PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ.
Mar 2022, Acta Medica, https://actamedica.org/index.php/actamedica/article/view/719, https://c19p.org/uyaroglu
1,481. Su et al., Efficacy of early hydroxychloroquine treatment in preventing COVID-19 pneumonia aggravation, the experience from Shanghai, China
vitamin C early treatment study: 135% higher progression (p=0.18) and 34% slower improvement (p=0.04).Retrospective 616 patients in China showing increased risk of disease progression with vitamin C treatment.
Dec 2020, BioScience Trends, https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.03340/_article/-char/ja/, https://c19p.org/suc
1,482. Li et al., Treatment of COVID-19 patients with hydroxychloroquine or chloroquine: A retrospective analysis
37 patient HCQ late treatment study: 40% slower viral clearance (p=0.06).Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death however the group is not specified. Confounding by indication is likely.
Jan 2021, Research Square, https://www.researchsquare.com/article/rs-119202/v1, https://c19p.org/li2
1,483. Rodriguez-Nava et al., Clinical characteristics and risk factors for mortality of hospitalized patients with COVID-19 in a community hospital: A retrospective cohort study
313 patient HCQ late treatment study: 6% higher mortality (p=0.77).Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, p = 0.77. Confounding by indication likely.
Nov 2020, Mayo Clinic Proceedings: Innovations, Quality & Outcomes, https://www.sciencedirect.com/science/article/pii/S2542454820302071, https://c19p.org/rodrigueznava
1,484. Çavuş et al., Kritik COVID-19 hastalarında kullanılan N-asetilsisteinin(NAC) klinik bulgulara, inflamatuar parametrelere böbrek fonksiyonlarına olan etkileri
190 patient N-acetylcysteine ICU study: 13% higher mortality (p=0.47), 20% higher ventilation (p=0.25), 12% shorter ICU admission (p=0.58), and 13% shorter hospitalization (p=0.09).Retrospective 190 critical COVID-19 patients in Turkey, showing no significant differences with N-acetylcysteine treatment in unadjusted results with no baseline details. NAC 2400mg/day.
Oct 2022, Aksaray Üniversitesi Tıp Bilimleri Dergisi, https://dergipark.org.tr/en/pub/asujms/issue/73171/1062868, https://c19p.org/cavus
1,485. Kamstrup et al., Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort study
60,334 patient HCQ prophylaxis study: 44% higher hospitalization (p=0.25) and 10% fewer cases (p=0.23).Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for example saying that "currently, no obvious connection exists between a known rheumatological disorder and the risk of contracting SARS-CoV-2". Many papers show that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, e.g., Ferri et al. show OR 4.42, p<0.001 [Ferri]. Supplementary data is not currently available.
May 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221004781, https://c19p.org/kamstrup
1,486. Sarohan et al., Retinol Depletion in Severe COVID-19
27 patient vitamin A late treatment study: 282% higher mortality (p=0.001).Retrospective 27 severe COVID-19 patients and 23 non-COVID-19 patients, showing significantly lower vitamin A levels in COVID-19 patients (0.37mg/L vs. 0.52 mg/L, p<0.001). 10 of 27 COVID-19 patients received vitamin A, with higher mortality. Group details are not provided but authors note that 8 of 10 had comorbidities.
Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.01.30.21250844v1, https://c19p.org/sarohan
1,487. Aboulenain et al., The Effect of Hydroxychloroquine on In-Hospital Mortality in COVID-19
175 patient HCQ late treatment study: 15% higher mortality (p=0.72).Retrospective 175 hospitalized COVID-19 patients in the USA, showing no significant difference in mortality with HCQ. Authors note that "patients treated with HCQ in our cohort were more likely to be sicker at baseline".
Nov 2020, HCA Healthcare J. Medicine, https://scholarlycommons.hcahealthcare.com/hcahealthcarejournal/vol1/iss0/20, https://c19p.org/aboulenain
1,488. Malundo et al., Predictors of Mortality among inpatients with COVID-19 Infection in a Tertiary Referral Center in the Philippines
1,215 patient HCQ late treatment study: 24% higher mortality (p=0.32).Retrospective 1,215 hospitalized patients in the Phillipines, showing no significant difference in outcomes with remdesivir or HCQ use in unadjusted results subject to confounding by indication.
Jul 2022, IJID Regions, https://www.sciencedirect.com/science/article/pii/S2772707622000935, https://c19p.org/malundo
903 patient HCQ late treatment study: 37% higher mortality (p=0.28).
Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, p = 0.28. Confounding by indication is likely.
Nov 2020, The American J. Pathology, https://www.sciencedirect.com/science/article/pii/S0002944020304892, https://c19p.org/salazar
1,490. Komissarov et al., Hydroxychloroquine has no effect on SARS-CoV-2 load in nasopharynx of patients with mild form of COVID-19
36 patient HCQ late treatment study: 25% worse viral load (p=0.45).Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, with significant differences seen between hospitalized and non-hospitalized patients. 9 of 10 hospitalized patients were in the HCQ group and only one in the control group. 2 additional control patients were added between the first and second version of this preprint (including the only hospitalized control patient).
Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.30.20143289v1, https://c19p.org/komissarov
1,491. Agustí et al., Add-on inhaled budesonide in the treatment of hospitalised patients with COVID-19: a randomised clinical trial
89 patient budesonide late treatment RCT: 23% higher mortality (p=1) and 39% lower progression (p=0.69).Small early-terminated RCT with 40 inhaled budesonide and 49 control patients, showing no significant differences. 400µg/12h via Pulmicort Turbuhaler.
Feb 2022, European Respiratory J., https://erj.ersjournals.com/content/early/2022/01/13/13993003.03036-2021, https://c19p.org/agusti2
1,492. Holt et al., Influence of inhibitors of the renin–angiotensin system on risk of acute respiratory distress syndrome in Danish hospitalized COVID-19 patients
689 patient aspirin prophylaxis study: 34% higher combined mortality/ICU admission (p=0.09).Retrospective 689 hospitalized COVID-19 patients in Denmark, showing higher risk of ICU/death with aspirin use in unadjusted results subject to confounding by indication.
May 2020, J. Hypertension, https://journals.lww.com/10.1097/HJH.0000000000002515, https://c19p.org/holt2e
1,493. Parsonnet et al., A Phase 2 Randomized, Double Blinded, Placebo Controlled Study of Oral Camostat Mesilate Compared to Standard of Care in Subjects With Mild-Moderate COVID-19
49 patient camostat early treatment RCT: 35% improved recovery (p=0.24), 86% improvement (p=0.11), and 41% improved viral clearance (p=0.24).RCT 49 outpatients in the USA, showing no significant differences with camostat treatment.
May 2021, NCT04524663, https://clinicaltrials.gov/study/NCT04524663, https://c19p.org/parsonnet
1,494. Yang et al., The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
185 patient budesonide late treatment study: 11% higher mortality (p=0.85).Retrospective 185 hospitalized COVID-19 patients in China, showing no significant difference in mortality with budesonide use in unadjusted results.
Aug 2022, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2022-0569/html, https://c19p.org/yang3
1,495. Cassione et al., COVID-19 infection in a northern-Italian cohort of systemic lupus erythematosus assessed by telemedicine
165 patient HCQ prophylaxis study: 50% more cases (p=0.59).Survey of 165 SLE patients, 127 on HCQ. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for concomitant medications or severity of SLE. Confounding by indication.
May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/23/annrheumdis-2020-217717.info, https://c19p.org/cassione
1,496. Alghamdi et al., Clinical characteristics and treatment outcomes of severe (ICU) COVID-19 patients in Saudi Arabia: A single centre study
171 patient HCQ ICU study: 39% higher mortality (p=0.52).Retrospective 171 ICU patients in Saudi Arabia showing no significant difference for HCQ treatment in unadjusted results.
Aug 2021, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016421001559, https://c19p.org/alghamdi2
1,497. Roomi et al., Efficacy of hydroxychloroquine and tocilizumab in patients with COVID-19: A single-center retrospective chart review
176 patient HCQ late treatment study: 38% higher mortality (p=0.54).Retrospective 176 hospitalized patients (144 HCQ, 32 control) showing no significant differences with HCQ or TCZ. Confounding by indication.
Aug 2020, J. Medical Internet Research, https://www.jmir.org/2020/9/e21758/, https://c19p.org/roomi
1,498. Zarabanda et al., The Effect of Povidone-Iodine Nasal Spray on COVID-19 Nasopharyngeal Viral Load in Patients: A Randomized Control Trial
24 patient povidone-iodine late treatment RCT: 27% worse recovery (p=1) and no change in viral clearance (p=1).Very late treatment (7 days from onset) RCT comparing 11 & 13 PVP-I (0.5% and 2%), and 11 saline spray patients in the USA, showing no significant differences. There was no control group (saline is likely not a placebo, showing efficacy in other trials). There are large unadjusted differences between groups, e.g. 7.1 days from onset for PVP-I versus 4.8 for saline. Baseline Ct was higher for PVP-I, providing less room for improvement. Authors note that they cannot determine if earlier use is more beneficial.
Oct 2021, Laryngoscope, https://onlinelibrary.wiley.com/doi/abs/10.1002/lary.29935, https://c19p.org/zarabanda
324 patient azvudine late treatment study: 42% higher mortality (p=0.64).
Retrospective 324 hospitalized kidney transplant recipients with COVID-19 showing no significant benefit with molnupiravir, paxlovid, or azvudine. The study was conducted during the omicron wave in China between December 2022 and January 2023. Adjusted results are only provided for all antivirals combined, however the results are similar before and after adjustment. Multivariable Cox regression analysis for all antivirals combined showed an adjusted hazard ratio for mortality of 6.06, p=0.099. While adjustment includes factors related to baseline severity, there may be residual confounding by indication.
Jun 2024, J. Zhejiang University - SCIENCE B (Biomedicine & Biotechnology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199089/, https://c19p.org/lv3azv
1,500. Zheng et al., No significant benefit of moderate-dose vitamin C on severe COVID-19 cases
397 patient vitamin C late treatment PSM study: 157% higher mortality (p=0.33) and 35% worse improvement (p=0.17).Retrospective 397 severe COVID-19 patients in China, showing worse outcomes with vitamin C treatment, without statistical significance. IV vitamin C 2-4g/day. Subject to confounding by indication and immortal time bias. Exclusion criteria were (a) the duration of hospitalization was less than 3 days; (b) vitamin C treatment started before admission; and (c) the length of vitamin C use was less than 3 days. Includes vitamin C use started at any time during hospitalization, for many patients this was >15 days later (Figure A2). Duration of treatment varied widely (Figure A1). Treatment was determined by clinicians according to the condition of each patient.
Sep 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0361/html, https://c19p.org/zheng
1,501. Barbosa et al., Clinical outcomes of hydroxychloroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study
63 patient HCQ late treatment study: 147% higher mortality (p=0.58).Small retrospective study with 63 patients (32 treated with HCQ), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been published several months later.
Apr 2020, Preprint, https://www.sefq.es/_pdfs/NEJM_Hydroxychlorquine.pdf, https://c19p.org/barbosa
100 patient colchicine early treatment RCT: 40% higher hospitalization (p=0.76) and 4% improved recovery (p=1).
RCT 150 patients in Egypt showing no significant difference in outcomes with colchicine. SOC included vitamin C, D, and zinc. Colchicine 0.5mg tid days 1-3, bid days 4-7.
Jun 2023, Research Square, https://www.researchsquare.com/article/rs-3049708/v1, https://c19p.org/hassano
1,503. Abolhassani et al., Genetic and immunological evaluation of children with inborn errors of immunity and severe or critical COVID-19
31 patient acetaminophen late treatment study: 56% higher mortality (p=0.64).Retrospective 31 hospitalized patients ≤19 with pre-existing inborn errors of immunity, showing no significant difference in mortality with acetaminophen. Only 6 patients were treated with acetaminophen.
Sep 2022, J. Allergy and Clinical Immunology, https://www.sciencedirect.com/science/article/pii/S009167492201185X, https://c19p.org/abolhassani
1,504. Kuderer et al., Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study
928 patient HCQ late treatment study: 5% higher mortality (p=0.88).Retrospective 928 cancer patients, showing higher mortality with HCQ+AZ. The relative risks of different treatments suggest significant confounding by indication. Authors note that HCQ+AZ might not be the cause of increased mortality, but instead was given to patients with more severe COVID-19.
May 2020, Lancet, June 20, 2020, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext, https://c19p.org/kuderer
1,505. Kuderer et al., Clinical impact of COVID-19 on patients with cancer (CCC19): a cohort study
928 patient azithromycin late treatment study: 27% higher mortality (p=0.46).Retrospective 928 cancer patients, showing higher mortality with HCQ+AZ. The relative risks of different treatments suggest significant confounding by indication. Authors note that HCQ+AZ might not be the cause of increased mortality, but instead was given to patients with more severe COVID-19.
May 2020, Lancet, June 20, 2020, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext, https://c19p.org/kudererazaz
1,506. Rahman et al., Clinical & Demographical Status of Hospitalized and Non-Hospitalized Covid-19 Cases: A Multicenter Hospital Based Study in Bangladesh
600 patient acetaminophen early treatment study: 23% higher hospitalization (p=0.11).Retrospective 416 non-hospitalized and 184 hospitalized COVID-19 patients in Bangladesh, showing higher acetaminophen and lower vitamin C usage for hospitalized patients. Confounding may be significant and baseline details per treatment group are not provided, however fever and symptomatic patients were more common in the non-hospitalized group. Note there is an alignment mismatch in Table 1.
Nov 2023, Molecular Mechanism Research, https://ojs.as-pub.com/index.php/MMR/article/view/133, https://c19p.org/rahman5ace
1,507. Elhadi et al., Epidemiology, outcomes, and utilization of intensive care unit resources for critically ill COVID-19 patients in Libya: A prospective multi-center cohort study
465 patient vitamin C ICU study: 12% higher mortality (p=0.15).Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.
Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadic
1,508. Kim et al., Aspirin Is Related to Worse Clinical Outcomes of COVID-19
259 patient aspirin late treatment PSM study: 34% lower mortality (p=0.22), 102% higher ventilation (p=0.16), and 91% higher ICU admission (p=0.36).Retrospective database analysis of 22,660 patients tested for COVID-19 in South Korea. There was no significant difference in cases according to aspirin use. Aspirin use before COVID-19 was related to an increased death rate and aspirin use after COVID-19 was related to a higher risk of oxygen therapy. Results for prophylaxis are listed separately [Kim].
Sep 2021, Medicina, https://www.mdpi.com/1648-9144/57/9/931, https://c19p.org/kim2b
1,509. Karimpour-Razkenari et al., Evaluating the Effects of Clinical Characteristics and Therapeutic Regimens on Mortality in Hospitalized Patients with Severe COVID-19
478 patient aspirin late treatment study: 123% higher mortality (p=0.008).Retrospective 478 moderate to severe hospitalized patients in Iran, showing higher mortality with aspirin treatment. Authors note confounding by indication for aspirin treatment.
Oct 2022, J. Pharmaceutical Care, https://publish.kne-publishing.com/index.php/JPC/article/view/10790, https://c19p.org/karimpourrazkenari2e
1,510. Ruzhentsova et al., Phase 3 Trial of Coronavir (Favipiravir) in Patients with Mild to Moderate COVID-19
168 patient favipiravir early treatment RCT: 39% faster recovery (p=0.007) and 22% improved viral clearance (p=0.16).RCT 168 patients, 112 receiving favipiravir and 56 SOC, showing shorter time to clinical improvement and faster viral clearance with favipiravir.
Oct 2020, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3696907, https://c19p.org/ruzhentsova
1,511. Li et al., The role of probiotics in coronavirus disease-19 infection in Wuhan: A retrospective study of 311 severe patients
311 patient probiotics late treatment study: 12% lower hospital discharge (p=0.68) and 35% slower viral clearance (p=0.001).Retrospective 311 severe condition hospitalized patients in China, 123 treated with probiotics, showing slower viral clearance and recovery with treatment. Authors note that probiotics were able to moderate immunity and decrease the incidence of secondary infections.
Mar 2021, Int. Immunopharmacology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934664/, https://c19p.org/li10
1,512. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
15,227 patient metformin prophylaxis study: 27% more cases (p=0.42).Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtmf
1,513. Albanghali et al., Clinical Characteristics and Treatment Outcomes of Mild to Moderate Covid-19 Patients in Saudi Arabia: A Single Centre Study
811 patient HCQ late treatment study: 35% higher mortality (p=0.46).Retrospective 811 hospitalized COVID+ patients in Saudi Arabia, showing higher mortality with HCQ treatment in unadjusted results subject to confounding by indication.
Feb 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S187603412200034X, https://c19p.org/albanghali
1,514. Hafez et al., Antiviral Used among Non-Severe COVID-19 Cases in Relation to Time till Viral Clearance: A Retrospective Cohort Study
1,505 patient favipiravir late treatment study: 3% slower viral clearance (p=0.09).Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir.
Apr 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/4/498, https://c19p.org/hafeza
1,515. Soto et al., Mortality and associated risk factors in patients hospitalized due to COVID-19 in a Peruvian reference hospital
1,418 patient ivermectin late treatment study: 41% higher mortality (p=0.001).Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing higher mortality with ivermectin. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22% for SpO2 >95%. The more extreme Cox result compared to the event counts also supports this. There may also be significant confounding by time with SOC changing substantially over the first few months of the pandemic. Patients may overlap with those in [Soto-Becerra]. The results in the table and text do not match.
Mar 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264789, https://c19p.org/soto
1,516. McGrail et al., COVID-19 Case Series at UnityPoint Health St. Luke’s Hospital in Cedar Rapids, IA
75 patient HCQ late treatment study: 70% higher mortality (p=0.69).HCQ+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HCQ patients survived and 92% of HCQ+AZ patients. Patients not receiving either had 93% survival but were not considered comparable because the treated groups were significantly more ill (100% hypoxic at admission vs. 59%) and this study does not adjust for the differences. Transition from an early intubation strategy to aggressive utilization of high flow nasal cannula and noninvasive ventilation (i.e, BiPAP) was successful in freeing up ICU resources.
Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.17.20156521v1, https://c19p.org/mcgrail
1,517. Silva et al., Clinical-Epidemiology Aspect of Inpatients With Moderate or Severe COVID-19 in a Brazilian Macroregion: Disease and Countermeasures
395 patient HCQ late treatment study: 46% higher mortality (p=0.22).Retrospective 395 hospitalized patients in Brazil, showing higher mortality with HCQ treatment, without statistical significance.
May 2022, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2022.899702/full, https://c19p.org/silva3
1,518. Alghamdi et al., Clinical Efficacy of Hydroxychloroquine in Patients with COVID-19: Findings from an Observational Comparative Study in Saudi Arabia
775 patient HCQ late treatment study: 7% higher mortality (p=0.88).Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indication is likely.
Mar 2021, Antibiotics, https://www.mdpi.com/2079-6382/10/4/365, https://c19p.org/alghamdi
1,519. Soto et al., Mortality and associated risk factors in patients hospitalized due to COVID-19 in a Peruvian reference hospital
1,418 patient HCQ late treatment study: 6% higher mortality (p=0.46).Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing no significant difference with HCQ. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22% for SpO2 >95%. There may also be significant confounding by time with SOC changing substantially over the first few months of the pandemic.
Mar 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264789, https://c19p.org/sotoh
1,520. Cheung et al., Association Between Famotidine Use and COVID-19 Severity in Hong Kong: A Territory-wide Study
952 patient famotidine prophylaxis study: 34% higher severe cases (p=0.72).Retrospective 952 COVID-19 patients in Hong Kong, showing no significant difference in severe disease with famotidine use or PPI use.
Apr 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34940-4/fulltext, https://c19p.org/cheung
1,521. Stufano et al., Oxidative Damage and Post-COVID Syndrome: A Cross-Sectional Study in a Cohort of Italian Workers
80 patient acetaminophen late treatment study: 19% higher PASC (p=0.62).Retrospective 80 mild COVID-19 patients in Italy, showing no significant difference in long COVID with acetaminophen use during infection.
Apr 2023, Int. J. Molecular Sciences, https://www.mdpi.com/1422-0067/24/8/7445, https://c19p.org/stufano
1,522. Azimi Pirsaraei et al., Anticoagulant Use in COVID-19 Patients: A Longitudinal Study From Zanjan, Iran
831 patient aspirin late treatment study: 97% higher mortality (p=0.002).Retrospective 831 hospitalized COVID-19 patients showing higher mortality with aspirin treatment in unadjusted results.
Aug 2024, Cureus, https://www.cureus.com/articles/263779-anticoagulant-use-in-covid-19-patients-a-longitudinal-study-from-zanjan-iran, https://c19p.org/azimipirsaraei
1,523. Choi et al., Comparison of antiviral effect for mild-to-moderate COVID-19 cases between lopinavir/ritonavir versus hydroxychloroquine: A nationwide propensity score-matched cohort study
1,402 patient HCQ late treatment study: 22% slower viral clearance (p=0.0001).Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for LPV/r and HCQ. There are large differences in severity across groups. Authors did PSM but chose not to prioritize severity, resulting in incomparable groups, e.g., baseline pneumonia of 44% in the HCQ group and 15% in the control group (after PSM). Authors note this but offer no explanation for not correcting for severity: "However, the disease severity and proportion of accompanying pneumonia were still significantly higher in the LPV/r and HCQ-group".
Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322669, https://c19p.org/choi
1,524. Mulhem et al., 3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study
3,219 patient vitamin C late treatment study: 32% higher mortality (p=0.01).Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhemc
1,525. Geleris et al., Observational Study of Hydroxychloroquine in Hospitalized Patients with Covid-19
1,446 patient HCQ late treatment study: 4% higher combined mortality/intubation (p=0.76).Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). Even if all propensity matched control patients had hypertension, the control prevalence would only be 14% compared to 49% for treatment. Since patients with hypertension are at much greater risk of mortality (HR 2.12, see [academic.oup.com]), this appears to invalidate the results. Observational study of 1,446 hospitalized patients showing no significant effect on a combined intubation/death outcome for late treatment. However, secondary analysis shows the success of HCQ was hidden by combining intubation and death - death / (combined death/intubation) for HCQ was 60% vs. control 89%, for details see: [twitter.com]. RCT recommended. No AZ or Zinc. HCQ group much sicker - patients already in mild/moderate ARDS, most of the control group not in ARDS. Control cases received other therapeutics.
May 2020, NEJM, May 7, 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2012410, https://c19p.org/geleris
1,526. Farah et al., Prevalence and risk factors of COVID-19 infection, mortality, and post-infection lung fibrosis in patients with type 2 diabetes: a cross-sectional study
1,039 patient metformin prophylaxis study: 3% more cases (p=0.87).Retrospective 1,039 diabetes patients in Jordan, showing no significant difference in COVID-19 cases with metformin use in unadjusted results. Severity outcomes are not provided for metformin.
Sep 2023, J. Int. Medical Research, http://journals.sagepub.com/doi/10.1177/03000605231198413, https://c19p.org/farah
1,527. Furtado et al., Azithromycin in addition to standard of care versus standard of care alone in the treatment of patients admitted to the hospital with severe COVID-19 in Brazil (COALITION II): a randomised clinical trial
397 patient azithromycin late treatment RCT: 8% higher mortality (p=0.63) and 30% improvement (p=0.08).Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. One notable result is that even within this extremely late stage population, results suggest increased efficacy with the addition of AZ for patients with earlier use of AZ/HCQ, OR 0.71 [0.25-2.03] (Figure S4). Patients received 8g of HCQ over 10 days, approaching the high levels used in the RECOVERY trial (9.2g over 10 days), showing significantly more adverse events than typical trials. 50% of patients were on mechanical ventilation at baseline. More than the increase in mortality at day 29 occurred on day 0, and more than 3x the increase occurred by day 2.
Sep 2020, The Lancet, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31862-6/fulltext, https://c19p.org/furtadoazaz
37 patient HCQ late treatment study: 29% worse viral clearance (p=0.7).
