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Summary of COVID-19 studies

Studies   Meta Analysis   Hide extended summaries

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

68,896 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

3,998 patient azvudine late treatment PSM study: 22% lower mortality (p=0.001), 13% higher hospital discharge (p=0.05), 1% shorter hospitalization (p=0.43), and 10% faster viral clearance (p<0.0001).
PSM retrospective 3,998 hospitalized COVID-19 patients aged 60 years and older in China showing lower all-cause mortality, higher rate of discharge, and shorter time to viral clearance with azvudine treatment.

Dec 2024, Acta Pharmaceutica Sinica B, https://www.sciencedirect.com/science/article/pii/S2211383524004611, https://c19p.org/zhu9

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

471 patient HCQ early treatment RCT: 71% lower mortality (p=0.03), 4% greater improvement (p=0.64), and 10% improved viral clearance (p=0.52).
RCT 471 mild COVID-19 patients in Pakistan showing no significant differences in clinical improvement and viral clearance between HCQ, azithromycin, oseltamivir, and combinations. Mortality was significantly lower in HCQ vs. non-HCQ arms. The best results for viral clearance and clinical improvement were seen with the combination of all treatments. There was no placebo group (the study compares different combinations of treatments). No serious adverse events were reported. All patients had mild COVID-19 and the paper indicates early treatment, however time from onset is not reported and minimal baseline information is provided.

Mar 2024, Pakistan J. Medical Sciences, https://www.pjms.org.pk/index.php/pjms/article/view/8757, https://c19p.org/azhar

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

2,006 patient favipiravir early treatment study: 25% lower transmission (p=0.05).
Retrospective 976 mild to moderate COVID-19 outpatients in Thailand showing significantly lower household transmission with favipiravir treatment of index cases.

Dec 2024, J. Virus Eradication, https://www.sciencedirect.com/science/article/pii/S2055664024001912, https://c19p.org/siripongboonsitti7

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

251 patient azelastine late treatment RCT: 13% improved recovery (p=0.42) and 6% improved viral clearance (p<0.0001).
RCT 294 low-risk subjects with mild COVID-19 showing significantly greater reduction in viral load with azelastine 0.1% nasal spray vs. placebo. There was no COVID-19 related hospitalization in either group. The reduction in viral load was significantly higher in the azelastine group at day 3, 6 and 11. Authors report that treatment was associated with significant improvement in fever (p=0.0046), weakness (p=0.0012) and hypoxia (p<0.0001) compared to placebo, however detailed results are not provided for these and other symptoms. Treatment delay from symptom onset is not specified, however the baseline viral load, lack of progression, and recovery profile are consistent with relatively late treatment among low-risk patients. Time to recovery results are not clear, with an inconsistent HR and 95% CI reported 0.32 [0.83-2.32].

Oct 2024, MDPI AG, https://www.preprints.org/manuscript/202410.2532/v1, https://c19p.org/meiser

251 patient azelastine late treatment RCT: 13% improved recovery (p=0.42) and 6% improved viral clearance (p<0.0001).
RCT 294 low-risk subjects with mild COVID-19 showing significantly greater reduction in viral load with azelastine 0.1% nasal spray vs. placebo. There was no COVID-19 related hospitalization in either group. The reduction in viral load was significantly higher in the azelastine group at day 3, 6 and 11. Authors report that treatment was associated with significant improvement in fever (p=0.0046), weakness (p=0.0012) and hypoxia (p<0.0001) compared to placebo, however detailed results are not provided for these and other symptoms. Treatment delay from symptom onset is not specified, however the baseline viral load, lack of progression, and recovery profile are consistent with relatively late treatment among low-risk patients. Time to recovery results are not clear, with an inconsistent HR and 95% CI reported 0.32 [0.83-2.32].

Oct 2024, MDPI AG, https://www.preprints.org/manuscript/202410.2532/v1, https://c19p.org/meiserazl

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

16 patient HCQ early treatment RCT: 64% lower hospitalization (p=1) and 10% slower recovery.
Early terminated NIAID RCT for HCQ. Patients >60 were only in the HCQ arm. 57% of patients were high risk in the HCQ arm vs. 22% for control. Treatment started up to 20 days after symptoms.

Jul 2020, NCT04358068, https://clinicaltrials.gov/study/NCT04358068, https://c19p.org/smith2

192 patient favipiravir late treatment study: 54% improved recovery (p=0.03).
Retrospective 192 hospitalized patients in Indonesia, 96 patients treated with favipiravir, showing improved recovery with treatment. Only the abstract is currently available.

Oct 2021, Kesmas: National Public Health J., https://journal.fkm.ui.ac.id/kesmas/article/view/5433, https://c19p.org/damayanti

36 patient camostat early treatment RCT: 33% improved recovery (p=0.7).
Small early terminated RCT showing better recovery with camostat treatment, without statistical significance.

Nov 2023, BJGP Open, http://bjgpopen.org/lookup/doi/10.3399/BJGPO.2023.0109, https://c19p.org/tarecm

466 patient hydrogen peroxide prophylaxis study: 93% fewer cases (p=0.06).
Retrospective 458 healthcare workers in Ghana, showing lower COVID-19 cases with hydrogen peroxide prophylaxis (oral and nasal rinse), without statistical significance.

Aug 2022, J. Hospital Infection, https://www.sciencedirect.com/science/article/pii/S0195670122001499, https://c19p.org/amoah

55 patient vitamin D early treatment study: 87% lower ICU admission (p=0.09) and 38% shorter hospitalization (p<0.0001).
Prospective study of 30 patients treated with vitamin D, magnesium, and vitamin B12, and 25 control patients, showing shorter hospitalization and lower oxygen and ICU requirements with treatment. Cholecalciferol 1000IU, magnesium oxide 150mg, vitamin B12 500μg.

Apr 2022, Int. J. Pharmaceutical and Clinical Research, http://impactfactor.org/PDF/IJPCR/14/IJPCR,Vol14,Issue5,Article113.pdf, https://c19p.org/valecha

208 patient HCQ late treatment study: 44% lower mortality (p=0.14) and 3% improved recovery (p=0.91).
Retrospective 208 hospitalized COVID-19 patients in Burkina Faso showing lower mortality with HCQ/CQ+AZ treatment, without statistical significance. There was no difference for recovery.

Feb 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-192.php?jid=jide, https://c19p.org/baguiya

44 patient vitamin C late treatment RCT: 87% lower mortality (p=0.13) and 18% shorter hospitalization (p=0.23).
RCT 54 late stage patients, 18 treated with IV vitamin C (2g every 6h for 5 days), showing significant relative improvements in oxygen saturation and respiratory rate.

Nov 2021, Urology J., https://journals.sbmu.ac.ir/urolj/index.php/uj/article/view/6863, https://c19p.org/tehrani3

1,938 patient various antiandrogen prophylaxis study: 17% lower mortality (p=0.61) and 7% fewer cases (p=0.04).
Retrospective 944 5ARI users in the USA and 944 matched controls, showing lower risk of COVID-19 cases with treatment.

Jan 2022, J. Urology, https://www.auajournals.org/doi/10.1097/JU.0000000000002180, https://c19p.org/lyon

181 patient HCQ prophylaxis study: 51% fewer cases (p=0.02).
Study of hospital health care workers showing HCQ prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94 positive health care workers with a matched sample of 87 testing negative. Full course prophylaxis was important in this study which used a low dose of 400mg/week HCQ (800mg for week 1), so it may take longer to reach therapeutic levels. Actual benefit of HCQ may be larger because severity of symptoms are not considered here but HCQ may also reduce severity.

Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.21.20159301v1, https://c19p.org/khurana

615 patient HCQ late treatment study: 27% lower mortality (p=0.0005).
Retrospective 615 hospitalized COVID-19 patients in Morocco, showing lower mortality with HCQ in unadjusted results.

Dec 2022, Cureus, https://www.cureus.com/articles/122896-predictive-factors-of-death-and-the-clinical-profile-of-hospitalized-covid-19-patients-in-morocco-a-one-year-mixed-cohort-study, https://c19p.org/charif

546 patient exercise study: 41% lower hospitalization (p=0.18).
Retrospective 546 COVID+ patients in the USA, showing lower risk of hospitalization with higher frequency of strength training, without statistical significance.

Oct 2022, American J. Lifestyle Medicine, http://journals.sagepub.com/doi/10.1177/15598276221135541, https://c19p.org/reis6ex

101 patient zinc late treatment study: 88% lower mortality (p=0.13), 26% lower ventilation (p=0.75), 3% lower ICU admission (p=1), and 73% lower progression (p=0.004).
Retrospective 101 hospitalized pediatric patients in Saudi Arabia, showing zinc treatment associated with lower respiratory failure and shorter hospitalization in unadjusted results. Patients receiving zinc were older. Authors note elevated serum creatinine and the possibility of kidney injury.

Mar 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000415, https://c19p.org/ibrahimalhajjaji

4,476 patient exercise study: 33% fewer cases (p=0.05).
Retrospective 4,476 participants in Brazil, showing lower risk of COVID-19 cases with a history of physical activity, statistically significant only for those following specific practices to protect against COVID-19.

Oct 2022, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/19/21/14155, https://c19p.org/pitanga

991 patient aspirin late treatment study: 25% lower mortality (p=0.04).
Retrospective 991 hospitalized patients in Iran, showing lower mortality with aspirin treatment.

Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27053, https://c19p.org/hajiaghajanie

462 patient N-acetylcysteine late treatment study: 29% lower mortality (p=0.42), 41% lower ventilation (p=0.16), 20% lower ICU admission (p=0.36), and 14% shorter hospitalization (p=0.002).
Prospective study of 217 patients treated with NAC and 245 matched controls, showing improved recovery with treatment. 1500mg intravenous NAC daily.

May 2023, Caspian J Intern Med, https://caspjim.com/article-1-3389-fa.html, https://c19p.org/afaghi2

60 patient N-acetylcysteine late treatment RCT: 67% lower mortality (p=0.61).
RCT 60 hospitalized COVID-19 patients evaluating the efficacy and safety of adding oral N-acetylcysteine (NAC) at 600mg three times daily to standard antiviral treatment regimens. The NAC group showed significantly greater reduction in C-reactive protein levels, indicating reduced inflammation. Authors conclude that oral NAC may provide benefits through reducing inflammation, increasing oxygen saturation, and potentially reducing mortality when combined with certain antiviral medications in hospitalized COVID-19 patients.

Nov 2023, Immunity, Inflammation and Disease, https://onlinelibrary.wiley.com/doi/10.1002/iid3.1083, https://c19p.org/atefi

278 patient vitamin C ICU RCT: 55% lower mortality (p=0.2), 44% lower ventilation (p=0.41), and 37% shorter hospitalization (p=0.91).
RCT 278 COVID-19 ICU patients in Pakistan, showing lower mortality and ventilation, and shorter length of stay with high dose vitamin C treatment, without statistical significance. 30 grams IV vitamin C for four days.

Jun 2023, Biological and Clinical Sciences Research J., http://bcsrj.com/ojs/index.php/bcsrj/article/view/343, https://c19p.org/rana2

609 patient ivermectin late treatment RCT: 31% lower mortality (p=0.36), 50% lower ventilation (p=0.07), 16% lower ICU admission (p=0.47), and 11% longer hospitalization (p=0.009).
RCT 609 inpatients in Iran. Reported outcomes are very different from the pre-specified outcomes [irct.ir]. The outpatient trial is listed separately. From the pre-specified outcomes, all are either positive or not reported. Pre-specified outcomes: - Reduction in persistent cough - RR 0.36 p = 0.06 - Negative RT-PCR - not reported - Main complaints recovery time - not reported - Mortality - RR 0.69 p = 0.36 - Side effects - reported as none (anomalous) - Reduction in tachypnea - RR 0.24 p = 0.38 - Oxygen saturation >94% - not reported All negative outcomes are protocol violations and are not listed in the protocol, including the novel "relative recovery" outcome. Authors include a researcher caught on video admitting that conclusions on ivermectin research were influenced by a funder [c19ivm.org]. Severe cases were more frequent in the ivermectin group, 49% vs. 43%. Dose was limited at a maximum of 30mg for 75+kg, resulting in underdosing for patients at higher risk. Almost..

Jun 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.919708/full, https://c19p.org/rezai2

2,148 patient vitamin B12 prophylaxis study: 24% lower hospitalization (p=0.15) and 27% lower severe cases (p=0.06).
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin B12 prophylaxis, without statistical significance.

Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerb12

140 patient N-acetylcysteine ICU RCT: 16% lower mortality (p=0.49).
RCT 140 ICU patients in Spain, 72 treated with N-acetylcysteine (NAC). NAC patients showed improved PaO2/FiO2, CRP, D-dimer, and LDH, and there were associations between glutathione and clinical outcomes and severity biomarkers in NAC-treated patients. There was no significant difference in mortality.

May 2023, Nutrients, https://www.mdpi.com/2072-6643/15/9/2235, https://c19p.org/gamarramorales

161 patient vitamin C late treatment study: 25% lower combined mortality/intubation (p=0.74) and 73% lower progression (p=0.002).
PSM retrospective 207 hospitalized patients in China, 46 treated with diammonium glycyrrhizinate and vitamin C, showing lower risk of ARDS with treatment.

Jul 2021, QJM: An Int. J. Medicine, https://academic.oup.com/qjmed/advance-article/doi/10.1093/qjmed/hcab184/6329274, https://c19p.org/tan3

75 patient ivermectin late treatment RCT: 57% lower mortality (p=0.35), 34% higher ventilation (p=0.62), and 37% higher ICU admission (p=0.52).
RCT 75 very late stage patients in Colombia, showing no significant difference in outcomes with a single dose of 400μg/kg ivermectin.

Oct 2022, Revista Infectio, http://revistainfectio.org/P_OJS/index.php/infectio/article/view/1105, https://c19p.org/ochoajaramillo

310 patient aspirin prophylaxis study: 14% lower mortality (p=0.72), 28% lower ICU admission (p=0.17), 25% lower ARDS (p=0.39), and 2% lower hospitalization (p=0.94).
Retrospective 539 patients in the USA, showing lower mortality, ICU admission, and ARDS with aspirin treatment, without statistical significance.

Jul 2022, Health Science Reports, https://onlinelibrary.wiley.com/doi/10.1002/hsr2.699, https://c19p.org/malik

48,988 patient metformin prophylaxis study: 11% lower progression (p=0.11).
N3C/PCORnet retrospective adults with type 2 diabetes in the USA showing lower incidence of mortality or long COVID with metformin use.

Sep 2024, Diabetes Care, https://diabetesjournals.org/care/article/doi/10.2337/DCa24-0032/157171/Prevalent-Metformin-Use-in-Adults-With-Diabetes, https://c19p.org/johnson

33 patient zinc late treatment RCT: 20% lower mortality (p=1).
Small early terminated RCT with 33 hospitalized patients in Australia, 15 treated with zinc, showing no significant difference in clinical outcomes. Treatment increased zinc levels above the deficiency cutoff. Intravenous zinc 0.5mg/kg/day (elemental zinc concentration 0.24mg/kg/day) for up to 7 days. ACTRN12620000454976.

Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26895, https://c19p.org/patel2

1,208 patient HCQ late treatment study: 23% lower mortality (p=0.26).
Retrospective 1255 patients in Spain showing lower mortality with HCQ. Subject to confounding by indication.

Nov 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857920304696, https://c19p.org/rodriguezgonzalez

293 patient exercise study: 98% lower severe cases (p=0.007).
Retrospective 293 COVID+ patients in Russia, showing lower risk of severe COVID-19 for individuals who regularly practice aerobic training in unadjusted results.

Oct 2020, Pulmonologiya, https://journal.pulmonology.ru/pulm/article/view/1376, https://c19p.org/tretyakov

144 patient vitamin C late treatment study: 63% lower mortality (p=0.22).
Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing lower mortality with vitamin C treatment.

Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocy

627 patient HCQ prophylaxis study: 41% lower combined mortality/intubation (p=0.38).
Retrospective 103 SLE and 524 RA patients in Italy, showing significantly lower mortality/ventilation with HCQ use for SLE patients, and no significant difference for RA patients in unadjusted results. Authors did not include HCQ in multivariable analysis, only including four variables "chosen among the most clinically relevant". Multivariable analysis may significantly improve results for RA patients because HCQ use may correlate with more severe disease due to use for patients that failed or do not tolerate first-line therapies. It is not clear how the patients were selected - the very high ~25% ventilation/mortality suggests that most were hospitalized COVID-19 patients, in which case any benefit of HCQ in reducing hospitalizations will not be reflected in the results. Authors falsely state that "subsequent studies have definitely proved that [HCQ] is not linked to COVID-19 prognosis", suggesting significant bias, and possibily indicating why HCQ..

Oct 2023, Lupus Science & Medicine, https://lupus.bmj.com/lookup/doi/10.1136/lupus-2023-000945, https://c19p.org/scirocco

47 patient HCQ prophylaxis study: 59% lower mortality (p=1), 81% lower ventilation (p=0.54), and 33% lower severe cases (p=0.7).
Retrospective 47 rheumatic disease patients not finding significant differences with HCQ.

Apr 2021, Rheumatology Int. , https://link.springer.com/article/10.1007/s00296-021-04857-9, https://c19p.org/alzahrani

92 patient montelukast late treatment study: 64% lower progression (p=0.09) and 12% shorter hospitalization (p=0.33).
Retrospective 92 hospitalized patients showing lower clinical deterioration with montelukast treatment, without statistical significance in multivariable analysis. The treatment group was older.

Mar 2021, J. Asthma, https://www.tandfonline.com/doi/full/10.1080/02770903.2021.1881967, https://c19p.org/khan7

393 patient HCQ late treatment study: 28% lower mortality (p=0.3), 50% lower ICU admission (p=0.004), and 17% shorter hospitalization (p=0.007).
Retrospective 393 hospitalized COVID-19 patients in Turkey, showing lower ICU admission and shorter hospitalization time with HCQ. There was no significant difference for mortality. Severity was higher in the HCQ group with greater baseline ventilation, high flow oxygen, fever, and dyspnea.

Jan 2022, The J. Infection in Developing Countries, https://jidc.org/index.php/journal/article/view/14933, https://c19p.org/omma

100 patient probiotics early treatment RCT: 80% lower hospitalization (p=0.2) and 18% improved recovery (p=0.42).
RCT 150 patients in Egypt showing no significant difference in outcomes with probiotic lactobacillus acidophilus, although hospitalization was 2% versus 10% for control. SOC included vitamin C, D, and zinc.

Jun 2023, Research Square, https://www.researchsquare.com/article/rs-3049708/v1, https://c19p.org/hassan

100 patient camostat late treatment RCT: 25% lower mortality (p=1).
RCT 100 patients showing no significant difference with camostat. Results are currently unclear—different mortality numbers were provided for all-cause mortality and mortality rate (2/50 vs. 3/46 for the treatment group at 28 days, with the 28 day all-cause mortality result removed in an updated submission). The main outcome measures appear to be different due to only including patients that submitted day 28 outcome data.

Mar 2024, NCT04470544, https://clinicaltrials.gov/study/NCT04470544, https://c19p.org/bryce

2,148 patient vitamin C prophylaxis study: 25% lower hospitalization (p=0.08) and 17% lower severe cases (p=0.18).
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin C prophylaxis, without statistical significance.

Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerc

34 patient povidone-iodine early treatment RCT: 89% improved viral clearance (p=0.05).
Small RCT comparing mouthwashing with PVP-I, chlorhexidine, and water, showing significant efficacy for both PVP-I and chlorhexidine, with PVP-I increasing Ct by a mean of 4.45 (p < 0.0001) and chlorhexidine by a mean of 5.69 (p < 0.0001), compared to no significant difference for water.

Mar 2021, J. Evidence Based Dental Practice, https://www.sciencedirect.com/science/article/abs/pii/S1532338221000592, https://c19p.org/elzein

139 patient vitamin C late treatment study: 44% lower mortality (p=0.19) and 10% lower ICU admission (p=0.66).
Retrospective 139 hospitalized patients in Turkey, 58 treated with high dose vitamin C, showing improved kidney functioning with treatment. Mortality was lower with treatment, but not reaching statistical significance with the small sample size.

Sep 2021, Annals of Medical Research, https://www.annalsmedres.org/index.php/aomr/article/view/3910, https://c19p.org/simsekc

89 patient diet study: 53% lower mortality (p=0.05).
Retrospective 89 COVID-19 patients in Spain, showing lower mortality with adherence to the Mediterranean diet.

Dec 2021, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457721009293, https://c19p.org/magana

421 patient metformin early treatment RCT: 27% lower mortality (p=0.53), 6% lower hospitalization (p=0.88), 14% more combined hospitalization/ER visits (p=0.58), and 31% lower progression (p=0.48).
Data for the primary outcome in this trial appears to be impossible [doyourownresearch.substack.com]. For example, considering the metformin arm and the ITT population: 24 were hospitalized and 8 had an ER visit (tables S2/S3), therefore the number for combined ER or hospitalization must be between 24 and 32. However, authors report 34 events for ER/hospitalization. RCT with 215 patients treated with metformin and 203 controls, showing no significant difference with treatment. For multiple major issues with this trial see [doyourownresearch.substack.com, doyourownresearch.substack.com]. An expression of concern was posted in 2024 [thelancet.com]. The hospitalization risk for off-protocol patients was several times higher in both arms, resulting in Simpson's paradox when combining per-protocol and off-protocol patients [web.archive.org]. 750mg twice daily for 10 days.

Aug 2021, The Lancet Regional Health - Americas, https://www.sciencedirect.com/science/article/pii/S2667193X21001381, https://c19p.org/reis3

1,267 patient vitamin D prophylaxis study: 12% higher mortality (p=0.59), 43% lower ventilation (p=0.22), 44% lower ICU admission (p=0.03), and 12% shorter hospitalization (p=0.2).
Retrospective 1,267 hospitalized patients in Spain, 189 on vitamin D supplementation before admission, showing lower ICU admission with supplementation, and no statistically significant difference for mortality or ventilation.

Sep 2021, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2021.758347/full, https://c19p.org/arroyodiaz

160 patient HCQ late treatment study: 55% lower mortality (p=0.21).
55% lower death with HCQ+AZ. Retrospective 160 hospitalized patients in the Democratic Republic of Congo, 92% receiving HCQ+AZ, showing adjusted OR 0.24 [0.03-2.2].

Dec 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244272, https://c19p.org/matangila

334 patient vitamin B9 prophylaxis study: 27% lower mortality (p=0.54) and 6% lower combined mortality/intubation (p=0.88).
Retrospective 333 hospitalized patients in Israel, showing no significant difference in outcomes with low folate levels or with folic acid supplementation.

Mar 2021, Nutrients, https://www.mdpi.com/2072-6643/13/3/812, https://c19p.org/meisel

1,317 patient metformin prophylaxis study: 20% lower mortality (p=0.46).
Analysis of 1,317 hospitalized COVID-19 patients with diabetes showing lower mortality with metformin use, without statistical significance.

May 2020, Diabetologia, https://link.springer.com/10.1007/s00125-020-05180-x, https://c19p.org/cariou

3,441 patient HCQ prophylaxis PSM study: 30% fewer cases (p=0.18).
Retrospective database analysis of prior HCQ usage in South Korea, showing non-statistically significantly lower mortality and cases with treatment.

Feb 2021, Viruses 2021, https://www.mdpi.com/1999-4915/13/2/329, https://c19p.org/bae

307 patient famotidine prophylaxis study: 22% fewer symptomatic cases (p=0.49) and 37% faster recovery (p=0.32).
Survey of 307 patients in the USA, showing no significant difference in COVID-19 cases with famotidine use.

Jan 2021, J. Voice, https://www.sciencedirect.com/science/article/pii/S0892199721000321, https://c19p.org/balouch

864 patient N-acetylcysteine late treatment study: 52% lower mortality (p=0.0001).
Retrospective 864 hospitalized late stage COVID-19 patients in the USA, 138 receiving NAC treatment for acute hepatitis, showing lower mortality with treatment. Results are adjusted for confounders, however details are not provided.

May 2021, Gastroenterology, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8108159/, https://c19p.org/pellegrini

44 patient nitazoxanide late treatment study: 68% lower mortality (p=0.38), 87% lower ventilation (p=0.15), 59% lower ICU admission (p<0.0001), and 52% shorter hospitalization (p=0.007).
Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.

Nov 2021, PAMJ - Clinical Medicine, https://www.clinical-medicine.panafrican-med-journal.com/content/article/7/15/full/, https://c19p.org/calderon2

38 patient colchicine early treatment RCT: 67% lower hospitalization (p=0.55) and 24% improved recovery (p=0.72).
RCT 38 low risk outpatients in Japan, showing no significant differences for colchicine and low-dose aspirin compared to loxoprofen. Hospitalization was lower, without statistical significance (4.3% vs. 13.3%, p=0.34). There were no critical cases, deaths, or severe adverse events in either group. Colchicine: 1.0mg loading dose, followed approximately half a day later by 0.5mg twice daily for 10 doses, and then 0.5 mg once daily for four doses. Aspirin: 100mg daily for 10 days. Both groups received probiotics and acetaminophen.

Mar 2024, The Kurume Medical J., https://www.jstage.jst.go.jp/article/kurumemedj/advpub/0/advpub_MS7012003/_article, https://c19p.org/inokuchi

211 patient vitamin D prophylaxis study: 33% lower severe cases (p=0.45) and 44% fewer cases (p=0.23).
Case control study with 39 COVID+ and 172 COVID- Parkinson's disease patients in Spain, showing positive and severe cases being less likely to use vitamin D supplementation compared to negative or mild/negative cases respectively. These differences were not statistically significant.

Oct 2020, J. Neurology, https://link.springer.com/article/10.1007/s00415-020-10272-0, https://c19p.org/sainzamo

HCQ early treatment study: 85% lower progression (p=0.006), 24% faster improvement (p=0.02), and 36% improved viral clearance (p=0.001).
85% lower disease progression with early use of HCQ. Retrospective 616 patients in China showing adjusted progression HR 0.15, p = 0.006.

Dec 2020, BioScience Trends, https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.03340/_article/-char/ja/, https://c19p.org/su

60 patient vitamin C ICU RCT: 23% lower mortality (p=0.6) and 21% lower ventilation (p=0.6).
RCT 60 ICU patients in India, showing no significant difference in outcomes with vitamin C. Mortality was lower in the vitamin C arm despite having more severe cases at baseline (87% vs. 67%). 1 gram intravenous vitamin C 8 hourly for four days.

Aug 2022, J. Family Medicine and Primary Care, https://journals.lww.com/10.4103/jfmpc.jfmpc_2437_21, https://c19p.org/kumar5

113 patient nitazoxanide early treatment study: 87% improved viral clearance (p<0.0001).
Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.

Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26880, https://c19p.org/elalfyn

60 patient probiotics late treatment RCT: 11% faster recovery (p=0.19) and 11% shorter hospitalization (p=0.18).
Small RCT 60 patients in India, 30 treated with ImmunoSEB and ProbioSEB CSC3, showing faster recovery with treatment. CTRI/2020/09/027685, CTRI/2020/08/027168.

Feb 2021, Advances in Clinical Toxicology, https://advancedenzymesdirect.com/wp-content/uploads/2021/05/Covid-Published-paper.pdf, https://c19p.org/shah

376 patient aspirin late treatment study: 14% lower mortality (p=0.61), 30% lower ventilation (p=0.24), 40% lower progression (p=0.05), and 6% worse results (p=0.88).
Retrospective 376 hospitalized COVID-19 patients in the United States showing no significant differences with aspirin. Mortality, mechanical ventilation, and hypoxia were lower with treatment, without statistical significance.

Jun 2024, Cardiology Research, http://www.cardiologyres.org/index.php/Cardiologyres/article/view/1645, https://c19p.org/vinod

2,066 patient HCQ prophylaxis study: 59% lower mortality (p=1) and 13% more cases (p=0.86).
Retrospective cohort study of RA and SLE patients not showing a significant difference in PCR+ cases. PCR+ does not distinguish asymptomatic cases or severity. There was only one death which was in the control group. No other information on severity is provided. 33% of the control group used HCQ within the last year. Remaining confounding by differences in the nature and severity of rheumatic disease is likely.

Dec 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20307527, https://c19p.org/jung

477 patient vitamin C prophylaxis study: 31% lower hospitalization (p=0.05).
Retrospective 477 COVID+ public transportation workers in Turkey, showing lower risk of hospitalization with vitamin C use in unadjusted results.

Nov 2022, Work, https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-220292, https://c19p.org/guldemir

2,148 patient vitamin B9 prophylaxis study: 28% lower hospitalization (p=0.23) and 28% lower severe cases (p=0.16).
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing lower risk of severity and hospitalization with vitamin B9 prophylaxis, without statistical significance.

Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerb9

52 patient diet study: 66% fewer cases (p=0.009).
Retrospective 84 flight attendants, 52 reporting COVID-19 status and diet quality, showing higher risk of COVID-19 with lower self-reported diet quality.

Dec 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-04350-0, https://c19p.org/yamamoto

144 patient HCQ prophylaxis PSM study: 13% fewer cases (p=0.006).
PSM retrospective 144 alopecia patients in the USA, showing lower risk of COVID-19 with HCQ prophylaxis. The supplemental appendix is not available.

Jun 2021, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961621P0914X, https://c19p.org/shaw

309 patient ivermectin prophylaxis study: 80% fewer cases (p<0.0001).
Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases are not provided, and the results are subject to survey bias. Authors also report on community prophylaxis but present only combined ivermectin/HCQ results.

Nov 2021, J. the Association of Physicians India, https://www.researchgate.net/publication/356294136_Ivermectin_and_Hydroxychloroquine_for_Chemo-Prophylaxis_of_COVID-19_A_Questionnaire_Survey_of_Perception_and_Prescribing_Practice_of_Physicians_vis-a-vis_Outcomes, https://c19p.org/samajdar

35 patient ivermectin early treatment study: 70% faster recovery (p=0.0001) and 97% improved viral clearance (p<0.0001).
Small study with 28 patients treated with ivermectin + AZ + cholecalciferol and 7 control patients. All treated patients were PCR- at day 10 while all control patients remained PCR+. The mean duration of symptoms was 3 days in the treatment group and 10 days in the control group.

Aug 2020, Biomedical Research, https://www.biomedres.info/biomedical-research/effects-of-ivermectinazithromycincholecalciferol-combined-therapy-on-covid19-infected-patients-a-proof-of-concept-study-14435.html, https://c19p.org/espitiahernandez

197 patient HCQ late treatment study: 40% lower severe cases (p=0.02).
Retrospective 197 hospitalized COVID-19 patients in Spain, showing lower progression to pneumonia with HCQ in unadjusted results.

Mar 2021, Advances in Laboratory Medicine / Avances en Medicina de Laboratorio, https://www.degruyter.com/document/doi/10.1515/almed-2021-0017/html, https://c19p.org/rubiosanchez

1,213 patient HCQ prophylaxis study: 35% lower mortality (p=0.19) and 19% lower hospitalization (p=0.36).
Retrospective 1,213 rheumatic disease patients in France, showing lower risk of mortality and severe cases with HCQ use in univariate analysis, without statistical significance.

Mar 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1152587/full, https://c19p.org/chevalier

509 patient diet study: 72% lower severe cases (p=0.23) and 11% fewer moderate/severe cases (p=0.66).
Retrospective 509 COVID-19 patients in Taiwan, showing higher risk of critical COVID-19 cases with non-vegetarian diets.

