Summary of COVID-19 studies
Studies
Meta Analysis
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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
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 control group. 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 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
HCQ was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues [sciencedirect.com, sciencedirect.com, sciencedirect.com]. Despite the limitations, this early observational study was a milestone in the discovery process, including detailed daily evolution of PCR positivity. This study should be viewed in the context of the series of studies from this group. An update to this paper, including originally excluded patients, confirms the effectiveness of HCQ+AZ on viral clearance and early discharge [sciencedirect.com]. Also see [sciencedirect.com] and the response from the authors [sciencedirect.com].
Mar 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920300996, https://c19p.org/gautretjaa
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
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
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. 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
158. 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
159. 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
160. 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
162. 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
163. 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
164. 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
165. 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
166. 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
167. 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
168. 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
169. 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
170. 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
173. 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
174. 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
175. 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
176. 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
177. 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
178. 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
180. 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
181. 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
182. 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
183. 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
184. 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
186. 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
187. 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
188. 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
189. 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
190. 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
191. 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
192. 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
193. 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
194. 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
195. 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
196. 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
197. 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
198. 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
199. 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
200. 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
202. 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
203. 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
204. 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
205. 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
206. 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
207. 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
208. 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
209. 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
210. 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
211. 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
212. 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
213. 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
214. 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
215. 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
216. 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
217. 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
218. 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
219. 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
220. 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
221. 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
222. 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
223. 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
224. 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
225. 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
226. 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
227. 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
228. 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
230. 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
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 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
232. 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
233. 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
234. 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
235. 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
237. 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
238. 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
239. 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
240. 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
241. 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
242. 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
243. 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
244. 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 control group. 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
245. 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
246. 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
247. 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
248. 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
249. 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
250. 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
251. 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
252. 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
253. 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
254. 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
255. 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
256. 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
257. 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
258. 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
259. 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
260. 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
261. 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
262. 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
263. 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
264. 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
265. 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
266. 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
267. 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
268. 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
269. 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
270. 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
271. 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
272. 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
274. 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
275. 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
277. 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
278. 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
280. 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
281. 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
282. 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
283. 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
284. 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
285. 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
286. 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
287. 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
288. 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
289. 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
290. 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
291. 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
292. 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
294. 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
295. 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
297. 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
298. 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
299. 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
300. 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
301. 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
302. 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
304. 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
305. 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
307. 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
308. 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
309. 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
310. 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
311. 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
312. 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
313. 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
314. 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
315. 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
316. 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
317. 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
319. 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
320. 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
321. 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
322. 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
323. 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
324. 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
326. 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
327. 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
328. 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
331. 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
332. 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
333. 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
334. 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
335. 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
336. 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
337. 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
338. 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
339. 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
340. 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
341. 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
342. 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
343. 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
344. 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
345. 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
346. 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
347. 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
348. 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
349. 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
350. 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
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 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
352. 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
353. 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
354. 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
355. 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
356. 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
357. 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
358. 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
359. 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
360. 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
361. 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
362. 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
363. 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
364. 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
365. 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
366. 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
368. 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
369. 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
370. 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
371. 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
372. 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
373. 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
374. 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
375. 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
376. 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
377. 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
378. 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
379. 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
380. 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
381. 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
382. 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
383. 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
385. 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
386. 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
387. 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
388. 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
389. 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
390. 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
391. 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
392. 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
393. 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
394. 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
395. 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
396. 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
397. 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
398. 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
399. 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
400. 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
401. 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
402. 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
403. 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
404. 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
405. 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
406. 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
407. 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
408. 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
409. 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
410. 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
411. 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
412. 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
413. 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
414. 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
415. 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
416. 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
417. 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
418. 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
419. 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
420. 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
421. 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
422. 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
423. 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
424. 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
425. 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
426. 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
427. 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
428. 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
429. 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
430. 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
431. 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
432. 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
433. 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
434. 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
435. 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
436. 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
437. 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
438. 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
439. 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
440. 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
441. 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
444. 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
445. 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
446. 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
447. 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
448. 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
449. 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
450. 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
451. 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
452. 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
453. 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
454. 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
456. 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
457. 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
458. 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
459. 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
460. 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
461. 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
463. 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
464. 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
465. 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
466. 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
467. 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
469. 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
470. 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
471. 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
472. 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
473. 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
474. 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
475. 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
477. 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