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76, p = 0.71. Small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR 1.29, p = 0.7. The RCT and retrospective study are listed separately [Chen, Chen].
Jul 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242763, https://c19p.org/chen26
1,529. de la Iglesia et al., Hydroxicloroquine for pre-exposure prophyylaxis for SARS-CoV-2
1,375 patient HCQ prophylaxis study: 43% more cases (p=0.15).Analysis of autoimmune disease patients on HCQ, compared to a control group from the general population (matched on age and sex, but not adjusted for autoimmune disease), showing non-significant differences between groups. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the mortality result becomes RR 0.35, p=0.23, suggesting a substantial benefit for HCQ treatment (as shown in other studies).
Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.31.20185314v1, https://c19p.org/delaiglesia
1,530. Fowotade et al., Efficacy and safety of nitazoxanide combined with ritonavir-boosted atazanavir for the treatment of mild to moderate COVID-19
57 patient nitazoxanide late treatment RCT: 11% worse recovery (p=0.73) and 5% improved viral clearance (p=0.92).Small RCT in Nigeria with 31 nitazoxanide and atazanavir/ritonavir patients, and 26 control patients, showing no significant differences with treatment. 4 treatment group patients discontinued treatment due to the size of the tablets. Time from onset is not provided, only time from diagnosis. NACOVID. 14-day course of nitazoxanide (1000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od). NCT04459286.
Feb 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.02.03.22270152, https://c19p.org/fowotade
1,531. Huh et al., Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
44,046 patient camostat prophylaxis study: 14% more cases (p=0.84).Retrospective database analysis showing no significant differences with camostat use.
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2cm
1,532. Ferreira et al., Outcomes associated with Hydroxychloroquine and Ivermectin in hospitalized patients with COVID-19: a single-center experience
102 patient ivermectin late treatment study: 54% higher combined mortality/intubation (p=0.37).Retrospective 230 hospitalized patients in Brazil showing no significant difference with ivermectin treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors note that they do not know if treatment was started before or after ICU admission and intubation. Baseline total chest CT opacities were higher for ivermectin (20% vs. 15%). 25% of control patients were admitted within 3 days, compared to 5 days for ivermectin. Only 38% of patients in the ivermectin arm were treated within 7 days, compared to 61% for HCQ. These are consistent with ivermectin being used for more severe patients. Dosage is unknown.
Nov 2021, Revista da Associação Médica Brasileira, https://www.scielo.br/j/ramb/a/kzbmDvJqjJdQR9GfqK65CZs/, https://c19p.org/ferreira2
1,533. Shah et al., The Impact of Androgen Deprivation Therapy on COVID-19 Illness in Men With Prostate Cancer
465 patient antiandrogen prophylaxis study: 16% higher mortality (p=0.59), 19% lower ventilation (p=0.73), 3% higher severe cases (p=0.91), and 4% lower hospitalization (p=0.9).Retrospective 465 prostate cancer patients, showing no significant difference in COVID-19 outcomes with ADT.
May 2022, JNCI Cancer Spectrum, https://academic.oup.com/jncics/article/6/3/pkac035/6584832, https://c19p.org/shah3
1,534. Jin et al., Effects of Azvudine on the Low-Risk Patients Infected with COVID-19 Omicron Variants: A Retrospective Case-Control Study
481 patient azvudine early treatment study: 1% slower recovery (p=0.9).Retrospective 481 low-risk COVID-19 patients in China showing no significant difference in recovery or symptomatic severity with azvudine, but slightly lower total viral load.
Feb 2024, J. Clinical Pharmacology and Therapeutics, https://www.medtextpublications.com/open-access/effects-of-azvudine-on-the-low-risk-patients-infected-with-covid-19-1584.pdf, https://c19p.org/jin
1,535. Chevalier et al., CovAID: Identification of factors associated with severe COVID-19 in patients with inflammatory rheumatism or autoimmune diseases
1,213 patient colchicine prophylaxis study: 28% higher mortality (p=0.54) and 8% lower hospitalization (p=0.83).Retrospective 1,213 rheumatic disease patients in France, showing no significant difference with colchicine use in univariate analysis.
Mar 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1152587/full, https://c19p.org/chevaliero
1,536. Mulhem et al., 3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study
3,219 patient aspirin prophylaxis study: 14% higher mortality (p=0.21).Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulheme
1,537. Lyashchenko et al., Systemic Exposure to Hydroxychloroquine and its relationship with outcome in severely ill COVID-19 patients in New York City
3,256 patient HCQ late treatment study: 48% higher mortality (p<0.0001).Retrospective very late stage hospitalized patients in New York during the first wave, showing no significant relationship between HCQ levels and outcomes. Authors note that the patients with data were the sickest patients.
Aug 2022, British J. Clinical Pharmacology, https://onlinelibrary.wiley.com/doi/10.1111/bcp.15489, https://c19p.org/lyashchenko
1,538. Holt et al., Risk factors for developing COVID-19: a population-based longitudinal study (COVIDENCE UK)
15,227 patient vitamin C prophylaxis study: 3% more cases (p=0.86).Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.
Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtc
1,539. Peters et al., Outcomes of Persons With COVID-19 in Hospitals With and Without Standard Treatment With (Hydroxy)chloroquine
1,949 patient HCQ late treatment study: 9% higher mortality (p=0.57).Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals started treatment only after further deterioration. Short cutoff (21 days) - other studies have shown treated patient cases resolved faster and more control patients remaining in hospital at this time. In the preprint, 58 of 341 control patients died. In the journal version, 53 of 353 control patients died. Significant differences between hospitals - HCQ hospitals had significantly older patients with significantly more comorbidities. Non-HCQ hospitals were "tertiary academic centres" whereas HCQ hospitals were "secondary care hospitals". Residual confounding likely. This study compares overcrowded regular hospitals with undercrowded academic hospitals. A subset of patients were excluded due to transfer to other hospitals. This introduces bias..
Aug 2020, Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30615-7/fulltext, https://c19p.org/peters
1,540. Gupta et al., Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US
2,215 patient HCQ late treatment study: 6% higher mortality (p=0.41).Analysis of 2,215 intensive care unit patients showing no significant differences with this very late stage use of HCQ.
Jul 2020, JAMA Intern. Med., https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2768602, https://c19p.org/gupta
1,541. Somi et al., Effect of vitamin A supplementation on the outcome severity of COVID-19 in hospitalized patients: A pilot randomized clinical trial
30 patient vitamin A late treatment RCT: 76% slower improvement (p=0.21) and 8% longer hospitalization (p=0.49).RCT 30 hospitalized patients in Iran, showing no significant difference with vitamin A treatment. All patients received HCQ. 50,000 IU/day intramuscular vitamin A for up to 2 weeks.
Oct 2022, Nutrition and Health, http://journals.sagepub.com/doi/10.1177/02601060221129144, https://c19p.org/somi
1,542. Hassaniazad et al., A triple-blind, placebo-controlled, randomized clinical trial to evaluate the effect of curcumin-containing nanomicelles on cellular immune responses subtypes and clinical outcome in COVID-19 patients
40 patient curcumin late treatment RCT: 46% worse recovery (p=0.9).Small RCT with 40 low risk patients in Iran, 20 treated with nano-curcumin, showing no significant difference in outcomes with treatment. Authors note that treatment can improve peripheral blood inflammatory indices and modulate immune response by decreasing Th1 and Th17 responses, increasing T regulatory responses, further reducing IL-17 and IFN-γ, and increasing suppressive cytokines TGF-β and IL-4.
Sep 2021, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/full/10.1002/ptr.7294, https://c19p.org/hassaniazad
1,543. Guillaume et al., Antirheumatic Drug Intake Influence on Occurrence of COVID-19 Infection in Ambulatory Patients with Immune-Mediated Inflammatory Diseases: A Cohort Study
459 patient HCQ prophylaxis study: 2% higher hospitalization (p=1) and 3% more cases (p=0.96).Retrospective 459 SLE, RA, SjS, or PsA patients in France, showing no significant difference with HCQ treatment. However, the statistical analysis shows significant mismatches with prior research, which may be due to overfitting with the limited data and very small number of events. For example, the analysis estimates lower risk OR 0.72 for age, and shows very different relative risks of SLE, RA, SjS, or PsA compared to other research. We note the very different distribution of diseases in the groups, for example there is a much higher prevalence of PsA in the no HCQ group. The inaccurate estimations of risk for the different diseases and for age likely makes the adjusted analysis very inaccurate.
Sep 2021, Rheumatology and Therapy, https://link.springer.com/10.1007/s40744-021-00373-1, https://c19p.org/guillaume
1,544. Ramos-Rincón et al., Association between prior cardiometabolic therapy and in-hospital mortality in very old patients with type 2 diabetes mellitus hospitalized due to COVID-19. A nationwide observational study in Spain
790 patient aspirin prophylaxis study: 29% higher mortality (p=0.02).Retrospective 790 hospitalized type 2 diabetes patients ≥80 years old in Spain, showing higher mortality with existing aspirin use.
Dec 2020, Research Square, https://www.researchsquare.com/article/rs-133358/v1, https://c19p.org/ramosrincone
1,545. Mulhem et al., 3219 hospitalised patients with COVID-19 in Southeast Michigan: a retrospective case cohort study
3,219 patient HCQ late treatment study: 28% higher mortality (p=0.1).Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.
Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhem
1,546. Sulaiman et al., When Antivirals Backfire: An Evaluation of Favipiravir’s Clinical Outcomes in Critically Ill Patients with COVID-19: A Multicenter Cohort Study
146 patient favipiravir ICU PSM study: 17% higher mortality (p=0.51), 47% longer ventilation (p=0.008), and 50% longer ICU admission (p=0.01).PSM retrospective 1,218 COVID-19 ICU patients in Saudi Arabia, showing no significant difference in mortality, and longer ICU/MV time with favipiravir treatment.
Jun 2023, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034123002162, https://c19p.org/sulaiman2
1,547. Hueda-Zavaleta et al., Determination of PaO2/FiO2 after 24 h of invasive mechanical ventilation and ΔPaO2/FiO2 at 24 h as predictors of survival in patients diagnosed with ARDS due to COVID-19
200 patient colchicine ICU study: 33% higher mortality (p=0.33).Retrospective 200 patients with ARDS due to COVID-19 on invasive mechanical ventilation, showing no significant difference in mortality with colchicine treatment. The Cox proportional hazards result is from [journals.plos.org].
Dec 2022, PeerJ, https://peerj.com/articles/14290, https://c19p.org/huedazavaleta2
1,548. Al Sulaiman et al., Evaluation of inhaled nitric oxide (iNO) treatment for moderate-to-severe ARDS in critically ill patients with COVID-19: a multicenter cohort study
815 patient nitric oxide ICU study: 40% higher mortality (p=0.1).Retrospective 815 COVID-19 ICU patients in Saudi Arabia, showing significant improvement in oxygenation. There was no significant difference in mortality, and ICU and hospitalization time was longer.
Oct 2022, Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-022-04158-y, https://c19p.org/alsulaiman4
1,549. Tamura et al., Outcome and death risk of diabetes patients with Covid-19 receiving pre-hospital and in-hospital metformin therapies
188 patient HCQ late treatment study: 299% higher mortality (p=0.04).Retrospective 188 hospitalized patients in Brazil, showing higher risk of mortality with HCQ. Relatively few patients received HCQ. The results are likely subject to confounding by indication with treatment more likely for severe cases, and severity was not used in adjustments. Confounding by time is likely, with declining use of HCQ and improving SOC over the study period.
Jul 2021, Diabetology & Metabolic Syndrome, https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-021-00695-8, https://c19p.org/tamurah
1,550. Reis et al., Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19
1,476 patient fluvoxamine early treatment RCT: 12% lower hospitalization (p=1) and 50% lower progression (p=0.04).Low-risk (1% hospitalization) outpatient RCT with 738 fluvoxamine + budesonide patients and 738 placebo patients, showing significantly lower hospitalization/ER visits with treatment.
Apr 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/epdf/10.7326/M22-3305, https://c19p.org/reis10
1,551. Reis et al., Oral Fluvoxamine With Inhaled Budesonide for Treatment of Early-Onset COVID-19
1,476 patient budesonide early treatment RCT: 12% lower hospitalization (p=1) and 50% lower progression (p=0.04).Low-risk (1% hospitalization) outpatient RCT with 738 fluvoxamine + budesonide patients and 738 placebo patients, showing significantly lower hospitalization/ER visits with treatment.
Apr 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/epdf/10.7326/M22-3305, https://c19p.org/reis10u
1,552. Baguma et al., Characteristics of the COVID-19 patients treated at Gulu Regional Referral Hospital, Northern Uganda: A cross-sectional study
481 patient vitamin C late treatment study: 48% higher mortality (p=0.54).Retrospective COVID+ hospitalized patients in Uganda, 385 patients receiving vitamin C treatment, showing higher mortality with treatment, without statistical significance.
Dec 2021, Research Square, https://www.researchsquare.com/article/rs-1193578/v1, https://c19p.org/bagumac
1,553. Fried et al., Patient Characteristics and Outcomes of 11,721 Patients with COVID19 Hospitalized Across the United States
11,721 patient HCQ late treatment study: 27% higher mortality (p=0.001).Database analysis of 11,721 hospitalized patients, 4,232 on HCQ. Strong evidence for confounding by indication and compassionate use of HCQ. 24.9% of HCQ patients were on mechanical ventilation versus 12.2% control. Ventilation mortality was 70.5% versus 11.6%. This study does not adjust for the differences in comorbid conditions and disease severity, and therefore does not make a conclusion. Unadjusted HCQ mortality was 24.8% versus control 19.6%. Adjusting for ventilation only gives us 17.7% HCQ versus 19.6% control (adjusting the HCQ group to have the same proportion of ventilation patients), RR 0.90. Hopefully authors can do a full adjustment analysis. Comorbidities may favor control, while patients remaining in the hospital (5.3%) may favor HCQ (other studies show faster resolution for HCQ patients). Data inconsistencies have been found in this study, for example 99.4% of patients treated with HCQ were treated in urban hospitals, compared to 65% of untreated patients ..
Aug 2020, Clinical Infectious Disease, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1268/5898276, https://c19p.org/fried
1,554. Rinott et al., Ibuprofen use and clinical outcomes in COVID-19 patients
134 patient acetaminophen early treatment study: 473% higher mortality (p=0.3) and 534% higher need for oxygen therapy (p=0.06).Retrospective 89 febrile COVID-19 patients in Israel taking paracetamol and 49 taking ibuprofen, showing higher need for respiratory support with paracetamol. Although not statistically significant, patients in the paracetamol group were older.
Sep 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20303438, https://c19p.org/rinottace
1,555. Lotfy et al., Use of Hydroxychloroquine in Patients with COVID-19: A Retrospective Observational Study
202 patient HCQ late treatment study: 25% higher mortality (p=0.76), 41% higher ventilation (p=0.34), and 17% higher ICU admission (p=0.53).Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confounding is also likely as HCQ became controversial during the period studied, therefore HCQ use was likely more frequent toward the beginning of the period, a time when overall treatment protocols were significantly worse.
Dec 2020, Turk. Thorac. J., https://turkthoracj.org/en/use-of-hydroxychloroquine-in-patients-with-covid-19-a-retrospective-observational-study-131729, https://c19p.org/lotfy
1,556. Bosaeed et al., Favipiravir and Hydroxychloroquine Combination Therapy in Patients with Moderate to Severe COVID19 (FACCT Trial): An Open-Label, Multicenter, Randomized, Controlled Trial
254 patient HCQ late treatment RCT: 4% lower mortality (p=0.91), 8% higher ventilation (p=0.78), 31% higher ICU admission (p=0.24), and 29% slower recovery (p=0.29).RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of enrolled patients is not provided.
Apr 2021, Infect. Dis. Ther., https://link.springer.com/epdf/10.1007/s40121-021-00496-6, https://c19p.org/bosaeed
1,557. Al Sulaiman et al., Survival implications vs. complications: unraveling the impact of vitamin D adjunctive use in critically ill patients with COVID-19—A multicenter cohort study
288 patient vitamin D ICU study: 22% higher mortality (p=0.25), 27% higher ventilation (p=0.05), 17% higher ICU admission (p=0.07), and no change in hospitalization (p=1).Retrospective 1,435 ICU patients in Saudi Arabia, showing no significant difference in mortality, and longer mechanical ventilation with treatment. Vitamin D patients had higher Q1, median, and Q3 SOFA scores after propensity score matching. 98% of patients were treated with cholecalciferol.
Aug 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1237903/full, https://c19p.org/alsulaiman5
1,558. De Luna et al., Clinical and Demographic Characteristics of COVID-19 Patients Admitted in a Tertiary Care Hospital in the Dominican Republic
150 patient HCQ late treatment study: 105% higher mortality (p=0.69).Retrospective 150 patients in the Dominican Republic, 132 treated with HCQ, showing higher mortality with treatment in unadjusted results. Confounding by indication is likely.
Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.11.20247437v1, https://c19p.org/deluna
1,559. Kazan et al., The clinical impact of androgen deprivation therapy on SARS-CoV-2 infection rates and disease severity
365 patient various antiandrogen prophylaxis study: 229% higher hospitalization (p=0.2) and 29% fewer cases (p=0.32).Retrospective 365 prostate cancer patients in Turkey, 138 treated with ADT, showing no significant differences with treatment.
Oct 2021, Türk Üroloji Dergisi/Turkish J. Urology, https://turkishjournalofurology.com/en/the-clinical-impact-of-androgen-deprivation-therapy-on-sars-cov-2-infection-rates-and-disease-severity-133775, https://c19p.org/kazan
1,560. Morrison et al., COVID-19 outcomes in patients taking cardioprotective medications
13,585 patient aspirin prophylaxis PSM study: 8% lower mortality (p=0.52), 1% higher ventilation (p=0.96), 12% higher ICU admission (p=0.36), and 18% higher hospitalization (p=0.04).Retrospective 13,585 COVID+ patients in the USA, showing higher hospitalization with aspirin use, and no significant difference for mortality, ventilation, and ICU admission.
Oct 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0275787, https://c19p.org/morrisone
1,561. Holt et al., Influence of inhibitors of the renin–angiotensin system on risk of acute respiratory distress syndrome in Danish hospitalized COVID-19 patients
689 patient spironolactone antiandrogen prophylaxis study: 129% higher combined mortality/ICU admission (p=0.0007).Retrospective 689 hospitalized COVID-19 patients in Denmark, showing higher risk of ICU/death with spironolactone use in unadjusted results subject to confounding by indication.
May 2020, J. Hypertension, https://journals.lww.com/10.1097/HJH.0000000000002515, https://c19p.org/holt2
1,562. Holt et al., Influence of inhibitors of the renin–angiotensin system on risk of acute respiratory distress syndrome in Danish hospitalized COVID-19 patients
689 patient spironolactone prophylaxis study: 129% higher combined mortality/ICU admission (p=0.0007).Retrospective 689 hospitalized COVID-19 patients in Denmark, showing higher risk of ICU/death with spironolactone use in unadjusted results subject to confounding by indication.
May 2020, J. Hypertension, https://journals.lww.com/10.1097/HJH.0000000000002515, https://c19p.org/holt2sp
1,563. Mahévas et al., Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data
173 patient HCQ late treatment study: 20% higher mortality (p=0.75).Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HCQ. Power of study appears too low to support conclusions [bmj.com]. None of the 15 patients receiving HCQ+AZ were transferred to intensive care or died compared to 23% overall.
May 2020, BMJ 2020, https://www.bmj.com/content/369/bmj.m1844, https://c19p.org/mahevas
1,564. Freedberg et al., Famotidine Use Is Associated With Improved Clinical Outcomes in Hospitalized COVID-19 Patients: A Propensity Score Matched Retrospective Cohort Study
1,620 patient proton pump inhibitor prophylaxis PSM study: 34% higher combined mortality/intubation (p=0.01).PSM retrospective 1,620 hospitalized patients in the USA, showing higher risk of combined death/intubation with PPI treatment.
May 2020, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34706-5/fulltext, https://c19p.org/freedbergppi
1,565. Hofmann-Winkler et al., Camostat Mesylate May Reduce Severity of Coronavirus Disease 2019 Sepsis: A First Observation
11 patient HCQ ICU study: 140% higher mortality (p=0.55), 157% longer ICU admission, and 125% worse recovery.Retrospective 11 critically ill COVID-19 ICU patients with organ failure treated with camostat mesylate (6 patients) or HCQ (5 patients). Over an 8 day period, the severity of COVID-19 decreased in the camostat group as measured by a decline in the SOFA score, inflammatory markers, and improvement in oxygenation. A similar effect was not seen in the HCQ group.
Nov 2020, Critical Care Explorations, https://journals.lww.com/10.1097/CCE.0000000000000284, https://c19p.org/hofmannwinklerh
1,566. Shokri et al., What is the role of proton pump inhibitors consumption on the clinical presentation and severity of COVID-19 infection?
670 patient proton pump inhibitor prophylaxis study: 81% higher severe cases (p=0.05) and 78% higher mortality (p=0.21).Retrospective 670 COVID-19 patients in Iran showing significantly higher COVID-19 severity scores and more symptomatic presentation in patients with a history of proton pump inhibitor (PPI) use. Adjusted results are only provided for severity. Several values in Table 4 are likely misreported raising concern for the reliability of the main result.
Mar 2023, Annales Pharmaceutiques Françaises, https://www.sciencedirect.com/science/article/pii/S0003450922001122, https://c19p.org/shokri
1,567. Çivriz Bozdağ et al., Clinical Characteristics and Outcome of COVID-19 in Turkish Hematological Malignancy Patients
175 patient HCQ late treatment study: 399% higher mortality (p=0.003).Retrospective 340 patients with hematological malignancy in Turkey, showing higher mortality with HCQ treatment. Confounding by time is likely because more HCQ patients were earlier in time when overall treatment protocols were significantly worse.
Sep 2021, Turk. J. Haematol., https://pubmed.ncbi.nlm.nih.gov/34521187/, https://c19p.org/civrizbozdag
1,568. Reese et al., Cyclooxygenase inhibitor use is associated with increased COVID-19 severity
11,474 patient ibuprofen prophylaxis PSM study: 9% lower mortality (p=0.65) and 303% higher severe cases (p<0.0001).N3C retrospective 250,533 patients showing higher COVID-19 severity with ibuprofen use. Note that results for individual treatments are not included in the journal version or v2 of this preprint.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reeseib
1,569. Lodigiani et al., Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy
388 patient aspirin prophylaxis study: 21% higher ICU admission (p=0.52).Retrospective 388 hospitalized COVID-19 patients in Italy showing higher use of aspirin in ICU patients, without statistical significance.
Jul 2020, Thrombosis Research, https://www.sciencedirect.com/science/article/pii/S0049384820301407, https://c19p.org/lodigiani
1,570. Bhatt et al., Hydroxychloroquine Prophylaxis against Coronavirus Disease-19: Practice Outcomes among Health-Care Workers
927 patient HCQ prophylaxis study: 49% more cases (p=0.02).Observational study of 927 low-risk healthcare workers in India, 731 volunteering for weekly HCQ prophylaxis, showing higher cases with treatment in unadjusted results. Clinical outcome was in the protocol, however no information on which patients were symptomatic is provided. There were no adverse events and no hospitalizations or deaths. Adherence was very low, decreasing weekly, with almost all participants discontinuing by week 11. The majority of infections occurred in later weeks when adherence was very low, and there was no per protocol analysis. #ECR/206/Inst/GJ/2013/RR-20.
Aug 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.08.02.21260750v1, https://c19p.org/bhatt
1,571. Gálvez-Barrón et al., COVID-19: Clinical Presentation and Prognostic Factors of Severe Disease and Mortality in the Oldest-Old Population: A Cohort Study
103 patient metformin prophylaxis study: 16% higher mortality (p=0.46) and 16% higher severe cases (p=0.46).Analysis of 103 elderly hospitalized COVID-19 patients in Spain, showing higher mortality with metformin, without statistical significance.