Apr 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.837458/full, https://c19p.org/hou

9,644 patient HCQ late treatment study: 27% lower mortality (p=0.06).
Retrospective study focused on eosinophil recovery with 9,644 hospitalized patients in Spain, showing lower mortality for HCQ (14.7% vs 29.2%, p<0.001), and AZ (15.3% vs. 18.4%, p<0.001). With a multivariate model including potential confounding factors, HCQ and AZ are associated with lower mortality, HCQ OR 0.662, p=0.057.

Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.18.20172874v1, https://c19p.org/gonzalez2

607 patient HCQ late treatment study: 20% lower mortality (p=0.36).
Retrospective 607 patients reporting results for early outpatient HCQ use with mortality odds ratio OR 0.092 [0.022-0.381], p = 0.001 (65 patients), and for hospital use, mortality odds ratio OR 0.737 [0.38-1.41], p = 0.36 (558 patients). Median age 69.

Oct 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303357, https://c19p.org/guisadovasco

100 patient fluvoxamine long COVID RCT: 51% lower PASC (p=0.06).
RCT 100 mild/moderate COVID-19 outpatients in Iran, showing lower post COVID symptoms 12 weeks after infection, statistically significant only for fatigue with the small sample size. All symptoms may occur for non-COVID-19 reasons, smell/taste disorder may be the most likely to be related to COVID-19 infection. Fluvoxamine 100mg daily for 10 days.

Mar 2023, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08172-5, https://c19p.org/farahani

130 patient HCQ prophylaxis study: 82% fewer symptomatic cases (p=0.17).
Small prophylaxis study with 130 healthcare workers in the USA, showing lower symptomatic cases with HCQ prophylaxis, without statistical significance. HCQ participants were significantly older. The only symptomatic HCQ patient reported headache only as a potential COVID-19 symptom.

Jul 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.07.01.22277058, https://c19p.org/raabe

1,847 patient exercise study: 11% fewer moderate/severe cases (p=0.3) and 14% lower PASC (p=0.24).
Retrospective 1,847 COVID+ patients in Poland, showing no significant difference in moderate/severe cases with physical activity. Hospitalized patients were excluded.

Oct 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.1036556/full, https://c19p.org/plywaczewska

91 patient N-acetylcysteine ICU RCT: 14% lower mortality (p=0.37).
RCT mechanically ventilated patients in Croatia, 39 treated with N-acetylcysteine and 52 control patients, showing no significant difference in mortality with treatment. Treated patients showed a lower incidence of gram-positive or MRSA-caused ventilator-associated pneumonia. ICU mortality results are from [repozitorij.mefst.unist.hr].

May 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/6/1118, https://c19p.org/delic

1,645 patient aspirin prophylaxis study: 28% lower mortality (p=0.07).
Retrospective 1,645 hospitalized patients in the USA, showing lower mortality with aspirin use, without statistical significance.

Nov 2022, Chest, https://www.sciencedirect.com/science/article/pii/S0012369222041617, https://c19p.org/ali7

600 patient HCQ late treatment study: 28% lower mortality (p=0.1).
Retrospective 600 hospitalized patients in Italy, showing lower mortality with HCQ treatment, without reaching statistical significance (p = 0.1).

Oct 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-00243-4/, https://c19p.org/guglielmetti2

162 patient favipiravir late treatment study: 51% improved viral clearance (p=0.02).
Retrospective 162 hospitalized COVID-19 patients in Indonesia, showing lower incidence of delayed viral clearance with favipiravir treatment in unadjusted results.

May 2023, Pathophysiology, https://www.mdpi.com/1873-149X/30/2/16, https://c19p.org/arfijanto

65 patient colchicine ICU study: 23% lower mortality (p=0.6) and 40% shorter ICU admission (p=0.03).
Retrospective 65 ICU patients in the USA and Honduras, showing shorter ICU stay with combined treatment including colchicine, LMWH, tocilizumab, dexamethasone, and methylprednisolone.

Jan 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245025, https://c19p.org/valeriopascua

122 patient HCQ late treatment study: 33% lower mortality (p=0.28) and 39% lower combined mortality/ICU admission (p=0.23).
33% lower mortality with HCQ+AZ, p=0.28. Retrospective 122 French dialysis patients. 69% lower combined mortality/ICU, p=0.11, for the subgroup not requiring O2 on diagnosis (slightly earlier treatment).

Oct 2020, Clinical Kidney J., October 2020, 878–888, https://academic.oup.com/ckj/article/13/5/878/5934808, https://c19p.org/lano

12,331 patient metformin prophylaxis PSM study: 7% lower combined mortality/hospitalization (p=0.61) and 15% lower progression (p=0.16).
Retrospective 12,331 diabetes patients in Hong Kong, showing no significant difference in outcomes with metformin use.

Sep 2022, SSRN Electronic J., https://www.ssrn.com/abstract=4225660, https://c19p.org/yip2

32 patient povidone-iodine late treatment RCT: 85% improved viral clearance (p=0.65).
Two RCTs with a total of 247 recently diagnosed COVID-19 patients showing a significant reduction in salivary SARS-CoV-2 viral load 30 minutes after rinsing with a cetylpyridinium chloride (CPC) mouthwash compared to rinsing with saline or water. No significant difference was seen 60 minutes post-rinse or with other mouthwashes. Supplementary tables 9 and 10 show that viral load was lower for all treatments at 60 minutes (including saline and water), without statistical significance. Authors only report short-term viral load, no clinical or longer term results are reported. Patients were late stage, 6-7 days post symptoms, when there has likely been significant viral spread to other tissues.

Dec 2024, JDR Clinical & Translational Research, https://journals.sagepub.com/doi/10.1177/23800844241296840, https://c19p.org/gravesp

100 patient metformin prophylaxis study: 78% lower mortality (p=0.01) and 41% improved recovery (p=0.0002).
Prospective study of 60 hospitalized type 2 diabetes patients with COVID-19 on metformin monotherapy compared to 40 patients on other diabetes treatments, showing significantly lower inflammatory biomarkers, oxidative stress, and mortality, and improvements in radiological and clinical outcomes with metformin. Confounding due to differences in baseline characteristics may be significant.

Nov 2023, European Review for Medical and Pharmacological Sciences, https://doi.org/10.26355/eurrev_202312_34583, https://c19p.org/alkuraishy3

477 patient various antiandrogen prophylaxis PSM study: 20% lower mortality (p=0.41) and 2% lower severe cases (p=0.94).
Retrospective 1,106 prostate cancer patients, showing no significant differences in COVID-19 outcomes with ADT.

Nov 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786026, https://c19p.org/schmidt

2,148 patient vitamin A prophylaxis study: 21% lower hospitalization (p=0.4) and 21% lower severe cases (p=0.36).
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with vitamin A prophylaxis.

Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimera

66 patient HCQ late treatment study: 81% improved viral reduction rate (p=0.4).
Viral load comparison for 34 HCQ and 32 control patients hospitalized with moderate COVID-19. All patients recovered limiting the room for beneficial effects. While not achieving statistical significance, results show faster recovery with HCQ. The greatest benefit is seen mid-recovery as expected for an effective treatment: Δt7-12: 81% improvement with HCQ Δt<7: 24% improvement with HCQ For Δt>12, everyone has recovered so there is no room for improvement. Since the HCQ group started slightly higher the improvement is slightly less. Most participants have also dropped out by this test, with only 6 HCQ and 9 control remaining (also suggesting HCQ patients recovered faster).

Jun 2020, Braz J Microbiol, https://link.springer.com/article/10.1007/s42770-020-00395-x, https://c19p.org/faicofilho

109 patient metformin prophylaxis study: 50% lower mortality (p=0.01).
Retrospective 109 hospitalized COVID-19 patients in Syria, 68 with diabetes, showing significantly lower mortality with metformin vs. sulfonylureas, and significantly higher mortality with discontinuation of metformin.

Nov 2023, Research J. Pharmacy and Technology, https://www.rjptonline.org/HTMLPaper.aspx?Journal=Research%20Journal%20of%20Pharmacy%20and%20Technology;PID=2023-16-11-25, https://c19p.org/mamari

8,157 patient diet study: 37% fewer cases (p=0.03).
Analysis of 8,157 adults showing significantly higher risk of COVID-19 with higher adherence to an unhealthy diet, characterized by higher intake of less healthy foods such as fruit juices, refined grains, potatoes, and sugar-sweetened beverages. The association was independent of socio-demographic status and BMI.

Nov 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-10115-7, https://c19p.org/darand2

1,847 patient sleep study: 17% fewer moderate/severe cases (p=0.06) and 7% lower PASC (p=0.51).
Retrospective 1,847 COVID+ patients in Poland, showing lower moderate/severe cases with improved sleep, without statistical significance. Hospitalized patients were excluded.

Oct 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.1036556/full, https://c19p.org/plywaczewskasl

9,267 patient zinc prophylaxis study: 18% lower ventilation (p=0.78) and 30% lower ICU admission (p=0.6).
Retrospective 9,748 COVID-19 patients in the USA showing lower ventilation and ICU admission with zinc prophylaxis, without statistical significance.

Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanz

105 patient HCQ late treatment RCT: no change in recovery (p=0.91) and 29% improved viral clearance (p=0.47).
Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatment to make improvements. Time since symptom onset is not specified, but the distribution of symptoms at baseline suggests that the enrollment is relatively late within a cohort of low risk patients.

Jun 2021, Research Square, https://www.researchsquare.com/article/rs-506195/v1, https://c19p.org/byakikakibwika

34 patient favipiravir late treatment study: 7% shorter hospitalization (p=0.84) and 55% faster viral clearance (p=0.04).
Retrospective 17 COVID+ patients treated with favipiravir and 17 matched controls in Japan, showing faster viral clearance with treatment. Favipiravir 3600mg day one, 1600mg per day for up to 14 days.

Mar 2022, Viruses, https://www.mdpi.com/1999-4915/14/4/670, https://c19p.org/shinada

63 patient favipiravir late treatment RCT: 68% lower mortality (p=0.15), 35% lower ICU admission (p=0.51), 25% shorter hospitalization (p=0.14), and 18% improved viral clearance (p=0.24).
RCT comparing favipiravir and lopinavir/ritonavir, showing no significant differences. All patients received interferon-beta. Favipiravir 1600mg bid for the first day and 600mg bid for the following 4 days.

Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27724, https://c19p.org/hassaniazad2

66 patient melatonin late treatment RCT: 17% improved recovery (p=0.38).
Early terminated low-risk patient RCT with 32 low-dose vitamin C, 32 melatonin, and 34 placebo patients, showing faster resolution of symptoms with melatonin in spline regression analysis, and no significant difference for vitamin C. All patients recovered with no serious outcomes reported. Baseline symptoms scores were higher in the melatonin and vitamin C arms (median 27 and 24 vs. 18 for placebo).

Jul 2022, The J. the American Board of Family Medicine, http://www.jabfm.org/lookup/doi/10.3122/jabfm.2022.04.210529, https://c19p.org/fogleman

95 patient diet study: 70% fewer cases (p=0.09).
Dietary analysis of 95 adults in Poland, showing lower risk of COVID-19 with higher intake of polyphenols, lignans, and phytosterols. Results were statistically significant for total phytosterols, secoisolariciresinol, β-sitosterol, matairesinol, and stigmasterol. Authors suggest that beneficial effects on gut microbiota and immune function may contribute to the lower risk.

Aug 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2023.1241016/full, https://c19p.org/micek

738 patient nigella sativa early treatment study: 24% lower hospitalization (p=0.09).
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.

May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihins

1,250 patient montelukast late treatment RCT: 1% fewer combined hospitalization/ER visits (p=1), 48% higher progression (p=0.29), and 2% improved recovery (p=0.72).
RCT 1,250 outpatients with mild to moderate COVID-19 showing no significant difference in time to sustained recovery with montelukast treatment. There were no deaths and only 2 hospitalizations in each group. Notably, results were better with patients that had mild COVID-19 at baseline compared to moderate/severe cases, and overall efficacy is reduced by poor results with extremely late treatment 9 days after onset, and with patients that had no symptoms at baseline. Authors note the treatment drug was voluntarily recalled and replaced from another source but do not report why the drug was recalled. Authors describe previous research testing 10mg and 20mg doses, noting that only 20mg showed improved pulmonary function testing, however authors do not indicate why they chose to test the lower dose for COVID-19. It is unclear why authors only report all-cause hospitalization and urgent care and do not report COVID-19 specific outcomes. Given the low rate of urgent care visits and..

May 2024, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2825081, https://c19p.org/rothman

182 patient alkalinization late treatment study: 57% lower mortality (p=0.37), 39% lower progression (p=0.52), and 19% improved recovery (p=0.03).
Prospective study of 182 COVID-19 pneumonia patients, 127 treated with sodium bicarbonate inhalation and nasal drops, showing significantly faster recovery and improved CT scores with treatment. Authors note that contacts of index cases also received sodium bicarbonate treatment, with none reporting COVID-19. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).

Jun 2022, Indian J. Respiratory Care, https://www.ijrc.in/abstractArticleContentBrowse/IJRC/98/10/3/30725/abstractArticle/Article, https://c19p.org/elbadrawy2

182 patient sodium bicarbonate late treatment study: 57% lower mortality (p=0.37), 39% lower progression (p=0.52), and 19% improved recovery (p=0.03).
Prospective study of 182 COVID-19 pneumonia patients, 127 treated with sodium bicarbonate inhalation and nasal drops, showing significantly faster recovery and improved CT scores with treatment. Authors note that contacts of index cases also received sodium bicarbonate treatment, with none reporting COVID-19. Inhalation of nebulized sodium bicarbonate 8.4% (5ml every 4h) 7:00am to 23:00pm every day for 30 days together with 8.4% nasal drops 4 times daily (three drops for each nostril).

Jun 2022, Indian J. Respiratory Care, https://www.ijrc.in/abstractArticleContentBrowse/IJRC/98/10/3/30725/abstractArticle/Article, https://c19p.org/elbadrawy2sb

20 patient famotidine late treatment RCT: 33% shorter hospitalization (p=0.04) and no change in recovery (p=1).
Very small RCT with 20 patients in Iran, showing shorter hospitalization time with famotidine treatment. There was no mortality or ICU admission. Famotidine 160mg four times a day. IRCT20200509047364N2.

Apr 2021, Research Square, https://www.researchsquare.com/article/rs-462937/v1, https://c19p.org/samimagham

967 patient HCQ prophylaxis study: 21% fewer cases (p=0.27).
PSM retrospective 322 rheumatological patients on HCQ and 645 matched controls, showing lower risk of COVID-19 with treatment, without statistical significance. Authors mention lower mortality with HCQ but do not provide details. Only an abstract is available.

May 2023, J. Clinical Rheumatology, https://journals.lww.com/10.1097/RHU.0000000000001986, https://c19p.org/dulcey

31 patient melatonin early treatment RCT: 73% improved recovery (p=0.06).
Small RCT 31 mild/moderate COVID-19 outpatients in Iran, 14 treated with melatonin, showing improved recovery with treatment.

May 2021, Iranian J. Allergy, Asthma and Immunology, https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3086, https://c19p.org/alizadeh

285 patient HCQ late treatment study: 35% shorter hospitalization (p=0.04).
Retrospective 333 patients in China, with only 8 HCQ patients, showing shorter duration of hospitalization with HCQ.

Dec 2020, Virus Research, https://www.sciencedirect.com/science/article/abs/pii/S0168170220311692, https://c19p.org/tan2

700 patient HCQ prophylaxis study: 37% fewer cases (p=0.17).
Retrospective 700 patients with autoimmune rheumatic disease in Qatar, showing lower risk of COVID-19 with HCQ use, without statistical significance. For patients having close contact with COVID-19 cases, there was a statistically significant association with HCQ use and lower risk of COVID-19 in unadjusted results.

Aug 2022, Qatar Medical J., https://www.qscience.com/content/journals/10.5339/qmj.2022.37, https://c19p.org/becetti

7,047 patient metformin prophylaxis study: 19% lower PASC (p=0.29).
Retrospective 7,047 outpatients with type 2 diabetes showing a lower risk of PASC (long COVID) with metformin compared to sulfonylurea or DPP-4 inhibitor use, without statistical significance.

May 2024, Clinical Epidemiology, https://www.dovepress.com/risk-of-post-acute-sequelae-of-sars-cov-2-infection-pasc-among-patient-peer-reviewed-fulltext-article-CLEP, https://c19p.org/olawore

94 patient HCQ late treatment study: 43% lower mortality (p=0.12).
Analysis of 94 hemodialysis COVID-19 positive patients, showing lower mortality with HCQ treatment, not reaching statistical significance.

May 2020, Kidney Int., 20-26, July 1, 2020, https://www.kidney-international.org/article/S0085-2538(20)30508-1/fulltext, https://c19p.org/alberici

901. Belmont et al., COVID-19 PrEP HCW HCQ Study
80 patient HCQ prophylaxis study: 79% fewer symptomatic cases (p=0.21).
Prospective study of HCQ prophylaxis in the USA, with 56 HCQ patients and 24 control patients, showing no significant differences. NCT04354870

Oct 2021, ClinicalTrials.gov, NCT04354870, https://clinicaltrials.gov/ct2/show/results/NCT04354870, https://c19p.org/belmont

80 patient colchicine late treatment RCT: 24% shorter hospitalization (p=0.009).
Open label RCT of colchicine showing improved recovery with treatment. Only the abstract is currently available. Colchicine 0.5mg bid for 14 days.

May 2022, Indian J. Rheumatology, http://www.indianjrheumatol.com/preprintarticle.asp?id=344591;type=0, https://c19p.org/jalal

90 patient metformin prophylaxis study: 45% lower mortality (p=0.1).
Retrospective 90 hospitalized COVID-19 patients with diabetes in Italy, showing lower mortality with metformin use, without statistical significance.

Oct 2020, Diabetes Care, https://diabetesjournals.org/care/article/43/12/3042/30894/Impact-of-Comorbidities-and-Glycemia-at-Admission, https://c19p.org/mirani

249 patient azvudine early treatment study: 20% lower mortality (p=0.44) and 3% lower progression (p=0.91).
Retrospective 249 elderly patients with severe COVID-19, 128 treated with azvudine, 66 treated with paxlovid, and 55 receiving neither treatment, showing no significant differences for Ct value changes, progression, or survival for either treatment. Early viral decline was faster with paxlovid, without statistical significance.

Feb 2024, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537024000476, https://c19p.org/wang25

10 patient povidone-iodine early treatment RCT: 86% improved viral clearance (p=0.17).
Tiny RCT with 5 PVP-I patients, gargling 30 seconds, 3x per day, and 5 control patients (essential oils and tap water were also tested), showing improved viral clearance with PVP-I.

Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.07.20180448v1, https://c19p.org/mohamed

50 patient curcumin early treatment RCT: 29% improved recovery (p=0.11) and 91% improved viral clearance (p=0.05).
Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.

Jan 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full, https://c19p.org/dinujjant

50 patient quercetin early treatment RCT: 29% improved recovery (p=0.11) and 91% improved viral clearance (p=0.05).
Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.

Jan 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full, https://c19p.org/dinujjanq

477 patient HCQ prophylaxis study: 45% lower hospitalization (p=0.18).
Retrospective 81 cases and 396 controls among rheumatic disease patients in the Netherlands, showing lower risk of hospitalization with HCQ prophylaxis, without statistical significance.

Feb 2022, Clinical Pharmacology & Therapeutics, https://ascpt.onlinelibrary.wiley.com/doi/10.1002/cpt.2551, https://c19p.org/opdam

56 patient vitamin C ICU RCT: 50% lower mortality (p=0.2).
Small RCT for high dose vitamin C for ICU patients showing reduced (but not statistically significant) mortality. Dosage was 12g of vitamin C/50ml every 12 hours for 7 days at a rate of 12ml/hour.

Aug 2020, Annals of Intensive Care, https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00792-3, https://c19p.org/zhang

6 patient povidone-iodine late treatment RCT: 33% improved viral load (p=0.01).
Small mouthwash RCT with 4 PVP-I patients and 2 water patients concluding that PVP-I may have a sustained effect on reducing the salivary SARS-CoV-2 level in COVID-19 patients. ISRCTN95933274.

Dec 2020, Infection, https://link.springer.com/article/10.1007/s15010-020-01563-9, https://c19p.org/seneviratne

60 patient vitamin D ICU RCT: 89% lower mortality (p=0.11), 41% lower hospitalization (p=0.25), and 45% improved recovery (p=0.001).
Small RCT 60 ICU patients in Iran, 30 treated with vitamins A, B, C, D, and E, showing significant improvement in SOFA score and several inflammatory markers at day 7 with treatment. 5,000 IU vitamin A daily, 600,000 IU vitamin D once, 300 IU of vitamin E twice a day, 500 mg vitamin C four times a day, and one ampule daily of B vitamins [thiamine nitrate 3.1 mg, sodium riboflavin phosphate 4.9 mg (corresponding to vitamin B2 3.6 mg), nicotinamide 40 mg, pyridoxine hydrochloride 4.9 mg (corresponding to vitamin B6 4.0 mg), sodium pantothenate 16.5 mg (corresponding to pantothenic acid 15 mg), sodium ascorbate 113 mg (corresponding to vitamin C 100 mg), biotin 60 μg, folic acid 400 μg, and cyanocobalamin 5 μg].

Nov 2021, Trials, https://link.springer.com/article/10.1186/s13063-021-05795-4/fulltext.html, https://c19p.org/beigmohammadi2

220 patient HCQ prophylaxis study: 92% lower mortality (p=1) and 12% lower hospitalization (p=0.34).
Retrospecttive 220 COVID-19 patients with rheumatic disease in Japan, showing lower mortality and hospitalization with HCQ prophylaxis, without statistical significance.

Sep 2022, Modern Rheumatology, https://academic.oup.com/mr/advance-article/doi/10.1093/mr/roac104/6692611, https://c19p.org/oku

100 patient ivermectin late treatment RCT: 32% greater improvement (p=0.28).
Multicenter double-blind RCT with 100 hospitalized patients in Bulgaria showing faster viral clearance, greater clinical improvement, and improved biomarkers with treatment. Limited data has been reported currently. No serious adverse events were observed.

Mar 2021, Huvemek, Press Release, https://huvemec.bg/covid-19-huvemec-klinichno-izpitanie/za-isledvaneto/, https://c19p.org/petkov

152 patient vitamin C late treatment study: 31% lower mortality (p=0.04).
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.

Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnanc

214 patient HCQ late treatment RCT: 12% lower mortality (p=0.66).
Very late stage RCT with 214 patients, mean SpO2 65%, 162 on mechanical ventilation, showing no significant difference in mortality. Patients not intubated at baseline show greater improvement, HR 0.43 [0.09-2.03]. Table 4 shows different results to the abstract - table 4 adjusted HR 0.80 [0.51-1.23], abstract HR 0.88 [0.51-1.53]. There was no significant difference in severe adverse events.

Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.01.21250371v1, https://c19p.org/hernandezcardenas

1,500 patient exercise study: 19% lower severe cases (p=0.04).
Retrospective 1,500 COVID+ patients in Bangladesh, showing lower risk of severe cases with regular exercise in unadjusted results.

Sep 2021, Infection and Drug Resistance, https://www.dovepress.com/lifestyle-and-comorbidity-related-risk-factors-of-severe-and-critical--peer-reviewed-fulltext-article-IDR, https://c19p.org/mohsinex

954 patient HCQ late treatment study: 8% lower mortality (p=0.005).
Retrospective database study of 1,021 patients in Ecuador, Germany, Italy, and Spain, showing HCQ propensity score adjusted mortality odds ratio aOR 0.88, p=0.005.

Nov 2020, Internal and Emergency Medicine, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649104/, https://c19p.org/nunezgil

206 patient indomethacin late treatment PSM study: 67% lower hospitalization (p=0.34) and 57% lower progression (p=0.21).
Analysis of interactions between viral and human proteins for SARS-CoV-2, SARS-CoV-1, and MERS-CoV and genetic screening to identify host factors that enhance or inhibit viral infection. Authors predict indomethacin will have antiviral activity for SARS-CoV-2 and perform a retrospective study of patients in the USA that started treatment within 21 days after COVID-19 infection - 103 with indomethacin, and 103 using a celecoxib, a clinically similar drug without predicted antiviral activity. There were fewer hospital visits and hospitalizations with indomethacin, without statistical significance.

Dec 2020, Science, https://www.science.org/doi/10.1126/science.abe9403, https://c19p.org/gordon3

247 patient HCQ late treatment study: 32% lower mortality (p=0.46).
Retrospective 247 mechanically ventilated patients showing lower mortality with HCQ, but not statistically significant on multiple Cox regression. The paper gives the p value for multiple Cox (0.46) and simple Cox (0.02), but does not specify the adjusted risk values.

Nov 2020, Critical Care Explorations, https://journals.lww.com/ccejournal/Fulltext/2020/12000/Predictors_of_Mortality_and_Effect_of_Drug.10.aspx, https://c19p.org/lambermont

524 patient metformin prophylaxis study: 29% lower mortality (p=0.5).
Retrospective 524 hospitalized COVID-19 patients with diabetes in Italy, showing lower risk of mortality with metformin use, without statistical significance. The results adjusted only for COVID-19 MRS differ between the text and Figure 2.

Mar 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/7/1874, https://c19p.org/silverii

62,069 patient HCQ prophylaxis study: 31% lower mortality (p=0.8) and 6% more cases (p=0.7).
Retrospective 3,074 patients with antimalarial prescriptions and 58,955 matched controls, showing no significant differences with antimalarial prophylaxis for PCR+ cases (99% HCQ). Authors provide only PCR+ and mortality outcomes, and do not provide intermediate clinical outcomes that may show a statistically significant benefit. Authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri] (for symptomatic disease).

Jun 2023, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961623P0840X, https://c19p.org/klebanov

192 patient ivermectin late treatment study: 17% lower mortality (p=0.82), 18% lower need for oxygen therapy (p=0.37), 23% lower progression (p=0.52), and 4% higher ICU admission (p=0.92).
Retrospective 96 late stage patients receiving a single dose of 200 μg/kg ivermectin for strongyloides and 96 matched controls, showing no significant difference in outcomes. Authors note that this may be due to the low dose used.

May 2023, Viruses, https://www.mdpi.com/1999-4915/15/5/1138, https://c19p.org/llenasgarcia

429 patient quercetin late treatment RCT: 94% lower ICU admission (p=0.39) and 78% higher hospital discharge (p=0.1).
RCT 447 moderate-to-severe hospitalized patients in Turkey, 52 treated with quercetin, bromelain, and vitamin C, showing no statistically significant difference in clinical outcomes.

Jan 2021, Turk. J. Biol.-529, https://journals.tubitak.gov.tr/biology/vol45/iss7/13/, https://c19p.org/onal

2,586 patient sleep study: 32% fewer symptomatic cases (p=0.09).
Analysis of 2,586 participants of a running injury prevention RCT in the Netherlands, showing higher risk of COVID-19 symptoms with sleep disturbance.

Oct 2020, J. Science and Medicine in Sport, https://www.sciencedirect.com/science/article/pii/S144024402030788X, https://c19p.org/cloostermansl

738 patient zinc early treatment study: 24% lower hospitalization (p=0.16).
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.

May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihiz

45 patient indomethacin late treatment RCT: 66% lower ventilation (p=1) and 40% slower recovery (p=0.52).
Very small RCT with 22 indomethacin and 23 control patients, showing no significant difference in outcomes. All patients were treated with HCQ.

Jan 2022, Immunopathologia Persa, https://immunopathol.com/Inpress/ipp-29284.pdf, https://c19p.org/salmasi

62 patient favipiravir late treatment RCT: 41% lower ICU admission (p=0.36), 6% improved recovery (p=0.76), and 25% shorter hospitalization (p=0.03).
Small 62 patient late stage RCT in Iran comparing favipiravir and lopinavir/ritonavir, showing significant improvement in fever, cough, and dyspnea with favipiravir on day 5. There was no significant difference in mortality, ICU admission, or chest CT improvement. IRCT20151227025726N14.

Sep 2021, Iranian J. Pharmaceutical Research, http://ijpr.sbmu.ac.ir/article_1101552.html, https://c19p.org/tabarsi

539 patient HCQ late treatment study: 34% lower mortality (p=0.12).
Retrospective 539 COVID-19 hospitalized patients in Milan, with treatment a median of 1 day after admission, showing lower mortality with HCQ and with HCQ+AZ, with statistical significance only for HCQ+AZ.

Jul 2020, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(20)30600-7/fulltext, https://c19p.org/darminiomonforte

242 patient zinc late treatment study: 34% lower mortality (p=0.09).
Retrospective 242 hospitalized patients in the USA showing adjusted hazard ratio for zinc treatment, aHR 0.66 [0.41-1.07]. [ncbi.nlm.nih.gov] notes that the study would be more informative if baseline serum zinc levels were known.

Jul 2020, Chest, https://journal.chestnet.org/article/S0012-3692(20)31961-9/fulltext, https://c19p.org/yao2

545 patient metformin prophylaxis study: 64% lower mortality (p=0.05).
Retrospective 545 hospitalized COVID-19 patients with diabetes showing high mortality (33%). Metformin, SGLT inhibitors, and DPP4 inhibitors were associated with lower mortality compared with insulin.

Jun 2024, The Review of Diabetic Studies, https://diabeticstudies.org/menuscript/index.php/RDS/article/view/393, https://c19p.org/hussein3

70 patient camostat early treatment RCT: 37% improved recovery (p=0.15).
RCT 70 outpatients showing significantly lower symptom scores at day 6, faster recovery, and improved taste/smell, and fatigue with camostat treatment. There was no significant difference for viral load. The recovery result is from [bmcinfectdis.biomedcentral.com].

Jan 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.01.28.22270035, https://c19p.org/chupp

218 patient HCQ late treatment study: 35% lower mortality (p=0.22).
Retrospective 218 hospitalized patients in Italy showing non-statistically significant 35% lower mortality with HCQ, hazard ratio aHR 0.65 [0.33–1.30].

Dec 2020, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034120307516, https://c19p.org/guglielmetti

113 patient ivermectin early treatment study: 87% improved viral clearance (p<0.0001).
Non-randomized controlled trial with 62 mild and early moderate patients with home treatment with ivermectin + nitazoxanide + ribavirin + zinc, showing significantly faster viral clearance.

Feb 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.26880, https://c19p.org/elalfy

7,019 patient budesonide prophylaxis study: 33% fewer cases (p=0.1).
Retrospective 44,968 patients in South Korea, 7,019 on inhaled corticosteroids, showing no statistically significant differences in COVID-19 cases.

Sep 2021, Research Square, https://www.researchsquare.com/article/rs-72221/v1, https://c19p.org/lee2

72 patient vitamin C late treatment RCT: 46% lower ICU admission (p=0.46) and 1% shorter hospitalization (p=0.82).
RCT with 38 patients treated with vitamin C and vitamin E, and 34 control patients, showing lower ICU admission with treatment, but not statistically significant.

Apr 2021, Immunopathologia Persa, https://immunopathol.com/Article/ipp-22230, https://c19p.org/hakamifard

64 patient HCQ prophylaxis study: 20% lower mortality (p=0.8), no change in hospitalization (p=0.94), and 40% lower severe cases (p=0.37).
Prospective study of 64 rheumatic disease patients with COVID-19, showing no significant difference in outcomes with HCQ use.