478. 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
479. 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
480. 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
481. 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
482. 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
483. 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
484. 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
485. 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
486. 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
487. 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
488. 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
489. 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
490. 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
491. 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
492. 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
493. 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
494. 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
495. 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
496. 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
497. 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
498. 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
499. 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
500. 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
501. 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
502. 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
503. 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
504. 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
505. 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
506. 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
507. 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
508. 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
509. 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
510. 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
511. 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
512. 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
514. 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
515. 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
516. 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
518. 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
519. 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
520. 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
521. 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
522. 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
523. 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
524. 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
525. 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
526. 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
529. 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
530. 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
531. 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
532. 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
533. 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
534. 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
535. 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
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 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
537. 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
538. 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
539. 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
540. 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
541. 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
542. 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
543. 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
544. 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
545. 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
546. 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
547. 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
548. 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
549. 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
550. 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
551. 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
552. 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
553. 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
554. 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
555. 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
556. 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
557. 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
558. 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
559. 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
560. 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
561. 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
562. 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
563. 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
564. 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
565. 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
566. 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
567. 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
568. 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
570. 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
571. 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
572. 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
573. 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
574. 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
575. 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
576. 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
577. 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
578. 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
579. 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
580. 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
581. 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
582. 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
584. 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
585. 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
586. 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
587. 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
588. 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
589. 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
590. 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
591. 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
592. 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
593. 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
594. 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
595. 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
596. 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
597. 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
598. 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
599. 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
600. 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
601. 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
602. 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
603. 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
604. 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
605. 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
606. 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
607. 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
608. 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
609. 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
610. 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
611. 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
612. 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
613. 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
614. 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
615. 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
616. 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
617. 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
618. 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
620. 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
621. 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
622. 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
623. 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
624. 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
625. 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
626. 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
627. 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
628. 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
629. 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
630. 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
631. 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
632. 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
633. 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
634. 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
636. 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
637. 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
638. 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
639. 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
640. 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
641. 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
643. 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
644. 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
645. 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
646. 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
647. 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
648. 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
649. 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
650. 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
651. 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
652. 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
654. 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
655. 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
656. 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
657. 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
658. 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
659. 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
660. 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
661. 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
662. 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
663. 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
664. 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
665. 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
666. 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
667. 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
668. 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
669. 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
670. 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
671. 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
672. 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
673. 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
674. 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
675. 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
676. 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
677. 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
678. 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
679. 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
680. 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
681. 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
682. 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
683. 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
684. 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
685. 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
686. 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
687. 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
688. 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
689. 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
690. 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
691. 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
692. 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
693. 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
694. 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
695. 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
696. 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
697. 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
698. 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
699. Gautret et al., Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial
36 patient HCQ early treatment study: 66% improved viral clearance (p=0.001).HCQ was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues [sciencedirect.com, sciencedirect.com, sciencedirect.com]. Despite the limitations, this early observational study was a milestone in the discovery process, including detailed daily evolution of PCR positivity. This study should be viewed in the context of the series of studies from this group. An update to this paper, including originally excluded patients, confirms the effectiveness of HCQ+AZ on viral clearance and early discharge [sciencedirect.com]. Also see [sciencedirect.com] and the response from the authors [sciencedirect.com].
Mar 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920300996, https://c19p.org/gautretjaa
700. 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
701. 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
702. 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
703. 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
704. 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
705. 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
706. 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
707. 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
708. 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
709. 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
710. 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
711. 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
712. 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
713. 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
714. 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
715. 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
716. 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
717. 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
718. 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
719. 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
720. 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
721. 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
722. 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
723. 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
725. 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
726. 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
727. 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
728. 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
729. 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
730. 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
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 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
732. 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
733. 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
734. 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
735. 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
736. 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
737. 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
738. 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
739. 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
740. 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
741. 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
742. 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
743. 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
744. 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
745. 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
746. 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
747. 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
748. 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
749. 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
750. 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
751. 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
752. 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
753. 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
754. 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
755. 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
756. 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
757. 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
758. 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
759. 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
760. 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
761. 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
762. 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
764. 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
765. 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
766. 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
768. 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
769. 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
770. 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
773. 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
774. 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
775. 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
776. 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
777. 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
778. 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
779. 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
780. 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
781. 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
782. 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
783. 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
784. 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
786. 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
787. 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
789. 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
790. 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
791. 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
792. 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
793. 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
794. 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
795. 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