Apr 2021, Gerontology, https://www.karger.com/Article/FullText/515159, https://c19p.org/galvezbarronmf
1,572. Singer et al., Hydroxychloroquine ineffective for COVID-19 prophylaxis in lupus and rheumatoid arthritis
32,758 patient HCQ prophylaxis study: 9% more cases (p=0.62).Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortality of severity information is provided to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity.
Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/08/19/annrheumdis-2020-218500, https://c19p.org/singer
1,573. Saito et al., Predictors of in-hospital mortality in elderly unvaccinated patients during SARS-CoV-2 Alpha variants epidemic
132 patient favipiravir late treatment study: 168% higher mortality (p=0.06).Retrospective 132 hospitalized COVID-19 patients over age 65 in Japan during the Alpha variant surge, showing higher mortality with favipiravir in unadjusted results, without statistical significance.
Jan 2024, Infection Prevention in Practice, https://www.sciencedirect.com/science/article/pii/S2590088924000052, https://c19p.org/saito2
1,574. Marrone et al., Ursodeoxycholic acid does not affect the clinical outcome of SARS‐CoV‐2 infection: A retrospective study of propensity score‐matched cohorts
629 patient ursodeoxycholic acid prophylaxis study: 7% higher mortality (p=0.77).PSM retrospective 629 hospitalized COVID-19 patients showing no significant difference in survival between 108 patients taking UDCA prior to infection compared to 521 matched controls not taking the drug. The lack of observed benefit in this retrospective inpatient cohort does not preclude potential protective effects of UDCA against infection or illness severe enough to require hospitalization.
Sep 2023, Liver Int., https://onlinelibrary.wiley.com/doi/10.1111/liv.15736, https://c19p.org/marrone
1,575. Auld et al., ICU and ventilator mortality among critically ill adults with COVID-19
217 patient HCQ late treatment study: 3% higher mortality (p=1).Retrospective 217 critically ill patients, 114 receiving HCQ, showing no significant difference in mortality.
Apr 2020, Critical Care Medicine, https://journals.lww.com/ccmjournal/Fulltext/2020/09000/ICU_and_Ventilator_Mortality_Among_Critically_Ill.35.aspx, https://c19p.org/auld
1,576. Burhan et al., Characteristics and outcomes of patients with severe COVID-19 in Indonesia: Lessons from the first wave
559 patient HCQ ICU study: 1% higher mortality (p=0.91).Retrospective 559 COVID-19 ICU patients in Indonesia, showing no difference in mortality with HCQ in unadjusted results.
Sep 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0290964, https://c19p.org/burhan
1,577. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
2,148 patient selenium prophylaxis study: 26% higher hospitalization (p=0.48) and 9% higher severe cases (p=0.8).Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with selenium prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerse
1,578. Mahto et al., Seroprevalence of IgG against SARS-CoV-2 and its determinants among healthcare workers of a COVID-19 dedicated hospital of India
689 patient vitamin C prophylaxis study: 26% higher IgG positivity (p=0.49).Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with vitamin C prophylaxis.
Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtoc
1,579. Basheer et al., Clinical Predictors of Mortality and Critical Illness in Patients with COVID-19 Pneumonia
390 patient aspirin prophylaxis study: 13% higher mortality (p=0.0003).Retrospective 390 hospitalized patients in Israel, showing higher risk of mortality with prior aspirin use. Details of the analysis are not provided.
Oct 2021, Metabolites, https://www.mdpi.com/2218-1989/11/10/679, https://c19p.org/basheer
1,580. Saib et al., Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective study
104 patient HCQ late treatment PSM study: 125% higher combined mortality/intubation (p=0.23).203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding.
Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252388, https://c19p.org/saib
1,581. Psevdos et al., Corona Virus Disease-19 (COVID-19) in a Veterans Affairs Hospital at Suffolk County, Long Island, New York
67 patient HCQ late treatment study: 63% higher mortality (p=0.52).Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended during the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S330/6057008, https://c19p.org/psevdos
1,582. Liu et al., Ursodeoxycholic acid administration did not reduce susceptibility to SARS‐CoV‐2 infection in children
226 patient ursodeoxycholic acid prophylaxis study: 2% more cases (p=0.88).Retrospective 280 Chinese families with children previously seen in a liver clinic assessing whether ursodeoxycholic acid (UDCA) reduced SARS-CoV-2 infection risk. Among infected families, the study found no significant difference in confirmed or suspected SARS-CoV-2 infections between children taking UDCA (80.9%) and those not taking it (77.6%) (p=0.843).
Jun 2023, Liver Int., https://onlinelibrary.wiley.com/doi/10.1111/liv.15660, https://c19p.org/liu12
1,583. Mehrizi et al., Drug prescription patterns and their association with mortality and hospitalization duration in COVID-19 patients: insights from big data
917,198 patient colchicine late treatment study: 13% higher mortality (p<0.0001).Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..
Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizio
1,584. Landi et al., Edoxaban and/or colchicine for patients with coronavirus disease 2019 managed in the out-of-hospital setting (CONVINCE): a randomized clinical trial
59 patient colchicine late treatment RCT: 4% higher hospitalization (p=0.98), 5% higher need for oxygen therapy (p=0.97), 40% improvement (p=0.97), and 11% improved viral clearance (p=0.77).Early terminated RCT with 14 colchicine, 13 edoxaban, 16 colchicine+edoxaban, and 16 control patients, showing no significant difference in outcomes with treatment up to 7 days after PCR diagnosis.
May 2024, J. Cardiovascular Medicine, https://journals.lww.com/10.2459/JCM.0000000000001639, https://c19p.org/landi
1,585. Pérez-Segura et al., Prognostic factors at admission on patients with cancer and COVID-19: Analysis of HOPE registry data
763 patient aspirin prophylaxis study: 49% higher mortality (p=0.0001).Retrospective 770 COVID-19 patients with cancer, showing increased mortality with aspirin use in unadjusted results.
Oct 2021, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S238702062100485X, https://c19p.org/perezsegura
1,586. Chandan et al., Nonsteroidal Antiinflammatory Drugs and Susceptibility to COVID-19
17,190 patient acetaminophen prophylaxis PSM study: 18% higher mortality (p=0.35) and 27% more cases (p=0.17).Retrospective 12,457 patients prescribed paracetamol with codeine/dihydrocodeine and 13,202 prescribed NSAIDs, showing no significant differences in cases and mortality. Patients prescribed codeine/dihydrocodeine may have different susceptibility to COVID-19.
Apr 2021, Arthritis & Rheumatology, https://onlinelibrary.wiley.com/doi/10.1002/art.41593, https://c19p.org/chandan
1,587. Shah et al., Proton-pump inhibitor use is not associated with severe COVID-19-related outcomes: a propensity score-weighted analysis of a national veteran cohort
14,958 patient proton pump inhibitor prophylaxis study: 3% lower mortality (p=0.66), 21% higher ventilation (p=0.06), 13% higher ICU admission (p=0.06), and 5% higher hospitalization (p=0.26).Retrospective 14,958 US veterans who tested positive for SARS-CoV-2, showing no significant difference in severe COVID-19 outcomes (mechanical ventilation, death, ICU admission, or hospitalization) with proton pump inhibitor (PPI) use compared to non-use in a propensity score weighted analysis.
Oct 2021, Gut, https://gut.bmj.com/lookup/doi/10.1136/gutjnl-2021-325701, https://c19p.org/shah8
108 patient zinc early treatment RCT: 44% higher hospitalization (p=0.72) and 12% faster recovery (p=0.38).
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. Study performed in the USA where zinc deficiency is relatively uncommon. The zinc dosage is relatively low, 50mg zinc gluconate (7mg elemental zinc), one tenth of that shown to reduce the duration of colds in other studies [patrickholford.com].
Feb 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305, https://c19p.org/thomas
1,370,600 patient acetaminophen prophylaxis study: 5% higher hospitalization (p=0.83) and 3% fewer cases (p=0.82).
PSM retrospective 1,370,600 osteoarthritis or back pain patients in the US, showing no significant differences in COVID-19 cases and hospitalization for paracetamol vs. ibuprofen.
Jul 2022, Drugs, https://link.springer.com/article/10.1007/s40265-022-01822-z, https://c19p.org/xie
1,590. Assiri et al., COVID-19 related treatment and outcomes among COVID-19 ICU patients: A retrospective cohort study
118 patient zinc ICU study: 81% higher mortality (p=0.44).Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.
Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiriz
1,591. Rentsch et al., Effect of pre-exposure use of hydroxychloroquine on COVID-19 mortality: a population-based cohort study in patients with rheumatoid arthritis or systemic lupus erythematosus using the OpenSAFELY platform
194,637 patient HCQ prophylaxis study: 3% higher mortality (p=0.83).Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 [0.80-1.33] (HR 0.78 before adjustments). 70 patients with HCQ prescriptions died. One major problem is that there is no knowlege of medication adherence for these 70 - for example, it is possible that they were part of the expected percentage of patients that did not take the medication as prescribed, invalidating the result. Other limitations include confounding by use of bDMARDs and confounding by severity of rheumatological disease.
Sep 2020, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991320303787, https://c19p.org/rentsch
1,592. Rivera et al., Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study
506 patient HCQ late treatment study: 2% higher mortality (p=0.92).Retrospective cancer patients, showing adjusted OR 1.03 [0.62-1.73] for HCQ. The study reports the number of HCQ+AZ patients but they do not provide results for HCQ+AZ (only HCQ + any other treatment). Significant confounding by indication and compassionate use is likely.
Jul 2020, Cancer Discovery, https://cancerdiscovery.aacrjournals.org/content/early/2020/09/12/2159-8290.CD-20-0941, https://c19p.org/rivera
1,593. Texeira et al., Characteristics and outcomes of COVID-19 patients admitted to a regional health system in the southeast
161 patient HCQ late treatment study: 79% higher mortality (p=0.1).Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.
Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S251/6058327, https://c19p.org/teixeira
1,594. Assiri et al., COVID-19 related treatment and outcomes among COVID-19 ICU patients: A retrospective cohort study
118 patient favipiravir ICU study: 79% higher mortality (p=0.5).Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.
Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiria
1,595. Huh et al., Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
44,046 patient HCQ prophylaxis study: 97% higher progression (p=0.11) and 6% fewer cases (p=0.82).Retrospective database analysis with 17 cases for existing HCQ users and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2
1,596. Ramadhan et al., The Effects of N-Acetylcysteine as Adjuvant Therapy To Reduce TNF-Α Level And Increase SPO2/FIO2 Ratio In Improving Hypoxemia In COVID-19 Patients
91 patient N-acetylcysteine late treatment study: 135% higher mortality (p=0.68).Prospective study with 75 NAC patients and 16 control patients, showing no significant difference in mortality.
Dec 2021, Indonesian J. Tropical and Infectious Disease, https://www.e-journal.unair.ac.id/IJTID/article/view/30874, https://c19p.org/ramadhan
1,597. Chen et al., Distinct temporal trajectories and risk factors for Post-acute sequelae of SARS-CoV-2 infection
354 patient acetaminophen long COVID study: 32% higher PASC (p=0.07).Prospective study of 494 COVID-19 patients showing higher risk of PASC with acetaminophen use in unadjusted results, without reaching statistical significance (p=0.07). Higher risk is also seen for dexamethasone and remdesivir (statistically significant for dexamethasone), however confounding by indication may be significant for these treatments, with increased use for more severe patients. While details of treatment timing and dose are not available, the result for acetaminophen can be compared with ibuprofen, with comparable indication for use. Notably there is no increased risk with ibuprofen, suggesting higher risk with acetaminophen, consistent with the higher risk seen in meta analysis.
Oct 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1227883/full, https://c19p.org/chen12
1,598. Pérez-Belmonte et al., Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study
498 patient metformin prophylaxis PSM study: 10% higher mortality (p=0.48).Retrospective 2,666 type 2 diabetes COVID-19 patients in Spain, showing higher mortality with existing metformin use (not statistically significant).
Nov 2020, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01832-2, https://c19p.org/perezbelmonte
1,599. Kelly et al., Clinical outcomes and adverse events in patients hospitalised with COVID-19, treated with off-label hydroxychloroquine and azithromycin
134 patient HCQ late treatment study: 143% higher mortality (p=0.03).Retrospective 82 hospitalized patients HCQ/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication - authors note that the HCQ/AZ patients were more severely ill, and do not attempt to adjust for confounders.
Jul 2020, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14482, https://c19p.org/kelly
262 patient HCQ prophylaxis study: 17% higher mortality (p=0.8), 78% higher combined mortality/ICU admission (p=0.21), and 45% higher hospitalization (p=0.12).
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extreme confounding - 77.5% of HCQ patients with systemic autoimmune diseases vs. 21.5% of control patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Jan 2021, Revue du Rhumatisme, https://www.sciencedirect.com/science/article/abs/pii/S1169833021002489, https://c19p.org/trefond
1,601. Aldwihi et al., Patients’ Behavior Regarding Dietary or Herbal Supplements before and during COVID-19 in Saudi Arabia
738 patient vitamin D prophylaxis study: 49% higher hospitalization (p=0.002).Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.
May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihid
1,602. Assiri et al., COVID-19 related treatment and outcomes among COVID-19 ICU patients: A retrospective cohort study
118 patient vitamin D ICU study: 66% higher mortality (p=0.6).Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.
Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiri
1,603. Huh et al., Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
44,046 patient metformin prophylaxis study: 1% higher progression (p=0.11) and 4% fewer cases (p=0.82).Retrospective database analysis showing no significant differences with pre-existing metformin use.
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2mf
325 patient HCQ late treatment study: 890% higher progression (p=0.03).
Retrospective 325 hospitalized COVID-19 patients in Malaysia, showing higher progression with HCQ, however the groups are not comparable. 17 HCQ vs. 3 control patients had severity category ≥3 at baseline (7 vs. 0 for severity ≥4).
Mar 2023, Malaysian J. Medicine and Health Sciences, https://medic.upm.edu.my/upload/dokumen/2023032211275502_MJMHS_0551.pdf, https://c19p.org/ho2
1,605. Choi et al., Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea
72 patient ibuprofen prophylaxis PSM study: 240% higher progression (p=0.26).Retrospective 293 patients in South Korea, showing higher risk of progression with ibuprofen use, without statistical significance.
Jun 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/6/1959, https://c19p.org/choi2
1,606. Akbar et al., The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank
10,000 patient vitamin B9 prophylaxis study: 18% more cases (p=0.29).Retrospective 10,000 adults in Qatar, showing higher risk of COVID-19 cases with vitamin B9 supplementation, without statistical significance. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2b9
1,607. Cravedi et al., COVID-19 and kidney transplantation: Results from the TANGO International Transplant Consortium
144 patient HCQ late treatment study: 53% higher mortality (p=0.17).Analysis of 144 hospitalized kidney transplant patients showing HCQ mortality HR 1.53, p = 0.17. Subject to confounding by indication.
Jul 2020, American J. Transplantation, https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.16185, https://c19p.org/cravedi
1,608. Pinto et al., Association Between the Use of Proton Pump Inhibitors and Severe Clinical Outcomes in COVID-19 Patients: A Retrospective Observational Study
518 patient proton pump inhibitor prophylaxis study: 57% higher hospitalization (p=0.15).Retrospective 506 outpatients in Oman showing no significant association between proton pump inhibitor (PPI) use and COVID-19 hospitalization in unadjusted results.
Oct 2024, Cureus, https://www.cureus.com/articles/310267-association-between-the-use-of-proton-pump-inhibitors-and-severe-clinical-outcomes-in-covid-19-patients-a-retrospective-observational-study, https://c19p.org/pinto2
1,609. Tanwettiyanont et al., Use of Andrographis paniculata (Burm.f.) Wall. ex Nees and risk of pneumonia in hospitalised patients with mild coronavirus disease 2019: A retrospective cohort study
605 patient andrographolide late treatment study: 26% higher progression (p=0.4).Retrospective 605 hospitalized patients in Thailand, showing higher progression with andrographis, without statistical significance.
Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.947373/full, https://c19p.org/tanwettiyanont
1,610. Choi et al., Clinical Characteristics and Disease Progression in Early-Stage COVID-19 Patients in South Korea
72 patient metformin prophylaxis PSM study: 120% higher progression (p=0.26).Retrospective 293 patients in South Korea, showing higher risk of progression with metformin use, without statistical significance.
Jun 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/6/1959, https://c19p.org/choi2mf
1,611. Wallace et al., Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study
7,944 patient famotidine prophylaxis study: 11% higher mortality (p=0.33).Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing no significant difference in mortality with famotidine use. The study provides results for use before, after, and before+after. Before+after should more accurately represent prophylaxis up to COVID-19 infection (and continued use). Before included use up to 2 years before, and after included use up to 60 days later.
Dec 2021, BMJ Open, https://bmjopen.bmj.com/content/11/12/e050051.info, https://c19p.org/wallacefm
1,612. Buonfrate et al., High dose ivermectin for the early treatment of COVID-19 (COVER study): a randomised, double-blind, multicentre, phase II, dose-finding, proof of concept trial
61 patient ivermectin early treatment RCT: 20% improved viral clearance (p=0.59).Early terminated 89 patient RCT with 29 high dose and 32 very high dose ivermectin patients, showing dose dependent viral load reduction, although not reaching statistical significance due to early termination. Since most patients have low viral load at day 7, there is little room for improvement with a treatment at day 7. Intermediate results may show significantly greater improvement, but are not provided. Authors note that ivermectin remained safe even at the very high dose used, although tolerability was reduced. Adherence was very low in the very high dose arm (~60%). The paper reports 4 SAEs, all resolved, with 3 patients hospitalized in the very high dose ivermectin arm, 1 in the high dose arm, and 0 in the control arm. However, the supplementary data is contradictory, showing 2 grade 3 events in both ivermectin arms (2 infections and infestations, and 2 COVID-19 pneumonia). While this result is not statistically significant, it may be in part due to randomization failure..
Sep 2021, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857921013571, https://c19p.org/buonfrate
1,613. Sammartino et al., Predictors for inpatient mortality during the first wave of the SARS-CoV-2 pandemic: A retrospective analysis
328 patient HCQ late treatment PSM study: 240% higher mortality (p=0.002).Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment. Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. Authors note that for every week or month later that a person was admitted, their risk of death dropped by 16% and 49%, respectively, yet they do not consider time based confounding.
May 2021, PLOS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251262, https://c19p.org/sammartino
1,614. Yan et al., Clinical Characteristics of Coronavirus Disease 2019 in Hainan, China
168 patient proton pump inhibitor prophylaxis study: 240% higher severe cases (p<0.0001).Retrospective 168 hospitalized COVID-19 patients in China showing higher risk of severe cases with acid suppression drugs.
Mar 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.03.19.20038539, https://c19p.org/yan6
1,615. Alsaraj et al., Consequence of Antivirals Versus Standard Care on Clinical Situation in Patients With COVID-19
104 patient favipiravir late treatment RCT: 87% higher mortality (p=0.26).RCT 156 COVID-19 patients showing higher mortality with favipiravir and remdesivir overall. Favipiravir and remdesivir were more effective when started earlier, however note that Table 10 compares earlier favipiravir/remdesivir+standard care with standard care at any time, which will exaggerate the benefits/harms of earlier/later treatment. The confidence intervals for the Cox results are unusually narrow suggesting a possible error in calculation.
Jan 2024, Infectious Diseases in Clinical Practice, https://journals.lww.com/10.1097/IPC.0000000000001336, https://c19p.org/alsaraja
1,616. Stewart et al., COVID-19 Evidence Accelerator: A parallel analysis to describe the use of Hydroxychloroquine with or without Azithromycin among hospitalized COVID-19 patients
11,157 patient HCQ late treatment study: 28% higher mortality (p=0.03) and 29% higher ventilation (p=0.09).Retrospective analysis of seven databases in the USA, showing higher mortality with treatment. Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confounding by indication. Time based confounding is very likely because HCQ became highly controversial and usage dramatically declined over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. This study includes anyone PCR+ during or prior to their visit, and anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore some patients in the control groups may be asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. Authors do not mention the possibility of any of these likely confounding factors.
Mar 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248128, https://c19p.org/stewart
1,617. Kim et al., Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study
324 patient acetaminophen prophylaxis PSM study: 71% higher mortality (p=0.34), 14% higher ventilation (p=1), 40% lower ICU admission (p=0.72), and 9% higher need for oxygen therapy (p=0.87).PSM retrospective in South Korea, showing no significant differences in outcomes with acetaminophen use vs. NSAID use. Adherence and dosage are unknown.
Feb 2023, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/20/5/3832, https://c19p.org/kim7
1,618. Alotaibi et al., Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study
437 patient HCQ late treatment study: 134% higher mortality (p=0.05).Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subject to significant confounding by indication and confounding by time.
Sep 2021, Int. J. General Medicine, https://www.dovepress.com/getfile.php?fileID=73585, https://c19p.org/alotaibi
1,619. Rosenberg et al., Association of Treatment With Hydroxychloroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State
1,483 patient HCQ late treatment study: 35% higher mortality (p=0.31).Retrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. [ijidonline.com] point out serious limitations that they say should be corrected on the record: patients receiving HCQ with or without AZ were overall sicker on presentation and had multiple other risk factors including much higher risk based on ethnicity; patients receiving HCQ were more likely to be obese, diabetic, have chronic lung disease, and cardiovascular conditions; yet these sicker patients had approximately the same mortality rates compared to patients with a milder course of the disease and less risk factors. However, the authors conclude that "there are no significant benefits." It is noteworthy that HCQ was associated with a significant survival benefit in a larger cohort of patients from New York City as reported by [Mikami]. See also [worldtribune.com].
May 2020, JAMA, May 11, 2020, https://jamanetwork.com/journals/jama/fullarticle/2766117, https://c19p.org/rosenberg
1,620. Vivanco-Hidalgo et al., Incidence of COVID-19 in patients exposed to chloroquine and hydroxychloroquine: results from a population-based prospective cohort in Catalonia, Spain, 2020
20,238 patient HCQ prophylaxis study: 46% higher hospitalization (p=0.1) and 8% more cases (p=0.5).Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].
Mar 2021, Eurosurveillance, https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.9.2001202, https://c19p.org/vivancohidalgo
1,621. AlQadheeb et al., Impact of common comorbidities on antimicrobial consumption and mortality amongst critically ill COVID-19 patients: A retrospective two center study in Saudi Arabia
848 patient azithromycin ICU study: 22% higher mortality (p=0.08).Retrospective 848 ICU patients in Saudi Arabia, showing higher mortality with azithromycin in unadjusted results.
May 2023, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170223000122, https://c19p.org/alqadheebazaz
1,622. Kaplan et al., Resveratrol and Zinc in the Treatment of Outpatients With COVID-19 – The Reszinate Study - A Phase 1/2 Randomized Clinical Trial Utilizing Home Patient-Obtained Nasal and Saliva Viral Sampling
30 patient zinc late treatment RCT: 14% higher ventilation (p=1), 14% higher ICU admission (p=1), and 14% higher hospitalization (p=1).Small RCT of zinc plus resveratrol in COVID-19+ outpatients, showing no significant differences in viral clearance or symptoms. Although the treatment group was older (46.3 vs. 38.5) and had more severe baseline symptoms, they had similar symptomatic recovery by the second week.
Sep 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3934228, https://c19p.org/kaplan
1,623. Kaplan et al., Resveratrol and Zinc in the Treatment of Outpatients With COVID-19 – The Reszinate Study - A Phase 1/2 Randomized Clinical Trial Utilizing Home Patient-Obtained Nasal and Saliva Viral Sampling
30 patient resveratrol late treatment RCT: 14% higher ventilation (p=1), 14% higher ICU admission (p=1), and 14% higher hospitalization (p=1).Small RCT of zinc plus resveratrol in COVID-19+ outpatients, showing no significant differences in viral clearance or symptoms. Although the treatment group was older (46.3 vs. 38.5) and had more severe baseline symptoms, they had similar symptomatic recovery by the second week.