Feb 2023, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkad025/7059537, https://c19p.org/mathew

6,256 patient metformin prophylaxis study: 12% lower mortality (p=0.65).
Retrospective 6,256 COVID-19+ diabetes patients in the USA, showing lower mortality with existing metformin treatment, statistically significant only for women.

Dec 2020, The Lancet Healthy Longevity, https://www.thelancet.com/journals/lanhl/article/PIIS2666-7568(20)30033-7/fulltext, https://c19p.org/bramante

44,977 patient metformin prophylaxis study: 22% lower hospitalization (p=0.11).
Retrospective 76,764 diabetes patients in Italy, showing that patients on metformin had lower rates of COVID-19 hospitalization compared to those on insulin/insulin secretagogues, GLP-1 receptor agonists, and DPP-4 inhibitors. Metformin vs. no metformin results are not provided. The most relevant result for COVID-19 and metformin may be the DPP-4i comparison, based on the DPP-4i group being the most similar to the metformin group in terms of baseline COVID-19 risk and confounders. Patients on insulin/secretagogues may have more severe or advanced diabetes.

Aug 2023, Biomedicines, https://www.mdpi.com/2227-9059/11/8/2292, https://c19p.org/greco

40 patient curcumin late treatment RCT: 50% lower mortality (p=0.3).
Small RCT with 40 nano-curcumin patients and 40 control patients showing lower mortality with treatment. Authors conclude that nano-curcumin may be able to modulate the increased rate of inflammatory cytokines especially IL-1β and IL-6 mRNA expression and cytokine secretion in COVID-19 patients, which may improve clinical outcomes.

Oct 2020, Int. Immunopharmacol., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574843/, https://c19p.org/valizadeh

40 patient melatonin late treatment study: 48% faster recovery (p=0.001).
40 hospitalized patients in Iran, 20 treated with melatonin, showing faster recovery and attenuated inflammatory cytokines with treatment.

May 2021, European J. Pharmacology, https://www.sciencedirect.com/science/article/abs/pii/S0014299921003460#, https://c19p.org/hosseini

56 patient HCQ early treatment study: 26% faster recovery (p=0.2).
Prospective 56 patients in Uganda, 29 HCQ and 27 control, showing 25.6% faster recovery with HCQ, 6.4 vs. 8.6 days (p = 0.20). There was no ICU admission, mechanical ventilation, or death. Treatment delay is not specified but at least a portion of patients appear to have been treated early.

Sep 2020, BMJ Open Respiratory Research, https://bmjopenrespres.bmj.com/content/7/1/e000646, https://c19p.org/kirenga

152 patient vitamin D ICU RCT: 21% lower mortality (p=0.2), no change in recovery (p=0.71), and 6% longer hospitalization (p=0.76).
Very late stage RCT 155 ICU patients in Croatia with low vitamin D levels, showing no significant differences with 10,000IU cholecalciferol daily. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage. The baseline mean age and median WHO scores for the treatment and control groups are both higher than the respective values reported for all patients combined, which is not possible. The trial was registered after completion in May 2022.

Feb 2023, Nutrients, https://www.mdpi.com/2072-6643/15/5/1234, https://c19p.org/domazetbugarin

199 patient HCQ late treatment study: 32% lower PASC (p=0.58).
Prospective observational study of 199 hospitalized COVID-19 patients in Belgium showing a high prevalence of persistent symptoms including dyspnea and fatigue at 6 months after discharge. Pulmonary function tests revealed reduced diffusion capacity, and CT scans showed a high prevalence of persistent lung abnormalities at 3 months, mainly ground glass opacities. Logistic regression shows lower risk of persistent symptoms with HCQ treatment, without statistical significance.

Aug 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221005725, https://c19p.org/darcis

849 patient aspirin prophylaxis study: 26% lower combined mortality/hospitalization (p=0.13).
Retrospective 849 COVID-19+ patients in skilled nursing homes, showing lower risk of combined hospitalization/death with aspirin prophylaxis, not reaching statistical significance.

Jan 2022, Gerontology, https://www.karger.com/Article/FullText/521412, https://c19p.org/levye

11,892 patient metformin prophylaxis study: 26% higher mortality (p=0.3) and 28% fewer cases (p<0.0001).
Retrospective 27,493 type II diabetes patients in the USA, 7,204 on metformin, showing significantly lower COVID-19 cases, but no significant difference in mortality.

Feb 2021, Acta Diabetologica, https://link.springer.com/article/10.1007%2Fs00592-020-01666-7, https://c19p.org/oh

459 patient HCQ late treatment study: 55% lower mortality (p=0.03).
Retrospective 459 patients in Iran with 93% treated with HCQ, showing HCQ mortality RR 0.45, p = 0.028. HCQ was the only antiviral that showed a significant difference. There was relatively few control patients and the result is subject to confounding by indication. Average admission delay 5.72 days.

Sep 2020, The Tohoku J. Experimental Medicine, https://www.jstage.jst.go.jp/article/tjem/252/1/252_73/_article/-char/ja/, https://c19p.org/alamdari

823 patient vitamin D prophylaxis study: 36% fewer cases (p=0.03).
Prospective study of 1,063 health workers in Colombia showing lower COVID-19 infection rates with adherence to a vitamin D and C supplementation plan, however very limited baseline information is provided for the adherent vs. non-adherent groups, and no adjusted results are provided. Higher risk patients had a much higher adherence rate, suggesting that the efficacy of treatment may be significantly higher than observed.

Mar 2024, Behavioural Public Policy, https://www.cambridge.org/core/product/identifier/S2398063X24000113/type/journal_article, https://c19p.org/arboleda

20,730 patient aspirin prophylaxis study: 3% lower mortality (p=0.06).
Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic aspirin use vs. sporadic NSAID use. Since aspirin is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.

May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2

821 patient HCQ prophylaxis RCT: 17% fewer cases (p=0.35).
Remote post-exposure prophylaxis RCT reporting that "[HCQ] did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure". However, this statement is incorrect - cases were reduced, just without statistical significance - it's not possible to conclude there was no efficacy. Additionally, treatment was not within 4 days - there was up to 68 hours shipping delay as below. Further, 6 independent analyses of the data in this study indicate efficacy: [arxiv.org, blog.philbirnbaum.com, drive.google.com, longdom.org, medrxiv.org, osf.io, researchgate.net]. COVID-19 cases were reduced by [49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of exposure (including shipping delay). The treatment delay-response relationship is significant at p=0.002. For more detailed analysis, see [c19hcq.org]. See also: [nejm.org]. Authors compare with treatment with folic acid. [Kaur] et al. note that folic..

Jun 2020, NEJM, June 3 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2016638, https://c19p.org/boulwarepep

281 patient HCQ prophylaxis study: 22% fewer cases (p=0.47).
Survey of Indian doctors not finding a significant effect of HCQ prophylaxis.

Nov 2020, J. Vaccines & Vaccination, S6:1000002, https://www.longdom.org/open-access/no-role-of-hcq-in-covid19-prophylaxis-a-survey-amongst-indian-doctors.pdf, https://c19p.org/datta

738 patient curcumin early treatment study: 31% lower hospitalization (p=0.1).
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.

May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihit

29,451 patient HCQ late treatment study: 15% lower mortality (p=0.001).
Retrospective database analysis focused on famotidine but also showing results for HCQ users, with unadjusted mortality RR 0.85, p<0.001 (13.6% vs. 16.1%).

Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.23.20199463v1, https://c19p.org/shoaibi

432 patient HCQ prophylaxis study: 43% lower hospitalization (p=0.09) and 6% more cases (p=0.25).
Retrospective 432 autoimmune disease patients in China showing lower hospitalization with HCQ without statistical significance (OR 0.566, p=0.085) in unadjusted results, slightly higher COVID-19 cases without statistical significance, and increased cough compared with CNI.

Dec 2023, J. Translational Autoimmunity, https://www.sciencedirect.com/science/article/pii/S2589909023000400, https://c19p.org/huang7

34 patient vitamin B12 late treatment RCT: 75% lower ICU admission (p=0.34) and 1% longer hospitalization (p=0.97).
Small RCT 34 hospitalized patients in Iran showing improved imflammatory markers and lower ICU admission with vitamin B12 treatment, without statistical significance. There was no mortality.

Sep 2023, Health Science Reports, https://onlinelibrary.wiley.com/doi/10.1002/hsr2.1509, https://c19p.org/erfani

79 patient nigella sativa late treatment RCT: 27% lower need for oxygen therapy (p=0.007) and 29% shorter hospitalization (p<0.0001).
Small RCT 41 patients treated with nigella sativa, glycyrrhiza glabra, punica granatum, and rheum palmatum, and 41 control patients, showing shorter hospitalization with treatment.

Jun 2022, Integrative Medicine Research, https://www.sciencedirect.com/science/article/pii/S2213422022000373, https://c19p.org/setayesh

467 patient vitamin D prophylaxis study: 27% lower mortality (p=0.12).
Retrospective 427 hospitalized COVID-19 patients in the United Kingdom, showing lower mortality with vitamin D supplementation (p=0.12), and higher mortality with both low and high vitamin D levels compared to a reference range of 50-74 nmol/L.

Jan 2022, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqac027/6518440, https://c19p.org/subramanian

83 patient N-acetylcysteine late treatment RCT: 2% lower mortality (p=1), 27% lower ventilation (p=0.57), 6% greater improvement (p=0.82), and 5% higher hospital discharge (p=0.8).
RCT 83 severe COVID-19 pnuemonia patients in Iran, 42 treated with acetylcysteine, showing no significant difference in clinical outcomes. All patients received remdesivir, famotidine, and vitamin C. More patients were at baseline category 4+ in the treatment group - 18 vs. 12. The trial focused on preventing liver injury in patients treated with remdesivir, showing improved AST/ALT levels with acetylcysteine.

Jun 2022, Gastroenterology and Hepatology from Bed to Bench, https://journals.sbmu.ac.ir/ghfbb/index.php/ghfbb/article/view/2565, https://c19p.org/mousapour

572 patient azvudine late treatment study: 24% lower progression (p=0.44).
Retrospective 572 fully vaccinated hospitalized patients in China, showing lower risk with azvudine treatment, without statistical significance. The composite outcome included intubation, non-invasive respiratory support, ICU admission, and all-cause death. Azvudine was not included in the multivariable analysis (only combined antiviral therapy was used without explanation).

Oct 2023, Heliyon, https://www.sciencedirect.com/science/article/pii/S240584402308595X, https://c19p.org/liu13azv

667 patient HCQ late treatment RCT: 16% lower mortality (p=0.77) and 28% higher hospitalization (p=0.3).
Late stage RCT of 667 hospitalized patients with up to 14 days of symptoms at enrollment and receiving up to 4 liters per minute supplemental oxygen, not finding a significant effect after 15 days. Authors note: "the trial cannot definitively rule out either a substantial benefit of the trial drugs or a substantial harm", sample sizes are too small. The paper uses the terms mild and moderate, however all patients had serious enough disease to be hospitalized, and 14% were actually randomized in the ICU. The trial had significant protocol deviations and unusually low medication adherence. Randomization resulted in 64.3% male patients (HCQ) vs. 54.2% (control) which may significantly affect results due to the much higher risk for male patients. Authors note: "our aim was to exclude patients already receiving longer and potentially therapeutic doses of the study treatments" in explanation for why the study protocol was changed to exclude patients with previous use of..

Jul 2020, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2019014, https://c19p.org/cavalcanti

202 patient ivermectin early treatment RCT: 41% lower progression (p=0.54) and 36% improved recovery (p=0.04).
RCT 99 ivermectin and 103 control low risk patients in China, up to 7 days from symptom onset, showing statistically significant improvement in recovery with treatment, and non-statistically significant improvements in recovery time and deterioration. Authors selectively omitted the p-value for recovery which shows statistical significance. Very little information on the patients is provided (only age, gender, and insurance status). The table, text, and abstract show three different versions of recovery numbers. The table and abstract show two different versions of recovery time. The abstract contains a hazard ratio that is not in the text, and no statistical methods are reported. Given the selective omission of the statistically significant recovery p-value, three different sets of numbers for that outcome, and other inconsistencies, the data in this study does not appear to be very reliable. Patients >50 were excluded.

Dec 2021, Indian J. Pharmaceutical Sciences, https://www.ijpsonline.com/abstract/the-effect-of-ivermectin-on-reducing-viral-symptoms-in-patients-with-mild-covid19-4455.html, https://c19p.org/abbas2

1,255 patient HCQ prophylaxis study: 80% lower hospitalization (p=0.001).
Analysis of 1255 COVID-19 patients in Wuhan Tongji Hospital finding 0.61% with systemic autoimmune diseases, much lower than authors expected (3%-10%). Authors hypothesise that protective factors, such as CQ/HCQ use, reduce hospitalization.

Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/79/9/1163, https://c19p.org/huangard

146 patient vitamin C late treatment study: 39% lower mortality (p=0.37), 19% lower combined mortality/ICU admission (p=0.24), 102% higher ICU admission (p=0.51), and 25% shorter hospitalization (p=0.16).
Prospective study of 146 hospitalized COVID-19 patients showing shorter hospitalization with high-dose intravenous vitamin C. 104 patients received 10g of vitamin C intravenously daily for 3 days and 42 patients received only standard care. Mortality was lower with treatment (8.7% vs 14.3%) without statistical significance. Treatment was associated with significantly shorter hospitalization in multivariable analysis (−4.95, p=0.041). No adverse events were reported in the vitamin C group.

Jul 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/13/3987, https://c19p.org/corrao

1,831 patient cannabidiol prophylaxis PSM study: 2% lower mortality (p=0.57), 5% lower ventilation (p=0.02), 9% lower ICU admission (p=0.02), and 3% lower need for oxygen therapy (p=0.27).
Retrospective 1,831 hospitalized COVID-19 patients in the USA, showing lower mechanical ventilation and ICU admission, but no significant difference in mortality.

Aug 2022, J. Cannabis Research, https://jcannabisresearch.biomedcentral.com/articles/10.1186/s42238-022-00152-x, https://c19p.org/shover

2,646 patient acetaminophen ICU study: 12% lower mortality (p=0.2).
Prospective study of 2,646 ICU patients ≥70 years old, showing no significant difference in mortality with acetaminophen use in the 10 days prior to ICU admission.

Dec 2022, BMC Geriatrics, https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-022-03709-w, https://c19p.org/baldia

179 patient vitamin D prophylaxis study: 33% fewer cases (p=0.21).
Retrospective 61 COVID+ kidney transplant patients and 122 matched controls, showing significantly lower vitamin D levels in COVID+ patients, and lower cases with vitamin D supplementation, without statistical significance.

Jan 2022, Nutrients, https://www.mdpi.com/2072-6643/14/2/317/htm, https://c19p.org/regalia

484 patient HCQ prophylaxis study: 27% lower progression (p=0.21) and 5% more cases (p=0.81).
Small prophylaxis trial with 29 low dose HCQ and 455 control healthcare workers in India, showing no statistically significant differences.

Sep 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.09.13.21262971v1, https://c19p.org/agarwal2

25 patient ivermectin early treatment study: 70% lower mortality (p=0.34) and 55% lower severe cases (p=0.11).
Small quasi-randomized (patient choice) study with 25 PCR+ patients in a nursing home offered ivermectin, of which 10 chose to be treated. The mean age was 83.5 in the treatment group and 81.8 in the control group. There was lower mortality and fewer serious cases with treatment.

Apr 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-202.php?jid=jide, https://c19p.org/loue

430 patient metformin prophylaxis study: 23% lower mortality (p=0.15).
Retrospective 430 hospitalized COVID-19 patients with type 2 diabetes in Poland showing lower mortality with metformin and higher mortality with remdesivir, convalescent plasma, and aspirin in univariable analysis. These results were not statistically significant except for aspirin, and no baseline information per treatment is provided to assess confounding.

Mar 2024, Biomedicines, https://www.mdpi.com/2227-9059/12/3/605, https://c19p.org/lewandowski

3,955 patient vitamin C prophylaxis study: 38% lower hospitalization (p=0.17) and 10% fewer symptomatic cases (p=0.71).
Analysis of nutrient intake and COVID-19 outcomes for 3,996 people in Iran, showing lower risk of COVID-19 hospitalization with sufficient vitamin A, vitamin C, and selenium intake, with statistical significance for vitamin A and selenium.

May 2023, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13632, https://c19p.org/vaisic

214 patient ivermectin late treatment RCT: 19% lower progression (p=0.46), 14% higher need for oxygen therapy (p=0.46), 23% worse improvement (p=0.61), and 60% improved recovery (p=0.17).
Late treatment (6.6 days after onset/PCR+) RCT with 221 low risk (no deaths) COVID-19 patients in Japan, showing no significant difference in viral clearance with a single dose of ivermectin under fasting. Authors note that a single 200 μg/kg dose under fasting was used as approved in Japan, and that the low dose, single day dosing, and fasting administration (~2.5 times lower plasma concentration according to [Guzzo]) limit applicability, and that studies with more favorable outcomes generally used a higher dose or multiday dosing. Details of PCR testing are not provided but the very slow clearance within the low risk population suggests a very high Ct value that may not accurately represent any reduction in replication-competent viral load. An erratum notes a conflict of interest for a reviewer that was a Merck employee: [frontiersin.org]

May 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1139046/full, https://c19p.org/wada

164 patient HCQ ICU study: 32% lower mortality (p=0.19).
Retrospective 164 ICU patients in Mexico showing 32% lower mortality with HCQ+AZ and 37% lower with CQ. HCQ+AZ vs. neither HCQ or CQ relative risk RR 0.68, p = 0.03 CQ vs. neither HCQ or CQ relative risk RR 0.63, p = 0.02 HCQ+AZ or CQ vs. neither relative risk RR 0.65, p = 0.006

Oct 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S014795632030412X, https://c19p.org/namendyssilva

176 patient vitamin C late treatment study: 29% lower mortality (p=0.18).
Retrospective 176 hospitalized patients, 96 treated with oral vitamin C (from 500mg to 1500mg daily), showing lower mortality with treatment.

Sep 2020, Chest Infections, https://journal.chestnet.org/article/S0012-3692(20)32508-3/fulltext, https://c19p.org/patel

54 patient lactoferrin late treatment RCT: 25% improved recovery (p=1).
RCT 54 hospitalized patients in Egypt, showing no significant differences in recovery with lactoferrin treatment. 200mg lactoferrin orally once daily (group 1) or 200mg lactoferrin orally twice daily (group 2).

Aug 2021, Medicina, https://www.mdpi.com/1648-9144/57/8/842, https://c19p.org/algahtani

508 patient vitamin D prophylaxis study: 30% lower mortality (p=0.45) and 64% lower ICU admission (p=0.009).
Retrospective 508 hospitalized COVID-19 patients in Iran showing lower mortality with vitamin D supplementation (not reaching statistical significance), and an association between lower vitamin D levels and disease severity, ICU admission, and increased mortality. Details of supplementation are not provided. The multivariate result for vitamin D deficiency is in the preprint, the journal version only contains the multivariate result for serum level.

Jan 2021, Scientific Reports, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8413335/, https://c19p.org/vasheghani

100 patient HCQ prophylaxis study: 99% fewer cases (p=0.08).
Retrospective type 1 diabetes patients in Saudi Arabia showing reduced risk of cases with HCQ prophylaxis.

Nov 2021, BioMed Research Int., https://www.hindawi.com/journals/bmri/2021/1676914/, https://c19p.org/ahmed2

40 patient N-acetylcysteine ICU RCT: 33% lower mortality (p=0.19) and 8% shorter hospitalization (p=0.63).
RCT 40 ICU patients in Iran, showing lower mortality with NAC treatment, without statistical significance. Single dose intravenous NAC 300 mg/kg.

Oct 2022, Jundishapur J. Natural Pharmaceutical Products, https://brieflands.com/articles/jjnpp-129817.html, https://c19p.org/rahimi

176 patient antihistamine H1RA late treatment PSM study: 25% lower mortality (p=0.4).
PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with H1RAs+H2RAs versus famotidine alone, without statistical significance.

Mar 2021, Signal Transduction and Targeted Therapy, https://www.nature.com/articles/s41392-021-00689-y, https://c19p.org/murah1

117 patient HCQ prophylaxis study: 92% lower mortality (p=0.09), 27% fewer moderate/severe cases (p=0.39), and 16% lower hospitalization (p=0.55).
Retrospective 117 COVID-19 positive doctors in India showing lower mortality and severity with HCQ prophylaxis, without statistical significance in unadjusted results without group details. Results do not include the risk of positive cases.

Jun 2024, J. College of Medical Sciences-Nepal, https://www.nepjol.info/index.php/JCMSN/article/view/43302, https://c19p.org/dey2

794 patient acetaminophen prophylaxis PSM study: 25% lower mortality (p=0.46) and 38% lower ventilation (p=0.42).
Retrospective 2,365 patients prescribed acetaminophen and 398 prescribed NSAIDs in South Korea, showing no significant differences.

Mar 2021, Scientific Reports, http://www.nature.com/articles/s41598-021-84539-5, https://c19p.org/park2

108 patient HCQ late treatment study: 43% lower mortality (p=0.15).
Observational prospective 108 hospitalized patients 65 and older, showing HCQ mortality OR 0.49, p = 0.15.

Jun 2020, Aging, 11306-11313, https://www.aging-us.com/article/103583/text, https://c19p.org/bousquet

5,211 patient various antiandrogen prophylaxis study: 21% lower mortality (p=1) and 18% more cases (p=0.54).
Retrospective 5,211 prostate cancer patients, 799 on ADT, showing no significant differences in COVID-19 outcomes with treatment.

Jan 2021, Annals of Oncology, https://www.annalsofoncology.org/article/S0923-7534(21)00095-8/fulltext, https://c19p.org/kwon

1,140 patient exercise study: 30% fewer moderate/severe cases (p=0.1) and 9% more cases (p=0.36).
Retrospective 1,544 participants in Slovakia, showing a lower risk of more severe COVID-19 for physically active participants, without statistical significance.

Jul 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/13/7158, https://c19p.org/bielik

32,085 patient fluvoxamine prophylaxis PSM study: 27% lower mortality (p=0.41) and 37% higher hospitalization (p=0.5).
Retrospective COVID+ patients in Croatia, showing no significant difference in outcomes with fluvoxamine prophylaxis.

Nov 2022, European J. Clinical Pharmacology, https://link.springer.com/10.1007/s00228-023-03479-3, https://c19p.org/trkulja2

90 patient ivermectin early treatment RCT: 86% lower progression (p=0.24) and 9% worse viral clearance (p=0.36).
Very high conflict of interest RCT with design optimized for a null result: very low risk patients, high existing immunity, post-hoc change to exclude patients more likely to benefit. There was no significant difference in viral clearance among low risk patients with high viral load at baseline. All 3 progression events occured in the control arm - one hospitalization and two cases of COVID-19 related rhabdomyolysis. Patients in both arms cleared the virus quickly with a viral clearance half-life of 21.1 hours vs. 19.2 hours, which may be in part due to prior immunity. With rapid viral clearance and very low risk patients, infection is less likely to spread to other tissues. Systemic treatment is less applicable, and has less time to reach therapeutic concentrations before self-recovery. Treatment administered directly to the respiratory tract, e.g. as in [ Albariqi , Albariqi (B) , Aref , Chaccour , Elkholy , Errecalde , Francés-Monerris , Mansour ] , may be more effective for COVID..

Jul 2022, eLife, https://elifesciences.org/articles/83201, https://c19p.org/schilling

247 patient metformin prophylaxis study: 37% lower mortality (p=0.13).
Retrospective 247 hospitalized COVID-19 diabetes patients, showing lower mortality with metformin use in unadjusted results.

Dec 2020, Diabetes, Obesity and Metabolism, https://dom-pubs.pericles-prod.literatumonline.com/doi/10.1111/dom.14256, https://c19p.org/sourij

320 patient ivermectin late treatment study: 56% lower progression (p=0.06), 33% improved recovery (p=0.27), and 27% faster viral clearance (p=0.01).
Prospective 320 hospitalized moderate COVID-19+ patients in Egypt, 160 treated with ivermectin, showing lower mortality, improved recovery, and decreased cytokine expression with treatment. All patients were treated with HCQ. 7890/26-8-2020.

Oct 2021, Zagazig University Medical J., https://journals.ekb.eg/article_202150_0.html, https://c19p.org/rezk

270 patient spironolactone antiandrogen early treatment study: 77% faster recovery (p=0.006) and 38% faster viral clearance (p=0.02).
Prospective study of 270 female COVID-19 patients in Brazil, 75 with hyperandrogenism, of which 8 were on spironolactone. Results suggest that HA patients may be at increased risk, and that spironolactone use may reduce the risk compared to both other HA patients and non-HA patients. SOC included other treatments and there was no mortality or hospitalization.

Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.05.20206870v1, https://c19p.org/cadegiani9

270 patient spironolactone early treatment study: 77% faster recovery (p=0.006) and 38% faster viral clearance (p=0.02).
Prospective study of 270 female COVID-19 patients in Brazil, 75 with hyperandrogenism, of which 8 were on spironolactone. Results suggest that HA patients may be at increased risk, and that spironolactone use may reduce the risk compared to both other HA patients and non-HA patients. SOC included other treatments and there was no mortality or hospitalization.

Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.05.20206870v1, https://c19p.org/cadegiani9sp

16,043 patient metformin prophylaxis study: 10% lower mortality (p=0.19) and 8% lower combined mortality/hospitalization (p=0.12).
Retrospective 31,006 diabetic COVID-19 patients in Spain, showing lower mortality with metformin treatment, without statistical significance. Authors provide results for metformin compared with untreated patients rather than all non-metformin patients, which may increase confounding due to higher prevalence for treatment of patients with more severe disease.

Oct 2022, Primary Care Diabetes, https://www.sciencedirect.com/science/article/pii/S175199182200167X, https://c19p.org/ouchi

10,000 patient vitamin C prophylaxis study: 14% fewer cases (p=0.29).
Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with vitamin C supplementation, without statistical significance. Authors do not analyze COVID-19 severity.

Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2c

60 patient melatonin early treatment study: 91% lower hospitalization (p=0.05).
Small study with 30 patients treated with melatonin, cannabidiol, and for 14 patients angiotensin 1-7, compared with an age/sex matched control group during the same period, showing lower hospitalization with treatment.

Dec 2020, J. Infectiology, https://www.infectiologyjournal.com/articles/covid-19-disease-as-an-acute-angiotensin-1-7-deficiency-a-preliminary-phase-2-study-with-angiotensin-1-7-in-association-with-melatonin-and-cannabidiol-in-symptomatic-covid19-infected-subjects, https://c19p.org/lissoni

60 patient vitamin A late treatment RCT: 38% improved recovery (p=0.53).
RCT 90 outpatients with post-COVID-19 anosmia showing significant improvements in smell alterations with olfactory training after 3 and 12 months. Adding oral vitamin A to olfactory training resulted in higher rates of improvement, but the difference was not statistically significant.

Jun 2024, Brazilian J. Otorhinolaryngology, https://www.sciencedirect.com/science/article/pii/S1808869424000661, https://c19p.org/taheri2

77 patient HCQ prophylaxis study: 85% lower severe cases (p=0.003) and 18% fewer moderate/severe cases (p=0.35).
Retrospective study of 77 outpatients with rheumatic diseases diagnosed with COVID-19, showing lower risk of severe COVID-19 with HCQ use in unadjusted results.

Dec 2023, Immunopathologia Persa, https://immunopathol.com/Article/ipp-40568, https://c19p.org/salesi

215 patient HCQ ICU study: 29% lower mortality (p=0.07).
Retrospective 215 mechanically ventilated COVID-19 patients in Brazil, 71 treated with HCQ, showing lower mortality with treatment in unadjusted results, without statistical significance. Authors note HCQ was used more toward the start of the pandemic, which may introduce confounding due to overall protocols improving over time, suggesting that the actual benefit may be greater.

Jun 2022, The J. Critical Care Medicine, https://www.sciendo.com/article/10.2478/jccm-2022-0015, https://c19p.org/osawa

15,227 patient selenium prophylaxis study: 80% fewer cases (p=0.11).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtse

487 patient HCQ prophylaxis PSM study: 23% fewer cases (p=0.52).
Retrospective PrEP analysis with 69 healthcare workers on PrEP HCQ, and 418 control. Authors report PCR and IgG results, with no baseline results for either. Authors note they "identified 69 HCWs receiving HCQ" while providing no information as to why or when they started HCQ. No conclusions can be drawn from this study because many workers may have been positive before starting HCQ. Only 14% of workers chose to use HCQ and they may have been motivated to do so because they had an infection. Authors perform several different adjustments, finding very different results. No information on death, hospitalization, symptoms, or severity is provided. Details on timing of serology and baseline serology status is not provided. Potential bias due to self-selection for risk. 25% of infections were detected before 7 days, indicating that they actually happened earlier (PCR false positive is very high initially). It is likely that many infections were before HCQ could reach therapeutic..

Nov 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/advance-article/doi/10.1093/jac/dkaa477/5997449, https://c19p.org/revollo

9,267 patient vitamin B9 prophylaxis study: 9% lower mortality (p=0.87), 1% lower ventilation (p=0.99), and 17% lower ICU admission (p=0.7).
Retrospective 9,748 COVID-19 patients in the USA showing no significant differences with vitamin B9 use, without statistical significance.

Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejanb9

323 patient camostat early treatment RCT: 8% faster recovery (p=0.54).
Double-blind RCT with 342 mild to moderate COVID-19 outpatients in South Korea, showing no significant difference in time to clinical improvement with camostat mesylate. In a post-hoc subgroup analysis of high-risk patients, there were non-statistically significant trends towards faster improvement in ordinal scale scores and subjective symptom scores at day 7 with treatment. Viral cultures suggested faster viral clearance with treatment, without statistical significance.

Jan 2023, Antimicrobial Agents and Chemotherapy, https://journals.asm.org/doi/10.1128/aac.00452-22, https://c19p.org/kim19

129 patient vitamin D prophylaxis study: 31% lower severe cases (p=0.25).
Retrospective 129 hospitalized patients with vitamin D levels measured within 90 days prior to admission, showing lower, but not statistically significant, risk of severe cases with vitamin D supplementation among patients with levels <20ng/mL or <12ng/mL. For <30ng/mL, lower (but not statistically significant) risk was seen overall but not for ≥50,000IU (the sample size is not given, it may be extremely small for this case). Only minimal details for <30ng/mL are provided, and no details for <20ng/mL or <12ng/mL are provided. The potential effect of supplementation on the risk of a case severe enough for hospitalization is not included.

May 2021, J. the Endocrine Society, https://academic.oup.com/jes/article/5/Supplement_1/A279/6240740, https://c19p.org/levitus

130 patient budesonide ICU PSM study: 32% lower mortality (p=0.13).
Combined retrospective (Mar-Jun 2020) and prospective (until Mar 2021) study of 954 COVID+ ICU patients in Saudi Arabia, 68 treated with ICS (80% budesonide or budesonide/formoterol, 20% fluticasone/salmeterol), showing lower mortality with treatment, statistically significant for 30-day but not in-hospital mortality.

Nov 2021, J. Intensive Care Medicine, https://journals.sagepub.com/doi/full/10.1177/08850666211053548, https://c19p.org/alsulaiman3

132 patient metformin prophylaxis study: 37% lower ICU admission (p=0.24).
Mouse models showing reduced lung and kidney injury with metformin. Metformin minimized lung damage and fibrosis in a mouse model of LPS-induced ARDS, and reduced UUO and FAN-induced kidney fibrosis. In Vitro study showing that metformin increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis, and inflammation markers in lung epithelial cells. Authors also include a retrospective study showing lower ICU admission with metformin without statistical significance.

Nov 2023, Redox Biology, https://www.sciencedirect.com/science/article/pii/S2213231723003580, https://c19p.org/miguel

976 patient ivermectin late treatment study: 99% lower mortality (p=0.04).
Retrospective 976 hospitalized patients with 34 treated with ivermectin showing lower mortality with ivermectin in unadjusted results.

Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.16.20232223v1, https://c19p.org/budhirajai

1,054 patient aspirin late treatment PSM study: 15% lower mortality (p=0.08).
PSM retrospective TriNetX database analysis of 1,379 severe COVID-19 patients requiring respiratory support, showing lower mortality with aspirin (not reaching statistical significance) and famotidine, and improved results from the combination of both.

Mar 2021, Signal Transduction and Targeted Therapy, https://www.nature.com/articles/s41392-021-00689-y, https://c19p.org/mura

52 patient colchicine late treatment RCT: 33% lower mortality (p=0.54).
Open-label RCT with 52 severe COVID-19 pneumonia patients showing no significant differences in mortality with colchicine. All patients received infliximab and remdesivir.

Feb 2024, Coronaviruses, https://www.eurekaselect.com/223567/article, https://c19p.org/yadollahzadeh

510 patient zinc prophylaxis study: 60% lower severe cases (p=0.41) and 41% lower hospitalization (p=0.37).
Retrospective 510 patients in Iran, showing lower risk of severity with vitamin D (statistically significant) and zinc (not statistically significant) supplementation. IR.TUMS.VCR.REC.1398.1063.

Aug 2021, J. Family & Reproductive Health, https://europepmc.org/article/PMC/PMC7868648, https://c19p.org/bagheriz

468,569 patient sleep study: 3% lower mortality (p=0.91).
Retrospective 468,569 adults in the UK, showing no significant difference in COVID-19 mortality based on sleep quality.

Aug 2021, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912100180X, https://c19p.org/ahmadi2sl

34 patient HCQ prophylaxis study: 89% lower ventilation (p=0.13), 64% lower ICU admission (p=0.14), and 64% lower severe cases (p=0.14).
Retrospective 34 rheumatological disease patients with COVID-19 in Saudi Arabia, showing lower risk of severe cases with HCQ use in unadjusted results, without statistical significance.

May 2023, J. Medicine and Life, https://europepmc.org/article/PMC/PMC10478665, https://c19p.org/alqatari

50 patient vitamin D early treatment RCT: 33% improved recovery (p=0.15) and 50% improved viral clearance (p=0.009).
RCT 50 COVID+ outpatients in Pakistan, 25 treated with curcumin, quercetin, and vitamin D, showing significantly faster viral clearance, significantly improved CRP, and faster resolution of acute symptoms (p=0.154). 168mg curcumin, 260mg quercetin and 360IU cholecalciferol.

Apr 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.898062/full, https://c19p.org/khan4

315 patient budesonide prophylaxis study: 31% lower hospitalization (p=0.18) and 24% fewer cases (p=0.0001).
Retrospective 315 COPD patients in China showing significantly lower COVID-19 cases with budesonide/formoterol or budesonide/glycopyrronium/formoterol use. Note that Table 4 includes only infected patients, we show the COVID-19 hospitalization risk among all patients with known medication status. Minimal details are provided for the groups on these medications.

May 2024, The Clinical Respiratory J., https://onlinelibrary.wiley.com/doi/10.1111/crj.13790, https://c19p.org/bai

64 patient vitamin D prophylaxis study: 22% fewer symptomatic cases (p=0.65).
Retrospective 64 patients with intellectual and developmental disability in the UK, showing no significant difference in COVID-19 status with vitamin D supplementation. Only 6 patients were not on vitamin D supplementation.

May 2021, BJPsych Bulletin, https://www.cambridge.org/core/journals/bjpsych-bulletin/article/revisiting-vitamin-d-status-and-supplementation-for-inpatients-with-intellectual-and-developmental-disability-in-the-north-of-england-uk/9ABB85B839DD2343107CCD98B10A81EA, https://c19p.org/dudley

4,020 patient HCQ late treatment study: 11% lower progression (p=0.63).
Retrospective 4020 hospitalized patients in China showing non-statistically significant lower risk of acute kidney injury with HCQ.

Dec 2020, Nephrology Dialysis Transplantation, https://academic.oup.com/ndt/article/35/12/2095/6020340, https://c19p.org/peng

74 patient vitamin C late treatment RCT: 33% lower mortality (p=0.74), 13% longer hospitalization (p=0.49), and 16% lower progression (p=0.12).
RCT 74 patients in Iran, showing no significant differences in outcomes with high dose vitamin C treatment. Tables 1b and 2a show conflicting baseline SOFA scores. The percentages of patients receiving antiviral treatments and corticosteroids are switched between the text and Table 1b. Authors indicate ICU admission was an outcome, but the result is not provided. AKI was lower with treatment, though not reaching statistical significance.

Dec 2022, J. Research in Pharmacy Practice, http://www.jrpp.net/text.asp?2022/11/2/64/363550, https://c19p.org/labbanimotlagh

309 patient HCQ prophylaxis study: 75% fewer cases (p<0.0001).
Physician survey in India with 164 ivermectin prophylaxis, 129 HCQ prophylaxis, and 81 control patients, showing significantly lower COVID-19 cases with treatment. Details of the treatment and control groups and the definition of cases are not provided, and the results are subject to survey bias. Authors also report on community prophylaxis but present only combined ivermectin/HCQ results.

Nov 2021, J. the Association of Physicians India, https://www.researchgate.net/publication/356294136_Ivermectin_and_Hydroxychloroquine_for_Chemo-Prophylaxis_of_COVID-19_A_Questionnaire_Survey_of_Perception_and_Prescribing_Practice_of_Physicians_vis-a-vis_Outcomes, https://c19p.org/samajdarh

111 patient N-acetylcysteine early treatment study: 20% shorter hospitalization (p=0.05).
Retrospective 111 patients with moderate COVID-19 pneumonia, 56 treated with NAC, showing shorter hospitalization time with treatment. NAC 1200mg daily intravenous, divided into two doses.

Nov 2021, Russian Medical Inquiry, https://www.rusmedreview.com/upload/iblock/b14/473-478.pdf, https://c19p.org/ignatova

255 patient probiotics prophylaxis RCT: 9% fewer cases (p=0.92).
Prophylaxis RCT with 127 probiotics and 128 control healthcare workers in Spain, showing no significant difference in cases. There were only 4 cases. Severity information by arm is not provided. L. coryniformis K8 CECT 5711. Treatment may help sustain the immune response to vaccination - in the subgroup of subjects for whom more than 81 days had passed since they received the first dose, IgG levels were significantly higher in the treatment group. Patients that started probiotic consumption before the first vaccine dose also reported significantly fewer side effects.

Aug 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.962566/full, https://c19p.org/rodriguezblanque

301 patient HCQ prophylaxis study: 39% lower severe cases (p=0.26).
Retrospective 301 consecutive SLE patients with COVID-19, showing lower risk of severe outcomes with HCQ use, with statistical significance in multivariable adjusted model 1 but not model 2.

Feb 2024, Lupus, http://journals.sagepub.com/doi/10.1177/09612033241230736, https://c19p.org/liu18

100 patient ivermectin late treatment study: 21% faster recovery (p=0.03) and 16% shorter hospitalization (p=0.01).
100 patient prospective trial of ivermectin + doxycycline showing reduced time to symptom resolution and shorter hospital stay with treatment.

Nov 2020, IAIM, 2020, 177-182, http://iaimjournal.com/wp-content/uploads/2020/10/iaim_2020_0710_23.pdf, https://c19p.org/spoorthi

108 patient xylitol late treatment study: 32% improved viral clearance (p=0.05).
108 patient prospective study showing improved viral clearance with Panthexyl nasal spray (a sterile hypertonic solution containing seawater, xylitol, panthenol and lactic acid).

Nov 2022, Pharmaceutics, https://www.mdpi.com/1999-4923/14/11/2502, https://c19p.org/cegolon

725 patient azvudine late treatment study: no change in mortality (p=1), 28% lower ventilation (p=0.04), 55% lower ICU admission (p=0.05), and 22% lower progression (p=0.07).
PSM retrospective 725 hospitalized COVID-19 patients in China compared the effectiveness and safety of the oral antivirals azvudine and paxlovid. There was no significant difference in the risk of disease progression between groups, but azvudine was associated with lower ICU admission and invasive ventilation use.

Oct 2023, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2023.1274294/full, https://c19p.org/wei2

87 patient ivermectin late treatment PSM study: 88% lower mortality (p=0.12), 55% higher hospital discharge (p=0.0001), and 95% improved viral clearance (p=0.001).
PSM retrospective 87 patients in Nigeria, 61 treated with ivermectin, showing lower mortality, faster recovery, and faster viral clearance with ivermectin treatment. All patients received zinc and vitamin C. A synergistic effect was seen for viral clearance when ivermectin and remdesivir were combined, as predicted by In Vitro research [Jeffreys]. Subject to confounding by time, with ivermectin patients from April-June 2021, and non-ivermectin patients from September-November 2021.

Feb 2022, J. Pharmaceutical Research Int., https://journaljpri.com/index.php/JPRI/article/view/36328, https://c19p.org/thairu

84 patient proton pump inhibitor prophylaxis study: 31% fewer symptomatic cases (p=0.34).
Retrospective 84 elderly nursing home residents in Spain showing no mortality, hospitalization, or ICU admission with early treatment with antihistamines alone or in combination with azithromycin.

Apr 2021, Pulmonary Pharmacology & Therapeutics, https://www.sciencedirect.com/science/article/pii/S1094553921000018, https://c19p.org/moranblancoppi

210 patient ivermectin late treatment study: 58% improved viral clearance (p<0.0001).
Prospective convenience sampling study of 210 hospitalized age-matched COVID-19 patients, showing faster viral clearance with ivermectin. Baseline information per group is not provided.

Aug 2022, Pakistan J. Medical and Health Sciences, https://pjmhsonline.com/index.php/pjmhs/article/view/2153, https://c19p.org/qadeer

20,859 patient zinc prophylaxis study: 100% lower hospitalization (p=0.04).
Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with calcium + zinc supplements (defined as being picked up within 35 days prior to PCR+), however only 10 patients took the supplements. Other patients may have acquired supplements outside of the healthcare system.

Jul 2021, Epidemiology and Global Health Microbiology and Infectious Disease, https://elifesciences.org/articles/68165, https://c19p.org/israel2z

45 patient vitamin D ICU study: 36% shorter ICU admission (p=0.01).
Retrospective 20 ICU patients treated with vitamin D in the UAE, and 25 matched controls, showing significantly shorter ICU stay with treatment. Lower proinflammatory cytokines were associated with lower severity markers. Authors also perform a PBMC In Vitro study, with both the clinical and in vitro studies showing vitamin D attenuated major proinflammatory signaling pathways.

Aug 2022, Life Sciences, https://www.sciencedirect.com/science/article/pii/S0024320522006099, https://c19p.org/sahebsharifaskari

477 patient favipiravir late treatment study: 48% lower mortality (p=0.21).
Retrospective 477 hospitalized patients in Indonesia, showing lower mortality with favipiravir in unadjusted results, not reaching statistical significance.

Feb 2022, J. Clinical Virology Plus, https://www.sciencedirect.com/science/article/pii/S2667038022000084, https://c19p.org/kurniyanto

179 patient metformin prophylaxis study: 79% lower mortality (p=0.06) and 44% more cases (p=0.12).
Retrospective 179 patients in France exposed to COVID-19 showing, without statistical significance, a higher risk of cases, and a lower risk of mortality among cases with existing metformin treatment.

Jul 2021, GeroScience, https://link.springer.com/article/10.1007/s11357-021-00397-z, https://c19p.org/blanc

60 patient N-acetylcysteine late treatment RCT: 15% lower need for oxygen therapy (p=0.6) and 12% shorter hospitalization (p=0.45).
RCT 60 hospitalized patients showing that oral N-acetylcysteine (NAC) at 1800mg daily significantly decreased plasma TNF-α levels and increased glutathione peroxidase levels. The NAC group had a shorter duration of oxygen support, while there were no significant difference for length of hospital stay, need for oxygen support, or mortality. Overall, the addition of high-dose NAC reduced inflammatory markers and oxidative stress in moderate COVID-19. Limitations include the small sample size, late treatment, lack of blinding, potential overlap of treatment effect with SOC, clinical significance of biomarker results, and limited adverse event reporting.

May 2023, Archives of Pharmaceutical Sciences Ain Shams University, https://aps.journals.ekb.eg/article_306468.html, https://c19p.org/sherkawy

100 patient HCQ early treatment study: 68% lower mortality (p=0.15).
Small limited trial with 100 patients concluding that HCQ improved clinical outcome, OR 0.016 [0.002-0.11] in regression analysis.

Apr 2020, medRxiv doi:10.1101/2020.04.20.20072421, https://www.researchgate.net/publication/341197843_COVID-19_in_Iran_a_comprehensive_investigation_from_exposure_to_treatment_outcomes, https://c19p.org/ashraf

3,322 patient HCQ late treatment study: 18% lower mortality (p<0.0001).
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More..

Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v1, https://c19p.org/sotobecerra

2,174 patient favipiravir late treatment study: 68% lower mortality (p=0.2).
Retrospective 2,174 hospitalized patients showing significantly shorter length of stay with favipiravir treatment.

Sep 2022, Iranian J. Science and Technology, Transactions A: Science, https://link.springer.com/10.1007/s40995-022-01351-0, https://c19p.org/behboodikhah

120 patient metformin prophylaxis study: 33% lower mortality (p=0.46).
Retrospective 120 COVID-19 diabetes patients, showing non-statistically significantly lower mortality with existing metformin treatment.

Jul 2020, Diabetes Care, https://care.diabetesjournals.org/content/43/7/1399, https://c19p.org/chen3

50 patient probiotics late treatment RCT: 62% lower mortality (p=0.17) and no change in ICU admission (p=1).
RCT 50 hospitalized patients in Pakistan, 25 treated with S. salivarius K12, showing lower mortality with treatment, without statistical significance. There were more patients with higher oxygen requirements at baseline in the control group - 18 vs. 6 with O2 ≥ 8 L/min.

Sep 2022, Microorganisms, https://www.mdpi.com/2076-2607/10/10/1926, https://c19p.org/dipierro6

58,562 patient melatonin late treatment study: 19% lower mortality (p=0.15).
Retrospective database analysis in France with 272 patients treated with melatonin, showing 19% lower mortality after adjustments, without statistical significance. Risk was lower for higher dosage (not statistically significant). Age was only in three age ranges and severe COVID was binary, likely leading to substantial residual confounding. Unadjusted differences were extreme with 60% >80 years old for melatonin compared to 15% for control. Mean daily dose 2.61mg. The title of the paper is incorrect, the most adjusted results show melatonin did reduce mortality (without reaching statistical significance).

Feb 2022, J. Travel Medicine, https://academic.oup.com/jtm/advance-article/doi/10.1093/jtm/taab195/6523003, https://c19p.org/sanchezrico

28 patient HCQ late treatment study: 50% higher hospital discharge (p=0.09).
Small RCT comparing HCQ and CQ in China with 88 very late stage (17.6 days from onset to hospitalization and ~10 days to randomization) patients. The primary clinical outcomes (TTCR and TTCI) were not significantly different. Authors note that HCQ may have more promising efficacy in immune system modulation, indicated by ferritin reduction in the moderate cases and improvement of CT scores and lymphocyte counts in the severe cases. HCQ and CQ were well tolerated. Authors also compare RCT patients to a matched sample of non-RCT patients in the same hospital, showing shorter time to discharge with CQ/HCQ, but not statistically significant due to the small size.

Jan 2021, Science China Life Sciences, https://link.springer.com/article/10.1007/s11427-020-1871-4, https://c19p.org/li3

22 patient HCQ late treatment study: 43% lower mortality (p=0.15).
Small retrospective study of 22 lung cancer patients, 14 treated with HCQ+AZ, showing HCQ+AZ mortality relative risk RR 0.57, p = 0.145.

Sep 2020, Ann. Oncol., 2020, Sep, 31, S1026, https://www.annalsofoncology.org/article/S0923-7534(20)41826-5/fulltext, https://c19p.org/serrano

689 patient zinc prophylaxis study: 37% lower IgG positivity (p=0.35).
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with zinc prophylaxis.

Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtoz

140 patient N-acetylcysteine ICU study: 39% lower mortality (p=0.08).
Retrospective 140 mechanically ventilated patients in Spain, showing lower mortality with acetylcysteine treatment in unadjusted results, not reaching statistical significance.

May 2022, J. Intensive Care Medicine, http://journals.sagepub.com/doi/10.1177/08850666221105423, https://c19p.org/farinagonzalez

496 patient aspirin late treatment PSM study: 13% lower mortality (p=0.53).
PSM retrospective 1,994 PCR+ patients in the USA, not showing a significant difference in mortality with aspirin treatment.

May 2021, Vascular Medicine, https://journals.sagepub.com/doi/10.1177/1358863X211012754, https://c19p.org/sahai

437 patient favipiravir late treatment study: 57% lower mortality (p=0.05).
Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subject to significant confounding by indication and confounding by time.

Sep 2021, Int. J. General Medicine, https://www.dovepress.com/getfile.php?fileID=73585, https://c19p.org/alotaibia

100 patient vitamin C ICU RCT: 14% lower mortality (p=0.03).
RCT 100 ICU patients in Iran, 31 treated with vitamin C, showing lower mortality with treatment.

Dec 2021, Frontiers in Immunology, https://www.frontiersin.org/articles/10.3389/fimmu.2021.717816/full, https://c19p.org/majidi

91 patient vitamin D late treatment study: 37% lower combined mortality/ICU admission (p=0.13).
Retrospective 91 hospitalized patients, 36 treated with high-dose cholecalciferol, showing lower combined death/ICU admission with treatment. Authors also analyze the relationship with comorbidity burden, finding that the positive effect of high-dose cholecalciferol on the combined endpoint was significantly amplified with increasing comorbidity burden.

Jan 2021, Nutrients , https://www.mdpi.com/2072-6643/13/1/219/htm, https://c19p.org/giannini

398 patient ivermectin early treatment RCT: 61% lower progression (p=0.11) and 15% improved recovery (p=0.53).
Phone survey based RCT with low risk patients, 200 ivermectin and 198 control, showing lower mortality, lower disease progression, lower treatment escalation, and faster resolution of symptoms with treatment, without reaching statistical significance. Authors find the results of this trial alone do not support the use of ivermectin. However the effects are all positive, especially for serious outcomes which are unable to reach statistical significance with the very small number of events in the low risk population. An open letter, signed by >100 physicians, concluding this study is fatally flawed can be found at [ jamaletter.com ] . With the low risk patient population, there is little room for improvement with an effective treatment - 59/57% (IVM/control) recovered within the first 2 days to either "no symptoms" or "not hospitalized and no limitation of activities"; 73/69% within 5 days. Less than 3% of all patients ever deteriorated. The primary outcome was changed mid-trial, it..

Mar 2021, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2777389, https://c19p.org/lopezmedina

291 patient HCQ late treatment study: 60% lower mortality (p=0.002).
Retrospective 346 hospitalized patients in Iraq, showing lower mortality with HCQ in unadjusted results. HCQ results are only provided within the 93% of patients treated with enoxaparin.

Oct 2022, Current Issues in Pharmacy and Medical Sciences, https://www.sciendo.com/article/10.2478/cipms-2022-0020, https://c19p.org/assad

238 patient HCQ late treatment study: 19% lower mortality (p=0.75).
Retrospective 238 hospitalized patients in Spain showing lower mortality with HCQ, adjusted hazard ratio aHR 0.81 [0.24-2.76].

Jul 2020, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S0025775320304486, https://c19p.org/riveraizquierdo

372,720 patient vitamin C prophylaxis study: no change in cases (p=1).
Survey analysis of dietary supplements showing no significant difference in PCR+ cases with vitamin C usage in the UK, however significant reductions were found in the US and Sweden. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.

Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucac

807 patient HCQ late treatment study: 11% lower mortality (p=0.74).
Retrospective 807 hospitalized patients, no statistically significant reduction in mortality or the need for mechanical ventilation with HCQ or HCQ+AZ, or for death with HCQ+AZ, HR 1.83, p=0.009 for HCQ mortality. The preprint notes that HCQ was more likely to be prescribed to patients with more severe disease, however this was deleted in the published version. 425 patients had dispositions of death or discharge by the end of the study period and thus did not encounter the issue of length-biased sampling and differential rates of right-censored observations among the groups. Also see: [mediterranee-infection.com]

Apr 2020, Med, https://www.sciencedirect.com/science/article/pii/S2666634020300064, https://c19p.org/magagnoli

15,968 patient famotidine prophylaxis study: 18% lower mortality (p=0.25).
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing lower mortality with existing use of several medications including metformin, HCQ, azithromycin, aspirin, vitamin D, vitamin C, and budesonide. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.

Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3fm

15 patient HCQ late treatment study: 50% lower mortality (p=0.53).
Very small observational study of 15 dialysis patients showing HCQ mortality RR 0.50, p = 0.53.

Jun 2020, Clinical Kidney J., 334–339, https://academic.oup.com/ckj/article/13/3/334/5860798, https://c19p.org/fontana

77 patient various antiandrogen late treatment study: 81% lower ICU admission (p=0.08).
Prospective study of 77 men hospitalized with COVID-19, 12 taking antiandrogens (9 dutasteride, 2 finasteride, 1 spironolactone), showing lower ICU admission with treatment (statistically significant with age-matched controls only when excluding the spironolactone patient). NCT04368897.

Sep 2020, J. the European Academy of Dermatology and Venereology, https://onlinelibrary.wiley.com/doi/10.1111/jdv.16953, https://c19p.org/goren

78 patient vitamin C ICU study: 25% lower mortality (p=0.26), 2% lower ventilation (p=1), no change in ICU admission, and 28% improved recovery (p=0.005).
Retrospective 78 ICU patients in Turkey, showing lower mortality with high-dose vitamin C treatment, without statistical significance. The SOFA score was significantly better with treatment at day 4. Authors incorrectly state that "HDVC treatment did not reduce the short-term mortality...". Mortality was lower with treatment, although not statistically significant given the sample size. 6g of vitamin C daily in 4 equal doses every 6h, for a total of 96h.

Mar 2023, SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital, https://sislietfaltip.org/jvi.aspx?un=SETB-66742&volume=, https://c19p.org/coskun

126 patient vitamin C early treatment study: 33% improved viral clearance (p=0.73).
Retrospective 126 patients in Turkey, showing no significant difference in PCR+ at day 14 with vitamin C treatment.

Jun 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7706&category_id=179&option=com_virtuemart, https://c19p.org/usanmakobanc

348 patient vitamin D late treatment study: 19% lower mortality (p=0.49) and 67% higher ventilation (p=0.08).
Retrospective 348 hospitalized patients in Italy showing vitamin D deficiency associated with acute hypoxemic respiratory failure. Vitamin D supplementation during hospitalization was not significantly associated with mortality or ventilation.

Mar 2021, J. Endocrinological Investigation, https://link.springer.com/article/10.1007/s40618-021-01535-2, https://c19p.org/mazziotti

301 patient colchicine late treatment study: 35% lower mortality (p=0.18).
Retrospective 301 pneumonia patients in Colombia showing lower mortality with colchicine treatment.

Oct 2020, Research Square, https://www.researchsquare.com/article/rs-94922/v1, https://c19p.org/pinzon

125 patient HCQ prophylaxis RCT: 5% fewer cases (p=1).
Very small early-terminated underpowered PrEP RCT with 64/61 HCQ/control patients and only 8 infections, HCQ infection rate 6.3% versus control 6.6%, RR 0.95 [0.25 - 3.64]. There was no hospitalization or death, no significant difference in QTc, no severe adverse events, no cardiac events (e.g., syncope and arrhythmias) observed. Medication adherence was 81%. Therapeutic levels of HCQ may not have been reached by the time of the infection in the first week. 2 infections were reported to be after discontinuation of the medication, but the authors do not specify which arm these were in. Hypothetically, if these were both in the HCQ arm, the resulting RR for treatment would be much lower.

Sep 2020, JAMA Internal Medicine, https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2771265, https://c19p.org/abella

188 patient exercise study: 69% lower severe cases (p=0.05).
Retrospective 206 patients in Iran, showing COVID-19 disease severity associated with lower physical activity.

Feb 2021, J. Public Health, http://link.springer.com/article/10.1007/s10389-020-01468-9/fulltext.html, https://c19p.org/tavakol

52 patient HCQ late treatment study: 40% lower ventilation (p=0.3).
Small 52 patient retrospective study of patients with acute respiratory failure showing lower rates of intubation with HCQ.

Nov 2020, Research Square, https://www.researchsquare.com/article/rs-113418/v1, https://c19p.org/capsoni

7,654 patient favipiravir early treatment study: 13% lower mortality (p=0.59), 2% higher ventilation (p=0.93), and 18% lower progression (p=0.1).
Retrospective database analysis of 7,654 hospitalized patients in Japan, showing no significant differences with favipiravir treatment. NCGM-G-003494-0.

Mar 2022, Infectious Diseases and Therapy, https://link.springer.com/article/10.1007/s40121-022-00617-9/fulltext.html, https://c19p.org/tsuzuki2

605 patient HCQ late treatment study: 99% lower mortality (p=0.6).
605 hospitalized patients in Saudi Arabia showing no mortality with HCQ (only 6 patients received HCQ).

Mar 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221002769, https://c19p.org/barry

59 patient famotidine ICU study: 29% lower mortality (p=0.19), 1% higher ventilation (p=1), and 26% shorter ICU admission (p=0.6).
Retrospective 59 ICU patients in Turkey, showing no significant difference in 30-day mortality or invasive mechanical ventilation with 160mg/day famotidine treatment. However, the famotidine group had lower fibrinogen and procalcitonin, suggesting possible benefits for coagulation, inflammation, and secondary infections. Limitations include the small sample size, lack of randomization, and other confounding treatments.

Feb 2023, Boğazi̇çi̇ Tip Dergi̇si̇, https://jag.journalagent.com/bmj/pdfs/BMJ-77044-ORIGINAL_RESEARCH-OZDEN.pdf, https://c19p.org/ozden

15,227 patient probiotics prophylaxis study: 30% fewer cases (p=0.11).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtk

26 patient curcumin early treatment RCT: 26% improved recovery (p=0.26).
Small RCT 46 outpatients in Iran, 23 treated with curcimin-piperine, showing no significant difference in recovery. 1000mg curcumin and 10mg piperine/day for 14 days.

Jun 2022, Trials, https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-022-06375-w, https://c19p.org/askari

199 patient various antiandrogen prophylaxis study: 11% lower mortality (p=0.37).
Retrospective 199 prostate cancer patients hospitalized with COVID-19 in Brazil, showing no significant difference in mortality with active ADT.

Nov 2021, Infectious Agents and Cancer, https://link.springer.com/article/10.1186/s13027-021-00406-y/fulltext.html, https://c19p.org/duarte

1,064. Taşdemir et al., Famotidine in COVID-19 treatment
179 patient famotidine late treatment study: 45% lower mortality (p=0.29), 37% lower ICU admission (p=0.36), 18% shorter hospitalization (p=0.003), and 20% faster recovery (p=0.04).
Retrospective 179 hospitalized patients in Turkey, 85 treated with famotidine and 94 treated with pantoprazole, showing faster recovery with famotidine in unadjusted results.

Jul 2021, Konuralp Tıp Dergisi, https://dergipark.org.tr/en/pub/ktd/article/935888, https://c19p.org/tasdemir

exercise study: 81% lower severe cases (p=0.02) and 56% lower hospitalization (p=0.07).
Mendelian randomization study showing lower risk of severe COVID-19 with physical activity.

Feb 2021, BMC Medical Genomics, https://bmcmedgenomics.biomedcentral.com/articles/10.1186/s12920-021-00887-1, https://c19p.org/li17

4,462 patient metformin prophylaxis PSM study: 1% lower mortality (p=0.91) and 5% shorter hospitalization (p=0.23).
Retrospective 4,462 COVID+ diabetes patients in the USA, showing no significant difference in outcomes with metformin use.

Nov 2022, Frontiers in Endocrinology, https://www.frontiersin.org/articles/10.3389/fendo.2022.1002834/full, https://c19p.org/miao

564 patient HCQ prophylaxis study: 30% lower progression (p=0.77) and 19% more cases (p=0.58).
Small prophylaxis survey showing lower, but not statistically significant, progression to pneumonia (3 of 148 HCQ, 12 of 416 control), RR 0.70, p = 0.77. There was a higher incidence of cases with HCQ, OR 1.19, p = 0.58, which may be due to survey bias, treatment self-selection, and inconsistent regimens. Improvement on severity may be related to the higher HCQ concentration in lung tissue, and also reflect that binary PCR does not distinguish replication-competence. Details of the pneumonia numbers for treatment/control are from the author, it's unclear why the lower progression to pneumonia was not reported in the paper.

Dec 2020, Infectious Diseases and Clinical Microbiology, https://www.idcmjournal.org/hqn-use-among-physicians-during-the-pandemic, https://c19p.org/gonenli

372,720 patient zinc prophylaxis study: 1% fewer cases (p=0.8).
Survey analysis of dietary supplements showing no significant difference in PCR+ cases with zinc usage. These results are for PCR+ cases only, they do not reflect potential benefits for reducing the severity of cases. A number of biases could affect the results, for example users of the app may not be representative of the general population, and people experiencing symptoms may be more likely to install and use the app.

Nov 2020, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/149, https://c19p.org/loucaz

125 patient HCQ late treatment study: 43% lower hospitalization (p=0.76).
Retrospective 125 pregnant women hospitalized with COVID-19 in Turkey, showing no significant difference in hospitalization length with HCQ, and longer hospitalization with lopinavir/ritonavir use.

Jul 2024, J. Controversies in Obstetrics & Gynecology and Pediatrics, http://journal-jcogp.com/Publication/DisplayArticle/27358, https://c19p.org/degirmencih

236 patient favipiravir late treatment RCT: 74% lower progression (p=0.37), 20% lower need for oxygen therapy (p=0.42), and 20% improved recovery (p=0.15).
Very late stage (9 days from symptom onset) RCT with 116 favipiravir patients and 120 arbidol patients in China, showing no significant difference in clinical recovery (relief of fever and cough, respiratory frequency ≤24 times/min, and oxygen saturation ≥98%), however the time to resolution of fever and cough was significantly lower with favipiravir. ChiCTR2000030254.

Sep 2021, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2021.683296/full, https://c19p.org/chen4

116 patient HCQ prophylaxis study: 38% fewer cases (p=0.3).
Case control study of healthcare workers in India, showing lower risk of cases with HCQ prophylaxis, without statistical significance. While authors comment negatively, as may be required for publication, and this study alone is not statistically significant, the result is consistent with the positive results in all studies to date.