Sep 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3934228, https://c19p.org/kaplanrsv
1,624. Obiri-Yeboah et al., Association of metformin, dipeptidyl dipeptidase-4 inhibitors, and insulin with COVID-19-related hospital outcomes in patients with type 2 diabetes
529 patient metformin prophylaxis study: 1% higher mortality (p=0.98), 4% higher ventilation (p=0.87), and 8% lower ICU admission (p=0.72).Retrospective 529 hospitalized COVID-19 patients with type 2 diabetes, showing no significant difference in outcomes with metformin use. This does not account for the different risk of being hospitalized based on metformin use. Authors note that "there is a lower-than-expected proportion of metformin prescription in our population (28%) compared to the general US population", without noting that this may reflect the lower risk of being hospitalized for metformin patients, as shown in other studies [c19early.org].
Jun 2023, Endocrine Practice, https://www.sciencedirect.com/science/article/pii/S1530891X23004299, https://c19p.org/obiriyeboah
1,625. Shahbaznejad et al., Effects of Ivermectin in Patients With COVID-19: A Multicenter, Double-blind, Randomized, Controlled Clinical Trial
69 patient ivermectin late treatment RCT: 32% faster recovery (p=0.05) and 15% shorter hospitalization (p=0.02).RCT in Iran showing shorter time to recovery and shorter hospitalization time with ivermectin. There were no adverse effects. There was one death in the treatment group, the patient was in critical condition at baseline and died within 24 hours of admission. Also see [sciencedirect.com] and the author response [clinicaltherapeutics.com].
Jan 2021, Clinical Therapeutics, https://www.sciencedirect.com/science/article/abs/pii/S0149291821002010, https://c19p.org/shahbaznejad
1,626. Souza-Silva et al., Dados de Vida Real sobre o Uso da Hidroxicloroquina ou da Cloroquina Combinadas ou Não à Azitromicina em Pacientes com Covid-19: Uma Análise Retrospectiva no Brasil
1,346 patient HCQ late treatment study: 5% higher mortality (p=0.68), 21% higher ventilation (p=0.08), 9% higher ICU admission (p=0.31), and 12% longer hospitalization (p=0.03).Retrospective 7,580 hospitalized patients in Brazil, showing longer hospitalization, and no significant difference in mortality, mechanical ventilation, and ICU admission with HCQ treatment. Authors note confounding by indication due to selected use in a compassionate use context. Authors match only on age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid, and only 10% of patients received HCQ/CQ, therefore confounding by indication is likely to be significant. A different matching list is included in the text, but neither includes COVID-19 severity. In the first line of the abstract authors falsely state that there is no evidence of benefit for HCQ treatment. While misrepresenting prior research is common, this is an extreme case and raises concern for validity of the analysis. In reality controlled studies show statistically significant positive results for one or more outcomes (including RCTs). Authors discussion of prior research shows similar bias.
Sep 2023, Arquivos Brasileiros de Cardiologia, https://abccardiol.org/article/dados-de-vida-real-sobre-o-uso-da-hidroxicloroquina-ou-da-cloroquina-combinadas-ou-nao-a-azitromicina-em-pacientes-com-covid-19-uma-analise-retrospectiva-no-brasil/, https://c19p.org/souzasilva
1,627. Hoertel et al., Medications Modulating the Acid Sphingomyelinase/Ceramide System and 28-Day Mortality among Patients with SARS-CoV-2: An Observational Study
5,772 patient antihistamine H1RA prophylaxis study: 7% higher mortality (p=0.5).Retrospective 72,105 COVID+ hospitalized patients in France, showing no significant difference in mortality with antihistamine H1RAs desloratadine and hydroxyzine.
Aug 2023, Pharmaceuticals, https://www.mdpi.com/1424-8247/16/8/1107, https://c19p.org/hoertel5h1
1,628. Vallejos et al., Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19) a randomized, double-blind, placebo-controlled trial
501 patient ivermectin early treatment RCT: 33% lower hospitalization (p=0.23) and 5% worse viral clearance (p=0.55).RCT with 501 relatively low-risk outpatients in Argentina showing hospitalization OR 0.65 [0.32-1.31]. With only 7% hospitalization, this trial is underpowered. The trial primarily includes low-risk patients that recover quickly without treatment, leaving minimal room for improvement with treatment. 74 patients had symptoms for >= 7 days. Among the 7 patients requiring ventilation, authors note that the earlier requirement in the ivermectin group may be due to those patients having higher severity at baseline. However, authors know the answer to this - it is unclear why it is not reported. There were more adverse events in the placebo group than the ivermectin group, suggesting a possible issue with dispensing or non-trial medication usage. 25+% of patients were hospitalized within 2/3 days for the placebo/treatment groups (Figure S2). The companion prophylaxis study [ IVERCOR PREP ] has reported results in the press and an online presentation [ lanacion.com.ar , web.archive.org (M) ..
Jul 2021, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06348-5, https://c19p.org/vallejos2
1,629. Nimer et al., The impact of vitamin and mineral supplements usage prior to COVID-19 infection on disease severity and hospitalization
2,148 patient zinc prophylaxis study: 25% higher hospitalization (p=0.21) and 13% higher severe cases (p=0.46).Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with zinc prophylaxis.
Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerz
1,630. Bryan et al., The Efficacy of Nitric Oxide Generating Lozenges on Outcome in Newly Diagnosed COVID-19 Patients of African American and Hispanic Origin
524 patient nitric oxide early treatment RCT: 1% higher progression (p=1) and 11% faster recovery (p=0.3).RCT 524 outpatients in the USA for a nitric oxide generating lozenge, showing no significant difference in combined hospitalization, ICU admission, intubation, dialysis, and death. There were only 3 events in each arm, all occuring in 2020, with zero events in 2021 or 2022. Recovery was 11% faster with treatment, without statistical significance. Authors note that a higher dose may have been more effective. Trials showing greater efficacy have used a nasal spray.
Jun 2023, The American J. Medicine, https://www.sciencedirect.com/science/article/pii/S0002934323003911, https://c19p.org/bryan
1,631. Shafrir et al., The Association Between Proton Pump Inhibitors and COVID-19 is Confounded by Hyperglycemia in a Population-Based Study
250,655 patient proton pump inhibitor prophylaxis PSM study: 47% higher severe cases (p=0.32) and 8% fewer cases (p=0.06).Retrospective 255,355 adults in Israel showing no significant association between proton pump inhibitor (PPI) use and SARS-CoV-2 positivity or COVID-19 severity.
Feb 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.791074/full, https://c19p.org/shafrir
1,632. Ojeda‐Fernández et al., UDCA treatment against COVID‐19: Do we have enough clinical evidence for drug repurposing?
1,360 patient ursodeoxycholic acid prophylaxis study: 7% higher mortality (p=0.67), 4% lower ICU admission (p=0.96), 6% higher hospitalization (p=0.66), and 3% fewer cases (p=0.77).Retrospective cohort study of 9,617 patients with liver disease in Italy, divided into UDCA users and non-users. UDCA exposure was not associated with reduced SARS-CoV-2 infection or improved COVID-19 outcomes including death, hospitalization, and ICU admission in this unvaccinated cohort. The large sample size provides power, but administrative data limitations include lack of important confounders like BMI and hypertension.
Aug 2023, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13711, https://c19p.org/ojedafernandez2
1,633. Huh et al., Association of prescribed medications with the risk of COVID-19 infection and severity among adults in South Korea
44,046 patient azithromycin prophylaxis study: 54% higher progression (p=0.33) and 42% fewer cases (p=0.1).Retrospective database analysis showing no significant differences with azithromycin use.
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2azaz
1,634. ANTICOV et al., ANTICOV Trial Finds Nitazoxanide/Ciclesonide Drug Combination Does Not Reduce Hospitalisation Risk in Patients With Mild COVID-19
905 patient nitazoxanide early treatment RCT: 188% higher progression (p=0.04).RCT with 462 nitazoxanide/ciclesonide and 443 paracetamol patients, up to 7 days from onset, showing no significant difference in progression. Minimal details, with the primary mortality outcome and treatment delay not being reported.
Feb 2022, ANTICOV, News, https://www.isglobal.org/en/new/-/asset_publisher/JZ9fGljXnWpI/content/ensayo-anticov-halla-combinacion-nitazoxanida-ciclesonida-no-reduce-riesgo-hospitalizacion-pacientes-covid-19-leve, https://c19p.org/anticovn
1,635. Laplana et al., Lack of protective effect of chloroquine derivatives on COVID-19 disease in a Spanish sample of chronically treated patients
638 patient HCQ prophylaxis study: 56% more cases (p=0.24).Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4% incidence. It not clear why authors did not compare with autoimmune patients not on CQ/HCQ. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the result becomes RR 0.36, p<0.001, suggesting a substantial benefit for HCQ/CQ treatment (as shown in other studies). There may also be significant survey bias - those experiencing COVID-19 may be more likely to respond to the survey. Authors note that they "could not eliminate completely the possibility of some bias due to the..
Sep 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243598, https://c19p.org/laplana
1,636. Blanc et al., Interest of Proton Pump Inhibitors in Reducing the Occurrence of COVID-19: A Case-Control Study
179 patient acetaminophen prophylaxis study: 51% more cases (p=0.19).Retrospective 179 elderly patients in France, showing higher risk of COVID-19 cases with acetaminophen use, without statistical significance.
May 2020, Preprints, https://www.preprints.org/manuscript/202005.0016/v1, https://c19p.org/blanc2
1,637. Kokturk et al., The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients
1,500 patient HCQ late treatment study: 4% higher mortality (p=0.97).Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQ treatment.
Apr 2021, Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S0954611121001396, https://c19p.org/kokturk
1,638. Sharif et al., Impact of Zinc, Vitamins C and D on Disease Prognosis among Patients with COVID-19 in Bangladesh: A Cross-Sectional Study
503 patient acetaminophen early treatment study: 77% higher mortality (p=0.74).Retrospective COVID-19 patients in Bangladesh, showing higher mortality with acetaminophen use in unadjusted results.
Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/shariface
1,639. Griffith et al., Cannabis, Tobacco Use, and COVID-19 Outcomes
72,501 patient cannabidiol prophylaxis study: 3% lower mortality (p=0.73), 27% higher ICU admission (p<0.0001), and 80% higher hospitalization (p<0.0001).Retrospective 72,501 COVID-19 patients in the USA showing cannabis use associated with higher risk of hospitalization and ICU admission.
Jun 2024, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820235, https://c19p.org/griffith
1,640. Abu Esba et al., Ibuprofen and NSAID Use in COVID-19 Infected Patients Is Not Associated with Worse Outcomes: A Prospective Cohort Study
397 patient ibuprofen early treatment study: 170% higher mortality (p=0.35), 45% higher need for oxygen therapy (p=0.64), 18% higher hospitalization (p=0.64), and 85% higher severe cases (p=0.42).Prospective study of 503 COVID-19 cases in Saudi Arabia, 40 using ibuprofen during infection, and 357 not using NSAIDs, showing no significant differences in outcomes. Results are subject to confounding by indication.
Nov 2020, Infectious Diseases and Therapy, http://link.springer.com/10.1007/s40121-020-00363-w, https://c19p.org/abuesba
1,641. Mohandas et al., Clinical review of COVID-19 patients presenting to a quaternary care private hospital in South India: A retrospective study
3,345 patient HCQ late treatment study: 81% higher mortality (p=0.007).Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overall treatment protocols improved dramatically) are likely.
Apr 2021, Clinical Epidemiology and Global Health, https://www.sciencedirect.com/science/article/pii/S2213398421000555, https://c19p.org/mohandas
1,996 patient exercise study: 42% more cases (p=0.55).
Retrospective survey of 1,997 college students in the USA, showing no significant difference in COVID-19 cases with exercise in unadjusted results.
Feb 2022, JMIR Mental Health, https://mental.jmir.org/2022/2/e34645, https://c19p.org/gilley
1,643. Campbell et al., Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19
22,385 patient acetaminophen prophylaxis study: 1% higher mortality (p=0.43).Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic acetaminophen use vs. sporadic NSAID use. Since acetaminophen is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2ace
1,644. Adrean et al., Does Prophylactic Oral Zinc Reduce the Risk of Contracting COVID-19?
8,426 patient zinc prophylaxis study: 12% more cases (p=0.58).Retrospective 8,426 patients in the USA, showing no significant difference in cases with zinc prophylaxis. Severity results were not reported due to the small number of events.
Oct 2022, Cureus, https://www.cureus.com/articles/119536-does-prophylactic-oral-zinc-reduce-the-risk-of-contracting-covid-19, https://c19p.org/adrean
1,645. Fairfield et al., Association of Vitamin D Prescribing and Clinical Outcomes in Adults Hospitalized with COVID-19
158,835 patient vitamin D late treatment study: 9% higher mortality (p<0.0001) and 41% higher ventilation (p<0.0001).N3C retrospective showing higher risk with vitamin D treatment for hospitalized patients. As noted by authors, confounding by indication may be significant. The more extreme ventilation result, which is a significant outlier among all studies, is consistent with such confounding. Timing, dose, and duration of treatment were not used.
Jul 2022, Nutrients, https://www.mdpi.com/2072-6643/14/15/3073, https://c19p.org/fairfield
1,646. Israelsen et al., Proton Pump Inhibitor Use Is Not Strongly Associated With SARS-CoV-2 Related Outcomes: A Nationwide Study and Meta-analysis
7,910 patient proton pump inhibitor prophylaxis PSM study: 5% lower mortality (p=0.7), 8% higher ventilation (p=0.73), 5% higher ICU admission (p=0.8), and 22% higher hospitalization (p=0.005).Retrospective 83,224 SARS-CoV-2 cases and 332,799 controls in Denmark showing increased risk of infection and hospital admission with proton pump inhibitor (PPI) use, but no significant association with ICU admission or mortality.
Sep 2021, Clinical Gastroenterology and Hepatology, https://www.sciencedirect.com/science/article/pii/S1542356521005140, https://c19p.org/israelsen
1,647. Tobback et al., Efficacy and safety of camostat mesylate in early COVID-19 disease in an ambulatory setting: a randomized placebo-controlled phase II trial
96 patient camostat early treatment RCT: 36% higher hospitalization (p=1) and 8% improved recovery (p=0.84).RCT 90 outpatients showing no significant difference in viral load or time to clinical improvement with camostat mesylate. The trial was discontinued early and did not reach the intended sample size. Authors note that combining camostat with a cathepsin inhibitor may improve efficacy.
Sep 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222003885, https://c19p.org/tobback
1,648. McKeigue et al., Relation of severe COVID-19 to polypharmacy and prescribing of psychotropic drugs: the REACT-SCOT case-control study
36,160 patient antihistamine H1RA prophylaxis study: 30% higher severe cases (p=0.0004).Retrospective 4,251 severe COVID-19 cases and 36,738 matched controls in Scotland showing increased risk of severe COVID-19 with PPI use and antihistamine H1RA use. Adjusted results are only provided for the patients not in care homes (2,357 cases and 33,803 controls).
Feb 2021, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-01907-8, https://c19p.org/mckeigueh1
1,649. Rezai et al., Non-effectiveness of Ivermectin on Inpatients and Outpatients With COVID-19; Results of Two Randomized, Double-Blinded, Placebo-Controlled Clinical Trials
549 patient ivermectin early treatment RCT: 9% higher ICU admission (p=0.95), 36% higher hospitalization (p=0.41), 2% worse recovery (p=0.49), and 23% worse viral clearance (p=0.16).RCT 549 low risk outpatients in Iran. Reported outcomes are very different from the pre-specified outcomes [irct.ir]. The inpatient trial is listed separately. The pre-specified primary clinical outcome was not reported. The reported components of this outcome are both positive. Pre-specified outcomes (3 not reported) [irct.ir]: - reduction in persistent cough and tachypnea and O2 saturation above 94% - not reported - negative PCR - reported - main complaints recovery time - not reported (only individual symptoms) - hospitalization - reported - time to hospitalization - not reported - mortality - reported - side effects - reported in only one patient (anomalous) A new outcome "relative recovery" is reported but not mentioned in the trial registration. The reported percentages and RR do not match. Authors include a researcher caught on video admitting that conclusions on ivermectin research were influenced by a funder [c19ivm.org]. Most/many patients were also treated with..
Jun 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.919708/full, https://c19p.org/rezai3
1,650. Mallat et al., Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study
34 patient HCQ late treatment study: 203% slower viral clearance (p=0.02).Very small retrospective analysis of 34 patients finding slower binary PCR viral clearance with HCQ. No information on severity for treatment versus control is provided. No deaths, ICU admission, or mechanical ventilation. Binary PCR does not distinguish replication-competence. HCQ treatment started very late for many patients with >= 9 days for 25%.
May 2020, Medicine, https://journals.lww.com/md-journal/Fulltext/2020/12240/Hydroxychloroquine_is_associated_with_slower_viral.34.aspx, https://c19p.org/mallat
1,651. Ravichandran et al., Use of indomethacin in COVID-19 patients: experience from two medical centres
144 patient acetaminophen late treatment PSM study: 2700% higher need for oxygen therapy (p<0.0001) and 75% slower recovery (p<0.0001).PSM retrospective 72 indomethacin and 72 paracetamol patients in India, showing higher progression and worse recovery with acetaminophen.
Jul 2021, J. the Indian Medical Association, https://sapiensfoundation.org/wp-content/uploads/2021/08/Use-of-Indomethacin-in-Covid-19-patients-JIMA-2021.pdf, https://c19p.org/ravichandran2ace
1,652. Awad et al., Impact of hydroxychloroquine on disease progression and ICU admissions in patients with SARS-CoV-2 infection
336 patient HCQ late treatment study: 19% higher mortality (p=0.6), 461% higher ventilation (p<0.0001), and 463% higher ICU admission (p<0.0001).This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, ICU admission, and intubation with treatment. Confounding by indication is likely. Time varying confounding is also likely due to declining usage over the early period when overall treatment protocols were also improving dramatically. Authors and reviewers appear to be unfamiliar with either of these.
Feb 2021, American J. Health-System Pharmacy, https://academic.oup.com/ajhp/advance-article/doi/10.1093/ajhp/zxab056/6144083, https://c19p.org/awad
1,653. Pan et al., Pre-hospital antiplatelet medication use on COVID-19 disease severity
762 patient aspirin prophylaxis study: 13% higher mortality (p=0.63) and 2% higher combined mortality/intubation (p=0.93).Retrospective 762 COVID+ hospitalized patients in the USA, 239 on antiplatelet medication (199 aspirin), showing no significant differences in outcomes. For more discussion see [sciencedirect.com].
May 2021, Heart & Lung, https://www.heartandlung.org/article/S0147-9563(21)00175-8/fulltext, https://c19p.org/pan
1,654. Rinott et al., Ibuprofen use and clinical outcomes in COVID-19 patients
403 patient ibuprofen early treatment study: 21% higher mortality (p=0.73), 12% higher ventilation (p=0.77), and 40% higher ICU admission (p=0.56).Retrospective 403 COVID-19 cases in Israel, showing no significant difference in outcomes with ibuprofen use. Patients were asked about ibuprofen use starting a week before diagnosis of COVID-19 - treatment time may have been early, late, or prophylactic.
Sep 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20303438, https://c19p.org/rinott
1,655. Faverio et al., Impact of N-acetyl-l-cysteine on SARS-CoV-2 pneumonia and its sequelae: results from a large cohort study
901 patient N-acetylcysteine late treatment study: 19% higher mortality (p=0.33), 34% higher ICU admission (p=0.08), and 1% higher hospital discharge (p=0.94).Retrospective 1,083 consecutive hospitalized COVID patients in Italy, showing no significant differences with NAC treatment. The number of patients transferred to another facility exceeds the number of deaths, which may significantly affect results.
Dec 2021, ERJ Open Research, https://openres.ersjournals.com/content/8/1/00542-2021, https://c19p.org/faverio
1,656. Solaymani-Dodaran et al., Safety and efficacy of Favipiravir in moderate to severe SARS-CoV-2 pneumonia
373 patient favipiravir late treatment RCT: 19% higher mortality (p=0.54), 53% higher ventilation (p=0.15), and 19% higher ICU admission (p=0.56).RCT late stage patients (median SpO2 89), 193 treated with favipiravir, 187 with lopinavir/ritonavir, showing no significant differences in mortality, intubation, or ICU admission.
Mar 2021, Int. Immunopharmacology, https://www.sciencedirect.com/science/article/pii/S1567576921001582, https://c19p.org/solaymanidodaran
1,657. Samimagham et al., The Association of Non-Steroidal Anti-Inflammatory Drugs with COVID-19 Severity and Mortality
158 patient ibuprofen prophylaxis study: 100% higher mortality (p=0.001), 428% higher severe cases (p=0.0007), and 13% higher progression (p=0.04).Retrospective 158 COVID-19 patients in Iran, showing higher risk of mortality with ibuprofen use.
Jul 2020, Archives of Clinical Infectious Diseases, https://brief.land/archcid/articles/106847.html, https://c19p.org/samimagham2
1,658. SOLIDARITY Trial Consortium et al., Repurposed antiviral drugs for COVID-19; interim WHO SOLIDARITY trial results
1,853 patient HCQ late treatment RCT: 19% higher mortality (p=0.23).WHO SOLIDARITY open-label trial with 954 very late stage (64% on oxygen/ventilation) HCQ patients, mortality relative risk RR 1.19 [0.89-1.59], p=0.23. HCQ dosage very high as in RECOVERY, 1.6g in the first 24 hours, 9.6g total over 10 days, only 25% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors state they do not know the weight or obesity status of patients to analyze toxicity (since they do not adjust dosage based on patient weight, toxicity may be higher in patients of lower weight). KM curves show a spike in HCQ mortality days 5-7, corresponding to ~90% of the total excess seen at day 28 (a similar spike is seen in the RECOVERY trial). Almost all excess mortality is from ventilated patients. Authors refer to a lack of excess mortality in the first few days to suggest a lack of toxicity, but they are ignoring the very long half-life of HCQ and the dosing regimen - much higher levels of HCQ will be reached later. Increased..
Oct 2020, SOLIDARITY Trial Consortium, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2023184, https://c19p.org/solidarity
1,659. Sands et al., No clinical benefit in mortality associated with hydroxychloroquine treatment in patients with COVID-19
1,669 patient HCQ late treatment study: 70% higher mortality (p=0.01).Retrospective database analysis of 1,669 patients in the US showing OR 1.81, p = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in the hospital for other reasons. While authors adjust for severity, the method used is very poor. 93.5% of patients are classified as "mild", which is patients with no documented care in a critical care unit within 8 hours of admission. Therefore almost all patients are in the same category, and those in a different category may be due to symptoms unrelated to COVID-19. Lower bias toward male patients in the control group also agrees with the hypothesis that the control group is made up of more people that were in hospital for another reason. Since the analysis covers the initial period of the pandemic in the USA, it is likely that HCQ was used more often earlier in the analysis period when treatment protocols were considerably worse. It's..
Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325832, https://c19p.org/sands
1,660. Gedeborg et al., Androgen deprivation therapy, comorbidity, cancer stage and mortality from COVID-19 in men with prostate cancer
24,174 patient antiandrogen prophylaxis study: 25% higher mortality (p=0.11).Case control study with 474 patients that died of COVID-19 in Sweden, showing higher risk with ADT, without statistical significance.
Dec 2021, Scandinavian J. Urology, https://www.tandfonline.com/doi/pdf/10.1080/21681805.2021.2019304, https://c19p.org/gedeborg
1,661. Ullah et al., COVID-19 in patients with hepatobiliary and pancreatic diseases in East London: a single-centre cohort study
14,849 patient vitamin D prophylaxis study: 42% higher mortality (p=0.35) and 146% more cases (p<0.0001).Retrospective 15,440 patients with hepatobiliary and pancreatic diseases in the United Kingdom, 226 with confirmed COVID-19, showing higher risk with vitamin D supplementation. Results are likely confounded by impaired vitamin D processing and propensity to prescribe supplementation based on specifics of each patient's disease and vitamin D levels. Adjustments used broad age ranges, likely adding to residual confounding.
Mar 2021, Pancreatology, https://www.sciencedirect.com/science/article/abs/pii/S1424390320307298, https://c19p.org/ullah2
1,662. Rossignol et al., A randomized double-blind placebo-controlled clinical trial of nitazoxanide for treatment of mild or moderate COVID-19
379 patient nitazoxanide early treatment RCT: 79% lower hospitalization (p=0.22), 85% lower severe cases (p=0.07), and 7% slower recovery (p=0.88).RCT with 184 outpatients treated with an extended release formulation of nitazoxanide, and 195 controls, showing lower hospitalization and progression to severe disease with treatment. There was one COVID-19 related death in the treatment arm. 600mg twice daily for five days.
Apr 2021, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00040-2/fulltext, https://c19p.org/rossignol
1,663. Oristrell et al., Vitamin D supplementation and COVID-19 risk: a population-based, cohort study
404,109 patient vitamin D prophylaxis study: 1% higher mortality (p=0.91) and 1% fewer cases (p=0.65).Retrospective study of cholecalciferol and calcitriol supplementation in Catalonia showing a small but significant lower risk of cases with cholecalciferol, but no significant difference for mortality, or for calcitriol supplementation. Significant benefit was found for cases, severity, and mortality in patients achieving serum vitamin D levels ≥30ng/ml.
Jul 2021, J. Endocrinological Investigation, https://link.springer.com/article/10.1007/s40618-021-01639-9, https://c19p.org/oristrell2
1,664. Kalligeros et al., Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study
108 patient HCQ late treatment study: 67% higher mortality (p=0.57).Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is likely.
Aug 2020, J. Global Antimicrobial Resistance, https://www.sciencedirect.com/science/article/pii/S2213716520301934, https://c19p.org/kalligeros
1,665. Adhikari et al., Efficacy of Favipiravir in treatment of mild & moderate COVID-19 infection in Nepal: a multi-center, randomized, open-labelled, phase III clinical trial
70 patient favipiravir early treatment RCT: 40% worse improvement (p=0.57).Preliminary report for an RCT in Nepal with 38 favipiravir patients and 32 control patients, showing no significant differences. There were no serious side effects.
Feb 2022, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)01001-8/fulltext, https://c19p.org/adhikari
1,666. Moreno-Martos et al., Characteristics and outcomes of COVID-19 patients with COPD from the United States, South Korea, and Europe
99,890 patient acetaminophen prophylaxis study: 29% higher hospitalization (p<0.0001).Aanlysis of prescriptions in multiple databases showing higher risk of COVID-19 hospitalization with acetaminophen use for COPD patients. Acetaminophen use was more prevalent in hospitalized patients compared to diagnosed patients (data from tables 1, 5, and S3).
Jan 2022, Wellcome Open Research, https://wellcomeopenresearch.org/articles/7-22/v3, https://c19p.org/morenomartos
1,667. Vila‐Corcoles et al., Use of distinct anti‐hypertensive drugs and risk for COVID‐19 among hypertensive people: A population‐based cohort study in Southern Catalonia, Spain
34,936 patient proton pump inhibitor prophylaxis study: 9% more cases (p=0.58).Retrospective 34,936 hypertensive outpatients in Spain showing no significant difference in COVID-19 cases with PPIs and antihistamine H1RAs.
Jul 2020, The J. Clinical Hypertension, https://onlinelibrary.wiley.com/doi/10.1111/jch.13948, https://c19p.org/vilacorcoles2
1,668. McKeigue et al., Relation of severe COVID-19 to polypharmacy and prescribing of psychotropic drugs: the REACT-SCOT case-control study
36,160 patient proton pump inhibitor prophylaxis study: 44% higher severe cases (p<0.0001).Retrospective 4,251 severe COVID-19 cases and 36,738 matched controls in Scotland showing increased risk of severe COVID-19 with PPI use and antihistamine H1RA use. Adjusted results are only provided for the patients not in care homes (2,357 cases and 33,803 controls).
Feb 2021, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-01907-8, https://c19p.org/mckeigue
1,669. García-García et al., Melatonin in the Prophylaxis of SARS-CoV-2 Infection in Healthcare Workers (MeCOVID): A Randomised Clinical Trial
314 patient melatonin prophylaxis RCT: 108% more cases (p=0.26).PrEP RCT healthcare workers in Spain, showing no significant difference in cases with melatonin prophylaxis. Most cases were asymptomatic or paucisymtomatic, there were two symptomatic cases, no moderate/severe cases, and no hospitalization. The registered primary outcome is symptomatic cases. Authors report on all cases due to the small number of symptomatic cases. They did not include the original primary outcome results in the paper, but have provided the results via email to a contributor. The dosage in this trial is very low, 2mg daily. Meta regression suggests higher doses are much more effective. EudraCT 2020-001530-35.
Feb 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/4/1139, https://c19p.org/garciagarcia
1,670. Corpechot et al., Exploring the impact of ursodeoxycholic acid therapy on COVID‐19 in a real‐world setting
10,147 patient ursodeoxycholic acid prophylaxis study: 19% lower ICU admission (p=1) and 40% lower hospitalization (p=0.17).Retrospective cohort study of 10,147 chronic liver disease patients in France, with 1,322 exposed to ursodeoxycholic acid (UDCA), showing lower risk of hospitalization for COVID-19 with UDCA exposure, without statistical significance (adjusted OR 0.48, 95% CI 0.20-1.19). A case-control analysis of 88 hospitalized patients and 840 matched controls showed no significant difference, and there was no significant difference for ICU admission and mortality. The study is underpowered due to the low number of COVID-19 hospitalizations.
Jan 2024, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.29418, https://c19p.org/corpechot
1,671. Sáenz-Aldea et al., Colchicine and risk of hospitalisation due to COVID-19: a population-based study
86,692 patient colchicine prophylaxis study: 8% higher hospitalization (p=0.68) and 12% more cases (p=0.68).Retrospective 86,652 patients in Spain, showing no significant difference in cases and hospitalization with colchicine use. The different risk for patients prescribed colchicine may not be fully adjusted for. See [onlinelibrary.wiley.com].
Jan 2023, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.28496, https://c19p.org/saenzaldea
1,672. Oztas et al., Frequency and Severity of COVID-19 in Patients with Various Rheumatic Diseases Treated Regularly with Colchicine or Hydroxychloroquine
650 patient HCQ prophylaxis study: 215% higher hospitalization (p=0.36), 40% more symptomatic cases (p=0.44), and 5% more cases (p=0.88).Retrospective 317 HCQ users and 333 household contacts, showing higher risk with HCQ.
Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27731, https://c19p.org/oztas
1,673. RECOVERY Collaborative Group et al., Effect of Hydroxychloroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial
4,716 patient HCQ late treatment RCT: 9% higher mortality (p=0.15) and 15% higher ventilation (p=0.19).RECOVERY trial finds no significant benefit for very late stage (9 days after symptom onset) very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) [twitter.com, twitter.com]. The overall dosage used is only 23% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors do not report results based on weight, BMI, or related conditions such as diabetes, which may provide additional evidence of toxic dosages. Authors do not adjust dosage based on patient weight, so toxicity may be higher in patients of lower weight. KM curves show a spike in HCQ mortality days 5-8, corresponding to ~85% of the total excess seen at day 28 (a similar spike is seen in the SOLIDARITY trial). Authors note: "we did not observe excess mortality in the first 2 days of treatment ... when early effects of dose-dependent toxicity might be expected", but they are ignoring the very long half-life of HCQ and the dosing..
Jun 2020, RECOVERY Collaborative Group, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2022926, https://c19p.org/recovery
1,674. Bramante et al., Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19
653 patient fluvoxamine early treatment RCT: 11% higher combined mortality/hospitalization (p=0.88), 16% higher progression (p=0.68), and 2% lower hospitalization (p=1).COVID-OUT remotely operated RCT, showing no significant difference in outcomes. Results for other treatments are listed separately - metformin , ivermectin . The "control" group includes patients receiving metformin, which is known to be beneficial for COVID-19 [ c19early.org ] . Authors note that the dosage used in the trial is lower than that of other trials [ twitter.com (H) ] . Control arm results are very different between treatments, for example considering hospitalization/death, this was 1.0% for ivermectin vs. 2.7% for overall control, however it was 1.3% for the ivermectin-specific control. 394 control patients are shared. The rate for the non-shared 261 metformin control patients is 5%, compared to 1.3% for ivermectin control patients. The metformin arm started earlier, however it is unclear why the difference in outcomes is so large. Results were delayed for 6 months with no explanation, with followup ending Feb 14, 2022. Multiple outcomes are missing, for example time to..
Aug 2022, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2201662, https://c19p.org/covidoutf
1,675. Eikelboom et al., Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial
2,119 patient aspirin late treatment RCT: 5% higher mortality (p=0.66) and 8% lower progression (p=0.32).RCT very late stage (baseline SpO2 77%) patients, showing no significant differences with rivaroxaban and aspirin treatment.
Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002983, https://c19p.org/eikelboome
1,697,522 patient ibuprofen prophylaxis study: 12% higher hospitalization (p=0.26) and 8% more cases (p=0.25).
PSM retrospective 1,697,522 osteoarthritis or back pain patients in the US, showing no significant differences in COVID-19 cases and hospitalization for ibuprofen vs. other NSAIDs.
Jul 2022, Drugs, https://link.springer.com/article/10.1007/s40265-022-01822-z, https://c19p.org/xieib
1,677. Cereda et al., Vitamin D supplementation and outcomes in coronavirus disease 2019 (COVID-19) patients from the outbreak area of Lombardy, Italy
197 patient vitamin D prophylaxis study: 73% higher mortality (p=0.14) and 17% higher hospitalization (p=0.68).Retrospective 105 Parkinson's disease patients, 92 caregivers, and 127 hospital inpatients, showing higher, but not statistically significant mortality and hospitalization with treatment. Supplementation was defined as >=25,000IU/month for at least 3 months.
Nov 2020, Nutrition, https://www.sciencedirect.com/science/article/pii/S0899900720303385, https://c19p.org/cereda2
44,866 patient acetaminophen prophylaxis study: 21% higher mortality (p<0.0001).
Retrospective 44,866 hospitalized COVID-19 patients in Sweden, showing higher mortality with vitamin D deficiency and with acetaminophen use. The study focuses on cardiorenal disease, finding higher risk of mortality with CRD. Authors also show that COVID-19 mortality was about 1.5x higher when compared with influenza in the first two pandemic waves, but there was no significant difference in the third wave (HR 1.53 [1.45-1.62] and 1.52 [1.44-1.61] in the first two waves and 1.07 [0.99-1.14] in the third).
Apr 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-069037, https://c19p.org/ritsinger
1,679. Gao et al., Risk of Metformin in Patients With Type 2 Diabetes With COVID-19: A Preliminary Retrospective Report
110 patient metformin prophylaxis study: 225% higher progression (p=0.05).Retrospective 110 hospitalized COVID-19 patients with diabetes in China, showing increased risk of severity with metformin.
Oct 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.12897, https://c19p.org/gao4
1,680. Juneja et al., Hydroxychloroquine pre-exposure prophylaxis provides no protection against COVID-19 among health care workers: a cross-sectional study in a tertiary care hospital in North India
2,200 patient HCQ prophylaxis study: 142% higher severe cases (p=0.59) and 6% more cases (p=0.67).Retrospective 2,200 healthcare workers in India, 996 taking HCQ prophylaxis, showing no significant differences. There were large differences in the occupation of participants and therefore exposure, and the authors make no adjustments.
Jan 2022, J. Basic and Clinical Physiology and Pharmacology, https://www.degruyter.com/document/doi/10.1515/jbcpp-2021-0221/html, https://c19p.org/juneja
1,681. Sakamaki et al., Insights from a multicenter nationwide cohort analysis in Japan on the association of underlying conditions and pharmacological interventions with COVID-19 disease severity
650,317 patient aspirin prophylaxis study: 37% higher severe cases (p<0.0001).Retrospective 650,317 COVID-19 patients in Japan showing higher risk of severe COVID-19 with low-dose apirin use. Although cardiovascular disease should have been adjusted for (details of adjustments are not provided), there may be significant residual confounding because aspirin use might indicate more severe or complex cardiovascular issues not fully captured by the adjustment.
Sep 2024, Discover Public Health, https://ete-online.biomedcentral.com/articles/10.1186/s12982-024-00225-7, https://c19p.org/sakamakie
1,682. Omrani et al., Randomized double-blinded placebo-controlled trial of hydroxychloroquine with or without azithromycin for virologic cure of non-severe Covid-19
304 patient azithromycin early treatment RCT: 33% higher hospitalization (p=1), 67% lower progression (p=0.62), 100% worse recovery (p=0.5), and 4% worse viral clearance (p=0.63).Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients, that positive PCR may simply reflect detection of inactive (non-infectious) viral remnants, that an alternative dosage regimen may be more effective, and that medication adherence was unknown. HCQ dosing was 600mg/day for 1 week, therapeutic levels may not be reached for several days. There were no deaths or serious adverse events. Viral load was already very high at baseline.
Nov 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303898, https://c19p.org/omraniazaz
1,683. Elkanzi et al., Effect of Preadmission Proton Pump Inhibitor (PPI) on the clinical outcome of Covid-19 Hospitalised Patients during the Pandemic
309 patient proton pump inhibitor prophylaxis study: 17% higher mortality (p=0.49), 25% higher ICU admission (p=0.05), 126% higher progression (p=0.14), and 19% shorter hospitalization (p=0.18).Retrospective 309 hospitalized patients showing higher risk of severe cases (ASA≥3) with PPI use.
Nov 2023, Academic J. Gastroenterology & Hepatology, https://www.researchgate.net/publication/375801185_Effect_of_Preadmission_Proton_Pump_Inhibitor_PPI_on_the_clinical_outcome_of_Covid-19_Hospitalised_Patients_during_the_Pandemic_Academic_Journal_of, https://c19p.org/elkanzi
1,684. Wong et al., Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts
1,977,972 patient ibuprofen prophylaxis study: 23% higher mortality (p=0.19).Retrospective 2,463,707 people in the UK, showing no significant difference in COVID-19 mortality with NSAID use. Current NSAID users were defined as those ever prescribed an NSAID in the 4 months prior to study start, and non-users were those with no record of NSAID prescription in the same time period.
Jan 2021, Annals of the Rheumatic Diseases, https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2020-219517, https://c19p.org/wong4ib
1,685. Jamir et al., Determinants of Outcome Among Critically Ill Police Personnel With COVID-19: A Retrospective Observational Study From Andhra Pradesh, India
266 patient ivermectin ICU study: 53% higher mortality (p=0.13).Retrospective 266 COVID-19 ICU patients in India, showing significantly lower mortality with PVP-I oral gargling and topical nasal use, and non-statistically significant higher mortality with ivermectin and lower mortality with remdesivir.
Dec 2021, Cureus, https://www.cureus.com/articles/73667-determinants-of-outcome-among-critically-ill-police-personnel-with-covid-19-a-retrospective-observational-study-from-andhra-pradesh-india, https://c19p.org/jamir
1,686. AlQahtani et al., Randomized controlled trial of favipiravir, hydroxychloroquine, and standard care in patients with mild/moderate COVID-19 disease
106 patient favipiravir late treatment RCT: 76% lower ICU admission (p=0.2), 42% worse recovery (p=0.51), and 43% improved viral clearance (p=0.21).RCT with 54 favipiravir, 51 HCQ, and 52 SOC hospitalized patients in Bahrain, showing no significant differences. Viral clearance improved with both treatments, but did not reach statistical significance with the small sample size.
Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-08794-w, https://c19p.org/alqahtani2a
1,687. Bramante et al., Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19
804 patient ivermectin early treatment RCT: 61% lower hospitalization for ivermectin vs. placebo (not reported in the paper which uses a control group including metformin), despite very late treatment, low-risk patients, and poor administration. ER results do not match symptoms.COVID-OUT remote RCT, showing no significant differences compared to a combined metformin/placebo "control" group. Results for other treatments are listed separately - metformin , fluvoxamine . Authors include metformin patients in the control group, allowing details of adjustments to affect results. Using standard treatment vs. placebo analysis shows 61% lower hospitalization, or 75% lower for patients with onset ≤5 days (not statistically significant with only 7 and 5 events). These results are not reported in the paper or the supplementary appendix, readers need to request the data. Authors note that "hospitalization is perhaps the most accurate and well-documented end point". There are many major issues as detailed below. We provide more detailed analysis of this study due to widespread incorrect press. Submit Updates or Corrections Severity Issue CRITICAL 1. Ivermectin vs. placebo analysis - 61% lower hospitalization CRITICAL 2. Severity mismatch for ivermectin treatment but not..
Aug 2022, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2201662, https://c19p.org/covidoutivm
1,688. Shoaibi et al., Comparative Effectiveness of Famotidine in Hospitalized COVID-19 Patients
28,636 patient famotidine late treatment study: 3% higher mortality (p=0.67) and 3% higher combined mortality/ICU admission (p=0.62).Retrospective 1,816 famotidine users and 26,820 non-users hospitalized for COVID-19 in the USA, showing no significant differences with treatment.
Sep 2020, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000001153, https://c19p.org/shoaibif
1,689. Visos-Varela et al., Repurposing selective serotonin reuptake inhibitors for severity of COVID-19: A population-based study
86,602 patient fluvoxamine prophylaxis study: 395% higher ICU admission (p=0.24), 40% lower hospitalization (p=0.39), and 12% fewer cases (p=0.6).Retrospective 86,602 patients in Spain, showing lower COVID-19 risk SSRIs citalopram and paroxetine. There were no significant difference for fluvoxamine, which few patients were taking.
Apr 2023, European Neuropsychopharmacology, https://www.sciencedirect.com/science/article/pii/S0924977X23000639, https://c19p.org/visosvarela
1,690. Vaezi et al., Favipiravir in the Treatment of Outpatient COVID-19: A Multicenter, Randomized, Triple-Blind, Placebo-Controlled Clinical Trial
77 patient favipiravir early treatment RCT: 105% higher hospitalization (p=0.43).RCT 77 outpatients in Iran, showing increased hospitalization with treatment, without statistical significance. Favipiravir 1600mg daily for five days. 21% of favipiravir patients did not complete treatment.
Jan 2023, Advances in Respiratory Medicine, https://www.mdpi.com/2543-6031/91/1/4, https://c19p.org/vaezi
1,691. Luvira et al., Clinical antiviral efficacy of favipiravir in early COVID-19 (PLATCOV): an open-label, randomised, controlled, adaptive platform trial
248 patient favipiravir early treatment RCT: 6% worse viral clearance (p=0.42).High conflict of interest RCT with very low risk patients, high existing immunity, and a post-hoc change to exclude patients more likely to benefit. There was no significant difference in viral clearance with favipiravir among patients with high viral load at baseline. Patients in both arms had very short viral clearance half-life times. With rapid viral clearance and very low risk patients, infection is less likely to spread to other tissues. Systemic treatment is less applicable, and has less time to reach therapeutic concentrations before self-recovery. Treatment administered directly to the respiratory tract, e.g. as in [Yildiz Pekoz], may be more effective for COVID-19 in general, and extend applicability to fast-resolving cases with infection primarily localized to the respiratory tract. Authors note that "all-cause hospitalisation for clinical deterioration (until day 28) was a secondary endpoint", but do not provide the result. For more discussion of the post-hoc..
Apr 2023, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08835-3, https://c19p.org/luvira
1,692. Montini et al., Modifiable risk factors of COVID-19 in patients with multiple sclerosis: a single-centre case–control study
441 patient smoking prophylaxis study: 270% more cases (p<0.0001).Case control analysis with 149 multiple sclerosis patients and 292 matched controls in Italy, showing lower risk of COVID-19 cases with smoking.
Feb 2023, J. Neurology, https://link.springer.com/10.1007/s00415-023-11618-0, https://c19p.org/montinism
1,693. Sakamaki et al., Insights from a multicenter nationwide cohort analysis in Japan on the association of underlying conditions and pharmacological interventions with COVID-19 disease severity
650,317 patient ursodeoxycholic acid prophylaxis study: 79% higher severe cases (p<0.0001).Retrospective 650,317 COVID-19 patients in Japan showing higher risk of severe COVID-19 with UDCA use. There may be significant residual confounding because authors do not appear to have adjusted for liver diseases (details of adjustments are not provided), and UDCA use is a strong indicator of certain liver conditions.
Sep 2024, Discover Public Health, https://ete-online.biomedcentral.com/articles/10.1186/s12982-024-00225-7, https://c19p.org/sakamakiudca
1,694. Perricone et al., Treatment with COLchicine in hospitalized patients affected by COVID-19: the COLVID-19 trial
152 patient colchicine late treatment RCT: 36% higher mortality (p=0.77), 7% higher progression (p=1), 76% lower ICU admission (p=0.21), and 4% shorter hospitalization (p=0.69).RCT 152 hospitalized patients in Italy, showing no significant difference in outcomes with colchicine treatment. Table 2 shows 13% of patients treated with antivirals in the colchicine arm, however 16.9% were treated with one specific antiviral (HCQ).
Oct 2022, European J. Internal Medicine, https://www.sciencedirect.com/science/article/pii/S0953620522003739, https://c19p.org/perricone
1,695. Gao et al., The impact of individual lifestyle and status on the acquisition of COVID-19: A case—Control study
315 patient exercise study: 105% more cases (p=0.0003).Case control study in China with 105 cases and 210 matched controls, showing COVID-19 cases associated with physical activity ≥5 times per week. Authors note that people may choose gyms for exercise in winter, leading to higher exposure risk.
Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241540, https://c19p.org/gao5
1,696. Almoosa et al., Favipiravir versus Standard of Care in Patients with Severe COVID-19 Infections: A Retrospective Comparative Study
226 patient favipiravir late treatment study: 42% higher mortality (p=0.1), 90% higher ICU admission (p=0.02), and 11% slower recovery (p=0.17).Retrospective 226 COVID-19 pneumonia patients, 110 treated with favipiravir, showing higher mortality (p=0.1) and ICU admission (p=0.02) with treatment in multivariate analysis.
Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002410, https://c19p.org/almoosa
1,697. Ahmadi et al., Lifestyle risk factors and infectious disease mortality, including COVID-19, among middle aged and older adults: Evidence from a community-based cohort study in the United Kingdom
468,569 patient diet study: 3% higher mortality (p=0.85).Retrospective 468,569 adults in the UK, showing no significant difference in COVID-19 mortality based on diet quality, however significantly lower mortality was seen with higher diet quality for pneumonia and infectious diseases.
Aug 2021, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912100180X, https://c19p.org/ahmadi2dt
1,698. Sobhy et al., Early Use of Ibuprofen in Moderate Cases of COVID-19 Might be a Promising Agent to Attenuate the Severity of Disease: A Randomized Controlled Trial
180 patient acetaminophen late treatment RCT: 110% higher ICU admission (p=0.05), 110% higher need for oxygen therapy (p=0.05), and 36% longer hospitalization (p=0.01).RCT 180 moderate hospitalized COVID-19 patients in Egypt, showing higher ICU admission and longer hospitalization with acetaminophen compared with ibuprofen.
Apr 2023, The Open Anesthesia J., https://openanesthesiajournal.com/VOLUME/17/ELOCATOR/e258964582303020/, https://c19p.org/sobhyace
1,699. de la Rocha et al., Ivermectin compared with placebo in the clinical course in Mexican patients with asymptomatic and mild COVID-19: a randomized clinical trial
56 patient ivermectin early treatment RCT: 15% worse recovery (p=0.58) and 2% improved viral clearance (p=0.64).Small low-risk patient RCT with 30 low-dose ivermectin and 26 control patients, with no primary outcome events in either arm. Viral load was significantly better with ivermectin on day 5, while there was no significant difference on day 1 or day 14. There was no significant difference in combined symptoms, however authors include cough which was the most frequent symptom and may persist long after infection has been cleared. Ivermectin patients were 4 years older with a higher standard deviation, had higher prevalence of obesity, diabetes, hypertension, and cardiovascular disease, and lower prevalence of hepatic and kidney disease. SOC included acetaminophen, which has . The slow viral clearance seen may be in part due to acetaminophen use. Authors conclude that "ivermectin is not effective to prevent progression to a severe state", however there was no progression to severe in either group. Authors report 92.9% of ivermectin patients compliant with the symptom diary,..