Nov 2022, F1000Research, https://f1000research.com/articles/11-1298/v1, https://c19p.org/sukumar

73 patient exercise study: 54% fewer moderate/severe cases (p=0.01).
Retrospective 68 COVID-19 patients showing physical activity and healthier nutrition associated with lower COVID-19 severity.

Oct 2023, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-023-00727-8, https://c19p.org/hegazy

63,369 patient HCQ late treatment study: 15% lower mortality (p=0.62).
Retrospective 63,369 hospitalized COVID-19 survivors aged 60 years or older in Korea, showing lower 1-year mortality with macrolides (including azithromycin), higher 1-year mortality with corticosteroids (including dexamethasone and methylprednisolone), and no significant difference with HCQ (only used for 0.2% of patients).

Oct 2024, Scientific Reports, https://www.nature.com/articles/s41598-024-76871-3, https://c19p.org/kim21h

41 patient povidone-iodine early treatment RCT: 99% improved viral load (p=0.37).
RCT with 21 PVP-I and 20 saline patients gargling for 30 seconds and testing PCR Ct after 30 minutes, showing greater improvement with PVP-I, without statistical significance. Ct values differ across testing platforms, however the reported Ct value difference can represent a large difference in viral load. For example, using the calibration included with the ct2vl converter, the reported difference in mean Ct values corresponds to a reduction in viral load of over 3x for PVP-I.

Jul 2022, Dental and Medical Problems, https://dmp.umw.edu.pl/en/ahead-of-print/150831/, https://c19p.org/sevincgul

300 patient exercise study: 16% lower hospitalization (p=0.53).
Retrospective 300 participants in Palestine, showing lower risk of hospitalization with physical activity, without statistical significance.

Dec 2021, J. Int. Medical Research, http://journals.sagepub.com/doi/10.1177/03000605211064405, https://c19p.org/hamdan

144 patient antiandrogen prophylaxis PSM study: 6% fewer cases (p=0.006).
PSM retrospective 144 alopecia patients in the USA, showing no significant difference in COVID-19 cases with anti-androgen use. The supplemental appendix is not available.

Jun 2021, J. Drugs in Dermatology, https://jddonline.com/articles/dermatology/S1545961621P0914X, https://c19p.org/shawaa

94 patient ursodeoxycholic acid prophylaxis PSM study: 17% fewer symptomatic cases (p=0.81) and no change in cases (p=1).
Retrospective 94 outpatients attending a university hospital gastroenterology clinic in Japan showing no significant difference in SARS-CoV-2 infection rates between ursodeoxycholic acid (UDCA)-treated patients and control groups without UDCA treatment. However, UDCA-treated patients tended to have higher rates of subclinical infection based on serology, suggesting UDCA may reduce COVID-19 severity.

Jul 2023, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13704, https://c19p.org/okushin

34 patient camostat early treatment RCT: 14% lower hospitalization (p=1).
Early terminated RCT with 34 patients showing no significant differences with camostat treatment.

Mar 2022, NCT04455815, https://clinicaltrials.gov/study/NCT04455815, https://c19p.org/dhaliwal

984 patient aspirin prophylaxis study: 7% higher mortality (p=0.65) and 30% lower combined mortality/intubation (p=0.01).
Retrospective 984 COVID-19 patients, 253 taking aspirin prior to admission, showing lower risk of respiratory support upgrade with treatment.

Oct 2021, Int. J. Cardiology, https://www.sciencedirect.com/science/article/abs/pii/S0167527321014996, https://c19p.org/sisinni

312 patient HCQ late treatment study: 24% lower mortality (p=0.27).
Retrospective 117 patients showing lower mortality for HCQ patients, without statistical significance. Version 1 of this paper stated: "HCQ, AZ, [and ...] were found to be independently associated with survival when treatment commenced at FACTCLINYCoD scores <3". FACTCLINYCoD scores predict mortality risk based on severity markers and comorbidities.

Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.09.05.20184655v2, https://c19p.org/synolaki

255 patient HCQ late treatment study: 27% lower mortality (p=0.002).
Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level. Although authors mention immortal time bias, full details on the timing of HCQ administration is not provided and this is not fully addressed. Survival curves indicate immortal time bias will significantly change results, although the observed benefit appears to exceed the potential bias.

May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.05.28.21258012v1, https://c19p.org/smith

149 patient HCQ ICU study: 40% lower mortality (p=0.12).
Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with HCQ in unadjusted results.

Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimerh

58 patient aspirin prophylaxis study: 58% lower mortality (p=0.43).
Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing no significant difference with aspirin treatment.

Jul 2020, J. Hematology & Oncology, https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00934-x, https://c19p.org/wang3e

58 patient metformin prophylaxis study: 58% lower mortality (p=0.43).
Retrospective 58 multiple myeloma COVID-19 patients in the USA, showing non-statistically significant lower mortality with metformin treatment.

Jul 2020, J. Hematology & Oncology, https://jhoonline.biomedcentral.com/articles/10.1186/s13045-020-00934-x, https://c19p.org/wang3

metformin prophylaxis study: 44% lower progression (p<0.0001) and 37% lower hospitalization (p<0.0001).
Retrospective 4,944 COVID-19 patients with type 2 diabetes in the USA, showing lower risk of hospitalization and combined ICU/intubation/death with metformin use.

Jun 2022, BMJ Open Diabetes Research & Care, https://drc.bmj.com/content/10/3/e002774.long, https://c19p.org/yeh2

46,535 patient sleep study: 43% lower mortality (p=0.02) and 36% lower hospitalization (p=0.008).
UK Biobank retrospective, 46,535 participants with sleep behavior assessed between 2006 and 2010, showing higher risk of hospitalization and mortality with poor sleep.

Jun 2021, Sleep, https://academic.oup.com/sleep/article/doi/10.1093/sleep/zsab138/6304657, https://c19p.org/li13

80 patient HCQ ICU study: 42% lower mortality (p=0.24), 6% lower treatment escalation (p=0.73), and 15% improved viral clearance (p=0.61).
Retrospective 80 ICU patients, 22 SOC, 20 lopinavir/ritonavir, 38 HCQ. 28 day mortality 24% (HCQ) versus 41% (SOC), a 41% decrease, but not statistically significant due to very small sample sizes. No statistically significant differences found for treatment escalation, ventilator-free days, viral load, or mortality. Authors consider treatment escalation more important than mortality, for unknown reasons.

Jul 2020, Critical Care, 2020, https://ccforum.biomedcentral.com/articles/10.1186/s13054-020-03117-9, https://c19p.org/lecronier

616 patient montelukast prophylaxis study: 13% lower hospitalization (p=0.61).
Retrospective 616 COVID-19 patients with asthma in Qatar showing no significant difference in hospitalization risk with montelukast use.

Sep 2023, Qatar Medical J., https://www.qscience.com/content/journals/10.5339/qmj.2023.15, https://c19p.org/alhmoud

1,195 patient ivermectin prophylaxis study: 100% fewer cases (p<0.0001).
Prophylaxis study using ivermectin and iota-carrageenan showing 0 of 788 cases from treated healthcare workers, compared to 237 of 407 control. See [doyourownresearch.substack.com] for discussion of issues with this trial.

Nov 2020, J. Biomedical Research and Clinical Investigation, https://medicalpressopenaccess.com/upload/1605709669_1007.pdf, https://c19p.org/carvalloprep

164 patient ivermectin late treatment RCT: 20% shorter hospitalization (p=0.09).
RCT 164 hospitalized patients in Egypt showing lower mortality and shorter hospitalization, but without statistical significance. There were no serious adverse effects. Authors suggest the low dosage may have resulted in lower efficacy than other trials, and recommend increased dosage in future trials. Time from symptom onset is not specified. The trial was retrospectively registered and the recruitment start date in the trial registration (June 2020) differs from the paper (March 2020) [osf.io]. For other concerns see [onlinelibrary.wiley.com].

Jun 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27122, https://c19p.org/abdelsalam3

60 patient ivermectin early treatment RCT: 39% improved recovery (p=0.19) and 6% improved viral clearance (p=0.75).
RCT 60 low-risk outpatients, median age 31, with mild to moderate COVID-19 showing no significant differences with combined favipiravir/ivermectin/niclosamide treatment compared to favipiravir alone. There was limited room for improvement with almost no progression and no hospitalization, ICU admission, supplemental oxygen, or mortality. The combined group showed significantly improved visual analog scale (VAS) scores for cough, runny nose, and diarrhea from day 3. Authors note that "the WHO-CPS were significantly decreased among FPV/IVM/NCL vs FPV alone on day 10", however the degree of improvement cannot be determined based on the values reported. Authors state that "All data generated or analyzed during this study are included in this published article", which is incorrect - only summary statistics are published. The trial registration states that data will not be made available. This raises concerns, especially given many inconsistencies in the published data:..

Mar 2024, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034124001060, https://c19p.org/siripongboonsitti6

90 patient ivermectin early treatment study: 92% improved recovery (p=0.04).
Retrospective 95 outpatients in Pakistan with strong clinical suspicion of COVID-19 (testing was not widely available), with 40 patients treated with ivermectin, showing significantly shorter duration of febrile illness with treatment. Most patients also received HCQ, AZ, zinc, and aspirin. Authors note that there was a treatment delay-response relationship.

Dec 2020, Int. J. Clinical Studies & Medical Case Reports, https://ijclinmedcasereports.com/pdf/IJCMCR-RA-00320.pdf, https://c19p.org/ghauri

372 patient HCQ prophylaxis study: 28% fewer cases (p=0.29).
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58

Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/behera

283 patient HCQ late treatment study: 32% lower mortality (p=0.72).
Retrospective 283 COVID-19+ diabetes patients in China, showing non-statistically significant lower mortality with HCQ/CQ treatment.

May 2020, The American J. Tropical Medicine and Hygiene, https://www.ajtmh.org/configurable/content/journals$002ftpmd$002f103$002f1$002farticle-p69.xml?t:ac=journals%24002ftpmd%24002f103%24002f1%24002farticle-p69.xml, https://c19p.org/luo3h

1,000 patient ivermectin late treatment study: 48% lower mortality (p=0.13).
Retrospective 1,000 hospitalized COVID-19 patients in Pakistan, showing lower mortality with ivermectin without statistical significance.

Apr 2023, Healthcare, https://www.mdpi.com/2227-9032/11/8/1192, https://c19p.org/munir

15,227 patient vitamin A prophylaxis study: 56% fewer cases (p=0.41).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holta

8,875 patient vitamin C late treatment study: 54% lower mortality (p=0.03).
Retrospective 8,634 hospitalized patients in India, showing lower mortality with high-dose vitamin C in unadjusted results. No group details are provided, the text and table appear to show different results, and some numbers do not match.

Jun 2021, Indian J. Basic and Applied Medical Research, https://www.ijbamr.com/assets/images/issues/pdf/FuXsaN_e2u6D7_ZY1348_LzacYt_766641.pdf, https://c19p.org/vishnuram

253 patient vitamin D prophylaxis study: 46% lower severe cases (p=0.2).
Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.

Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehab

209 patient vitamin A prophylaxis study: 64% fewer cases (p<0.0001) and 32% faster recovery.
Treatment and prophylaxis studies of vitamin A in Iraq. The prophylaxis study contained 209 contacts of COVID-19 patients, 97 treated with vitamin A, showing significantly lower cases with treatment, and shorter duration of symptoms. The treatment study is listed separately [Al-Sumiadai].

Jan 2021, Systematic Reviews in Pharmacy, https://www.researchgate.net/publication/351637178_THERAPEUTIC_EFFECT_OF_VITAMIN_A_ON_COVID-19_PATIENTS_AND_ITS_PROPHYLACTIC_EFFECT_ON_CONTACTS, https://c19p.org/alsumiadaip

21 patient povidone-iodine late treatment RCT: 34% improved viral load (p=0.82).
Small very late (>50% 7+ days from symptom onset, 9 PVP-I patients) RCT testing mouthwashing with cetylpyridinium chloride, chlorhexidine, povidone-iodine, hydrogen peroxide, and distilled water, showing no significant differences. Over 30% of patients show >90% decrease in viral load @2 hrs with all 5. Authors note that a trend was observed for viral load decrease with PVP-I @2h for patients <6 days from onset (p=0.06, Wilcox test).

Dec 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-03461-y, https://c19p.org/ferrer2

133 patient vitamin D prophylaxis study: 14% lower mortality (p=0.61).
Retrospective 133 COVID+ hemodialysis patients in Poland, showing lower mortality with existing vitamin D use, without statistical significance.

Jan 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/2/285, https://c19p.org/tylicki

153 patient HCQ prophylaxis study: 25% lower mortality (p=0.77) and 22% lower hospitalization (p=0.29).
Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically significant due to the small number of events. The actual benefit for HCQ could be much larger. The study does not address the risk of being sick enough to visit the hospital. HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].

Jan 2021, J. the American Academy of Dermatology, https://www.sciencedirect.com/science/article/pii/S0190962221001109, https://c19p.org/rangel

200 patient exercise study: 46% fewer moderate/severe cases (p=0.11).
Analysis of 200 mild and moderate COVID-19 outpatients showing an association between higher ESSAP scores (measuring exercise, sugar and prebiotic consumption, sleep, and antibiotic use) and milder COVID-19 disease. Authors find increased risk with daily yogurt containing probiotics. Probiotic intake based on yogurt only may be inaccurate. Authors hypothesize that commercial yogurt products may not contain sufficient beneficial bacteria or may be contaminated. Other research shows that probiotic food labels are often misleading—of 26 probiotic foods tested, only 5 contained Bifidobacterium in sufficient concentration for exhibiting a therapeutic effect [Hazan]. For sleep, authors compare <8 hours and ≥8 hours, while sleep for less than or longer than a recommended range may indicate increased risk.

Jun 2021, British J. Nutrition, https://www.cambridge.org/core/product/identifier/S0007114521001926/type/journal_article, https://c19p.org/hegazy2

198 patient proton pump inhibitor prophylaxis study: 26% lower mortality (p=0.44) and 8% more symptomatic cases (p=0.54).
Retrospective 1,084 residents from 6 long-term care facilities in Spain showing no signficant difference in cases and mortality with PPI use in unadjusted results.

Oct 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241030, https://c19p.org/masromero

100 patient HCQ late treatment study: 36% lower mortality (p=0.12).
Retrospective 100 hospitalized patients in Spain showing lower mortality with HCQ+AZ.

Jul 2020, Research Square, https://www.researchsquare.com/article/rs-39421/v1, https://c19p.org/trullas

191 patient zinc late treatment RCT: 1% lower mortality (p=0.99), 34% lower ventilation (p=0.54), 6% improved recovery (p=0.97), and 4% shorter hospitalization (p=0.55).
191 patient RCT in Egypt comparing the addition of zinc to HCQ, not showing a significant difference. No information on baseline zinc values was recorded. Egypt has a low rate of zinc deficiency so supplementation may be less likely to be helpful [ncbi.nlm.nih.gov, ncbi.nlm.nih.gov]. For several issues with this trial, see [osf.io]. See also [link.springer.com]. The primary outcome was changed from viral clearance to "improvement or mortality" in the last month of the trial. The pre-specified outcome was not reported.

Nov 2020, Biological Trace Element Research, https://link.springer.com/article/10.1007/s12011-020-02512-1, https://c19p.org/abdelsalam2z

66 patient vitamin C late treatment RCT: 4% improved recovery (p=0.83).
Early terminated low-risk patient RCT with 32 low-dose vitamin C, 32 melatonin, and 34 placebo patients, showing faster resolution of symptoms with melatonin in spline regression analysis, and no significant difference for vitamin C. All patients recovered with no serious outcomes reported. Baseline symptoms scores were higher in the melatonin and vitamin C arms (median 27 and 24 vs. 18 for placebo).

Jul 2022, The J. the American Board of Family Medicine, http://www.jabfm.org/lookup/doi/10.3122/jabfm.2022.04.210529, https://c19p.org/foglemanc

600 patient diet study: 25% lower progression (p<0.0001).
Retrospective 600 COVID-19 patients in Iran with moderate/severe CT scans, showing lower prevalence of dyspnea, fever, taste/smell abnormalities, and cough with high adherence to the Mediterranean diet in unadjusted results.

Jan 2023, Medicina, https://www.mdpi.com/1648-9144/59/2/227, https://c19p.org/mohajeri2

107 patient ursodeoxycholic acid prophylaxis study: 38% improved recovery (p=0.05).
Retrospective 115 COVID-19 patients hospitalized during an Omicron outbreak in China, of which 65 received ursodeoxycholic acid (UDCA) treatment and 50 received standard care. It found that UDCA was associated with faster body temperature recovery, with a hazard ratio of 1.62 (95% CI 0.99-2.60, p=0.053) compared to standard care after adjusting for covariates. Patients receiving higher UDCA doses (≥300mg daily) had significantly faster recovery than the standard care group, with a hazard ratio of 1.82 (95% CI 1.07-3.10, p=0.028). To further analyze the exposure-response relationship, the authors developed an AI model called VirtualBody that accurately predicted individualized UDCA pharmacokinetic profiles. Additional analysis using VirtualBody-generated data found UDCA AUC, indicating total exposure over time, had a stronger correlation with clinical outcome than cumulative dose. Overall, the study suggests UDCA may shorten recovery time from COVID-19, especially at higher doses,..

May 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.05.02.23289410, https://c19p.org/yu5

favipiravir late treatment study: 76% lower mortality (p=0.0005).
Retrospective 689 hospitalized patients in Indonesia, showing lower mortality with favipiravir treatment.

Feb 2023, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368223000276, https://c19p.org/hartantri

favipiravir early treatment study: 68% lower progression (p=0.003).
Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided.

Sep 2021, Southeast Asian J. Tropical Medicine and Public Health, https://journal.seameotropmednetwork.org/index.php/jtropmed/article/view/490, https://c19p.org/sawanpanyalerta

colchicine prophylaxis PSM study: 80% lower mortality (p=0.02).
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.

Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoroo

2,664 patient aspirin prophylaxis PSM study: 67% lower combined mortality/intubation (p=0.0003).
PSM retrospective 2,664 COVID-19 hospitalized patients receiving steroids/antiviral therapy in Hong Kong, showing lower risk of combined death/intubation with aspirin use.

Jun 2023, Heart, https://heart.bmj.com/content/109/Suppl_3/A244.2, https://c19p.org/tse

53,030 patient metformin late treatment study: 74% lower mortality (p<0.0001).
Retrospective 53,030 COVID-19 patients from 138 hospitals in Hubei, China showing lower mortality with metformin.

Nov 2024, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906724002409, https://c19p.org/he2

exercise study: 98% lower mortality (p=0.05).
Retrospective 234 COVID-19 cases in the United Arab Emirates, showing lower risk of mortality with increased physical activity.

Aug 2021, J. Epidemiology and Global Health, https://link.springer.com/article/10.1007/s44197-021-00006-4/fulltext.html, https://c19p.org/baynounaalketbi

exercise study: 74% lower hospitalization (p=0.001).
Retrospective 246 COVID-19 patients in the USA, showing the risk of hospitalization inversely associated with maximal exercise capacity. Adjusted results are only provided for MET as a continuous variable.

Oct 2020, Mayo Clinic Proceedings, https://www.mayoclinicproceedings.org/article/S0025-6196(20)31130-7/fulltext, https://c19p.org/brawner

loratadine prophylaxis PSM study: 80% lower mortality (p=0.05).
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of loratadine.

Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoroh1

70 patient HCQ prophylaxis study: 50% lower mortality (p=0.67).
Retrospective hospitalized rheumatic disease patients showing 50% lower mortality for patients on HCQ.

Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.26.20219154v1, https://c19p.org/arleo

50 patient vitamin D early treatment RCT: 29% improved recovery (p=0.11) and 91% improved viral clearance (p=0.05).
Small RCT with 50 outpatients, 25 treated with curcumin, quercetin, and vitamin D, showing improved recovery and viral clearance with treatment. 168mg curcumin, 260mg, 360IU vitamin D3 daily for 14 days.

Jan 2023, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.1023997/full, https://c19p.org/dinujjan

215 patient vitamin C prophylaxis study: 18% fewer cases (p=0.58).
Retrospective matched case-control prophylaxis study for HCQ, ivermectin, and vitamin C with 372 healthcare workers, showing lower COVID-19 incidence for all treatments, with statistical significance reached for ivermectin. HCQ OR 0.56, p = 0.29 Ivermectin OR 0.27, p < 0.001 Vitamin C OR 0.82, p = 0.58

Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163, https://c19p.org/beherac

7,846 patient smoking prophylaxis study: 3% lower mortality (p=0.8).
Retrospective 10,074 hospitalized veterans with COVID-19 in the USA, showing higher risk of mortality for former smokers and no significant difference for current smokers.

Oct 2021, Nicotine & Tobacco Research, https://academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntab223/6409756?login=false, https://c19p.org/razjouyansm

253 patient zinc prophylaxis study: 47% lower severe cases (p=0.24).
Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.

Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabz

sleep study: 39% lower mortality (p=0.001), 32% lower hospitalization (p<0.0001), and 7% fewer cases (p=0.04).
FinnGen Mendelian randomization study showing higher risk of COVID-19 mortality, hospitalization, and infection with insomnia.

Jul 2022, Sleep Medicine, https://www.sciencedirect.com/science/article/pii/S1389945722005536, https://c19p.org/jones

27 patient antihistamine H1RA long COVID study: 29% lower PASC (p=0.1).
Retrospective 14 patients with long-COVID symptoms attributed to mast cell activation treated with H1 and H2 antihistamines compared to 13 control patients, showing significant improvements in several symptoms in the treatment group compared to controls after 20 days. 29% of treated patients had complete resolution of long-COVID symptoms, compared with none in the control group.

Jul 2023, Frontiers in Cardiovascular Medicine, https://www.frontiersin.org/articles/10.3389/fcvm.2023.1202696/full, https://c19p.org/salvucci

7,158 patient azithromycin late treatment study: 7% lower mortality (p=0.84).
Retrospective 7,158 hospitalized COVID-19 patients in the USA analyzing famotidine treatment, showing no significant difference in mortality with associated azithromycin treatment.

Feb 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)35249-5/fulltext, https://c19p.org/yeramaneniazaz

24 patient povidone-iodine early treatment RCT: 74% improved viral load (p=0.27).
60 patient RCT comparing chlorhexidine, PVP-I, and saline in Saudi Arabia with a single mouth rinse treatment and PCR testing 5 minutes later, showing statistically significant improvement in Ct value for PVP-I. PVP-I showed greater improvement than saline, without statistical significance.

Jul 2022, Medicine, https://journals.lww.com/md-journal/Fulltext/2022/07290/The_short_term_effect_of_different_chlorhexidine.78.aspx, https://c19p.org/natto

20 patient zinc ICU RCT: 33% lower progression (p=1) and 6% shorter ICU admission (p=0.3).
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.

Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darbanz

20 patient melatonin ICU RCT: 33% lower progression (p=1) and 6% shorter ICU admission (p=0.3).
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.

Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darban

75 patient metformin prophylaxis study: 60% lower mortality (p=0.21) and 76% lower ventilation (p=0.05).
Retrospective 75 diabetes patients, 34 on metformin, showing lower mortality with treatment in unadjusted results with minimal group details.

Nov 2021, Circulation, 144:A12228, https://www.ahajournals.org/doi/abs/10.1161/circ.144.suppl_1.12228, https://c19p.org/bliden

11 patient camostat ICU study: 58% lower mortality (p=0.55), 61% shorter ICU admission, and 56% improved recovery.
Retrospective 11 critically ill COVID-19 ICU patients with organ failure treated with camostat mesylate (6 patients) or HCQ (5 patients). Over an 8 day period, the severity of COVID-19 decreased in the camostat group as measured by a decline in the SOFA score, inflammatory markers, and improvement in oxygenation. A similar effect was not seen in the HCQ group.

Nov 2020, Critical Care Explorations, https://journals.lww.com/10.1097/CCE.0000000000000284, https://c19p.org/hofmannwinkler

10,000 patient exercise study: 7% fewer cases (p=0.4).
Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with increased leisure time physical activity, without statistical significance. Authors do not analyze COVID-19 severity.

Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2ex

73 patient HCQ late treatment study: 13% lower mortality (p=1).
Small retrospective study of 73 diabetic patients in Belgium, 55 HCQ patients, showing HCQ RR 0.87, p = 1.0.

Dec 2020, Diabetes & Metabolic Syndrome: Clinical Research & Reviews, https://www.sciencedirect.com/science/article/pii/S1871402120305154, https://c19p.org/orioli

689 patient diet study: 20% lower IgG positivity (p=0.32).
Retrospective 689 healthcare workers in India, showing non-statistically significant lower risk of IgG positivity with a vegetarian diet in unadjusted results.

Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtodt

110 patient colchicine late treatment RCT: 7% lower mortality (p=1), 7% lower ventilation (p=1), 24% higher ICU admission (p=0.63), and 28% improved recovery (p=0.59).
Very late treatment (10 days from onset) RCT 110 patients in Iran, showing no significant difference in outcomes with colchicine. Colchicine 2mg loading dose followed by 0.5mg bid for 7 days.

Jan 2023, J. Investigative Medicine, http://journals.sagepub.com/doi/10.1177/10815589221141815, https://c19p.org/kasiri

277 patient HCQ late treatment study: 35% lower mortality (p=0.12).
Retrospective 277 hospitalized patients in Italy, showing lower mortality with HCQ treatment, not reaching statistical significance, and subject to confounding by indication.

Sep 2021, PharmAdvances, http://www.pharmadvances.com/a-retrospective-analysis-on-pharmacological-approaches-to-covid-19-patients-in-an-italian-hub-hospital-during-the-early-phase-of-the-pandemic-2/, https://c19p.org/menardi

1,358 patient ivermectin early treatment RCT: while presented as negative, the co-principal investigator privately reported that "there is a clear signal that IVM works in COVID patients".
Together Trial Ivermectin: impossible data, critical issues, blinding broken, randomization failure, data pledge violation, protocol violations.

Aug 2021, New England J. Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2115869, https://c19p.org/togetherivm

38 patient povidone-iodine late treatment RCT: 57% improved viral load and 31% improved viral clearance (p=0.26).
Mouthrinse RCT in Italy comparing short-term viral load after a single 60 second treatment with povidone-iodine, hydrogen peroxide, chlorhexidine, and saline. The greatest efficacy was seen with povidone-iodine, especially for patients with low viral load at baseline.

Jul 2022, American J. Otolaryngology, https://www.sciencedirect.com/science/article/pii/S0196070922001764, https://c19p.org/fantozzi

32 patient aspirin ICU study: 46% lower mortality (p=0.63).
Retrospective 32 ICU patients showing lower mortality with aspirin treatment, without statistical significance.

Aug 2021, Microbial Drug Resistance, https://www.liebertpub.com/doi/full-xml/10.1089/mdr.2020.0489, https://c19p.org/karruli

40 patient vitamin D prophylaxis study: 89% fewer symptomatic cases (p=0.11).
Prospective study of 40 acute coronary syndrome patients in Pakistan, 20 given a single dose of 200,000IU vitamin D, showing lower incidence of COVID-19 in the following 2 months.

May 2022, Pakistan J. Medical and Health Sciences, https://pjmhsonline.com/index.php/pjmhs/article/view/773, https://c19p.org/jabeen

481 patient ivermectin late treatment study: 97% lower mortality (p=0.31).
Retrospective COVID+ hospitalized patients in Uganda, showing no statistically significant difference in mortality with ivermectin, however there were only 7 patients receiving ivermectin.

Dec 2021, Research Square, https://www.researchsquare.com/article/rs-1193578/v1, https://c19p.org/baguma

43 patient metformin prophylaxis study: 15% lower severe cases (p=0.05).
Retrospective 43 diabetes patients hospitalized for COVID-19 in Italy, showing lower risk of severe cases with metformin vs. insulin.

Jan 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/1/145, https://c19p.org/pinchera

829 patient HCQ late treatment study: 56% lower severe cases (p=0.13).
Retrospective 829 hospitalized COVID-19 patients in Spain focused on gastrointestinal symptoms, showing lower risk of severe COVID-19 with HCQ treatment in bivariate analysis, without statistical significance.

Jun 2023, Gastroenterología y Hepatología, https://www.sciencedirect.com/science/article/pii/S2444382423001104, https://c19p.org/cardenasjaen

2,512 patient HCQ late treatment study: 1% lower mortality (p=0.93).
Retrospective study of late stage use on 2,512 hospitalized patients showing no significant differences in associated mortality for patients receiving any HCQ during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), HCQ alone (HR, 1.02 [95% CI, 0.83-1.27]), or HCQ+AZ (HR, 0.98 [95% CI, 0.75-1.28]). Misclassification is possible due to manual abstraction of EHR data. They observed a change in the prescribing patterns of HCQ during the study timeframe. Confounding by indication.

May 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0237693, https://c19p.org/ip2

9,229 patient aspirin prophylaxis study: 1% lower ventilation (p=0.97).
Retrospective 9,748 COVID-19 patients in the USA showing no signficant difference with aspirin use.

Feb 2021, Clinical Pharmacology & Therapeutics, https://onlinelibrary.wiley.com/doi/10.1002/cpt.2376, https://c19p.org/bejane

167 patient HCQ late treatment study: 33% lower mortality (p=0.2).
Retrospective 167 multiple myeloma patients in Spain, showing no significant difference in mortality with HCQ treatment in unadjusted results without group details.

Jun 2020, Blood Cancer J., https://www.nature.com/articles/s41408-020-00372-5, https://c19p.org/martinezlopez

22,125 patient ibuprofen prophylaxis study: no change in mortality (p=0.54).
Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic ibuprofen use vs. sporadic NSAID use. Since ibuprofen is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.

May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2ib

237 patient vitamin D late treatment RCT: 49% higher mortality (p=0.43), 48% lower ventilation (p=0.09), 25% lower ICU admission (p=0.3), and 7% higher hospital discharge (p=0.63).
Very late stage (mean 10 days from symptom onset, 90% on oxygen at baseline) vitamin D supplementation RCT not showing significant differences. Ethnicity was poorly matched between arms, and diabetes was 41% in the treatment arm vs. 29% in the control arm. Baseline ventilation was 15% in the treatment arm vs. 12% control. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage. Treatment was dissolved in 10mL of peanut oil.

Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2776738, https://c19p.org/murai

60 patient azithromycin late treatment study: 85% lower mortality (p=0.31).
RCT 60 hospitalized COVID-19 patients evaluating the efficacy and safety of adding oral N-acetylcysteine (NAC) at 600mg three times daily to standard antiviral treatment regimens. There was lower mortality for patients that received azithromycin, without statistical significance.

Nov 2023, Immunity, Inflammation and Disease, https://onlinelibrary.wiley.com/doi/10.1002/iid3.1083, https://c19p.org/atefiazaz

152 patient HCQ late treatment study: 20% lower mortality (p=0.48).
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.

Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnan

1,486 patient HCQ late treatment study: 12% faster viral clearance (p=0.59).
Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir.

Apr 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/4/498, https://c19p.org/hafez

43 patient HCQ late treatment study: 59% lower mortality (p=0.23).
Small prospective study of 43 hospitalized patients with 39 taking HCQ, showing unadjusted mortality relative risk RR 0.41, p=0.23.

Nov 2020, Medicina Intensiva, https://www.sciencedirect.com/science/article/pii/S2173572720301739, https://c19p.org/rodriguez

296 patient HCQ late treatment study: 14% lower combined mortality/intubation (p=0.55).
Retrospective 296 hospitalized patients in France, showing no significant difference with HCQ treatment.

Feb 2022, Infectious Diseases Now, https://www.sciencedirect.com/science/article/pii/S266699192200032X, https://c19p.org/beaumont

89 patient HCQ late treatment study: 11% lower mortality (p=0.88).
Retrospective of 89 hospitalized patients, survival HR 0.89 [0.23-3.47], not statistically significant. Authors note that unmeasured confounders may have persisted and the study may be underpowered.

Jun 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/doi/10.1093/cid/ciaa791/5859555, https://c19p.org/paccoud

9,565 patient famotidine late treatment PSM study: no change in mortality (p=0.97).
PSM retrospective 9,565 COVID-19 hospitalized patients in the USA, 1,593 receiving famotidine, showing no significant difference in mortality.

Oct 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.27375, https://c19p.org/kuno2

322 patient azvudine late treatment study: 22% lower mortality (p=0.15).
Retrospective 322 hospitalized patients ≥65 in China, showing lower mortality with azvudine treatment, without statistical significance.

Oct 2023, Frontiers in Microbiology, https://www.frontiersin.org/articles/10.3389/fmicb.2023.1280026/full, https://c19p.org/zhou13azv

230 patient resveratrol late treatment study: 44% lower mortality (p=0.06).
Retrospective 230 severe COVID-19 patients in India, showing lower mortality with resveratrol + copper, without statistical significance. This study followed preclinical data showing that sepsis-related cytokine storm and fatality in mice could be prevented with oral administration of resveratrol and copper.

Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.21.20151423, https://c19p.org/mittra

1,858 patient HCQ prophylaxis study: 17% fewer cases (p=0.59).
Survey analysis of 1,858 RA patients in Iran, showing no significant difference in cases with HCQ prophylaxis.

Jan 2021, Postgraduate Medical J., https://pmj.bmj.com/content/early/2021/01/13/postgradmedj-2020-139561, https://c19p.org/khoubnasabjafari

2,102 patient vitamin D prophylaxis study: 8% fewer cases (p=0.68).
Retrospective 2,102 rheumatology patients in Spain showing no significant difference in cases with vitamin D supplementation. Details of vitamin D supplementation are not providied - other patients may have also independently taken vitamin D.

Oct 2020, Aging, https://www.aging-us.com/article/104117/text, https://c19p.org/blanchrubio

175 patient vitamin D ICU study: 25% lower mortality (p=0.32).
Retrospective 175 ICU patients, 113 treated with a single dose of 300,000IU intramuscular cholecalciferol, showing lower mortality with treatment, but not reaching statistical significance. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage.

Jul 2021, European J. Clinical Nutrition, https://www.nature.com/articles/s41430-021-00984-5, https://c19p.org/guven

30 patient povidone-iodine early treatment RCT: 6% improved viral clearance (p=0.74).
Small mouth rinsing and gargling RCT with 15 1% PVP-I, 12 0.5% PVP-I, 15 3% hydrogen peroxide, 12 1.5% hydrogen peroxide, and 15 water patients, showing rapid improvement in Ct value in all groups, and no significant differences between groups.

Mar 2022, F1000Research, https://f1000research.com/articles/11-1238/v1, https://c19p.org/sulistyani

397 patient HCQ late treatment study: 22% lower mortality (p=0.46).
Study focused on remdesivir but with results for HCQ in the supplementary appendix, showing 9% death with HCQ versus 12% control, unadjusted relative risk uRR 0.78, p = 0.46.

May 2020, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2015301, https://c19p.org/goldmanh

62 patient ivermectin late treatment RCT: 16% faster recovery (p=0.34).
Small RCT with 32 ivermectin patients and 30 control patients. The mean recovery time after enrolment in the intervention arm was 5.31 ± 2.48 days vs. 6.33 ± 4.23 days in the control arm, p > 0.05. Negative PCR results were not significantly different between control and intervention arms, p>0.05. We are not sure what the results were because the abstract and Table 5 have switched the results.

Sep 2020, IMC J. Med. Science, http://imcjms.com/registration/journal_abstract/353, https://c19p.org/podder

253 patient curcumin prophylaxis study: 42% lower severe cases (p=0.55).
Retrospective survey-based analysis of 349 COVID-19 patients, showing a lower risk of severe cases with vitamin D, zinc, turmeric, and honey prophylaxis in unadjusted analysis, without statistical significance. REC/UG/2020/03.

Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabt

31 patient melatonin ICU study: 39% lower mortality (p=0.37), 43% shorter ventilation (p=0.13), and 2% shorter ICU admission (p=0.85).
Retrospective 31 ICU patients, 12 treated with melatonin, showing lower mortality with treatment, without statistical significance. Melatonin 15mg daily.

Mar 2022, Annals of Medicine and Surgery, https://www.sciencedirect.com/science/article/pii/S2049080122002527, https://c19p.org/karimpourrazkenari

134 patient HCQ late treatment study: 29% lower mortality (p=0.36).
Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with HCQ treatment in unadjusted results.

Dec 2020, Indian J. Critical Care Medicine, https://www.ijccm.org/doi/pdf/10.5005/jp-journals-10071-23599, https://c19p.org/mahaleh

284 patient vitamin C late treatment PSM study: 15% lower mortality (p=0.27).
Retrospective 158 critically ill patients receiving vitamin C and propensity matched controls, showing mortality OR 0.77 [0.48-1.23], and statistically significantly lower thrombosis, OR 0.42 [0.18-0.94]. 1000mg of vitamin C was given daily.

Apr 2021, Research Square, https://www.researchsquare.com/article/rs-354711/v1, https://c19p.org/alsulaiman2

53,030 patient HCQ late treatment study: 53% lower mortality (p<0.0001).
Retrospective 53,030 COVID-19 patients from 138 hospitals in Hubei, China showing lower mortality with metformin.

Nov 2024, IJC Heart & Vasculature, https://www.sciencedirect.com/science/article/pii/S2352906724002409, https://c19p.org/he2h

672 patient vitamin C early treatment study: 53% lower mortality (p=0.0004).
Retrospective 672 COVID-19 patients in Zimbabwe, showing lower mortality with vitamin C treatment.

Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombe

vitamin C prophylaxis study: 46% lower severe cases (p=0.001).
Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.

Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharifc

zinc prophylaxis study: 40% lower severe cases (p=0.0001).
Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.

Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharifz

budesonide prophylaxis PSM study: 49% lower mortality (p=0.01).
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.

Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoro

metformin prophylaxis study: 49% lower mortality (p=0.002).
Retrospective 375 hospitalized diabetes patients in Belgium, showing lower risk of COVID-19 mortality with metformin use.

Dec 2022, Annals of Endocrinology, https://pubmed.ncbi.nlm.nih.gov/37574109/, https://c19p.org/servais

exercise study: 54% fewer symptomatic cases (p<0.0001).
Retrospective 29,875 university staff and students in Spain, 3,662 with data, showing lower risk of COVID-19 symptoms for people that exercise. Exercise more than 5 days/week was the most protective, and intense exercise was more effective than moderate exercise.

Apr 2023, Fisioterapia, https://www.sciencedirect.com/science/article/pii/S0211563823002006, https://c19p.org/sanchez

exercise study: 48% lower severe cases (p=0.02).
Retrospective 857 severe COVID-19 cases and matched controls in Sweden, showing lower risk of severe COVID-19 with higher cardiorespiratory fitness.

Oct 2021, Int. J. Behavioral Nutrition and Physical Activity, https://link.springer.com/article/10.1186/s12966-021-01198-5/fulltext.html, https://c19p.org/ekblombak

exercise study: 52% lower hospitalization (p=0.02).
Retrospective 3,139 adults >50 in Europe, with 66 COVID-19 hospitalizations, showing lower risk of hospitalization with higher physical activity and with higher muscle strength. Note that model 2 includes muscle strength which is correlated with physical activity [eurapa.biomedcentral.com].

Aug 2021, J. Sports Sciences, https://www.tandfonline.com/doi/pdf/10.1080/02640414.2021.1964721, https://c19p.org/maltagliati

diet study: 40% lower seropositivity (p<0.0001).
Retrospective 10,427 volunteers in India, 1,058 anti-nucleocapsid antibody positive, showing lower risk of seropositivity with a vegetarian diet.

Apr 2021, eLife, https://elifesciences.org/articles/66537, https://c19p.org/naushin

azelastine prophylaxis study: 45% fewer cases (p=0.03).
Retrospective 219,000 patients showing lower risk of COVID-19 with antihistamine H1RA use. In Vitro study showing these drugs exhibit direct antiviral activity against SARS-CoV-2. Molecular docking suggests hydroxyzine and azelastine may exert antiviral effects by binding ACE2 and the sigma-1 receptor.

Jan 2021, Biochemical and Biophysical Research Communications, https://www.sciencedirect.com/science/article/pii/S0006291X20321409, https://c19p.org/reznikovazl

672 patient azithromycin early treatment study: 40% lower mortality (p=0.03).
Retrospective 672 COVID-19 patients in Zimbabwe, showing lower mortality with azithromycin treatment.

Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombeazaz

azithromycin prophylaxis study: 58% lower mortality (p=0.02).
Retrospective study of 367 hematology patients with COVID-19 in Spain. Among 216 patients with very severe COVID-19, there was significantly lower mortality with azithromycin treatment. Mortality was also lower with HCQ, but without statistical significance.

Aug 2020, Experimental Hematology & Oncology, https://ehoonline.biomedcentral.com/articles/10.1186/s40164-020-00177-z, https://c19p.org/pinanaazaz

144 patient zinc late treatment study: 41% lower mortality (p=0.41).
Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing lower mortality with zinc treatment, without statistical significance.

Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocyz

630 patient HCQ late treatment study: 22% lower mortality (p=0.09).
Retrospective 630 elderly patients in Spain showing lower mortality with HCQ treatment, unadjusted relative risk RR 0.78, p = 0.09. HCQ was used more often with patients that were hospitalized (24% versus 3% use in the nursing homes). Median age 87.

Dec 2020, J. the American Medical Directors Association, https://www.sciencedirect.com/science/article/pii/S1525861020310525, https://c19p.org/bielza

150 patient ivermectin ICU RCT: 15% lower mortality (p=0.64) and 24% improvement (p=0.57).
Early terminated REMAP-CAP results delayed >600 days, showing no significant differences with very low dose, poor administration, very late treatment of ICU patients. Results trend towards benefit for non-critical patients, with 32% lower mortality in unadjusted results, despite higher baseline severity in the treatment group. Results are currently only available in a CCR24 presentation. There are many critical issues as below. Authors appear to have post-hoc removed adjustment for severity to favor the control group. Preliminary analysis, please report errors or other issues. Severity Issue CRITICAL 1. Severity adjustment deleted in second post-hoc SAP CRITICAL 2. Baseline severity favors control CRITICAL 3. 32% lower mortality for non-critical patients CRITICAL 4. Expected failure based on design CRITICAL 5. Inclusion change to ICU only CRITICAL 6. >600 days delay in reporting CRITICAL 7. Adjustment direction different from expected CRITICAL 8. Remdesivir use CRITICAL 9. Bias in..

Jun 2024, Critical Care Reviews, CCR24, https://criticalcarereviews.com/meetings/ccr24#1, https://c19p.org/hashmi

689 patient HCQ prophylaxis study: 27% lower IgG positivity (p=0.38).
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with HCQ prophylaxis in unadjusted results.

Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahto

246 patient zinc late treatment study: 25% lower mortality (p=0.28).
Retrospective 246 severe COVID-19 patients in Uganda, showing lower mortality with zinc treatment in unadjusted results, without statistical significance.

May 2023, Infection and Drug Resistance, https://www.dovepress.com/thirty-day-outcomes-of-young-and-middle-aged-adults-admitted-with-seve-peer-reviewed-fulltext-article-IDR, https://c19p.org/kyagambiddwaz

118 patient various antiandrogen prophylaxis study: 95% lower mortality (p=1), 119% higher ICU admission (p=0.4), 25% lower hospitalization (p=0.6), and 8% lower severe cases (p=1).
Retrospective 118 prostate cancer patients, 4 on androgren deprivation therapy, not showing significant differences (as expected with only 4 patients in the treatment group).

Aug 2020, Annals of Oncology, https://www.annalsofoncology.org/article/S0923-7534(20)42103-9/fulltext, https://c19p.org/bennani

67 patient melatonin ICU RCT: 4% lower mortality (p=0.73), 14% improved recovery (p=0.19), and 27% shorter ventilation (p=0.09).
RCT 67 extremely late stage intubated patients in Iran, showing lower CRP with melatonin treatment, but no significant difference in outcomes.

May 2022, J. Taibah University Medical Sciences, https://www.sciencedirect.com/science/article/pii/S1658361222000877, https://c19p.org/alizadeh2

106 patient vitamin D ICU RCT: 27% lower mortality (p=0.18), 7% lower ventilation (p=0.68), 94% longer ICU admission (p=0.001), and 41% longer hospitalization (p=0.007).
RCT ICU patients in Russia, showing significantly increased lymphocyte counts with treatment. Mortality was lower but without statistical significance. 40% of patients were on mechanical ventilation at baseline in the treatment group, compared to 30% in the placebo group. Authors state that there has been 6 RCTs for COVID-19 and vitamin D, however there was at least 23 at the time of publication: [c19early.org].

Nov 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-22045-y, https://c19p.org/bychinin2

86 patient vitamin C ICU PSM study: 19% lower mortality (p=0.04).
PSM retrospective 86 ICU patients on mechanical ventilation in Turkey, showing lower mortality with high dose vitamin C treatment (≥200mg/kg for 4 days).

Sep 2020, Intensive Care Medicine Experimental, 9:S1, 001458, https://icm-experimental.springeropen.com/track/pdf/10.1186/s40635-021-00413-8.pdf, https://c19p.org/yuksel

30 patient HCQ late treatment PSM study: 25% faster recovery (p=0.45), 13% longer hospitalization (p=0.75), and no change in viral clearance (p=0.99).
Retrospective 25 hospitalized patients treated with cephalosporin, azithromycin, and HCQ, and 217 SOC patients in South Korea, reporting no significant differences. 5 patients receiving lopinavir/ritonavir and HCQ >5 days were excluded for unknown reasons. HCQ was typically initiated based on progression or side effects from another treatment. Conflicting results are reported. Table 2 indicates 15 CA/HCQ patients after matching, while Table S2 shows 25, and the Table 3 count is blank. S2 appears to incorrectly show before matching results, and the after matching results are missing in Table 3. 200mg HCQ bid.

May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267645, https://c19p.org/hong2

29 patient HCQ late treatment study: 29% faster recovery (p=0.008).
Retrospective 12 hospitalized patients in India treated with CQ and 17 controls, showing faster recovery with treatment. There was no significant difference in viral clearance. The CQ group mean age was 41.3 vs. 47.6 for controls.

Oct 2020, Advances in Respiratory Medicine, https://journals.viamedica.pl/advances_in_respiratory_medicine/article/view/69692, https://c19p.org/niwas

42 patient vitamin D late treatment study: 94% lower mortality (p=0.07).
Retrospective 49 severe COVID-19 patients treated with tocilizumab, showing lower mortality with vitamin D treatment and a dose-dependent response.

Aug 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/8/1078, https://c19p.org/hafez2

50 patient ivermectin late treatment RCT: 10% improved recovery (p=0.5).
Small RCT with 25 ivermectin and 25 control patients, not finding a significant difference in recovery at day 7.

Sep 2020, Int. J. Sciences-35, https://www.ijsciences.com/pub/article/2378, https://c19p.org/chachar

105 patient zinc prophylaxis study: 20% lower mortality (p=0.71).
Case control study of 105 COVID-19 patients in India, 55 with mucormycosis and 50 without, showing zinc prophylaxis and diabetes both associated with mucormycosis in unadjusted results. This is likely confounded because zinc supplementation is commonly used with diabetes [academic.oup.com], and Arora et al. show lower risk of mucormycosis with zinc prophylaxis, aOR 0.05 [0.01–0.19] [Arora]. There was no significant difference in mortality based on zinc prophylaxis in unadjusted results.

Feb 2022, Cureus, https://www.cureus.com/articles/87998-role-of-zinc-and-clinicopathological-factors-for-covid-19-associated-mucormycosis-cam-in-a-rural-hospital-of-central-india-a-case-control-study, https://c19p.org/kumar4

135 patient zinc prophylaxis study: 18% lower severe cases (p=1).
Retrospective 448 pregnant women with COVID-19. Patients with calcium, zinc, and magnesium supplementation, or magnesium only, had a significantly higher titer of SARS-CoV-2 anti-RBD antibodies. There was no statistically significant difference in severe cases based on supplementation.

Mar 2022, Nutrients, https://www.mdpi.com/2072-6643/14/7/1445, https://c19p.org/citu

diet study: 69% lower severe cases (p=0.004), 56% lower hospitalization (p=0.07), and 68% improved recovery (p=0.003).
Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases and shorter recovery and hospitalization times with a healthy diet. Notably, all individual symptoms show lower incidence with a healthy diet with the exception of fever and chills. Fever and chills help the immune system fight infections (shivering helps to raise the body temperature).

Aug 2022, Frontiers in Nutrition, https://www.frontiersin.org/articles/10.3389/fnut.2022.929384/full, https://c19p.org/ebrahimzadeh

15,968 patient vitamin B9 prophylaxis study: 1% lower mortality (p=0.88).
Retrospective 15,968 COVID-19 hospitalized patients in Spain, showing no significant difference in mortality with existing use of folic acid. Since only hospitalized patients are included, results do not reflect different probabilities of hospitalization across treatments.

Aug 2022, Virology J., https://virologyj.biomedcentral.com/articles/10.1186/s12985-023-02195-9, https://c19p.org/loucera3b9

1,047 patient colchicine prophylaxis study: 4% fewer cases (p=0.72).
Prospective analysis of 1,047 Behçet’s syndrome patients in Turkey, showing no significant difference in cases with colchicine use.

Nov 2021, Rheumatology Int., https://link.springer.com/10.1007/s00296-021-05056-2, https://c19p.org/ozcifci

12 patient HCQ late treatment study: 91% lower mortality (p=0.17).
Very small retrospective of 12 dialysis patients showing 1/11 deaths with HCQ and 1/1 without HCQ.

Nov 2020, Nefrología, https://www.sciencedirect.com/science/article/pii/S0211699520301661, https://c19p.org/maldonado

92 patient HCQ ICU study: 59% lower mortality (p=0.41).
Retrospective 92 ICU patients with almost all treated with HCQ and only one non-HCQ treated patient that died, showing unadjusted non-statistically significant lower mortality with treatment.

Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21253121v1, https://c19p.org/martinvicente

991 patient HCQ late treatment study: 19% lower mortality (p=0.09).
Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.

Apr 2021, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27053, https://c19p.org/hajiaghajani

723 patient azithromycin late treatment study: 7% lower mortality (p=0.79).
Retrospective 723 hospitalized COVID-19 patients in Italy showing no significant difference with azithromycin treatment.

Jan 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09034-4, https://c19p.org/donidaazaz

207 patient azvudine early treatment study: 12% slower recovery (p=0.95) and 32% improved viral clearance (p=0.04).
Retrospective 207 COVID-19 patients in China, showing azvudine associated with faster viral clearance, with azvudine-treated patients obtaining a negative PCR test result 1.7 days faster on average compared to supportive care alone after adjusting for age and sex.

Jan 2023, medRxiv, https://www.medrxiv.org/content/10.1101/2023.01.05.23284180, https://c19p.org/chen13

71 patient HCQ late treatment study: 27% lower mortality (p=0.47).
Retrospective 71 hospitalized haematologic patients in Spain, showing lower mortality with HCQ treatment in unadjusted results and without statistical significance.

Jan 2022, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S259017022200005X, https://c19p.org/fernandezcruz

24 patient ivermectin early treatment RCT: 96% improved symptoms (p=0.05), 95% improved viral load (p=0.01), and 8% improved viral clearance (p=1).
Tiny RCT for early treatment of mild COVID-19 in low risk patients, with 12 400mcg/kg single dose ivermectin patients and 12 control patients, showing significantly faster viral load reduction and symptom improvement with ivermectin. Average median viral load for gene E and gene N mid-viral recovery at day 7: Ivermectin: 1637, control: 30175 (supplementary appendix).

Dec 2020, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30464-8/fulltext, https://c19p.org/chaccour

2,496 patient proton pump inhibitor prophylaxis study: 19% lower mortality (p=0.32) and 10% higher hospitalization (p=0.51).
Retrospective 2,594 COVID-19 patients in the United States showing no significant association between proton pump inhibitor (PPI) use and COVID-19 severity, including need for hospitalization or 30-day mortality. There was increasing mortality with increasing PPI use with 14%, 20%, and 27% mortality for low, standard, and high use, without statistical significance.

May 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-11680-0, https://c19p.org/shupp

1,811 patient sleep study: 67% lower PASC (p<0.0001).
Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with good sleep quality in the month before infection.

Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paul

1,846 patient proton pump inhibitor prophylaxis study: 13% lower mortality (p=0.31) and 2% higher ventilation (p=0.89).
Retrospective 1,846 hospitalized COVID-19 patients in North America showing no significant association between preadmission proton pump inhibitor (PPI) use and mechanical ventilation or mortality. Results do not account for the risk of hospitalization based on PPI use.

Mar 2021, Gastroenterology, https://www.sciencedirect.com/science/article/pii/S0016508520353956, https://c19p.org/elmunzer

366 patient metformin prophylaxis study: 30% lower mortality (p=0.42).
Retrospective 1,035 hospitalized patients in India. Of 366 diabetic patients, there was lower mortality for the 53 that were on metformin.

May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.20.21255792v2, https://c19p.org/ravindra

802 patient favipiravir early treatment study: 14% lower PASC (p=0.34).
Prospective analysis of 802 COVID-19 pediatric patients in Thailand, showing no significant difference in long COVID with favipiravir treatment in unadjusted results.

May 2023, Frontiers in Pediatrics, https://www.frontiersin.org/articles/10.3389/fped.2023.1127582/full, https://c19p.org/lokanuwatsatien

763 patient metformin prophylaxis study: 15% lower hospitalization (p=0.56).
Retrospective 763 COVID-19 patients with type 2 diabetes in Uzbekistan, showing lower hospitalization with metformin use in unadjusted results, without statistical significance.

Jun 2023, Obesity and metabolism, https://www.omet-endojournals.ru/jour/article/view/12801, https://c19p.org/alieva

164 patient zinc ICU PSM study: 36% lower mortality (p=0.11), 25% longer ICU admission (p=0.28), and 6% longer hospitalization (p=0.61).
Retrospective 266 ICU patients showing lower mortality with zinc treatment, reaching statistical significance only for 30 day mortality, and lower odds of acute kidney injury, without statistical significance. NRC21R/287/07.

Jun 2021, Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-021-03785-1, https://c19p.org/alsulaiman

587 patient exercise study: 9% fewer symptomatic cases (p=0.71).
Retrospective 904 patients in Sweden, showing higher risk of COVID-19-like symptoms with poor muscle strength. Risk was slightly higher for physical inactivity, without statistical significance.

Oct 2021, Aging Clinical and Experimental Research, https://link.springer.com/article/10.1007/s40520-021-02006-7/fulltext.html, https://c19p.org/saadeh

metformin prophylaxis study: 38% lower mortality (p=0.02) and 15% lower hospitalization (p=0.25).
Retrospective 54,009 diabetes patients in Italy, showing lower mortality with metformin use.

Oct 2022, Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, https://www.dovepress.com/infection-rates-and-impact-of-glucose-lowering-medications-on-the-clin-peer-reviewed-fulltext-article-DMSOhttps://www.dovepress.com/getfile.php?fileID=84551, https://c19p.org/mannucci

32 patient HCQ ICU study: 65% lower mortality (p=0.21) and 3% worse viral clearance (p=1).
Retrospective 45 ICU patients, 17 treated with HCQ+AZ, showing no significant difference in viral clearance after 6 days, or mortality 6 days from ARDS.

May 2020, Ann. Intensive Care, https://annalsofintensivecare.springeropen.com/articles/10.1186/s13613-020-00678-4, https://c19p.org/hraiech

22 patient thermotherapy late treatment study: 53% greater improvement (p=0.05).
Single-blind, sham-controlled, crossover study of 17 COVID-19 outpatients showing significantly increased peripheral oxygen saturation (SpO2) levels correlated with hyperthermia (up to 44°C) produced by 30 minutes of low-field thoracic magnetic stimulation (LF-ThMS) applied to the dorsal thorax. The safety and lack of adverse events supports future research into mechanisms and potential therapeutic use of localized heat therapy for improving respiratory function in COVID-19 patients.

May 2021, Medicine, https://journals.lww.com/10.1097/MD.0000000000027444, https://c19p.org/domingueznicolas

131 patient HCQ late treatment study: 18% shorter hospitalization (p=0.11).
Prospective observational study of 131 COVID-19 patients in Jordan, showing 18% shorter hospital stay with HCQ, p = 0.11.

Dec 2020, F1000Research, https://f1000research.com/articles/9-1439, https://c19p.org/alqassieh

587 patient aspirin late treatment study: 22% lower mortality (p=0.56) and 10% higher ICU admission (p=0.67).
Retrospective 587 COVID+ hospitalized patients in Iran, showing no significant differences in outcomes with aspirin treatment.

Jul 2021, Identification of Biomarkers, New Treatments, and Vaccines for COVID-19, https://link.springer.com/chapter/10.1007%2F978-3-030-71697-4_17, https://c19p.org/vahedianazimi2

12 patient hydrogen peroxide early treatment study: 50% improved viral clearance (p=0.18).
Study of SARS-CoV-2 burden in whole mouth fluid and respiratory droplets with povidone iodine, hydrogen peroxide, and chlorhexidine mouthwashes in 36 hospitalized COVID-19 patients using PCR and rapid antigen testing. There were significant reductions in SARS-CoV-2 burden with all treatments in both respiratory droplets and whole mouth fluid. . Authors perform antigen testing for 6 hydrogen peroxide patients, showing that 50% became negative after treatment.

Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.25.21252488v1, https://c19p.org/jayaramanhp

749 patient HCQ late treatment study: 34% lower mortality (p=0.61).
Low molecular weight heparin study also showing results for HCQ treatment, unadjusted HCQ mortality relative risk RR 0.66, p = 0.61.

Nov 2020, Thrombosis Research, https://www.sciencedirect.com/science/article/pii/S0049384820306277, https://c19p.org/qin

40 patient HCQ late treatment study: 12% faster viral clearance (p=0.05).
Retrospective 40 pediatric hospitalized patients, 15 treated with HCQ, showing 7.2 vs. 8.2 days until PCR-, not quite reaching statistical significance.

Sep 2021, Northern Clinics of Istanbul, https://northclinist.com/jvi.aspx?pdir=nci&plng=eng&un=NCI-65471&look4=, https://c19p.org/uygen

1,072 patient HCQ late treatment study: 95% lower mortality (p=1).
Retrospective 1,072 hospitalized patients in Kazakhstan showing no mortality for HCQ treated patients, however only 23 patients received treatment - this result is not statistically significant.

Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.01.06.20249091v1, https://c19p.org/yegerov

336 patient colchicine late treatment study: 13% lower mortality (p=0.72), 16% lower ICU admission (p=0.5), and 25% shorter hospitalization (p=0.0001).
Retrospective 356 hospitalized COVID-19 patients, shorter hospitalization time with colchicine treatment. There were no statistically significant differences for mortality or ICU admission. Significantly lower mortality was seen with higher dosage (1mg/day vs 0.5mg/day). More control patients were on oxygen at baseline (65% vs. 54%).

Jan 2022, The J. Infection in Developing Countries, https://jidc.org/index.php/journal/article/view/14924, https://c19p.org/karakas

245 patient HCQ late treatment study: 33% lower mortality (p=0.1), 448% higher ventilation (p=0.003), and 17% lower combined mortality/intubation (p=0.21).
Prospective study of 245 hospitalized patients, 121 treated with HCQ, showing lower (non-statistically significant) mortality and higher ventilation at 30 days. Confounding by indication is likely.

Mar 2021, Cureus, https://www.cureus.com/articles/53247-clinical-features-and-prognostic-factors-of-245-portuguese-patients-hospitalized-with-covid-19, https://c19p.org/salvador

991 patient favipiravir late treatment study: 26% lower mortality (p=0.28).
Retrospective 991 hospitalized patients in Iran focusing on aspirin use but also showing results for HCQ, remdesivir, and favipiravir.

Apr 2021, J. Medical Virology, https://europepmc.org/article/med/33913549, https://c19p.org/hajiaghajania

140 patient HCQ prophylaxis study: 38% lower severe cases (p=1) and 24% lower hospitalization (p=1).
Retrospective case-control study of 140 COVID-19 patients with autoimmune rheumatic diseases (AIRDs) and 140 matched controls showing higher rates of hospitalization, oxygen therapy, and mechanical ventilation with AIRDs. For the AIRD patients, there was no significant difference in outcomes based on HCQ use (only 10 patients).

Aug 2024, Medicina, https://www.mdpi.com/1648-9144/60/9/1377, https://c19p.org/rutskayamoroshan

4,002 patient ibuprofen prophylaxis study: 4% lower progression (p=0.78).
Retrospective 4,002 COVID-19 patients in Denmark, 264 with ibuprofen prescriptions, showing no significant difference for COVID-19 severity.

Oct 2020, Clinical and Translational Science, https://onlinelibrary.wiley.com/doi/10.1111/cts.12904, https://c19p.org/kragholm

38 patient HCQ prophylaxis study: 92% lower mortality (p=0.19).
Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].

Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos

655 patient antiandrogen prophylaxis study: 2% lower IgG positivity (p=0.95).
Retrospective 655 prostate cancer patients in Sweden, showing no significant difference in seropositivity with ADT.

Jan 2023, The Prostate, https://onlinelibrary.wiley.com/doi/10.1002/pros.24485, https://c19p.org/davidsson

444 patient ivermectin late treatment study: 64% lower mortality (p=0.09).
Retrospective 444 hospitalized patients in Pakistan, showing lower mortality with ivermectin treatment in unadjusted results, not reaching statistical significance. Ivermectin was mostly used with patients in severe condition. Dose ranged from 12mg to 36mg for up to seven days.

Dec 2021, Exploratory Research in Clinical and Social Pharmacy, https://www.sciencedirect.com/science/article/pii/S2667276621001013, https://c19p.org/mustafa

93 patient HCQ late treatment study: 15% improved viral clearance (p=0.66).
Retrospective 93 hospitalized patients in Saudi Arabia showing a non-statistically significant 15% reduction in PCR positive results at day 5, RR 0.85, p = 0.65. The treatment group had significantly more severe illness and significantly more male patients.

May 2020, medRxix, https://www.medrxiv.org/content/10.1101/2020.05.08.20095679v1, https://c19p.org/shabrawishi

952 patient proton pump inhibitor prophylaxis study: 25% lower severe cases (p=0.8).
Retrospective 952 COVID-19 patients in Hong Kong, showing no significant difference in severe disease with famotidine use or PPI use.

Apr 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34940-4/fulltext, https://c19p.org/cheungppi

140 patient vitamin A early treatment study: 86% lower mortality (p=0.002).
Retrospective 70 severe condition patients treated with vitamin A (200,000IU for two days), salbutamol, and budesonide, and 70 patients not treated with vitamin A, showing significantly lower mortality with the addition of vitamin A.