May 2022, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-022-07890-6, https://c19p.org/delarocha
1,700. Burdick et al., Is Machine Learning a Better Way to IdentifyCOVID-19 Patients Who Might Benefit fromHydroxychloroquineTreatment?—The IDENTIFY Trial
290 patient HCQ late treatment study: 59% higher mortality (p=0.12).290 patient observational trial in the USA, not showing a significant difference with HCQ treatment overall, but showing significantly lower mortality in a subgroup of patients where HCQ is expected to be beneficial based on a machine learning algorithm.
Nov 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/12/3834, https://c19p.org/burdick
1,701. Chandel et al., Inhaled Nitric Oxide via High-Flow Nasal Cannula in Patients with Acute Respiratory Failure Related to COVID-19
272 patient nitric oxide late treatment study: 54% higher mortality (p=0.25) and 27% higher ventilation (p=0.26).Retrospective 272 acute respiratory failure patients in the USA treated with high-flow nasal cannula, 66 treated with inhaled nitric oxide, showing increased mortality with inhaled nitric oxide. There were significant differences in the usage of several other treatments between the groups.
Jan 2021, Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, http://journals.sagepub.com/doi/10.1177/11795484211047065, https://c19p.org/chandel
1,702. Klein et al., Androgen Deprivation Therapy in Men with Prostate Cancer Does Not Affect Risk of Infection with SARS-CoV-2
1,779 patient various antiandrogen prophylaxis study: 124% higher mortality (p=0.12) and 7% fewer cases (p=0.8).Retrospective 1,779 prostate cancer patients, showing no significant differences in COVID-19 outcomes with ADT.
Jan 2021, J. Urology, https://www.auajournals.org/doi/10.1097/JU.0000000000001338, https://c19p.org/klein
1,703. Pablos et al., Clinical outcomes of hospitalised patients with COVID-19 and chronic inflammatory and autoimmune rheumatic diseases: a multicentric matched cohort study
228 patient HCQ late treatment study: 126% higher severe cases (p=0.002).Retrospective 228 rheumatic disease and 228 non-rheumatic disease hospitalized COVID-19 patients in Spain, showing higher risk of severe COVID-19 with HCQ treatment.
Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2020-218296, https://c19p.org/pablos
1,704. Brunvoll et al., Prevention of covid-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial
34,601 patient vitamin D prophylaxis RCT: 11% lower hospitalization (p=1), 20% higher severe cases (p=0.17), and no change in cases (p=0.98).RCT 17,278 low-risk patients (zero mortality) treated with 5mL/day cod liver oil (~400IU vitamin D) and 17,323 placebo patients in Norway with, showing no significant differences with treatment. The placebo group had higher vitamin D at baseline, and both groups had comparable vitamin D during treatment (74 vs. 63 nmol/L). 23% of control patients took vitamin D supplements and 62% consumed fatty fish (typically a good source of vitamin D). Adherence was low (<70% for "strict" compliance, which only required >0.5L consumed, or treatment for > "2-3" months).
Sep 2022, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj-2022-071245, https://c19p.org/brunvoll
1,705. Zhang et al., Efficacy of Azvudine Therapy in Patients with Severe and Non-Severe COVID‐19: A Propensity Score-Matched Analysis
606 patient azvudine late treatment study: 32% higher mortality (p=0.2), 62% higher ventilation (p=0.22), 7% higher ICU admission (p=0.89), and 9% shorter hospitalization (p=0.05).PSM retrospective 303 hospitalized patients treated with azvudine and 303 matched controls in China, showing shorter hospital stay and higher lymphocyte improvement rate, particularly for non-severe patients, however there were no significant differences for mortality, ICU admission, or mechanical ventilation.
Oct 2024, Infection and Drug Resistance, https://www.dovepress.com/efficacy-of-azvudine-therapy-in-patients-with-severe-and-non-severe-co-peer-reviewed-fulltext-article-IDR, https://c19p.org/zhang35
1,706. Oztas et al., Frequency and Severity of COVID-19 in Patients with Various Rheumatic Diseases Treated Regularly with Colchicine or Hydroxychloroquine
1,278 patient colchicine prophylaxis study: 406% higher hospitalization (p=0.12), 73% more symptomatic cases (p=0.07), and 24% more cases (p=0.35).Retrospective 635 HCQ users and 643 household contacts, showing higher risk with colchicine in unadjusted results. Patients with conditions leading to the use of colchicine may have significantly different baseline risk, e.g. [Topless].
Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27731, https://c19p.org/oztaso
1,707. Babayigit et al., The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort
1,302 patient favipiravir late treatment study: 184% higher ventilation (p=0.01), 181% higher ICU admission (p=0.001), and 100% longer hospitalization (p=0.001).Retrospective 1,472 hospitalized patients in Turkey, showing a higher ICU admission and ventilation with favipiravir. Results may be subject to confounding by indication.
Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full, https://c19p.org/babayigit
1,708. Mariani et al., High-dose vitamin D versus placebo to prevent complications in COVID-19 patients: Multicentre randomized controlled clinical trial
218 patient vitamin D late treatment RCT: 25% lower ventilation (p=0.85), 27% lower ICU admission (p=0.62), and 3% lower progression (p=0.82).Late stage RCT with 115 patients treated with a single dose of 500,000IU cholecalciferol and 103 placebo patients, showing no significant differences. Authors do not explain why they did very late treatment with cholecalciferol instead of calcifediol or calcitriol, which would avoid several days delay in conversion. Baseline vitamin D levels were relatively high, limiting the potential benefit.
May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267918https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0267918&type=printable, https://c19p.org/mariani
1,709. Eikelboom et al., Colchicine and the combination of rivaroxaban and aspirin in patients hospitalised with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial
2,611 patient colchicine late treatment RCT: 8% higher mortality (p=0.38) and 4% higher progression (p=0.58).RCT very late stage (baseline SpO2 80%) patients, showing no significant differences with colchicine treatment.
Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002983, https://c19p.org/eikelboom
1,710. Liwang et al., High vs Low Dose Proton Pump Inhibitor (PPI) related Mortality in Hospitalized Coronavirus Disease-19 (COVID-19): A Retrospective Cohort Study
365 patient proton pump inhibitor late treatment study: 204% higher mortality (p=0.02).Retrospective hospitalized COVID-19 patients in Indonesia showing higher mortality with high dose proton pump inhibitor (PPI) use compared to low dose.
Aug 2022, J. Of The Indonesian Medical Association, https://mki-ojs.idionline.org/jurnal/article/view/802, https://c19p.org/liwang
1,711. Liu et al., Increased ACE2 Levels and Mortality Risk of Patients With COVID-19 on Proton Pump Inhibitor Therapy
686 patient proton pump inhibitor prophylaxis study: 127% higher mortality (p=0.001).Prospective study showing COVID- PPI users had higher salivary ACE2 expression, and retrospective analysis of 694 hospitalized COVID-19 patients, showing higher mortality with PPI use.
May 2021, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000001311, https://c19p.org/liu22
1,712. Shahrin et al., Hospital-Based Quasi-Experimental Study on Hydroxychloroquine Pre-Exposure Prophylaxis for COVID-19 in Healthcare Providers with Its Potential Side-Effects
336 patient HCQ prophylaxis study: 88% more cases (p=0.09).Retrospective 230 low risk healthcare workers taking HCQ prophylaxis, and 106 that declined, showing higher cases without statistical significance. No case severity information is provided. The point estimate favored HCQ when excluding the first 14 days and including participants that worked for at least 16 days. Authors note a significant dose response relationship.
Dec 2022, Life, https://www.mdpi.com/2075-1729/12/12/2047, https://c19p.org/shahrin
1,713. Gerlovin et al., Pharmacoepidemiology, Machine Learning and COVID-19: An intent-to-treat analysis of hydroxychloroquine, with or without azithromycin, and COVID-19 outcomes amongst hospitalized US Veterans
1,199 patient HCQ late treatment study: 22% higher mortality (p=0.18) and 55% higher ventilation (p=0.02).Retrospective 1,769 hospitalized patients in the USA showing no significant differences for HCQ, and higher intubation for HCQ+AZ.
Jun 2021, American J. Epidemiology, https://academic.oup.com/aje/advance-article/doi/10.1093/aje/kwab183/6308675, https://c19p.org/gerlovin
1,714. Bianconi et al., Treatment with proton pump inhibitors is associated with secondary bacterial infections and sepsis in patients with COVID-19: a retrospective analysis of their joint impact on in-hospital prognosis
1,087 patient proton pump inhibitor prophylaxis study: 37% higher combined mortality/ICU admission (p=0.09) and 96% worse results (p=0.0001).Retrospective 1,087 hospitalized COVID-19 patients showing significantly increased risk of secondary bacterial infections (SBIs) and secondary bacterial sepsis (SBS) sepsis with pre-admission proton pump inhibitor (PPI) use. Combined ICU admission/mortality was higher but without statistical significance.
Oct 2024, Annals of Medicine, https://www.tandfonline.com/doi/full/10.1080/07853890.2024.2399761, https://c19p.org/bianconi2
1,715. Madamombe et al., Factors associated with COVID-19 fatality among patients admitted in Mashonaland West Province, Zimbabwe 2020-2022: a secondary data analysis
672 patient dexamethasone early treatment study: 130% higher mortality (p<0.0001).Retrospective 672 COVID-19 patients in Zimbabwe, showing higher mortality with dexamethasone treatment.
Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombedxdex
98 patient vitamin C early treatment RCT: 18% faster recovery (p=0.15).
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. A secondary analysis concludes that vitamin C increases recovery rate by 71% (p = 0.036) [pubpeer.com]. See also [patrickholford.com].
Feb 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305, https://c19p.org/thomasc
1,717. Mockeliunas et al., Risk Factors for COVID-19 and Respiratory Tract Infections during the Coronavirus Pandemic
1,000 patient smoking early treatment study: 134% more cases (p<0.0001).Retrospective 1,000 frontline healthcare workers in South Africa showing higher risk of COVID-19 for non-smokers.
Mar 2024, Vaccines, https://www.mdpi.com/2076-393X/12/3/329, https://c19p.org/mockeliunas
1,718. Ferreira et al., Outcomes associated with Hydroxychloroquine and Ivermectin in hospitalized patients with COVID-19: a single-center experience
192 patient HCQ late treatment study: 151% higher mortality (p=0.03) and 46% higher combined mortality/intubation (p=0.23).Retrospective 230 hospitalized patients in Brazil showing higher mortality with HCQ treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors note that they do not know if treatment was started before or after ICU admission and intubation. Dosage is unknown.
Nov 2021, Revista da Associação Médica Brasileira, https://www.scielo.br/j/ramb/a/kzbmDvJqjJdQR9GfqK65CZs/, https://c19p.org/ferreira2h
1,719. Al-Momani et al., Proton pump inhibitors and gastrointestinal symptoms among patients with COVID-19 infection
253 patient proton pump inhibitor prophylaxis study: 100% higher mortality (p=0.39), 48% higher ventilation (p=0.54), and 25% higher ICU admission (p=0.64).Retrospective 254 hospitalized COVID-19 patients in Jordan showing higher rates of gastrointestinal symptoms such as abdominal pain and diarrhea with proton pump inhibitor (PPI) use. There were no significant differences for mortality, ventilation, and ICU admission. Authors hypothesize that PPIs may facilitate SARS-CoV-2 survival and invasion in the gastrointestinal tract.
Jun 2024, Annals of Medicine, https://www.tandfonline.com/doi/full/10.1080/07853890.2024.2355581, https://c19p.org/almomani
1,720. Iwata et al., Findings from a discontinued clinical trial of favipiravir in high-risk patients with early-onset COVID-19
86 patient favipiravir early treatment RCT: 16% higher need for oxygen therapy (p=0.73) and 16% worse viral clearance (p=0.66).Early terminated RCT 84 patients in Japan, showing no significant difference in outcomes with favipiravir treatment. There was a trend for improved efficacy for patients enrolled within 48 hours of symptom onset.
Oct 2023, J. Infection and Chemotherapy, https://www.sciencedirect.com/science/article/pii/S1341321X23002556, https://c19p.org/iwata
1,721. Ramachandran et al., Pre-hospitalization proton pump inhibitor use and clinical outcomes in COVID-19
295 patient proton pump inhibitor prophylaxis study: 92% higher mortality (p=0.02) and 80% higher progression (p=0.02).Retrospective 295 hospitalized COVID-19 patients showing higher mortality and acute respiratory distress syndrome (ARDS) with pre-hospitalization proton pump inhibitor (PPI) use. Authors hypothesize that hypochlorhydria caused by PPIs may allow SARS-CoV-2 to more easily infect the gastrointestinal tract.
Nov 2021, European J. Gastroenterology & Hepatology, https://journals.lww.com/10.1097/MEG.0000000000002013, https://c19p.org/ramachandran
1,722. Pecina et al., Vitamin D Status and Severe COVID-19 Disease Outcomes in Hospitalized Patients
92 patient vitamin D prophylaxis study: 70% higher mortality (p=0.52), 10% higher ventilation (p=0.89), and 30% higher ICU admission (p=0.61).Retrospective 92 hospitalized patients not showing significant differences in outcomes based on vitamin D status or supplementation.
Aug 2021, J. Primary Care & Community Health , https://journals.sagepub.com/doi/full/10.1177/21501327211041206, https://c19p.org/pecina
1,723. Krolewiecki et al., Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial
41 patient ivermectin early treatment RCT: 66% improved viral load (p=0.09).Proof of concept RCT with 30 ivermectin patients and 15 control patients, showing a concentration dependent antiviral activity, but no significant difference in clinical outcomes. There was no significant difference in viral load reduction between groups overall, but a significant difference was found in patients with higher median plasma ivermectin levels (72% vs. 42%, p=0.004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r=0.47, p=0.02). The change in viral load is provided for the <160ng/mL and >160ng/mL groups, but not the overall treatment group. The corrigendum provides individual viral decay rates for computing the overall treatment group viral decay rate. Authors published a corrigendum: [sciencedirect.com].
Jun 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S258953702100239X, https://c19p.org/krolewiecki
1,724. Babalola et al., A Randomized Controlled Trial of Ivermectin Monotherapy Versus Hydroxychloroquine, Ivermectin, and Azithromycin Combination Therapy in Covid-19 Patients in Nigeria
60 patient HCQ late treatment RCT: 55% lower hospital discharge (p=0.2) and 10% improved viral clearance (p=0.78).Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ.
Sep 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-233.php?jid=jide, https://c19p.org/babalola2h
1,725. Alshamrani et al., Comprehensive evaluation of six interventions for hospitalized patients with COVID-19: A propensity score matching study
2,539 patient favipiravir late treatment PSM study: 14% higher mortality (p=0.13), 2% higher progression (p=0.83), 19% longer ICU admission (p=0.005), and 29% longer hospitalization (p=0.001).PSM retrospective 29 hospitals in Saudi Arabia, showing higher mortality with favipiravir treatment, without statistical significance.
Feb 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000348, https://c19p.org/alshamrania
1,726. Sullerot et al., Premorbid aspirin use is not associated with lower mortality in older inpatients with SARS-CoV-2 pneumonia
1,047 patient aspirin prophylaxis study: 10% higher mortality (p=0.52), 110% higher ICU admission (p=0.007), and 10% longer hospitalization (p=0.02).Retrospective 1,047 pneumonia patients in 5 COVID-19 geriatric units in France and Switzerland, significantly higher ICU admission and longer hospital stays with existing aspirin treatment. Numbers in this study appear to be inconsistent, for example the abstract says 147 of 301 aspirin patients died, shown as 34.3%, while Table 1 shows 104 of 301 (34.6%).
Jan 2022, GeroScience, https://link.springer.com/article/10.1007%2Fs11357-021-00499-8, https://c19p.org/sullerot
1,727. Formiga et al., Does admission acetylsalicylic acid uptake in hospitalized COVID-19 patients have a protective role? Data from the Spanish SEMI-COVID-19 Registry
20,641 patient aspirin prophylaxis PSM study: 3% higher mortality (p=0.48), 3% higher ventilation (p=0.75), and 4% higher ICU admission (p=0.65).Retrospective 20,641 hospitalized patients in Spain, showing no significant difference in outcomes with existing aspirin use.
Nov 2021, Internal and Emergency Medicine, https://link.springer.com/10.1007/s11739-021-02870-1, https://c19p.org/formiga2
1,728. García-Menaya et al., Outcomes and Laboratory and Clinical Findings of Asthma and Allergic Patients Admitted With Covid-19 in a Spanish University Hospital
113 patient proton pump inhibitor prophylaxis study: 228% higher mortality (p=0.008) and 392% higher ICU admission (p=0.02).Retrospective 113 hospitalized COVID-19 patients in Spain showing higher mortality and ICU admission with PPI use.
Sep 2020, Frontiers in Pharmacology, https://www.frontiersin.org/article/10.3389/fphar.2020.570721/full, https://c19p.org/garciamenaya
1,729. Gramont et al., Proton pump inhibitors and risk of severe COVID-19 in older people
834 patient proton pump inhibitor prophylaxis study: 59% higher severe cases (p=0.002).Retrospective 834 elderly patients in France showing higher risk of severe COVID-19 with PPI use, and increasing risk with increasing dosage.
Apr 2024, Age and Ageing, https://academic.oup.com/ageing/article/doi/10.1093/ageing/afae082/7645558, https://c19p.org/gramont
1,730. Ravichandran et al., An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients
210 patient acetaminophen late treatment RCT: 43% worse recovery (p=0.002), 3925% higher progression (p<0.0001), and 20% worse viral clearance (p=0.19).RCT with 107 paracetamol and 103 indomethacin patients, showing higher progression and worse recovery with paracetamol.
Apr 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-10370-1, https://c19p.org/ravichandranace
1,731. Sagent Pharmaceuticals et al., A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of the Efficacy of Camostat Mesilate for Treatment of COVID-19 in Outpatients
295 patient camostat early treatment RCT: 152% higher mortality (p=1), 13% lower progression (p=0.79), and 16% improved viral clearance (p=0.36).RCT 295 outpatients in the USA, showing no significant differences with camostat.
Mar 2021, Sagent Pharmaceuticals, NCT04583592, https://clinicaltrials.gov/study/NCT04583592, https://c19p.org/sagent
1,732. Puskarich et al., Efficacy of Losartan in Hospitalized Patients With COVID-19–Induced Lung Injury
205 patient losartan late treatment RCT: 3% higher mortality (p=1), 27% higher ventilation (p=0.47), and 3% lower need for oxygen therapy (p=0.66).RCT 205 hospitalized COVID-19 patients showing no significant difference in lung injury (PaO2:FiO2 ratio) at day 7 with losartan treatment, and no difference in clinical outcomes including mortality. Losartan was associated with more adverse events including acute kidney injury and need for vasopressors. Results suggest losartan is not beneficial and may cause harm in this setting.
Mar 2022, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790162, https://c19p.org/puskarich2
1,734. Tirupakuzhi Vijayaraghavan et al., Hydroxychloroquine plus personal protective equipment versus personal protective equipment alone for the prevention of laboratory-confirmed COVID-19 infections among healthcare workers: a multicentre, parallel-group randomised controlled trial from India
414 patient HCQ prophylaxis RCT: 196% higher progression (p=1), 52% lower hospitalization (p=0.62), and 14% fewer cases (p=0.73).Low-dose prophylaxis RCT with low-risk healthcare workers in India, showing no significant differences. Symptomatic case results are not provided. Followup was over 6 months, however treatment ended after 3 months. 21% of patients discontinued treatment before 3 months (Table S2).
May 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2021-059540, https://c19p.org/tirupakuzhi
1,735. Zhou et al., Proton pump inhibitor or famotidine use and severe COVID-19 disease: a propensity score-matched territory-wide study
3,114 patient famotidine late treatment PSM study: 84% higher severe cases (p=0.0001).Retrospective 4,445 COVID+ patients in China, showing higher risk of combined death/intubation/ICU with famotidine and with PPIs.
Dec 2020, Gut, https://gut.bmj.com/content/70/10/2012.full, https://c19p.org/zhou3
1,736. Zhou et al., Proton pump inhibitor or famotidine use and severe COVID-19 disease: a propensity score-matched territory-wide study
3,144 patient proton pump inhibitor late treatment PSM study: 165% higher severe cases (p=0.0001).Retrospective 4,445 COVID+ patients in China, showing higher risk of combined death/intubation/ICU with famotidine and with PPIs.
Dec 2020, Gut, https://gut.bmj.com/content/70/10/2012.full, https://c19p.org/zhou3ppi
1,737. Strickland et al., Safety and practicality of high dose inhaled nitric oxide in emergency department COVID-19 patients
34 patient nitric oxide late treatment RCT: 179% higher ventilation (p=1), 21% lower hospitalization (p=1), and 38% worse results (p=0.72).Early terminated RCT with 47 ER patients in the USA, less than 12 days of symptoms, showing no significant difference in outcomes with a single high-dose administration of inhaled nitric oxide by mask, 250ppm for 30 min.
May 2022, The American J. Emergency Medicine, https://www.sciencedirect.com/science/article/pii/S0735675722002832, https://c19p.org/strickland
1,738. Yen et al., Predictors for cause-specific and timing of deaths in patients with COVID-19: a cohort study in Taiwan
2,196 patient dexamethasone early treatment study: 103% higher mortality (p=0.0002).Retrospective 2,196 COVID-19 patients in Taiwan (49% mild cases, 44% moderate, 7% severe) showing significantly higher mortality with dexamethasone. Authors report that all infected patients were hospitalized at the time of the study in Taiwan.
Aug 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09654-w, https://c19p.org/yen2dexdex
1,739. Chandiwana et al., Safety and efficacy of four drug regimens versus standard-of-care for the treatment of symptomatic outpatients with COVID-19: A randomised, open-label, multi-arm, phase 2 clinical trial
76 patient favipiravir early treatment RCT: 13% higher progression (p=0.89), 23% slower recovery (p=0.42), and 67% worse viral clearance (p=0.13).Very high COI low-risk patient RCT in South Africa, showing no significant differences with favipiravir plus nitazoxanide. There were no deaths and no COVID-19 hospitalizations for favipiravir plus nitazoxanide. More patients were seropositive at baseline in the treatment arm (28% vs 22%). Favipiravir 1600mg 12-hourly for 1 day, then 600mg 12-hourly for 6 days. Nitazoxanide 1000mg 12-hourly for 7 days.
Oct 2022, eBioMedicine, https://www.sciencedirect.com/science/article/pii/S2352396422005047, https://c19p.org/chandiwana
1,740. Chandiwana et al., Safety and efficacy of four drug regimens versus standard-of-care for the treatment of symptomatic outpatients with COVID-19: A randomised, open-label, multi-arm, phase 2 clinical trial
76 patient nitazoxanide early treatment RCT: 13% higher progression (p=0.89), 23% slower recovery (p=0.42), and 67% worse viral clearance (p=0.13).Very high COI low-risk patient RCT in South Africa, showing no significant differences with favipiravir plus nitazoxanide. There were no deaths and no COVID-19 hospitalizations for favipiravir plus nitazoxanide. More patients were seropositive at baseline in the treatment arm (28% vs 22%). Favipiravir 1600mg 12-hourly for 1 day, then 600mg 12-hourly for 6 days. Nitazoxanide 1000mg 12-hourly for 7 days.