Dec 2020, EurAsian J. Biosciences-7350, http://ejobios.org/article/therapeutic-effect-of-vitamin-a-on-severe-covid-19-patients-8517, https://c19p.org/alsumiadai2

491 patient HCQ ICU study: 38% lower mortality (p=0.23).
Retrospective 491 ICU patients in Spain showing lower mortality with HCQ without statistical significance in unadjusted results.

Jun 2023, Respiratory Research, https://respiratory-research.biomedcentral.com/articles/10.1186/s12931-023-02462-x, https://c19p.org/degonzalocalvo

19 patient vitamin C late treatment study: 51% improved recovery (p=0.15).
Retrospective 19 COVID-19 ECMO patients in South Korea, showing a higher rate of weaning from ECMO with vitamin C treatment, without statistical significance. Authors perform multivariate analysis but do not provide full results, only reporting p > 0.05.

Dec 2020, Heart & Lung, https://www.sciencedirect.com/science/article/pii/S0147956320304027, https://c19p.org/jang2

31 patient ivermectin late treatment RCT: 85% lower ventilation (p=0.25), 85% lower ICU admission (p=0.25), and 1% improved viral clearance (p=1).
Very small RCT with 4 control patients and 28 ivermectin patients split across 3 different dosage levels, showing lower (non-statistically significant) ICU admission with treatment. Authors suggest that ivermectin for SARS-CoV-2 is safe and reduces symptoms and viral load, and that the antiviral effect appears to be dose-dependent. NCT04431466. Retraction/censorship: this paper appears to have been censored at the request of the journal's founding editor [pubmed.ncbi.nlm.nih.gov]. An external review is mentioned but is not provided, and there is no reply from the authors, or indication that the authors were notified. Conclusions in this study are limited due to the small size, however we should consider all information in the context of the full body of research.

Mar 2021, Toxicology Reports, https://www.sciencedirect.com/science/article/pii/S2214750021000445, https://c19p.org/pottjunior

38 patient HCQ late treatment study: 26% lower mortality (p=0.6).
Prospective study of 38 hospitalized rheumatic disease patients with COVID-19 in Spain, showing no mortality with existing HCQ use compared to 32% without, not reaching statistical significance. Authors also report on the use of HCQ/CQ after hospitalization. The prophylaxis and late treatment results are listed separately [Santos, Santos].

Jul 2020, Clinical Rheumatology, https://link.springer.com/10.1007/s10067-020-05301-2, https://c19p.org/santos2

71 patient povidone-iodine early treatment study: 29% improved viral clearance (p=0.4).
Small prospective study with 31 patients gargling povidone-iodine, 17 hydrogen peroxide, and 40 control patients, showing lower viral load mid-recovery with povidone-iodine, without reaching statistical significance. Oropharyngeal only, and only every 8 hours for two days. Results may be better with the addition of nasopharyngeal use, more frequent use, and without the two day limit. Authors report only one of the 7 previous trials for PVP-I and COVID-19. Non-randomized study with no adjustments or group details. Some results in Figure 1 appear to be switched compared to the text and the labels in the figure. The viral clearance figures do not match the group sizes - for example authors report 62% PCR- for PVP-I at the 3rd test, however there is no number of 31 patients that rounds to 62%.

Oct 2021, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/pii/S0213005X21002950, https://c19p.org/pablomarcos

HCQ ICU study: 22% lower mortality (p=0.01).
Prospective study of 9,058 COVID-19 ICU patients in Romania, showing lower mortality with HCQ treatment.

Nov 2022, European J. Anaesthesiology, https://journals.lww.com/10.1097/EJA.0000000000001776, https://c19p.org/bubenekturconi

HCQ late treatment study: 55% lower mortality (p=0.03).
Retrospective 759 hospitalized patients in the USA, showing lower mortality with combined HCQ+AZ+methylprednisolone treatment compared to methylprednisolone monotherapy.

Sep 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.935370/full, https://c19p.org/go2

vitamin D prophylaxis study: 28% lower severe cases (p=0.001).
Retrospective 962 COVID-19 patients in Bangladesh, showing significantly lower severity with vitamin C, vitamin D, and zinc supplementation, and improved results from the combination of all three.

Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/sharif

exercise study: 28% lower hospitalization (p=0.0004).
UK Biobank retrospective analysis of 387,109 people, showing lower risk of COVID-19 hospitalization with physical activity.

Jul 2020, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912030996X?via%3Dihub, https://c19p.org/hamer

2,884 patient sleep study: 17% fewer moderate/severe cases (p=0.03) and 11% fewer cases (p=0.003).
Retrospective 2,884 high-risk healthcare workers in France, Germany, Italy, Spain, UK, and the USA, showing shorter sleep duration associated with increased risk of COVID-19 cases and severity.

Mar 2021, BMJ Nutrition, Prevention & Health, https://nutrition.bmj.com/content/4/1/132.info, https://c19p.org/kim5

sunlight study: 32% lower mortality (p=0.004).
Analysis of UVA exposure and COVID-19 mortality in the USA, England, and Italy, showing increased UVA exposure associated with lower mortality.

Apr 2021, British J. Dermatology, https://onlinelibrary.wiley.com/doi/10.1111/bjd.20093, https://c19p.org/cherrie

antihistamine H1RA prophylaxis study: 34% fewer cases (p<0.0001).
Retrospective 219,000 patients showing lower risk of COVID-19 with antihistamine H1RA use. In Vitro study showing these drugs exhibit direct antiviral activity against SARS-CoV-2. Molecular docking suggests hydroxyzine and azelastine may exert antiviral effects by binding ACE2 and the sigma-1 receptor.

Jan 2021, Biochemical and Biophysical Research Communications, https://www.sciencedirect.com/science/article/pii/S0006291X20321409, https://c19p.org/reznikov

azithromycin early treatment PSM study: 27% lower combined mortality/ICU admission (p=0.0005).
Independent analysis of the IHU-Mediterranean data [Brouqui] with 30,423 COVID-19 patients showing significantly lower risk of ICU admission or death with early treatment of hydroxychloroquine plus azithromycin (HCQ-AZ), and with azithromycin, both compared to no treatment.

Feb 2024, Archives of Microbiology & Immunology, https://www.fortunejournals.com/articles/an-independent-analysis-of-a-retrospective-cohort-of-30423-covid19-patients-treated-at-ihumediterranean-in-marseille-france-part-1.html, https://c19p.org/lounnas2azaz

502 patient HCQ late treatment study: 33% lower mortality (p=0.17).
Retrospective multiple myeloma patients showing lower mortality with HCQ treatment, unadjusted RR 0.67, p = 0.17 (data is in the supplementary material).

Dec 2020, Blood, https://www.sciencedirect.com/science/article/pii/S0006497120839044, https://c19p.org/chari

205 patient HCQ late treatment study: 10% lower mortality (p=0.15).
Retrospective 205 patients in Italy, 160 treated with HCQ, showing lower mortality with treatment in multivariate analysis, but not reaching statistical significance.

Jun 2021, Vaccines, https://www.mdpi.com/2076-393X/9/6/640, https://c19p.org/turrini

323 patient vitamin C late treatment study: 21% lower mortality (p=0.52) and 2% higher ICU admission (p=1).
Retrospective 323 hospitalized patients, 153 treated with vitamin C, showing no significant differences. Patients in each group were in different time periods, with the vitamin C group first. Time based confounding is possible due to improvements in SOC.

May 2021, Med. Clin., https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112281/, https://c19p.org/suna

831 patient HCQ late treatment study: 39% lower mortality (p=0.16).
Retrospective 831 hospitalized COVID-19 patients showing lower mortality with HCQ in unadjusted results, without statistical significance.

Aug 2024, Cureus, https://www.cureus.com/articles/263779-anticoagulant-use-in-covid-19-patients-a-longitudinal-study-from-zanjan-iran, https://c19p.org/azimipirsaraeih

113 patient vitamin C ICU study: 58% lower mortality (p=0.11).
Retrospective 113 consecutive mechanically ventilated COVID+ ICU patients in Greece, 10 receiving high dose IV vitamin C, showing lower mortality with treatment, without statistical significance (p=0.11). The associated meta analysis includes only 11 studies, while there are currently studies, with mortality results. Authors only include critical patients, however not all studies with critical patients are included, for example [Hamidi-Alamdari, Majidi, Yüksel, Özgünay]. The meta analysis also uses unadjusted results, while PSM, Cox proportional hazards, or KM results are reported by [Al Sulaiman, Gao, Zhang, Zheng]. For [Zhang] authors use 28 day mortality, while the study reports longer term in-hospital mortality.

Feb 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.814587/full, https://c19p.org/gavrielatou

125 patient aspirin prophylaxis study: 6% higher mortality (p=0.87), 50% lower ventilation (p=0.16), and 49% lower ICU admission (p=0.41).
Retrospective 125 COVID+ hospitalized patients in the USA, showing no significant differences with aspirin prophylaxis.

Mar 2022, World J. Critical Care Medicine, https://www.wjgnet.com/2220-3141/full/v11/i2/92.htm, https://c19p.org/gogtay

500 patient HCQ late treatment study: 5% lower progression (p=1) and 26% improved viral clearance (p=0.001).
Study of 349 low-risk hospitalized patients with 151 non-consenting or ineligible patients used as controls. SOC included zinc, vitamin C and vitamin D. A statistically significant improvement in PCR negativity is shown at day 7 with HCQ treatment, 52.1% (HCQ) versus 35.7% (control), p=0.001, but no statistically significant difference at day 14, or in progression. Patients were relatively young and there was no mortality. Only 3% of patients had any disease progression and all patients recovered, so there is little if any room for treatment benefit. Progression among higher-risk patients with comorbidities was lower with treatment (12.9% versus 28.6%, p=0.3, very few cases). Despite the title, this is not an RCT since patients self-selected the arm, or were chosen based on allergies/contraindications. The treatment group had about twice the number of patients with comorbidities. Treatment delay is unknown - it was recorded but not reported in the paper. Viral load was not measured...

Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.30.20165365v1, https://c19p.org/kamran

108 patient HCQ late treatment RCT: 26% lower mortality (p=0.39), 26% higher hospital discharge (p=0.39), and 25% longer hospitalization (p=0.06).
Small 108 patient RCT comparing HCQ vs. remdesivir in very late stage treatment. All patients received tocilizumab. There were significant unadjusted baseline differences in ventilation and ICU admission. NCT04779047. REC-H-PhBSU-21011.

Nov 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121003452, https://c19p.org/sarhan

427 patient vitamin D prophylaxis study: 41% lower hospitalization (p=0.3).
Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.

Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateef

77,381 patient ivermectin early treatment study: 74% lower hospitalization (p=0.001).
Analysis of Mexico City's use of an ivermectin-based medical kit, showing significantly lower hospitalization with use. Authors use logistic-regression models with matched observations, including adjustments for age, sex, COVID severity, and comorbidities. This preprint was censored by the original preprint host. Censors claim that the government treatment program, which used approved medications and saved over 500 people from hospitalization, was unethical. In part they also indicate that studies of "the effects of a medication on a disease outcome" are outside the scope of their site, however retroactively censoring a paper for this reason is not appropriate. The author's response (not provided by the censors) can be found here: [twitter.com]. Author's provide the data and code for the study, and the results have been independently verified. See also: [doyourownresearch.substack.com].
This study was censored.
May 2021, Preprint, http://web.archive.org/web/20211218011849/https://files.osf.io/v1/resources/r93g4/providers/osfstorage/609085945533b4031ee1c789?action=download&direct&version=1, https://c19p.org/merino

vitamin A prophylaxis study: 35% lower severe cases (p=0.28), 24% lower hospitalization (p=0.29), and 31% fewer cases (p=0.006).
Mendelian randomization study suggesting a causal association between retinol and related proteins (RBP4, RDH16, CRABP1) and COVID-19. The study found that genetically-predicted higher retinol levels were associated with lower COVID-19 susceptibility. There was a lower risk of hospitalization and severity without statistical significance. Authors conclude that the results support a potential protective effect of vitamin A treatment for COVID-19. Given the lack of clear evidence for pleiotropy, and the lower precision of the MR-Egger estimates, the IVW estimates are likely more reliable in this case when the IVW and MR-Egger estimates differ.

Apr 2024, BMC Pulmonary Medicine, https://bmcpulmmed.biomedcentral.com/articles/10.1186/s12890-024-03013-w, https://c19p.org/wang31

73 patient ivermectin late treatment RCT: 14% lower mortality (p=1), 9% lower progression (p=1), 37% lower hospital discharge (p=0.71), and 20% longer hospitalization (p=0.43).
RCT late stage severe condition (93% SOFA ≥ 2, 96% APACHE ≥ 8) high comorbidity hospitalized patients in Mexico with 36 low dose ivermectin and 37 control patients not finding significant differences. NCT04391127. Another study reports results on a larger group of patients in the same hospital, showing ivermectin mortality RR 0.81 [0.53-1.24] [ Guzman ] . Questions have been raised about this study and the early termination of the study and discontinuation of treatments, because the hospital statistics show a dramatically lower (~75%) case fatality rate during the period of the study [ web.archive.org ] (data from [ gob.mx ] ). Date Cases Deaths CFR 3/2020 2 1 50% 4/2020 4 1 25% 5/2020 13 1 8% 6/2020 37 2 5% 7/2020 65 5 8% 8/2020 79 23 29% 9/2020 54 12 22% 10/2020 62 21 34% 11/2020 80 26 33% 12/2020 41 13 32% Several other inconsistencies have been reported [ Chamie ] . Although the data from this study is reported to be available and has been shared with an anti-treatment group,..

Feb 2021, Infectious Disease Reports, https://www.mdpi.com/2036-7449/14/2/20, https://c19p.org/beltrangonzalez

547 patient lactoferrin late treatment study: 79% lower mortality (p=0.11).
Retrospective 547 hospitalized COVID+ patients in Egypt, showing lower mortality with lactoferrin treatment (without statistical significance).

Oct 2021, World J. Gastroenterology, https://www.wjgnet.com/1007-9327/full/v27/i40/6951.htm, https://c19p.org/shoushalf

46 patient favipiravir late treatment study: 38% lower mortality (p=0.51).
Retrospective 46 idiopathic pulmonary fibrosis patients with COVID-19 in Turkey, showing lower mortality with favipiravir in unadjusted results, without statistical significance.

Mar 2022, Respiratory Medicine and Research, https://www.sciencedirect.com/science/article/pii/S2590041222000174?via%3Dihub, https://c19p.org/cilli

229 patient ivermectin prophylaxis study: 96% fewer cases (p<0.0001).
Prophylaxis study using ivermectin and carrageenan showing 0 of 131 cases from treated healthcare workers, compared to 11 of 98 control. The effect is likely to be primarily due to ivermectin - the author has later reported that carrageenan is not necessary [youtube.com]. See [doyourownresearch.substack.com] for discussion of issues with this trial.

Oct 2020, NCT04425850, https://clinicaltrials.gov/ct2/show/results/NCT04425850, https://c19p.org/carvalloprep2

1,820 patient HCQ late treatment study: 5% lower mortality (p=0.72) and 19% lower ventilation (p=0.26).
EHR analysis of 3,372 hospitalized COVID-19 patients not showing a significant difference for mortality or the risk of mechanical ventilation. Subject to the limitations of EHR analysis. Misclassification is possible. Confounding by indication is likely.

May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.12.20099028v1, https://c19p.org/singh

87 patient ivermectin late treatment study: 42% shorter hospitalization (p<0.0001).
Small trial of hospitalized patients with 16 of 87 patients being treated with ivermectin, showing a significantly lower mean hospital stay with ivermectin: 7.62 vs. 13.22 days, p=0.00005. 0 of 16 ivermectin patients died vs. 2 of 71 control patients.

Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.07.20145979v1, https://c19p.org/gorial

199 patient HCQ prophylaxis study: 17% fewer cases (p=1).
Retrospective 199 sarcoidosis patients showing non-statistically significant HCQ RR 0.83, p=1.0.

Jul 2020, Research Square, https://www.researchsquare.com/article/rs-41653/v1, https://c19p.org/desbois

26 patient ivermectin late treatment study: 40% lower ventilation (p=0.67), 33% lower ICU admission (p=1), 33% worse improvement (p=1), and 25% worse viral clearance (p=1).
Tiny 26 patient retrospective study of very late treatment with ivermectin 200 μg/kg, median 12 days after symptoms, not showing significant differences. Authors suggest the dose is too low and recommend evaluation of higher doses. All patients received HCQ which may reduce the potential benefit for adding ivermectin.

Nov 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242184, https://c19p.org/camprubi

198 patient azvudine late treatment PSM study: 6% lower mortality (p=0.88).
PSM retrospective 332 hospitalized moderate to critically ill COVID-19 patients with myocardial injury in China, showing improved 14 day mortality but no difference in overall in-hospital mortality with azvudine treatment.

Apr 2023, Cardiology Plus, https://journals.lww.com/10.1097/CP9.0000000000000049, https://c19p.org/chen16

1,214 patient HCQ late treatment study: 33% lower mortality (p=0.34).
Retrospective 1,214 hospitalized patients in Pakistan, 77 HCQ patients, showing 33% lower mortality with HCQ, multivariate Cox HR 0.67, p = 0.34.

Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.13.20247254v1, https://c19p.org/naseem

15 patient HCQ late treatment study: 29% faster viral clearance (p=0.45).
Retrospective 15 pediatric patients in Spain, showing faster viral clearance with HCQ+AZ, without statistical significance. Treatment time and details are not provided.

Apr 2022, Anales de Pediatría, https://www.sciencedirect.com/science/article/pii/S1695403321000126, https://c19p.org/bassetsbosch

679 patient HCQ prophylaxis study: 5% lower PASC (p=0.78).
Retrospective 679 healthcare workers post COVID-19 discharge, 76 using HCQ prophylaxis, showing no significant difference in PASC.

Dec 2022, The Lancet Regional Health - Southeast Asia, https://www.sciencedirect.com/science/article/pii/S2772368222001469, https://c19p.org/shukla

250 patient vitamin C prophylaxis study: 69% lower severe cases (p=0.003).
Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases with higher vitamin C intake.

Mar 2023, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457723000803, https://c19p.org/asoudeh

diet study: 65% fewer cases (p<0.0001).
Retrospective 133 COVID-19 patients and 322 controls, showing higher risk of COVID-19 for diets that have a higher inflammatory index (E-DII).

Mar 2022, Int. J. Clinical Practice, https://www.hindawi.com/journals/ijclp/2022/5452488/, https://c19p.org/firoozi

diet study: 92% fewer cases (p<0.0001).
Retrospective 60 COVID-19 hospitalized patients and 60 controls in Iran, showing pro-inflammatory diets associated with COVID-19 cases and severity. IR.KUMS.REC.1399·444, IR.TBZMED.REC.1399·225.

Aug 2021, British J. Nutrition, https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0007114521003214, https://c19p.org/moludi

15,227 patient vitamin D prophylaxis study: 7% fewer cases (p=0.53).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtd

142 patient exercise study: 6% fewer cases (p=0.85).
Retrospective 142 patients in Saudi Arabia, showing no significant difference in cases with physical activity.

Feb 2022, J. Multidisciplinary Healthcare, https://www.dovepress.com/the-influence-of-physical-activity-on-covid-19-prevention-among-quaran-peer-reviewed-fulltext-article-JMDH, https://c19p.org/almansour

465 patient vitamin D ICU study: 23% lower mortality (p=0.29).
Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.

Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadi

79 patient HCQ late treatment study: 16% lower mortality (p=0.76).
Retrospective 79 hospitalized nonagenarian patients showing unadjusted HCQ mortality RR 0.84, p = 0.76.

Jan 2021, Revista Espanola de Quimioterapia, https://europepmc.org/article/med/33522213, https://c19p.org/roig

790 patient metformin prophylaxis study: 1% lower mortality (p=0.78).
Retrospective 790 hospitalized type 2 diabetes patients ≥80 years old in Spain, showing no significant difference in mortality with existing metformin use.

Dec 2020, Research Square, https://www.researchsquare.com/article/rs-133358/v1, https://c19p.org/ramosrincon

444 patient aspirin late treatment study: 44% lower mortality (p=0.28).
Retrospective 444 hospitalized patients in Pakistan, showing lower mortality with aspirin treatment in unadjusted results, not reaching statistical significance.

Dec 2021, Exploratory Research in Clinical and Social Pharmacy, https://www.sciencedirect.com/science/article/pii/S2667276621001013, https://c19p.org/mustafae

183 patient famotidine late treatment study: 75% lower mortality (p=0.21).
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.

Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsifm

255 patient HCQ late treatment study: 13% lower mortality (p=0.63).
Retrospective 255 hospitalized patients, 65 treated with HCQ, showing unadjusted RR 0.87, p=0.63. Confounding by indication is likely.

Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322761, https://c19p.org/tehrani

152 patient zinc late treatment study: 18% lower mortality (p=0.18).
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.

Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnanz

7,713 patient acetaminophen prophylaxis study: 2% lower mortality (p=0.97).
Retrospective 7,713 COVID-19 patients in Korea, showing no significant difference in mortality with paracetamol use.

Jun 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/13/6804, https://c19p.org/oh3

20 patient vitamin C ICU RCT: 33% lower progression (p=1) and 6% shorter ICU admission (p=0.3).
Small RCT in Iran with 20 ICU patients, 10 treated with high-dose vitamin C, melatonin, and zinc, not showing significant differences.

Dec 2020, J. Cellular & Molecular Anesthesia, https://journals.sbmu.ac.ir/jcma/article/view/32182, https://c19p.org/darbanc

505 patient HCQ ICU study: 11% lower mortality (p=0.31).
Retrospective 505 ECMO patients showing no significant difference in mortality in unadjusted results.

Feb 2022, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/abs/pii/S0003497522001989, https://c19p.org/hall

249 patient ivermectin early treatment RCT: 51% improved viral clearance (p=0.03).
RCT 249 hospitalized patients with mild to moderate COVID-19 in Sri Lanka, showing statistically significant lower viral load. There was no significant difference in clinical outcomes. Only one patient had a serious outcome. Mid-recovery 11/15 symptoms showed lower scores with treatment on day 5 and on day 10. On day 10, 19% of treatment patients were asymptomatic vs. 13% of placebo patients. WHO score analysis is limited by the large percentage of missing data. Authors report that ivermectin blood levels taken before or with meals were not significantly different, however authors note that most patients consumed low fat meals. [Guzzo] show that absorption of ivermectin was significantly higher when administered following a high-fat meal.

Jul 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09563-y, https://c19p.org/wijewickrema

2,468 patient N-acetylcysteine late treatment study: 11% lower mortality (p=0.43).
Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with NAC treatment. IR.MUQ.REC.1399.013.

May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholina

183 patient aspirin prophylaxis study: 4% lower mortality (p=0.89).
Retrospective 183 hospitalized patients in China, 52 taking low-dose aspirin prior to hospitalization, showing no significant difference with treatment.

Dec 2020, J. Cellular and Molecular Medicine, https://onlinelibrary.wiley.com/doi/10.1111/jcmm.16198, https://c19p.org/yuan

722 patient HCQ prophylaxis study: 26% lower hospitalization (p=1) and 49% more cases (p=0.53).
Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HCQ 0.5-4.0%, no-HCQ 0.4-2.7%). Confirmed cases were 1 HCQ and 2 no-HCQ, confirmed+likely cases were 1 HCQ and 3 no-HCQ. 1 HCQ and 2 no-HCQ patients were admitted to hospital. We do not think a conclusion can be drawn based on these sample sizes. There are very significant differences between the groups, for example 30% of the HCQ group have SLE vs. 2.5% of the no-HCQ group. SLE patients have a 5.7 times relative risk of pneumonia according to [ncbi.nlm.nih.gov], whereas the relative risk with glucocorticoids and TNF-α inhibitors is significantly lower [academic.oup.com]. Two more recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.

May 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.05.16.20104141v1, https://c19p.org/macias

149 patient vitamin D ICU study: 21% lower mortality (p=0.31).
Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with vitamin D prophylaxis in unadjusted results.

Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimer

4,642 patient HCQ late treatment study: 5% higher mortality (p=0.74) and 20% higher hospital discharge (p=0.002).
Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HCQ and HCQ+AZ. No significant effect is seen on 28-day mortality, however many more control patients are still in hospital at 28 days. Other studies show faster resolution for HCQ, suggesting there will be a significant improvement when extending past 28 days. Hopefully authors will extend the analysis. Note that the median age is higher in the group not treated with HCQ or AZ. For other issues with the adjustments see [medrxiv.org]. Also see the analysis here [web.archive.org].

Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.16.20132597v1, https://c19p.org/sbidian

93 patient HCQ late treatment study: 15% improved viral clearance (p=0.65).
Retrospective 93 hospitalized patients in Saudi Arabia, 45 treated with CQ/HCQ, showing no significant difference in viral clearance. More patients treated with CQ/HCQ had severe cases at baseline (20% vs. 2%).

Jan 2022, Cureus, https://www.cureus.com/articles/82181-negative-nasopharyngeal-sars-cov-2-pcr-conversion-in-response-to-different-therapeutic-interventions, https://c19p.org/alwafi

exercise study: 26% lower mortality (p=0.17) and 18% fewer cases (p=0.01).
UK Biobank retrospective showing significantly lower COVID-19 cases with objectively measured physical activity.

Dec 2020, J. Global Health, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719276/, https://c19p.org/zhang4

183 patient favipiravir late treatment study: 96% lower mortality (p=0.14).
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.

Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsi

103 patient nitric oxide ICU study: 14% lower mortality (p=0.1).
Retrospective 103 mechanically ventilated patients, 41 treated with inhaled nitric oxide, and 62 with inhaled epoprostenol, showing no significant difference in outcomes.

Jun 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0270646, https://c19p.org/poonam

2,468 patient vitamin C late treatment study: 13% lower mortality (p=0.38).
Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing no significant difference with vitamin C treatment. IR.MUQ.REC.1399.013.

May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholi

24 patient ivermectin late treatment study: 86% lower mortality (p=0.04) and 93% lower hospitalization (p=0.001).
Small study of 24 consecutive patients in serious condition (9 days post symptoms, mean SpO2 87.4) using combined treatment with ivermectin, doxycycline, zinc, vitamin D, and vitamin C, showing no mortality or hospitalization with treatment. Two patients declined treatment and both died. This study uses a synthetic control arm.

Jul 2021, Future Microbiology, https://www.futuremedicine.com/doi/full/10.2217/fmb-2022-0014, https://c19p.org/hazan

180 patient HCQ late treatment study: 17% lower mortality (p=0.81).
Retrospective 180 hospitalized COVID-19 patients in Sierra Leone, showing no significant difference with HCQ treatment in unadjusted results, however HCQ was significantly more likely to be used for severe patients (33% vs. 12%).

Jan 2022, Infectious Diseases & Immunity, https://journals.lww.com/10.1097/ID9.0000000000000037, https://c19p.org/tu

80 patient HCQ late treatment study: 17% lower mortality (p=0.5).
Retrospective 80 hospitalized severe COVID-19 patients in Turkey, showing no significant difference with HCQ treatment in unadjusted results. All patients received favipiravir.

Jul 2023, Acta Clinica Croatica, https://www.researchgate.net/publication/372951875_FACTORS_AFFECTING_PROGNOSIS_AND_MORTALITY_IN_SEVERE_COVID-19_PNEUMONIA_PATIENTS, https://c19p.org/afsin

100 patient vitamin A early treatment study: 67% lower progression (p=0.27) and 38% faster recovery.
Treatment and prophylaxis studies of vitamin A in Iraq. The treatment study contained 100 patients, 50 treated with 200,000IU vitamin A for two days, showing lower progression to severe disease, and shorter duration of symptoms. The prophylaxis study is listed separately [Al-Sumiadai].

Jan 2021, Systematic Reviews in Pharmacy, https://www.researchgate.net/publication/351637178_THERAPEUTIC_EFFECT_OF_VITAMIN_A_ON_COVID-19_PATIENTS_AND_ITS_PROPHYLACTIC_EFFECT_ON_CONTACTS, https://c19p.org/alsumiadai

51 patient HCQ ICU study: 16% lower mortality (p=0.34).
Retrospective 51 ICU patients under mechanical ventilation, 33 treated with HCQ, showing unadjusted lower mortality with treatment.

Aug 2020, J. Antimicrobial Chemotherapy, https://academic.oup.com/jac/article/75/11/3359/5896161, https://c19p.org/pasquini

30 patient HCQ late treatment RCT: 29% lower progression (p=0.57) and 100% worse viral clearance (p=1).
30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HCQ but not statistically significant. One HCQ patient developed to a severe case. Treatment group 4 years older and with higher incidence of hypertension.

Mar 2020, J. Zhejiang University, https://pubmed.ncbi.nlm.nih.gov/32391667/, https://c19p.org/chenmedsci

165 patient ivermectin late treatment study: 50% lower mortality (p=0.03).
Retrospective 165 hospitalized patients in Pakistan showing unadjusted lower mortality with combined ivermectin and doxycycline treatment. Details of the ivermectin group compared to other patients are not provided, however ivermectin was given to a similar percentage of patients in the mild, moderate, and severe/critical groups (34.5%, 29.1%, and 36.4%), suggesting that ivermectin treatment was not based on severity.

Apr 2021, Cureus, https://www.cureus.com/articles/56545-clinical-variants-characteristics-and-outcomes-among-covid-19-patients-a-case-series-analysis-at-a-tertiary-care-hospital-in-karachi-pakistan, https://c19p.org/ahsan

71 patient hydrogen peroxide early treatment study: 12% improved viral clearance (p=0.67).
Small prospective study with 31 patients gargling povidone-iodine, 17 hydrogen peroxide, and 40 control patients, showing lower viral load mid-recovery with povidone-iodine, without reaching statistical significance. Oropharyngeal only, and only every 8 hours for two days. Results may be better with the addition of nasopharyngeal use, more frequent use, and without the two day limit. Authors report only one of the 7 previous trials for PVP-I and COVID-19. Non-randomized study with no adjustments or group details. Some results in Figure 1 appear to be switched compared to the text and the labels in the figure. The viral clearance figures do not match the group sizes - for example authors report 62% PCR- for PVP-I at the 3rd test, however there is no number of 31 patients that rounds to 62%.

Oct 2021, Enfermedades Infecciosas y Microbiología Clínica, https://www.sciencedirect.com/science/article/pii/S0213005X21002950, https://c19p.org/pablomarcoshp

84 patient favipiravir late treatment PSM study: 67% lower mortality (p=1), 200% higher ICU admission (p=1), and 11% longer hospitalization (p=0.9).
PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ.

Mar 2022, Acta Medica, https://actamedica.org/index.php/actamedica/article/view/719, https://c19p.org/uyaroglua

HCQ prophylaxis study: 12% fewer cases (p=0.01).
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of HCQ.

Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfadden

250 patient zinc prophylaxis study: 57% lower severe cases (p=0.03).
Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases with higher zinc intake.

Mar 2023, Clinical Nutrition ESPEN, https://www.sciencedirect.com/science/article/pii/S2405457723000803, https://c19p.org/asoudehz

432 patient favipiravir late treatment study: 85% lower mortality (p=0.05).
Retrospective hospitalized patients in Indonesia, showing lower mortality and shorter hospitalization with favipiravir.