Oct 2022, eBioMedicine, https://www.sciencedirect.com/science/article/pii/S2352396422005047, https://c19p.org/chandiwanan
1,741. Schmidt et al., Association Between Androgen Deprivation Therapy and Mortality Among Patients With Prostate Cancer and COVID-19
477 patient HCQ late treatment PSM study: 333% higher mortality (p=0.0001) and 613% higher severe cases (p<0.0001).Retrospective 1,106 prostate cancer patients, showing higher mortality with HCQ treatment.
Nov 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786026, https://c19p.org/schmidth
1,742. Cheng et al., Metformin Is Associated with Higher Incidence of Acidosis, but Not Mortality, in Individuals with COVID-19 and Pre-existing Type 2 Diabetes
1,213 patient metformin prophylaxis PSM study: 65% higher mortality (p=0.25).Retrospective 1,213 hospitalized diabetic COVID-19 patients in China, showing no significant difference in mortality with pre-existing metformin use.
Aug 2021, Cell Metabolism, https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30426-5, https://c19p.org/cheng2
1,743. Ulrich et al., Treating Covid-19 With Hydroxychloroquine (TEACH): A Multicenter, Double-Blind, Randomized Controlled Trial in Hospitalized Patients
128 patient HCQ late treatment RCT: 6% higher mortality (p=1) and 173% higher ICU admission (p=0.13).Small RCT on very late stage use of HCQ, with 48% on oxygen at baseline. 67 HCQ patients, 61 control. Baseline states were not comparable - 82% more HCQ patients had the highest severity at baseline, there was 32% more male HCQ patients, and 44% more control patients used AZ. The HCQ group also had significantly more patients with cerebrovascular disease, cardiovascular disease (non-hypertension), renal disease (non-dialysis), and a history of organ transplants.
Sep 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa446/5910201, https://c19p.org/ulrich
1,744. Yao et al., Impact of proton pump inhibitors on the in-hospital outcome of COVID-19 patients: a retrospective study
3,024 patient proton pump inhibitor late treatment study: 600% higher severe cases (p<0.0001).Retrospective 3,024 hospitalized COVID-19 patients in China showing increased risk of the composite outcome of ICU admission, mechanical ventilation, or death with proton pump inhibitor (PPI) use. Intravenous administration was significantly worse than oral. Authors hypothesize that PPIs may lead to worse COVID-19 outcomes by increasing the risk of secondary infections, cardiac damage, renal damage, and liver complications.
Jan 2022, Therapeutic Advances in Gastroenterology, http://journals.sagepub.com/doi/10.1177/17562848221104365, https://c19p.org/yao3
1,745. de Alencar et al., Double-blind, Randomized, Placebo-controlled Trial With N-acetylcysteine for Treatment of Severe Acute Respiratory Syndrome Caused by Coronavirus Disease 2019 (COVID-19)
135 patient N-acetylcysteine late treatment RCT: 3% higher mortality (p=0.94), 16% higher ventilation (p=0.64), 9% lower ICU admission (p=0.65), and 10% longer hospitalization (p=0.87).RCT 135 severe stage patients in Brazil, showing no significant differences. NAC 21g (~300mg/kg) for 20 hours. U1111-1250-356 [ensaiosclinicos.gov.br].
Sep 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/72/11/e736/5910353, https://c19p.org/dealencar
1,746. Zeng et al., Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study
160,923 patient proton pump inhibitor prophylaxis study: 46% higher mortality (p=0.02), 33% higher severe cases (p=0.004), and 8% more cases (p=0.1).UK Biobank retrospective with 160,923 patients showing increased risks of influenza, pneumonia, COVID-19 severity, and COVID-19 mortality with proton pump inhibitor (PPI) use.
Jul 2024, eLife, https://elifesciences.org/articles/94973, https://c19p.org/zeng2
1,747. Lou et al., Clinical Outcomes and Plasma Concentrations of Baloxavir Marboxil and Favipiravir in COVID-19 Patients: An Exploratory Randomized, Controlled Trial
19 patient favipiravir late treatment RCT: 422% higher ICU admission (p=0.21), 11% improved recovery (p=1), and 422% worse viral clearance (p=0.21).Small late stage RCT with 10 favipiravir, 10 baloxavir marboxil, and 10 control patients in China, showing no significant differences.
Oct 2020, European J. Pharmaceutical Sciences, https://www.sciencedirect.com/science/article/pii/S092809872030419X, https://c19p.org/lou
1,748. Reis et al., Effect of spirulina on risk of hospitalization among patients with COVID-19: the TOGETHER randomized trial
1,126 patient spirulina early treatment RCT: 21% higher progression (p=0.29).RCT 1,126 patients in Brazil showing no significant differences with low dose spirulina. The dose used was 7.6 times lower than the dose used by [Aghasadeghi] which shows significantly lower mortality. eFigure 1 shows 12 events in the treatment group before the first event in the placebo group. The probability of this happening is very low, ~ 0.001. One possible cause would be if some process resulted in patients expected to visit the ER soon being more likely to be placed in the treatment group. (Another possibility is treatment side effects causing ER visits, however the were fewer adverse events and fewer severe adverse events in the treatment group).
Aug 2024, The American J. Clinical Nutrition, https://www.sciencedirect.com/science/article/pii/S0002916524005884, https://c19p.org/reis13spi
1,749. Winchester et al., Astodrimer Sodium Nasal Spray versus Placebo in Non-Hospitalised Patients with COVID-19: A Randomised, Double-Blinded, Placebo-Controlled Trial
197 patient astodrimer sodium early treatment RCT: 19% improved recovery (p=0.41) and 24% improved viral clearance (p=0.3).RCT 222 non-hospitalized low risk COVID-19 patients showing lower SARS-CoV-2 viral load, faster viral clearance, and improvements in symptoms, particularly anosmia, with astodrimer sodium nasal spray compared to placebo. The reduction in viral load and benefits were statistically significant in patients aged 45 years and older, with greater effects in older age groups. There was only one hospitalization event. Treatment delay is not specified and may be relatively late - authors suggest that patients were "already at or past the time of peak viral load, and the infection was already in its decline phase".
Sep 2024, Pharmaceutics, https://www.mdpi.com/1999-4923/16/9/1173, https://c19p.org/winchester2
1,750. Calderón et al., Treatment with hydroxychloroquine vs nitazoxanide in patients with COVID-19: brief report
44 patient HCQ late treatment study: 215% higher mortality (p=0.38), 652% higher ventilation (p=0.15), 145% higher ICU admission (p<0.0001), and 107% longer hospitalization (p=0.007).Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.
Nov 2021, PAMJ - Clinical Medicine, https://www.clinical-medicine.panafrican-med-journal.com/content/article/7/15/full/, https://c19p.org/calderon2h
1,751. Correa-Rodríguez et al., Clinical course of Covid-19 in a cohort of patients with Behçet disease
244 patient colchicine prophylaxis study: 150% higher need for oxygen therapy (p=1), 150% higher hospitalization (p=1), 7% improved recovery (p=1), and 1% fewer cases (p=1).Retrospective 244 Behçet disease patients in Spain, showing no significant difference in outcomes with colchicine treatment. Confounding by indication may significantly affect results - colchicine may be prescribed more often for more serious cases, which may have a higher baseline risk for COVID-19.
Sep 2022, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S238702062200417X, https://c19p.org/correarodriguez
1,752. Merianos et al., Concurrent use of e-cigarettes and cannabis and associated COVID-19 symptoms, testing, and diagnosis among student e-cigarette users at four U.S. Universities
800 patient cannabidiol prophylaxis study: 212% more symptomatic cases (p<0.0001) and 3% more cases (p=0.33).Retrospective 800 e-cigarette users in the USA, showing higher risk of COVID-19 diagnosis and symptoms with cannabis use.
Mar 2022, Addictive Behaviors, https://www.sciencedirect.com/science/article/pii/S0306460321003555, https://c19p.org/merianos
1,753. Stolow et al., A Retrospective Review: Famotidine Use Is Not Associated With Improved Outcomes in Hospitalized Patients With COVID-19
489 patient famotidine late treatment study: 519% higher mortality (p=0.001) and 2390% higher ICU admission (p=0.001).Retrospective 489 COVID+ hospitalized patients in the USA, showing higher mortality with famotidine treatment.
Oct 2021, American J. Gastroenterology, https://journals.lww.com/ajg/Fulltext/2021/10001/S1301_A_Retrospective_Review__Famotidine_Use_Is.1305.aspx, https://c19p.org/stolow
1,754. Spivak et al., A Randomized Clinical Trial Testing Hydroxychloroquine for Reduction of SARS-CoV-2 Viral Shedding and Hospitalization in Early Outpatient COVID-19 Infection
367 patient HCQ late treatment RCT: 73% higher hospitalization (p=0.54), 20% improved recovery (p=0.19), and 17% improved viral clearance (p=0.19).Delayed publication of an early terminated late treatment RCT with low-risk (no mortality) outpatients in the USA, showing no significant differences with HCQ. Authors do not provide symptom onset data, but the subgroup analysis suggests that more patients may have been in the 5+ days group (the estimate for the 5+ days group has a smaller confidence interval, and the overall mean/median for HCQ is much closer to the 5+ days group). Treatment was started one day after enrollment according to Table S1 (authors report "commonly 1 day after randomization" in the text). This suggests that most patients were treated 6+ days after onset. Subgroup analysis for <5, ≥5 days is provided only for viral shedding duration, and shows improved results for earlier treatment. Adherence was only 66% (Figure 1). Publication was 21 months after the trial ended. Registered outcomes were modified November 2022, December 2022, and January 2023, all over a year after completion of the trial. For..
Mar 2023, Microbiology Spectrum, https://journals.asm.org/doi/10.1128/spectrum.04674-22, https://c19p.org/spivak
1,755. Shah et al., Colchicine and high-intensity rosuvastatin in the treatment of non-critically ill patients hospitalised with COVID-19: a randomised clinical trial
250 patient colchicine late treatment RCT: 75% higher mortality (p=0.54), 200% higher ventilation (p=0.28), and 46% higher severe cases (p=0.34).RCT 250 late stage (80% on oxygen) hospitalized patients in the USA, showing no significant differences with combined colchicine/rosuvastatin treatment. There was a trend towards increased risk, which authors note may be due to chance because the patients enrolled in the treatment arm were in more serious condition, for example, patients in the treatment arm were more frequently on oxygen, more frequently on HFNC/NIV, and had higher mean SOFA scores. Colchicine 0.6mg two times daily for 3 days followed by 0.6mg daily, and high-intensity rosuvastatin 40mg daily.
Feb 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-067910, https://c19p.org/shah6
1,756. Akbar et al., The Association between Lifestyle Factors and COVID-19: Findings from Qatar Biobank
10,000 patient smoking prophylaxis study: 82% more cases (p<0.0001).Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with smoking. Authors do not analyze COVID-19 severity.
Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2sm
1,757. Shenoy et al., Favipiravir In Adults with Moderate to Severe COVID-19: A Phase 3 Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial
353 patient favipiravir late treatment RCT: 29% higher mortality (p=0.54), 33% higher ventilation (p=0.54), 2% higher ICU admission (p=0.54), and 1% slower recovery (p=0.94).Late stage RCT with 353 hospitalized patients, showing no significant differences with favipiravir treatment overall, however a trend towards benefit was seen within patients treated relatively early, including a statistically significant shorter time to discharge with treatment.
Nov 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.11.08.21265884v1, https://c19p.org/shenoy
1,758. Syed et al., Pre-exposure Prophylaxis With Various Doses of Hydroxychloroquine Among Healthcare Personnel With High-Risk Exposure to COVID-19: A Randomized Controlled Trial
101 patient HCQ prophylaxis RCT: 60% more symptomatic cases (p=0.41) and 92% more cases (p=0.12).Small PrEP RCT of low risk healthcare workers, showing no significant differences. Authors report that there was no hospitalization, ICU care, or death from COVID-19, however table 3 of the preprint shows severe events labeled as "requiring hospitalization". Symptomatology and disease severity results in tables 3 and 4 appear inconsistent. NCT04359537.
May 2021, Cureus, https://www.cureus.com/articles/77806-pre-exposure-prophylaxis-with-various-doses-of-hydroxychloroquine-among-healthcare-personnel-with-high-risk-exposure-to-covid-19-a-randomized-controlled-trial, https://c19p.org/syed
1,759. Luxenburger et al., Treatment with proton pump inhibitors increases the risk of secondary infections and ARDS in hospitalized patients with COVID‐19: coincidence or underestimated risk factor?
152 patient proton pump inhibitor prophylaxis study: 248% higher mortality (p=0.02), 124% higher ARDS (p=0.02), and 86% worse results (p=0.03).Retrospective 152 hospitalized COVID-19 patients showing increased risk of secondary infections, ARDS, and mortality with proton pump inhibitor (PPI) use. Authors hypothesize that reduced gastric acid production from PPIs leads to bacterial overgrowth and microaspiration, increasing the risk of secondary lung infections. PPIs may also have immunomodulatory effects.
Jul 2020, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13121, https://c19p.org/luxenburger
1,760. Lee et al., Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching
27,746 patient proton pump inhibitor prophylaxis PSM study: 79% higher severe cases (p=0.009) and 10% fewer cases (p=0.11).PSM retrospective 132,316 patients in South Korea, showing significantly higher risk of severe COVID-19 with PPI use, but no significant difference in cases.
Jul 2020, Gut, https://gut.bmj.com/lookup/doi/10.1136/gutjnl-2020-322248, https://c19p.org/lee15
1,761. Siripongboonsitti et al., Efficacy of Combination Therapy of Fluvoxamine and Favipiravir versus Favipiravir Monotherapy to Prevent Severe COVID-19 among Mild to Moderate COVID-19 Patients: Open-label Randomized Controlled Trial (EFFaCo Study)
327 patient fluvoxamine early treatment RCT: 2% higher need for oxygen therapy (p=1) and 22% higher hospitalization (p=0.77).RCT 327 outpatients in Thailand, showing no significant difference with 50mg fluvoxamine bid added to favipiravir. Authors note that trials showing benefit mostly used 100mg bid.
Jun 2023, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(23)00641-0/fulltext, https://c19p.org/siripongboonsitti2
1,762. Kwon et al., Effectiveness of famotidine on the risk of poor prognosis in patients with COVID-19: A nationwide cohort study in Korea
6,556 patient famotidine prophylaxis study: 107% higher progression (p=0.06) and 109% higher need for oxygen therapy (p=0.07).PSM retrospective 6,556 COVID-19 patients in South Korea, showing higher risk of poor outcomes with famotidine vs. other H2-blocker use.
May 2023, Heliyon, https://www.sciencedirect.com/science/article/pii/S2405844023033789, https://c19p.org/kwon2
1,763. Pavlidou et al., Association of COVID-19 Infection with Sociodemographic, Anthropometric and Lifestyle Factors: A Cross-Sectional Study in an Older Adults’ Population Aged over 65 Years Old
5,197 patient smoking prophylaxis study: 72% more cases (p=0.02).Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity, depression, anxiety, stress, and poor health-related quality of life.
Nov 2023, Diseases, https://www.mdpi.com/2079-9721/11/4/165, https://c19p.org/pavlidousm
1,764. Self et al., Effect of Hydroxychloroquine on Clinical Status at 14 Days in Hospitalized Patients With COVID-19: A Randomized Clinical Trial
477 patient HCQ late treatment RCT: 6% higher mortality (p=0.85) and 3% worse 7-point scale results (p=0.87).Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients showing no significant difference in outcomes. For the subgroup not on supplemental oxygen at baseline (relatively early treatment), the odds ratio for the 7 point outcome scale is: aOR 0.61 [0.34-1.08]. Dosage may be too low: Dose in first 24 hours - 1g (compare to Boulware et al. 2g) Dose in 5 days - 2.4g (compare to Boulware et al. 3.8g) Dosage note: Boulware 2g within 24 hours includes the second day dose. Note two important differences with the RECOVERY/SOLIDARITY dosage which is believed to be dangerously high - in RECOVERY/SOLIDARITY the total dose is much higher, which is problematic because the half-life of HCQ is very long, and it is given to patients that are already in very serious condition. Note the paper reports primary outcome values with OR>1 favoring HCQ, we have converted to OR<1 favoring HCQ. Subgroup analysis is in the supplemental appendix.
Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2772922, https://c19p.org/self
1,765. Kim et al., Aspirin Is Related to Worse Clinical Outcomes of COVID-19
272 patient aspirin prophylaxis PSM study: 700% higher mortality (p=0.03), 433% higher ventilation (p=0.14), 433% higher ICU admission (p=0.14), and 33% fewer cases (p=0.29).Retrospective database analysis of 22,660 patients tested for COVID-19 in South Korea. There was no significant difference in cases according to aspirin use. Aspirin use before COVID-19 was related to an increased death rate and aspirin use after COVID-19 was related to a higher risk of oxygen therapy. Results for late treatment are listed separately [Kim].
Sep 2021, Medicina, https://www.mdpi.com/1648-9144/57/9/931, https://c19p.org/kim2
1,766. Wu et al., Use of proton pump inhibitors are associated with higher mortality in hospitalized patients with COVID-19
4,634 patient proton pump inhibitor prophylaxis study: 197% higher mortality (p=0.0004) and 10% worse viral clearance (p=0.02).Retrospective 4,634 hospitalized COVID-19 patients in China, showing higher mortality and slower viral clearance with proton pump inhibitor (PPI) use. Authors hypothesize that PPIs may increase susceptibility to COVID-19 by increasing ACE2 expression.
Feb 2022, J. Global Health, http://jogh.org/documents/2022/jogh-12-05005.pdf, https://c19p.org/wu12
1,767. Finberg et al., US201 Study: A Phase 2, Randomized Proof-of-Concept Trial of Favipiravir for the Treatment of COVID-19
50 patient favipiravir late treatment RCT: 20% longer hospitalization, 58% improved recovery (p=0.08), and 47% faster viral clearance (p=0.04).Small very late treatment RCT in the USA, with 25 favipiravir and 25 control patients, showing faster viral clearance with treatment. The benefit was only seen in patients <8 days from symptom onset. There were no significant differences in clinical outcomes. The death in the favipiravir group occurred after discharge and was believed to be unrelated to COVID-19 or favipiravir.
Dec 2021, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/8/12/ofab563/6455602, https://c19p.org/finberg
1,768. Rodrigues et al., Hydroxychloroquine plus azithromycin early treatment of mild COVID-19 in outpatient setting: a randomized, double-blinded, placebo-controlled clinical trial evaluating viral clearance
84 patient HCQ early treatment RCT: 14% improved viral clearance (p=0.15).RCT 84 low risk patients, 42 treated with HCQ/AZ, showing no significant differences. There was only one hospitalization which was in the treatment arm.
Aug 2021, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857921002065, https://c19p.org/rodrigues
1,769. Botton et al., No association of low-dose aspirin with severe COVID-19 in France: A cohort of 31.1 million people without cardiovascular disease
31,072,642 patient aspirin prophylaxis study: 4% higher combined mortality/intubation (p=0.18) and 3% higher hospitalization (p=0.05).Retrospective 31 million people without cardiovascular disease in France, showing no significant difference in hospitalization or combined intubation/death with low dose aspirin prophylaxis.
Jun 2022, Research and Practice in Thrombosis and Haemostasis, https://onlinelibrary.wiley.com/doi/10.1002/rth2.12743, https://c19p.org/botton
1,770. Mikamo et al., Efficacy and safety of ivermectin in patients with mild COVID-19 in Japan and Thailand
1,029 patient ivermectin early treatment RCT: 205% higher progression (p=0.49), 4% worse improvement (p=0.62), and 4% improved recovery (p=0.72).RCT very low risk patients (mean age 35.7, SpO2 97.4) showing no significant differences with rapid recovery and almost no progression in both groups. The groups were unbalanced. There were 41% more patients with dyspnea at baseline in the treatment group. Similarly, at baseline patients with 4+ symptoms scored 2+ were more common in the treatment group - 7% for ivermectin vs. 4% for placebo. Table S8 shows only one case of COVID-19 pneumonia. Authors report 3 and 1 cases of progression, this matches the 3 and 1 cases of the adverse event "COVID-19" in Table S8. It's unclear how the COVID-19 adverse events were defined since all patients are meant to have COVID-19. Authors definition of progression includes "use of COVID-19 therapeutic agents" and therefore the significance for progression of disease is not clear. The study is designed to produce a null result with very low risk patients, administration on an empty stomach, the primary outcome including symptoms..
Sep 2022, J. Infection and Chemotherapy, https://www.sciencedirect.com/science/article/pii/S1341321X23003161, https://c19p.org/mikamo
1,771. Almario et al., Increased Risk of COVID-19 Among Users of Proton Pump Inhibitors
51,973 patient proton pump inhibitor prophylaxis study: 179% more cases (p=0.0001).Survey of 53,130 individuals with a history of GI symptoms showing increased risk of COVID-19 positivity with proton pump inhibitor (PPI) use, especially twice-daily PPI use. There was a dose-response relationship between PPI use and COVID-19 risk. Those taking PPIs twice daily had 3.67 times higher odds of testing positive compared to those not taking PPIs. The authors hypothesize that PPI-induced hypochlorhydria may impair the body's defense against ingested pathogens like SARS-CoV-2.
Aug 2020, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000000798, https://c19p.org/almario
1,772. Reese et al., Cyclooxygenase inhibitor use is associated with increased COVID-19 severity
9,842 patient aspirin prophylaxis PSM study: 61% higher mortality (p<0.0001) and 309% higher severe cases (p<0.0001).N3C retrospective 250,533 patients showing significantly higher mortality with aspirin use. Note that aspirin results were not included in the journal version or v2 of this preprint.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reesee
1,773. Freilich et al., COVIDMED – An early pandemic randomized clinical trial of losartan treatment for hospitalized COVID-19 patients
12 patient losartan late treatment RCT: 533% higher mortality (p=0.49) and 160% longer hospitalization (p=0.3).RCT 15 hospitalized COVID-19 patients showing no significant differences with losartan treatment. The study was terminated early due to low enrollment.
Oct 2022, Contemporary Clinical Trials Communications, https://www.sciencedirect.com/science/article/pii/S2451865422000850, https://c19p.org/freilich
1,774. Recovery Collaborative Group et al., Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
11,340 patient colchicine late treatment RCT: 1% higher mortality (p=0.77), 18% higher ventilation (p=0.06), 2% higher combined mortality/intubation (p=0.47), and 2% lower hospital discharge (p=0.44).RCT with 5,610 colchicine and 5,730 control patients showing mortality RR 1.01 [0.93-1.10]. Very late stage treatment, median 9 days after symptom onset, baseline 32% ventilation (5% invasive). ISRCTN 50189673. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor, patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m², and those with an estimated bodyweight of less than 70kg.
May 2021, Recovery Collaborative Group, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260021004355, https://c19p.org/recoveryc
1,775. Barnabas et al., Hydroxychloroquine for Post-exposure Prophylaxis to Prevent Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Randomized Trial
829 patient HCQ prophylaxis RCT: 27% more cases (p=0.33).Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences. Different results were reported at IDWeek from the AIM results. The study enrolled people with their last exposure within 4 days, i.e., if someone was exposed for 30 days in a row, they could be enrolled anywhere from day 1 to day 34. Therefore many were likely infected earlier than the enrollment date. Note that PCR has a very high false negative rates, e.g., 100% on day 1 and 67% on day 4 here [ncbi.nlm.nih.gov]. 50% of infections were detected by day 4. With the PCR false negatives and treatment delays it is likely that a majority of infections happened before enrollment or before HCQ can reach therapeutic levels. Significantly more cases were caught at baseline in the control group (54 vs. 29 for HCQ) and excluded from analysis. The early presentation stated that therapy started one day after enrollment and study supplies were sent to the..
Dec 2020, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M20-6519, https://c19p.org/barnabas
1,776. Llanos-Cuentas et al., Hydroxychloroquine to prevent SARS-CoV-2 infection among healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial
68 patient HCQ prophylaxis RCT: 69% more cases (p=0.46).Early terminated healthcare worker PrEP RCT with only 68 patients and 8 cases, showing no significant difference with HCQ. No information on symptoms per group, case severity, or the timing of cases is provided.
Feb 2023, BMC Research Notes, https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-023-06281-7, https://c19p.org/llanoscuentas
1,778. Mann et al., Hen egg white bovine colostrum supplement reduces symptoms of mild/moderate COVID-19: a randomized control trial
156 patient lactoferrin early treatment RCT: 26% improved recovery (p=0.24), 11% worse viral clearance (p=0.36), and 8% lower PASC (p=0.84).RCT 156 mild/moderate COVID-19 patients, 77 treated with hen egg white and bovine colostrum, showing faster recovery of severe symptoms with treatment. There were no significant differences in overall symptom duration, viral clearance, or post-COVID symptoms. Only one participant progressed to severe COVID-19.
Jul 2023, Future Science OA, https://www.future-science.com/doi/10.2144/fsoa-2023-0024, https://c19p.org/mann
1,779. Higgins et al., Long-term (180-Day) Outcomes in Critically Ill Patients With COVID-19 in the REMAP-CAP Randomized Clinical Trial
352 patient HCQ ICU RCT: 51% higher mortality (p=0.06).Long-term followup for the REMAP-CAP very late stage ICU trial, showing higher risk with HCQ, not quite reaching statistical significance.
Dec 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2799870, https://c19p.org/higgins
874 patient proton pump inhibitor prophylaxis PSM study: 28% higher mortality (p=0.63), 75% higher ventilation (p=0.37), 150% higher ICU admission (p=0.11), and 21% higher progression (p=0.6).
PSM retrospective in South Korea, showing lower risk of COVID-19 cases with H2RA (including famotidine) and PPI use, but no significant difference in severe outcomes (results provided for the combined groups only).
Mar 2023, J. Korean Medical Science, https://jkms.org/DOIx.php?id=10.3346/jkms.2023.38.e99, https://c19p.org/kim11ppi
1,781. Barrat-Due et al., Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19
93 patient HCQ late treatment RCT: 120% higher mortality (p=0.35).Small RCT in Norway showing no significant differences with HCQ treatment. Add-on trial to WHO Solidarity.
Jul 2021, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M21-0653, https://c19p.org/barratdue
1,782. Matino et al., Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial
218 patient lactoferrin late treatment RCT: 12% higher mortality (p=0.85), 45% higher ventilation (p=0.39), 6% higher combined mortality/ICU admission (p=0.87), and 34% worse recovery (p=0.12).RCT 218 hospitalized patients in Italy, showing no significant differences with lactoferrin treatment. Authors note that in several previous studies showing clinical improvement, lactoferrin was given at an earlier stage of disease. Authors also note that potential benefits with the late treatment in this study could be masked by other SOC medications - corticosteroids may have masked immunomodulatory effects of lactoferrin, and there may be heparin-dependent reduction in lactoferrin antiviral activity. 800mg oral bovine lactoferrin daily.
Mar 2023, Nutrients, https://www.mdpi.com/2072-6643/15/5/1285, https://c19p.org/matino
1,783. Horcajada et al., Safety and efficacy of favipiravir in COVID-19 patients with pneumonia. A randomized, double-blind, placebo-controlled study (FAVID)
44 patient favipiravir late treatment RCT: 383% higher mortality (p=0.49), 37% higher ventilation (p=1), no change in improvement (p=0.45), and 17% improved recovery (p=0.64).Underpowered RCT with 44 hospitalized patients in Spain, showing no significant difference with favipiravir treatment in the primary outcome of time to clinical improvement, or in the secondary efficacy outcomes. Adverse events were more frequent in the favipiravir group (68%) compared to placebo (32%), but most were mild.
Aug 2023, Pneumonia, https://pneumonia.biomedcentral.com/articles/10.1186/s41479-023-00124-6, https://c19p.org/horcajada
1,784. Cheung et al., Proton pump inhibitors associated with severe COVID‐19 among two‐dose but not three‐dose vaccine recipients
439,154 patient proton pump inhibitor prophylaxis study: 49% higher mortality (p=0.005), 36% higher severe cases (p=0.27), 20% higher hospitalization (p=0.0003), and 9% more cases (p<0.0001).Retrospective 627,514 patients in Hong Kong showing slightly higher risk of COVID-19 with pre-vaccination proton pump inhibitor (PPI) use in two-dose or three-dose vaccine recipients, and higher risk of hospitalization and severe outcomes only in two-dose recipients.
May 2024, J. Gastroenterology and Hepatology, https://onlinelibrary.wiley.com/doi/10.1111/jgh.16601, https://c19p.org/cheung2
1,785. Lowe et al., Favipiravir, lopinavir-ritonavir, or combination therapy (FLARE): A randomised, double-blind, 2 × 2 factorial placebo-controlled trial of early antiviral therapy in COVID-19
119 patient favipiravir early treatment RCT: 28% improved viral clearance (p=0.03).240 patient RCT comparing favipiravir, favipiravir + LPV/r, LPV/r, and placebo, showing improved viral clearance with favipiravir. Efficacy was lower in the combined favipiravir + LPV/r arm, where plasma levels of favipiravir were lower. Favipiravir 1800mg twice daily on day 1 followed by 400mg four times daily on days 2-7.
Feb 2022, PLOS Medicine, https://journals.plos.org/plosone/article?id=10.1371/journal.pmed.1004120, https://c19p.org/lowe
1,786. McMahon et al., Favipiravir in early symptomatic COVID-19, a randomised placebo-controlled trial
199 patient favipiravir early treatment RCT: 1% higher need for oxygen therapy (p=1) and 56% higher hospitalization (p=0.38).RCT with 99 favipiravir and 100 placebo patients in Australia, all except one being outpatients, showing no significant differences with treatment.
Jun 2022, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00433-3/fulltext, https://c19p.org/mcmahon
1,787. Reese et al., Cyclooxygenase inhibitor use is associated with increased COVID-19 severity
41,652 patient acetaminophen prophylaxis PSM study: 61% higher mortality (p<0.0001) and 816% higher severe cases (p<0.0001).N3C retrospective 250,533 patients showing significantly higher mortality with acetaminophen use. Note that acetaminophen results were not included in the journal version or v2 of this preprint, which focuses on NSAID analysis.
Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reese
1,788. Fernández-Ferreiro et al., Effects of Loigolactobacillus coryniformis K8 CECT 5711 on the Immune Response of Elderly Subjects to COVID-19 Vaccination: A Randomized Controlled Trial
198 patient probiotics prophylaxis RCT: 2% higher mortality (p=1), 38% slower recovery (p=0.56), 28% higher severe cases (p=0.75), and 2% more symptomatic cases (p=1).RCT 200 nursing home residents over 60 years old in Spain showing Loigolactobacillus coryniformis K8 probiotic administration enhanced IgG antibody response in subjects previously infected with SARS-CoV-2 and tended to improve IgA antibody response in those over 85 years old not previously infected, in the context of COVID-19 vaccination. There was no significant difference in incidence of COVID-19 infection between the probiotic and placebo groups during the study. The probiotic group had a higher percentage of asymptomatic COVID-19 cases compared to placebo, without statistical significance.
Jan 2022, Nutrients, https://www.mdpi.com/2072-6643/14/1/228, https://c19p.org/fernandezferreiro
1,789. Visser et al., Vitamin K2 Supplementation in Hospitalised COVID-19 Patients: A Randomised Controlled Trial
40 patient vitamin K late treatment RCT: 200% higher mortality (p=1), 200% higher ICU admission (p=0.6), and 17% shorter hospitalization (p=0.52).RCT 40 hospitalized COVID-19 patients showing vitamin K2 supplementation was well-tolerated and reduced dp-ucMGP levels, reflecting improved vitamin K status, but did not affect desmosine, a marker of elastic fiber degradation. The study was not powered to assess effects on clinical outcomes. Authors suggest that the dose may have been insufficient to fully correct the vitamin K deficiency seen in COVID-19, and that higher doses might be required to achieve potential protective effects against inflammation or lung damage.
Jun 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/12/3476, https://c19p.org/visser
1,790. Puskarich et al., A multi-center phase II randomized clinical trial of losartan on symptomatic outpatients with COVID-19
117 patient losartan early treatment RCT: 2% higher ICU admission (p=1), 205% higher hospitalization (p=0.36), and 27% higher progression (p=0.74).RCT 117 symptomatic outpatients showing no significant difference in hospitalization, functional status, dyspnea, or viral load with losartan treatment. The trial was terminated early due to low event rates. Losartan 25mg twice daily for 10 days.
Jul 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537021002376, https://c19p.org/puskarich
1,791. Reiersen et al., The STOP COVID 2 study: Fluvoxamine vs placebo for outpatients with symptomatic COVID-19, a fully-remote randomized controlled trial
547 patient fluvoxamine early treatment RCT: 201% higher need for oxygen therapy (p=0.5), 9% lower hospitalization (p=1), and 12% lower progression (p=0.85).Remote RCT 547 outpatients a median of 5 days from onset, showing no significant differences with fluvoxamine. The trial was stopped early and underpowered due to low event rates. The trial does not report outcomes that may not be underpowered like time to recovery. Authors note that treatment may have been too late.
Aug 2021, Open Forurm Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofad419/7238414, https://c19p.org/reiersen
1,792. Adhikari et al., Intravenous Vitamin C for Patients Hospitalized With COVID-19 Two Harmonized Randomized Clinical Trials
2,206 patient vitamin C late treatment RCT: 19% higher mortality (p=0.08) and 35% higher ventilation (p=0.04).Very late stage (APACHE II 8 and 12 for non-critical and critical) RCT with publication delayed over a year showing higher ventilation and no significant difference in mortality with vitamin C. Authors have combined what was to be two separate trials into one trial, however there are very large differences between the trials. The results for each source trial are shown separately here [Adhikari, Adhikari]. eTable 15 shows that results in LOVIT-COVID were substantially better than those in REMAP-CAP. eTable 13 shows improved survival for LOVIT-COVID and worse survival for REMAP-CAP (authors provide mortality breakdown only for hospital survival): LOVIT-COVID shows 85% and 82% probability of superiority of vitamin C (critical and non-critical). REMAP-CAP shows 12% and 7% probability of superiority of vitamin C. Notably, LOVIT-COVID patients were blinded, while REMAP-CAP was open-label, introducing additional opportunity for bias on this highly politicized treatment. REMAP-CAP had more..
Oct 2023, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2811212, https://c19p.org/adhikari2
1,793. Crippa et al., Cannabidiol for COVID-19 Patients with Mild to Moderate Symptoms (CANDIDATE Study): A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
91 patient cannabidiol late treatment RCT: 557% higher hospitalization (p=0.25) and 33% slower recovery (p=0.21).RCT 105 patients recruited in an ER in Brazil, 49 treated with CBD, showing no significant differences with treatment. 300mg CBD for 14 days. For discussion see [liebertpub.com].
Oct 2021, Cannabis and Cannabinoid Research, https://www.liebertpub.com/doi/full/10.1089/can.2021.0093, https://c19p.org/crippa
1,794. Babayigit et al., The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort
1,472 patient HCQ late treatment study: 112% higher ventilation (p=0.21), 53% higher ICU admission (p=0.33), and 17% longer hospitalization (p=0.05).Retrospective 1,472 hospitalized patients in Turkey, showing a higher risk of ICU admission and ventilation with HCQ, without statistical significance.
Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full, https://c19p.org/babayigith
1,795. Manjani et al., Effects of acetaminophen on outcomes in patients hospitalized with COVID-19
524 patient acetaminophen late treatment study: 220% higher mortality (p=0.001), 434% higher ventilation (p=0.001), 244% higher progression (p=0.005), and 100% longer hospitalization (p=0.001).Retrospective 524 hospitalized patients in the USA, showing higher mortality and progression with acetaminophen use.
Oct 2021, Chest, https://www.sciencedirect.com/science/article/pii/S0012369221024430, https://c19p.org/manjani
1,796. Patil et al., Factors Associated With Poor Outcomes Among Patients With SARS-CoV-2 Coronavirus Infection and Gastrointestinal Symptoms
19,915 patient proton pump inhibitor prophylaxis study: 48% higher mortality (p<0.0001), 119% higher ARDS (p<0.0001), 88% worse results (p<0.0001), and 73% higher need for oxygen therapy (p<0.0001).Retrospective 19,915 hospitalized COVID-19 patients with gastrointestinal symptoms, showing that use of proton pump inhibitors or H2 receptor antagonists was associated with higher mortality, ARDS, sepsis, and ventilator or oxygen requirement among patients
Dec 2023, Gastro Hep Advances, https://www.sciencedirect.com/science/article/pii/S277257232200142X, https://c19p.org/patil3
1,797. Bekker et al., Transmission of COVID19 in Crowded Environments
245 patient PPE prophylaxis RCT: 164% worse results (p=0.08).RCT 245 people in South Africa, showing no significant difference in COVID-19 cases with PPE use.
Oct 2021, NCT05119348, https://clinicaltrials.gov/study/NCT05119348, https://c19p.org/bekker
1,798. Jilg et al., One Week of Oral Camostat Versus Placebo in Nonhospitalized Adults With Mild-to-Moderate Coronavirus Disease 2019 (COVID-19): A Randomized Controlled Phase 2 Trial
216 patient camostat late treatment RCT: 198% higher mortality (p=1), 18% higher hospitalization (p=1), and no change in recovery (p=0.99).RCT 216 patients, 55% >5 days from symptom onset, showing no significant difference with camostat treatment.
Jun 2023, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad342/7190261, https://c19p.org/jilg
1,799. Eikelboom et al., Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial
3,881 patient colchicine late treatment RCT: 9% higher mortality (p=0.84), 2% higher combined mortality/hospitalization (p=0.93), and 2% higher hospitalization (p=0.92).Late (5.4 days) outpatient RCT showing no significant difference in outcomes with colchicine treatment. Authors include a meta analysis of 6 colchicine RCTs, however there were 19 RCTs as of the publication date [c19colchicine.com].
Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002995, https://c19p.org/eikelboom2
1,800. Navarro et al., Bovine lactoferrin for the prevention of COVID-19 infection in health care personnel: a double-blinded randomized clinical trial (LF-COVID)
209 patient lactoferrin prophylaxis RCT: 59% more symptomatic cases (p=0.34) and 23% more cases (p=0.65).Early terminated low-risk patient prophylaxis RCT in Peru, showing no significant difference in cases with lactoferrin. There were no moderate or severe cases.
Dec 2022, BioMetals, https://link.springer.com/10.1007/s10534-022-00477-3, https://c19p.org/navarro
1,801. Topless et al., Folic acid and methotrexate use and their association with COVID-19 diagnosis and mortality: a case–control analysis from the UK Biobank
376,254 patient vitamin B9 prophylaxis study: 164% higher mortality (p<0.0001) and 51% more cases (p<0.0001).UK Biobank retrospective showing higher cases and mortality with folic acid supplementation.
Aug 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-062945, https://c19p.org/topless2
1,802. Rocco et al., Early use of nitazoxanide in mild Covid-19 disease: randomized, placebo-controlled trial (preprint 10/23)
392 patient nitazoxanide early treatment RCT: 404% higher ICU admission (p=0.24), 2% higher hospitalization (p=1), 16% worse recovery (p=0.37), and 12% improved viral clearance (p=0.006).RCT 392 patients, median treatment delay 5 days, showing improved viral recovery at 5 days. Symptom recovery was no different at 5 days, and the treatment arm had two ICU admissions compared to zero for control. There were no serious adverse events.
Oct 2020, European Respiratory J., https://erj.ersjournals.com/content/early/2020/12/17/13993003.03725-2020, https://c19p.org/rocco
1,803. Ivashchenko et al., AVIFAVIR for Treatment of Patients with Moderate COVID-19: Interim Results of a Phase II/III Multicenter Randomized Clinical Trial
60 patient favipiravir late treatment RCT: 46% improved viral clearance (p=0.03) and 67% lower hospital discharge (p=0.51).Interim results for a small RCT with 40 favipiravir and 20 control patients showing faster viral clearance with favipiravir. There is limited data in this report to evaluate the results. 75% of the control group received HCQ/CQ.
Aug 2020, Clinical Infectious Diseases, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454388/, https://c19p.org/ivashchenko
1,804. Sunil Naik et al., Effect of colchicine and aspirin given together in patients with moderate COVID-19
105 patient colchicine late treatment RCT: 7% improved recovery (p=0.21).RCT 122 hospitalized patients in India, showing improved recovery with colchicine treatment. All patients received aspirin. There was one death and higher progression in the colchicine arm, however 3 patients in the colchicine arm had baseline ordinal scores ≥5, while no patients in the control arm did.
Jan 2023, Contemporary Clinical Trials Communications, https://www.sciencedirect.com/science/article/pii/S2451865423000169, https://c19p.org/sunilnaik
1,805. Schwartz et al., Assessing the efficacy and safety of hydroxychloroquine as outpatient treatment of COVID-19: a randomized controlled trial
179 patient HCQ late treatment RCT: 37% improved recovery (p=0.15).Small early terminated late treatment RCT showing no significant differences. The HCQ group was a median of 7 days from symptom onset at baseline, which may not include the delay delivering the medication. From the 4 HCQ hospitalizations, only one is in the per-protocol analysis, and that patient was hospitalized one day after randomization (authors do not specify if the patient received and took any HCQ before the hospitalization). The trial was terminated early due to the fraudulent Lancet article (wording here is notably different between the submitted and published versions). Per-protocol analysis, the submitted version, and the peer-review comments (two reviewers, only one with substantial feedback) are in the supplementary material. Long-term recovery results are reported in [Ganesh]. When a patient reported a symptom, they were asked whether they were still experiencing that symptom, and to choose between these three options when comparing the symptom to their pre-COVID-19..
Jun 2021, CMAJ Open, http://cmajopen.ca/content/9/2/E693.full, https://c19p.org/schwartz2
1,806. Franco-Moreno et al., Effect of early administration of dexamethasone in patients with COVID-19 pneumonia without acute hypoxemic respiratory failure and risk of development of acute respiratory distress syndrome: EARLY-DEX COVID-19 trial
126 patient dexamethasone late treatment RCT: 134% higher ventilation (p=0.41), 217% higher ICU admission (p=0.46), 17% higher ARDS (p=0.81), and 3% shorter hospitalization (p=0.88).RCT 126 hospitalized COVID-19 pneumonia patients not requiring oxygen at admission, showing no significant difference in outcomes with dexamethasone treatment.
Jul 2024, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2024.1385833/full, https://c19p.org/francomorenodexdex
1,807. Sarojvisut et al., An Open Label Randomized Controlled Trial of Ivermectin Plus Favipiravir-Based Standard of Care versus Favipiravir-Based Standard of Care for Treatment of Moderate COVID-19 in Thailand
317 patient ivermectin late treatment RCT: 104% higher ICU admission (p=0.62), 104% worse improvement (p=0.62), and 4% faster recovery (p=0.63).RCT low risk hospitalized patients in Thailand showing no significant difference with the addition of ivermectin to favipiravir based SOC. Only the abstract is currently available. The trial was registered retrospectively [thaiclinicaltrials.org]. The primary outcome was WHO-category ordinal scale improvement of 2 points at days 3, 7, 14, 21, for which only a single unspecified time point (when almost all patients have recovered) is provided in the abstract (details may be in the full paper). The registration indicates that the intervention was only provided "after laboratory result", without explanation.
Dec 2022, Infection & Chemotherapy, https://icjournal.org/DOIx.php?id=10.3947/ic.2022.0127, https://c19p.org/sarojvisut
1,808. Réa-Neto et al., An open-label randomized controlled trial evaluating the efficacy of chloroquine/hydroxychloroquine in severe COVID-19 patients
105 patient HCQ late treatment RCT: 57% higher mortality (p=0.2), 115% higher ventilation (p=0.03), and 147% worse recovery (p=0.02).Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247.
Apr 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-88509-9, https://c19p.org/reanato
1,809. Chuah et al., Efficacy of Early Treatment with Favipiravir on Disease Progression among High Risk COVID-19 Patients: A Randomized, Open-Label Clinical Trial
500 patient favipiravir late treatment RCT: 1154% higher mortality (p=0.08), 20% higher ventilation (p=0.76), and 9% higher ICU admission (p=0.84).RCT 500 hospitalized patients in Malaysia, showing no significant differences with favipiravir treatment.
Nov 2021, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab962/6432025, https://c19p.org/chuah
1,810. Bosaeed et al., Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicenter, placebo-controlled trial clinical trial
231 patient favipiravir early treatment RCT: 619% higher ICU admission (p=0.11), 219% higher hospitalization (p=0.16), 12% slower recovery (p=0.51), and 15% slower viral clearance (p=0.51).RCT with 112 favipiravir and 119 control patients showing no significant differences in outcomes. Viral clearance and clinical recovery for patients treated within 48 hours was better than those treated later. NCT04464408.
Jan 2022, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X21007345, https://c19p.org/bosaeed2
1,811. Naggie et al., Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial
1,591 patient ivermectin late treatment RCT: 99%, 98%, 97% posterior probability of efficacy for mean time unwell and clinical progression @14 and 7 days, despite very late treatment, low-risk patients, and poor administration. All exceed the pre-specified threshold for superiority. Clinical progression results were changed without explanation in a later version.RCT low-risk outpatients with very late treatment (median 6 days, 25% ≥8 days) in the USA, showing 98% probability of efficacy for clinical progression at day 14, a treatment delay-response relationship, and significant efficacy for patients with severe symptoms at baseline. The posterior probability ivermectin is effective was 99%, 98%, 97% for mean time unwell and clinical progression @14 and 7 days. All exceed the pre-specified threshold for superiority [ fnih.org ] . Note that the clinical progression results exceeding the superiority threshold in the preprint [ medrxiv.org (C) ] changed in the journal version for the 400µg/kg arm, with no explanation for over 700 days). The 600µg/kg arm was reported separately [ Naggie ] . When not specified, comments refer to the 400µg/kg arm. We provide more detailed analysis of this study due to widespread incorrect press. There was one death reported in each of the 400µg/kg and 600µg/kg ivermectin arms. For 400µg/kg, the patient did not take..
Jun 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2797483, https://c19p.org/activ6ivm
1,812. Jolliffe et al., Effect of a test-and-treat approach to vitamin D supplementation on risk of all cause acute respiratory tract infection and covid-19: phase 3 randomised controlled trial (CORONAVIT)
4,464 patient vitamin D prophylaxis RCT: 41% higher hospitalization (p=0.16) and 9% more cases (p=0.55).RCT 5,979 low risk patients (0 COVID-19 deaths) in the UK, showing no significant differences with vitamin D prophylaxis. CORONAVIT. NCT04579640. For more discussion see [ reddit.com , twitter.com (I) ] . 51% of confirmed COVID-19 cases were hospitalized in the control arm which is 7 times the median rate in other studies reporting both cases and hospitalization as of Sep 2022 (7.2%), suggesting possible issues with the data or major differences between the study population and the general population. Authors do not provide exact start/end dates (month only) or specify when infections occurred, however based on cases in the UK, most infections may have been closer to the start of the trial when vitamin D levels may still have been relatively low. Reportedly, authors do not plan to analyze this issue, and have declined to allow one of the funders access to the data. [ Villasis-Keever ] present an RCT showing conflicting results, 78% lower cases with vitamin D prophylaxis. In..
Mar 2022, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj-2022-071230, https://c19p.org/jolliffe2
Please send us corrections, updates, or comments.
c19early involves the extraction of 100,000+ datapoints from
thousands of papers. Community updates
help ensure high accuracy.
Treatments and other interventions are complementary.
All practical, effective, and safe
means should be used based on risk/benefit analysis.
No treatment or intervention is 100% available and effective for all current
and future variants.
We do not provide medical advice. Before taking any medication,
consult a qualified physician who can provide personalized advice and details
of risks and benefits based on your medical history and situation. FLCCC and WCH
provide treatment protocols.
Thanks for your feedback! Please search before submitting papers and note
that studies are listed under the date they were first available, which may be
the date of an earlier preprint.