Mar 2022, Pathophysiology, https://www.mdpi.com/1873-149X/29/1/9, https://c19p.org/yulia

exercise study: 76% lower hospitalization (p=0.05).
Retrospective 420 people in Spain, showing lower risk of COVID-19 hospitalization with a history of physical activity.

Jun 2021, Research in Sports Medicine, https://www.tandfonline.com/doi/full/10.1080/15438627.2021.1937166, https://c19p.org/latorreroman

diet study: 19% fewer cases (p=0.008).
Analysis of 42,935 participants showing lower risk of COVID-19 with healthier diets. Risk of severe cases was also lower with healthier diets, while not reaching statistical significance. Severity results are only provided with diet indices as a continuous variable.

Aug 2022, The American J. Clinical Nutrition, https://academic.oup.com/ajcn/advance-article/doi/10.1093/ajcn/nqac219/6659183, https://c19p.org/yue

14,335 patient sleep study: 16% fewer symptomatic cases (p=0.0007).
Prospective survey based study with 14,335 participants, showing risk of viral symptoms associated with shorter sleep duration.

Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253120, https://c19p.org/marcussl

7,766 patient vitamin B9 prophylaxis study: 16% fewer cases (p=0.02).
Analysis of 7,766 adults in France, showing higher intakes of vitamin C, folate, vitamin K, dietary fibre, and fruit and vegetables associated with lower seropositivity.

Nov 2021, BMC Medicine, https://link.springer.com/article/10.1186/s12916-021-02168-1/fulltext.html, https://c19p.org/deschasauxtanguyb9

60 patient andrographolide late treatment study: 19% improved viral clearance (p=0.61).
Retrospective 120 patients in Thailand, showing improved viral clearance with andrographis compared with favipiravir.

Dec 2022, OSIR, https://www.osirjournal.net/index.php/osir/article/download/311/251, https://c19p.org/prempree

7,766 patient vitamin K prophylaxis study: 14% fewer cases (p=0.04).
Analysis of 7,766 adults in France, showing higher intakes of vitamin C, folate, vitamin K, dietary fibre, and fruit and vegetables associated with lower seropositivity.

Nov 2021, BMC Medicine, https://link.springer.com/article/10.1186/s12916-021-02168-1/fulltext.html, https://c19p.org/deschasauxtanguyvk

144 patient vitamin A late treatment study: 26% lower mortality (p=1).
Prospective study of 144 hospitalized COVID-19 patients in the DRC and South Sudan, showing no significant difference with vitamin A treatment in unadjusted results with only 8 patients receiving vitamin A.

Oct 2022, PLOS Global Public Health, https://journals.plos.org/plosone/article?id=10.1371/journal.pgph.0000924, https://c19p.org/doocyva

183 patient aspirin late treatment study: 96% lower mortality (p=0.22).
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.

Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsie

74 patient favipiravir late treatment PSM study: 80% lower mortality (p=0.49), 75% longer hospitalization (p=0.63), and 40% lower hospital discharge (p=0.74).
Retrospective 200 hospitalized COVID-19 patients in Saudi Arabia, showing no significant difference in outcomes between HCQ and favipiravir.

Nov 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/12/1456, https://c19p.org/alosaimia

100 patient favipiravir ICU study: 16% lower mortality (p=0.38) and 10% lower ventilation (p=0.75).
Retrospective 100 ICU patients in Turkey, showing improved survival with favipiravir vs. lopinavir/ritonavir.

Jun 2022, SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital, https://sislietfaltip.org/jvi.aspx?un=SETB-35902&volume=, https://c19p.org/acarsevinc

354 patient metformin prophylaxis study: 37% lower mortality (p=0.12), 39% higher ICU admission (p=0.26), and 3% higher ARDS (p=0.92).
Prospective multicenter study of 354 hospitalized type 2 diabetes patients with COVID-19 in Greece showing increased risk with DPP4 inhibitor use as part of chronic diabetes treatment. There was no significant difference with metformin use in unadjusted results. Results do not account for differences in the risk of hospitalization.

May 2023, Microorganisms, https://www.mdpi.com/2076-2607/11/6/1416, https://c19p.org/akinosoglou

15,227 patient zinc prophylaxis study: 7% fewer cases (p=0.77).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtz

31 patient HCQ ICU study: 18% lower mortality (p=0.64).
Retrospective ICU patients in the Philippines showing unadjusted HCQ RR 0.82, p = 0.64.

Jan 2021, Critical Care Research and Practice, https://www.hindawi.com/journals/ccrp/2021/7510306/, https://c19p.org/ubaldo

3,881 patient aspirin late treatment RCT: 9% higher mortality (p=0.84), 20% lower progression (p=0.21), and 17% lower hospitalization (p=0.31).
Late (5.4 days) outpatient RCT showing no significant difference in outcomes with aspirin treatment.

Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002995, https://c19p.org/eikelboom2e

77,221 patient aspirin prophylaxis PSM study: 9% lower mortality (p=0.12), 2% lower hospitalization (p=0.47), 9% more symptomatic cases (p=0.18), and 7% more cases (p=0.09).
UK Biobank retrospective 77,271 patients aged 50-86, showing no significant differences with aspirin use. Matching lead to different results for the gender vs. overall analysis, for example the overall result for cases was OR 1.07, however both gender results are lower OR 0.97 and 1.02.

Aug 2021, Drugs & Aging, https://link.springer.com/article/10.1007%2Fs40266-021-00886-y, https://c19p.org/ma3

HCQ early treatment study: 42% lower progression (p=0.37).
Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided.

Sep 2021, Southeast Asian J. Tropical Medicine and Public Health, https://journal.seameotropmednetwork.org/index.php/jtropmed/article/view/490, https://c19p.org/sawanpanyalert

116,209 patient proton pump inhibitor prophylaxis study: 15% lower hospitalization (p=0.27) and 15% fewer cases (p=0.002).
Retrospective 116,209 pediatric patients showing lower risk of COVID-19 with PPI use. There was no significant difference for hospitalization.

Jun 2024, The J. Pediatrics, https://www.sciencedirect.com/science/article/pii/S0022347624002828, https://c19p.org/hirsch2

734 patient HCQ late treatment study: 4% lower mortality (p=0.83).
Retrospective database analysis with PSM not including COVID-19 severity, finding mortality OR 0.95 [0.62-1.46] for HCQ, and 1.24 [0.70-2.22] for HCQ+AZ. Confounding by indication likely.

Oct 2020, Pharmacotherapy, https://accpjournals.onlinelibrary.wiley.com/doi/10.1002/phar.2467, https://c19p.org/annie

exercise study: 26% lower mortality (p=0.08) and 7% fewer cases (p=0.02).
Retrospective 4,363 COVID-19 patients and 67,125 controls in South Korea, showing higher risk of mortality and cases with insufficient physical activity.

Feb 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1072198/full, https://c19p.org/park3

183 patient vitamin D late treatment study: 58% lower mortality (p=0.7).
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.

Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsid

490 patient vitamin D prophylaxis study: 9% lower mortality (p=0.67).
Retrospective 517 hip fracture patients in the UK with vitamin D levels measured during COVID-19 admission, not showing significant differences in mortality for supplementation in unadjusted analysis with no group details and subject to confounding by indication. There was also no significant effect based on deficiency.

Dec 2021, European J. Medical and Health Sciences, https://ej-med.org/index.php/ejmed/article/view/1159, https://c19p.org/mahmood

152 patient vitamin D late treatment study: 19% lower mortality (p=0.42).
Retrospective 152 mechanically ventilated patients in the USA showing unadjusted lower mortality with vitamin C, vitamin D, HCQ, and zinc treatment, statistically significant only for vitamin C.

Jul 2020, J. Clinical Anesthesia, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369577/, https://c19p.org/krishnand

200 patient probiotics late treatment RCT: 2% higher mortality (p=1), 18% lower ventilation (p=1), 27% lower ICU admission (p=0.77), and 5% faster recovery (p=0.47).
RCT 200 patients, 99 treated with a probiotic (Lacticaseibacillus rhamnosus PDV 1705, Bifidobacterium bifidum PDV 0903, Bifidobacterium longum subsp. infantis PDV 1911, and Bifidobacterium longum subsp. longum PDV 2301). There was no significant difference in mortality or recovery time, however benefits were seen for diarrhea. NCT04854941.

Oct 2021, Probiotics Antimicrob Proteins, https://pubmed.ncbi.nlm.nih.gov/34643888/, https://c19p.org/ivashkin

966 patient HCQ ICU study: no change in mortality (p=0.94).
Prospective study of 966 ICU patients in France, 289 treated with HCQ, showing no significant difference with treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.

Jul 2021, Anaesthesia Critical Care & Pain Medicine, https://www.sciencedirect.com/science/article/pii/S2352556821001351, https://c19p.org/roger

47 patient vitamin C ICU RCT: 19% lower mortality (p=0.75) and 2% worse results (p=0.28).
RCT 47 ICU patients showing no significant differences with vitamin C treatment.

Apr 2024, NCT04344184, https://clinicaltrials.gov/study/NCT04344184, https://c19p.org/fowler

HCQ long COVID study: 40% lower PASC (p=0.08).
Retrospective 755 autoimmune rheumatic disease patients, showing lower risk of PASC (long COVID) with HCQ use, without statistical significance.

Apr 2023, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991323000668, https://c19p.org/sen2

42 patient HCQ prophylaxis study: 20% lower mortality (p=0.77) and 35% higher ICU admission (p=0.61).
Tiny retrospective database analysis of hospitalized COVID-19 patients with rheumatologic disease containing 14 chronic HCQ and 28 control patients. Patients are very poorly matched. Bias against HCQ is clear in the abstract which mentions differences favoring HCQ but ignores those favoring control (large differences in ethnicity, rheumatic conditions, hypertension, coronary artery disease, solid organ transplant recipients, immunosuppresive drugs). 61% of control patients also received HCQ. Adherence for chronic HCQ patients was not examined. Despite the very large differences between the groups, no adjustments are made. The study claims that HCQ did not prevent severe cases, but the study is among hospitalized patients, i.e., they already have cases severe enough for hospitalization - this study can not identify a protective effect of HCQ that reduces the probability of disease severe enough for hospitalization.

Mar 2021, Rheumatology Advances in Practice, https://academic.oup.com/rheumap/advance-article/doi/10.1093/rap/rkab014/6156645, https://c19p.org/pham

246 patient vitamin C late treatment study: 50% lower mortality (p=0.06).
Retrospective 246 severe COVID-19 patients in Uganda, showing lower mortality with vitamin C treatment, without statistical significance (p = 0.06).

May 2023, Infection and Drug Resistance, https://www.dovepress.com/thirty-day-outcomes-of-young-and-middle-aged-adults-admitted-with-seve-peer-reviewed-fulltext-article-IDR, https://c19p.org/kyagambiddwa

exercise study: 47% fewer cases (p=0.4).
Prospective survey analysis of 28,575 people in 99 countries, showing a lower risk of COVID-19 with a exercise, without statistical significance.

Sep 2021, BMJ Open, https://bmjopen.bmj.com/content/11/9/e052025, https://c19p.org/lin

148 patient azvudine late treatment PSM study: 45% lower progression (p=0.36).
Retrospective 148 hospitalized kidney transplant patients with COVID-19 in China showing lower risk of disease progression with azvudine treatment compared, and higher risk with paxlovid treatment.

Apr 2024, Infections in the immunosuppressed and immunocompromised host, https://www.atsjournals.org/doi/10.1164/ajrccm-conference.2024.209.1_MeetingAbstracts.A2917, https://c19p.org/liu23

12 patient povidone-iodine early treatment study: 33% improved viral load (p=0.58).
Small single-arm trial testing short-term viral load change after a single administration of three puffs of 0.4% PVP-I, showing lower viral titer at 3 minutes and 4 hours, not reaching statistical significance. Authors note that one reason for the lower change compared to in vitro results is that the spray administration may be less effective.

Aug 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.08.18.22278340, https://c19p.org/sirijatuphat3

247 patient ivermectin early treatment study: 94% lower ventilation (p=0.005) and 98% lower hospitalization (p<0.0001).
Comparison of HCQ, nitazoxanide, and ivermectin showing similar effectiveness for overall clinical outcomes in COVID-19 when used before seven days of symptoms, and overwhelmingly superior compared to the untreated COVID-19 population, even for those outcomes not influenced by placebo effect, at least when combined with azithromycin, and vitamin C, D and zinc in the majority of the cases. 585 patients with mean treatment delay 2.9 days. There was no hospitalization, mechanical ventilation, or mortality with treatment. Control group 1 was a retrospectively obtained group of untreated patients of the same population.

Nov 2020, New Microbes and New Infections, https://www.sciencedirect.com/science/article/pii/S2052297521000792, https://c19p.org/cadegianii

816 patient HCQ late treatment study: 18% lower mortality (p=0.15) and 9% higher ICU admission (p=0.7).
Retrospective 1376 hospitalized patients in Italy, 211 treated with HCQ and 166 with HCQ+AZ.

Aug 2020, J, Clinical Medicine, https://www.mdpi.com/2077-0383/9/9/2800, https://c19p.org/albani

1,699 patient favipiravir ICU study: 3% lower mortality (p=0.81).
Retrospective 1,699 ICU patients in Saudi Arabia, 193 treated with favipiravir, showing no significant difference in mortality.

Jun 2022, J. Ayub Medical College Abbottabad, https://jamc.ayubmed.edu.pk/jamc/index.php/jamc/article/view/10305, https://c19p.org/abdulrahman2

7,592 patient HCQ late treatment study: 6% lower mortality (p=0.63).
Database analysis of 7,592 patients in NYC, showing adjusted HCQ mortality odds ratio OR 0.96, p = 0.82, and HCQ+AZ OR 0.94, p = 0.63

Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.11.20128926v1, https://c19p.org/wangrx

603 patient vitamin D prophylaxis study: 12% fewer cases (p=0.09).
Retrospective 603 patients in Iran, 192 taking vitamin D supplements, showing no significant difference in COVID-19 cases in unadjusted results. IR.SHOUSHTAR.REC.1399.015.

Aug 2021, Nutrition & Food Science, https://www.emerald.com/insight/content/doi/10.1108/NFS-11-2020-0421/full/html, https://c19p.org/mohseni

225 patient HCQ prophylaxis study: 4% fewer cases (p=0.93).
Small study of SLE patients taking HCQ with a phone survey for COVID-19 suggestive symptoms. There was 2 hospitalizations (group not identified) and no ICU or death cases. A similar percentage of suspected infections were reported for HCQ users and non-HCQ users, RR 0.96, p = 0.93. There was no mortality and severity was not analyzed to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity of SLE. Only 5 cases were PCR confirmed.

Jun 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/06/25/annrheumdis-2020-218244, https://c19p.org/gendebien

253 patient vitamin C prophylaxis study: 4% lower severe cases (p=1).
Retrospective survey-based analysis of 349 COVID-19 patients, showing no significant difference with vitamin C prophylaxis in unadjusted analysis. REC/UG/2020/03.

Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabc

427 patient vitamin C prophylaxis study: 19% lower hospitalization (p=0.69).
Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.

Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateefc

226 patient HCQ late treatment study: 3% faster viral clearance (p=0.92).
Retrospective of hospitalized patients with 31 HCQ patients and 195 standard treatment patients, not showing a significant difference in terms of viral clearance or recovery. There was no mortality in either group. "It is notable that HQ plus antibiotics group had worse baseline clinical profiles (i.e. higher percentage of moderate severity patients, more patients with fever >=37.5C, higher average body temperature) and prognostic indicators such as age, LDH, lymphocyte count, and CRP". We note that propensity score matching removed almost all of the male patients in the control group (40% -> 5%) but increased the percentage of male patients in the treatment group. This provides a large advantage to the control group because there is a very large difference in severity and mortality based on gender [ncbi.nlm.nih.gov]. In terms of viral RNA clearance we note that other research has found that "active viral replication drops quickly after the first week, and viable virus..

Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.04.20146548v1, https://c19p.org/an

4,666 patient HCQ prophylaxis study: 9% fewer cases (p=0.54).
Retrospective 4666 people with autoimmune or inflammatory conditions, showing HCQ adjusted risk of COVID-19 OR 0.91 [0.68-1.23]. Results are not adjusted for the significantly different risk of COVID-19 depending on the type and severity of autoimmune or inflammatory condition.

Feb 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.02.03.21251069v1, https://c19p.org/fitzgerald

600 patient HCQ prophylaxis study: 3% lower hospitalization (p=0.82).
Analysis of rheumatic disease patients showing no significant association between antimalarial therapy and hospitalisation, OR=0.94 [0.57-1.57], p=0.82 after adjustments.

May 2020, Annals of the Rheumatic Diseases, 859-866, https://europepmc.org/article/med/32471903, https://c19p.org/gianfrancesco

aspirin prophylaxis study: 1% lower mortality (p=0.95) and 12% fewer cases (p=0.04).
Retrospective database analysis of 328,374 adults in South Korea, showing lower risk of COVID-19 cases with aspirin use, but no difference in mortality for COVID-19 patients.

Jun 2021, Yonsei Medical J., https://eymj.org/DOIx.php?id=10.3349/ymj.2021.62.7.577, https://c19p.org/oh2

428 patient zinc prophylaxis study: 13% lower hospitalization (p=0.83).
Survey of 428 recovered COVID-19 patients in Iraq, showing fewer hospital visits for patients on prophylactic vitamin C or D. Hospitalization was lower for those on vitamin C, D, or zinc, without statistical significance.

Apr 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0273/html, https://c19p.org/abdulateefz

21,669 patient aspirin prophylaxis PSM study: 11% lower mortality (p=0.67), 7% higher progression (p=0.8), and 11% more cases (p=0.21).
PSM retrospective case control study in South Korea, showing a trend towards lower mortality, but no significant differences with aspirin use.

Jul 2021, Medicine, https://journals.lww.com/10.1097/MD.0000000000026670, https://c19p.org/son

147 patient HCQ ICU study: 3% lower mortality (p=0.85).
Retrospective 147 ICU patients in Turkey, showing no significant difference in outcomes based on HCQ treatment before ICU admission. This is not very informative, for example we do not know if HCQ treated patients were much less likely to be admitted to the ICU.

Apr 2021, South. Clin. Ist. Euras., https://jag.journalagent.com/scie/pdfs/SCIE-89847-RESEARCH_ARTICLE-CIYILTEPE.pdf, https://c19p.org/ciyiltep

198 patient HCQ late treatment PSM study: 15% lower mortality (p=0.71) and 49% longer hospitalization (p=0.002).
Retrospective 840 hospitalized patients in Switzerland showing non-statistically significant lower mortality with HCQ but significantly longer hospitalization times. Confounding by indication is likely. PSM fails to adjust for severity with a 16% higher mNEWS score for HCQ vs. SOC in the matched cohort. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse. Authors note: "overall, there was an indication bias, with the reason of prescription being associated with the outcome of interest. Indeed, patients with more severe COVID-19 were more likely to receive experimental therapies."

Dec 2020, Swiss Medical Weekly, https://smw.ch/article/doi/smw.2020.20446, https://c19p.org/vernaz

1,758 patient ivermectin late treatment study: 20% lower mortality (p=0.12).
Retrospective 2017 hospitalized patients in India, showing lower mortality with ivermectin treatment in unadjusted results. No group details are provided and this result is subject to confounding by indication.

Aug 2021, Lung India, https://journals.lww.com/lungindia/Fulltext/2022/01000/Clinical_features,_demography,_and_predictors_of.5.aspx, https://c19p.org/elavarasi

1,294 patient HCQ prophylaxis study: 11% fewer cases (p=0.68).
Prospective PrEP study with low risk healthcare workers in India showing RR=0.89 [0.53-1.52]. There were no significant adverse effects. Only mean age and gender distribution are provided for baseline characteristics, no severity information is provided, and no adjustments were made. Authors analyze HCQ use for <8 vs. ≥8 weeks, noting a lack of statistical significance, but not providing the results.

Dec 2021, Expert Review of Anti-infective Therapy, https://www.tandfonline.com/doi/abs/10.1080/14787210.2022.2015326, https://c19p.org/rao

477 patient vitamin D prophylaxis study: 5% lower hospitalization (p=0.89).
Retrospective 477 COVID+ public transportation workers in Turkey, showing no significant difference in hospitalization with vitamin D use in unadjusted results.

Nov 2022, Work, https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/WOR-220292, https://c19p.org/guldemird

406 patient metformin prophylaxis study: 10% lower severe cases (p=0.53).
Retrospective 406 COVID-19 patients in Iran, showing lower risk of severe cases with metformin use in unadjusted results, without statistical significance.

Oct 2023, Cureus, https://www.cureus.com/articles/194481-development-of-a-scoring-method-based-on-a-chest-ct-scan-to-determine-the-outcomes-of-covid-19-patients, https://c19p.org/bidari

668 patient HCQ late treatment study: 11% lower mortality (p=1).
Retrospective 668 hospitalized patients in Argentina, 18 treated with HCQ, not showing a significant difference in unadjusted results.

Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.30.21261220v1, https://c19p.org/barra

HCQ prophylaxis study: 36% lower mortality (p=0.11).
Retrospective study of 367 hematology patients with COVID-19 in Spain. Among 216 patients with very severe COVID-19, there was significantly lower mortality with azithromycin treatment. Mortality was also lower with HCQ, but without statistical significance.

Aug 2020, Experimental Hematology & Oncology, https://ehoonline.biomedcentral.com/articles/10.1186/s40164-020-00177-z, https://c19p.org/pinana

382 patient zinc late treatment study: 33% lower PASC (p=0.07).
Prospective study of 382 hospitalized COVID-19 patients in New York City, showing significantly worse 6-month functional outcomes, activities of daily living, and return to work with neurological complications during initial hospitalization.

Jul 2021, J. the Neurological Sciences, https://www.sciencedirect.com/science/article/pii/S0022510X21001805, https://c19p.org/frontera3

298 patient azithromycin late treatment RCT: 1% lower combined mortality/hospitalization (p=0.99) and 80% lower progression (p=0.24).
RCT 298 mild-to-moderate COVID-19 outpatients in the UK showing no significant difference in hospitalization or death with late azithromycin treatment. Treatment was delayed an average of 6 days from onset. 7 vs. 3 hospitalizations occurred by day 1 in the treatment vs. control groups in this open label trial (Figure 2).

Oct 2021, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260021002630, https://c19p.org/hinksaz

465 patient famotidine ICU study: 7% lower mortality (p=0.57).
Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.

Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadifm

313 patient colchicine late treatment study: 6% lower mortality (p=0.87).
Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support. Confounding by indication likely.

Nov 2020, Mayo Clinic Proceedings: Innovations, Quality & Outcomes, https://www.sciencedirect.com/science/article/pii/S2542454820302071, https://c19p.org/rodrigueznavao

113 patient HCQ prophylaxis study: 19% fewer symptomatic cases (p=1) and 6% more cases (p=1).
Small PEP trial with 51 HCQ patients, not showing a significant difference in cases. IRCT20130917014693N10.

Aug 2021, Pulmonary Pharmacology & Therapeutics, https://www.sciencedirect.com/science/article/abs/pii/S109455392100081X, https://c19p.org/shabani

200 patient HCQ late treatment study: 7% lower mortality (p=0.74).
Prospective study of 200 ECMO patients showing no significant difference in unadjusted results for HCQ treatment. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (as shown in figure 4), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.

Jul 2021, The Annals of Thoracic Surgery, https://www.sciencedirect.com/science/article/pii/S0003497521011772, https://c19p.org/jacobs

239 patient vitamin D prophylaxis study: 27% fewer cases (p=1).
Analysis of 239 consecutive diabetic patients, 97 taking vitamin D supplements, showing significantly higher vitamin D levels in supplemented patients. There was no statistically significant difference in cases based on supplementation, with only 3 cases total.

Sep 2021, Endocrine Abstracts, https://www.endocrine-abstracts.org/ea/0070/ea0070ep552, https://c19p.org/lazaro

465 patient aspirin ICU study: 10% lower mortality (p=0.5).
Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.

Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadie

2,833 patient ivermectin late treatment study: 17% lower mortality (p=0.01).
Retrospective database study of 5683 patients, 692 received HCQ/CQ+AZ, 200 received HCQ/CQ, 203 received ivermectin, 1600 received AZ, 358 received ivermectin+AZ, and 2630 received standard of care. This study includes anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore many patients in the control group are likely asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. For those that had symptomatic COVID-19, there is also likely significant confounding by indication. In this study all medications show higher mortality at day 30, which is consistent with asymptomatic (for COVID-19) or mild condition patients being more common in the control group. For ivermectin they show 30 day mortality aHR = 1.39 [0.88 - 2.22]. KM curves show that the treatment groups were in more serious condition, and also that after about day 35 survival became better with ivermectin. The last day available for ivermectin shows RR 0.83, p = 0.01. More..

Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.06.20208066v1, https://c19p.org/sotobecerrai

253 patient nigella sativa prophylaxis study: no change in severe cases (p=1).
Retrospective survey-based analysis of 349 COVID-19 patients, showing no significant difference with nigella sativa prophylaxis in unadjusted analysis. REC/UG/2020/03.

Feb 2022, Tropical J. Pharmaceutical Research, https://www.tjpr.org/admin/12389900798187/2022_21_2_14.pdf, https://c19p.org/shehabns

14,520 patient HCQ prophylaxis study: 8% fewer cases (p=0.88).
Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HCQ patient cases. Only considers people tested at a time when primarily symptomatic cases were tested. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. Adjusting for the difference in baseline risk using the result in Ferri et al. shows substantial benefit for HCQ, RR 0.211, but with only 3 HCQ cases the result is inconclusive. More recent studies with rheumatic disease/autoimmune condition patients provide higher confidence.

May 2020, Autoimmunity Reviews, July 2020, https://www.sciencedirect.com/science/article/pii/S1568997220301282, https://c19p.org/gendelman

965 patient ivermectin late treatment study: 3% lower mortality (p=0.82).
Retrospective 965 late stage (44% severe, 27% ICU) hospitalized patients in India, showing no significant difference with ivermectin treatment. Overall mortality was very high, suggesting very late treatment. The low non-weight-adjusted dose may not be very effective with such late stage patients. 210 patients were excluded due to early discharge, which may have been patients with earlier onset that are more likely to benefit with ivermectin. Age grouping is very unusual with no breakdown of ages for the 71% of patients >45. Numbers may be unreliable, e.g., cardiovascular disease counts and/or percentages for IVM appear incorrect. Details of adjustments are not provided, there may be extreme confounding by age within the >45 groups which contain the majority of the patients, in addition to confounding by indication.

Apr 2022, Research Square, https://www.researchsquare.com/article/rs-1522422/v1, https://c19p.org/ravikirti2

spironolactone antiandrogen prophylaxis study: 7% fewer cases (p=0.008).
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of spironolactone.

Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenaa

acetaminophen prophylaxis study: 7% fewer cases (p=0.004).
UK Biobank retrospective showing lower cases with acetaminophen use.

Aug 2021, COVID, https://www.mdpi.com/2673-8112/1/1/18, https://c19p.org/leal

ibuprofen prophylaxis study: 3% fewer cases (p=0.29).
UK Biobank retrospective showing no significant difference in cases with ibuprofen use.

Aug 2021, COVID, https://www.mdpi.com/2673-8112/1/1/18, https://c19p.org/lealib

spironolactone prophylaxis study: 7% fewer cases (p=0.008).
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing lower cases with chronic use of spironolactone.

Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenaasp

80 patient HCQ prophylaxis study: 3% lower hospitalization (p=0.88).
Analysis of 80 SLE patients diagnosed with COVID-19, showing the frequency of hospitalisation did not differ between individuals using an antimalarial versus non-users (55% (16/29) vs 57% (29/51), p=ns. Authors suggest that the dosage used may be too low to reach therapeutic levels.

May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/20/annrheumdis-2020-217690, https://c19p.org/konig

32 patient HCQ ICU study: 5% lower mortality (p=1).
Retrospective 32 ICU patients, showing no significant difference with HCQ treatment in unadjusted results.

Aug 2021, Microbial Drug Resistance, https://www.liebertpub.com/doi/full-xml/10.1089/mdr.2020.0489, https://c19p.org/karrulih

30 patient probiotics early treatment study: 29% faster viral clearance (p=0.22).
Small case control analysis with 15 probiotics patients and 15 contol patients, showing no significant differences. PCR tests were only done weekly. Dosage is unknown. 115/LOE/301.4.2/IX/2020.

Jun 2021, Indian J. Forensic Medicine & Toxicology, http://medicopublication.com/index.php/ijfmt/article/view/15003/13584, https://c19p.org/veterini

1,349 patient various antiandrogen prophylaxis study: 33% lower mortality (p=0.41), 8% higher progression (p=0.77), and 68% more cases (p=0.15).
Retrospective 1,349 prostate cancer patients in Spain, 156 on ADT, showing no significant differences in COVID-19 outcomes with treatment.

Sep 2021, The Prostate, https://onlinelibrary.wiley.com/doi/full/10.1002/pros.24232, https://c19p.org/jimenezalcaide

193 patient HCQ late treatment study: 9% lower mortality (p=0.83), 20% higher ICU admission (p=0.61), and 12% shorter hospitalization.
Retrospective 193 hospitalized patients in Brazil not finding a significant difference with HCQ. The control group was composed of patients refusing HCQ or with contraindications. Time based confounding is very likely because HCQ became more controversial in Brazil over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients (those refusing HCQ) likely come later in the period when treatment protocols were greatly improved. The paper does not mention the word "confounding" or make any adjustments.

Feb 2021, The Brazilian J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S141386702100012X, https://c19p.org/lamback

1,811 patient exercise study: 38% lower PASC (p=0.16).
Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with 3+ hours of exercise per week in the month before infection, without statistical significance (p=0.16).

Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paulex

1,811 patient smoking long COVID study: 37% lower PASC (p=0.14).
Retrospective 1,811 COVID-19 patients in the UK, showing lower risk of self-reported long COVID with no smoking in the month before infection, not reaching statistical significance (p=0.14).

Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paulsm

aspirin prophylaxis study: 37% lower mortality (p=0.28) and 1% higher ICU admission (p=0.79).
Retrospective 4,017 coronary artery disease patients hospitalized for COVID-19 in the USA, showing no significant difference in outcomes with low dose aspirin use.

Dec 2022, Innovation in Aging, https://academic.oup.com/innovateage/article/6/Supplement_1/850/6939246, https://c19p.org/zadeh

15,227 patient exercise study: 17% fewer cases (p=0.18).
Prospective survey-based study with 15,227 people in the UK, showing reduced risk of COVID-19 cases with lower impact physical activity. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtex

15,227 patient sleep study: 12% fewer cases (p=0.5).
Prospective survey-based study with 15,227 people in the UK, showing reduced risk of COVID-19 cases with 8 hours sleep, with statistical significance when compared with ≥9 hours. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtsl

ibuprofen prophylaxis study: 10% lower mortality (p=0.36).
Prospective study of 78,674 COVID-19 patients, showing no significant difference in mortality with ibuprofen use.

Jul 2021, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991321001041, https://c19p.org/drake

46 patient ivermectin early treatment study: 85% lower mortality (p=0.08).
Prospective trial of ivermectin, dexamethasone, enoxaparin, and aspirin, showing no hospitalization for mild cases, and lower mortality for moderate/severe patients.

Sep 2020, J. Clinical Trials, https://www.longdom.org/open-access/safety-and-efficacy-of-the-combined-use-of-ivermectin-dexamethasone-enoxaparin-and-aspirina-against-covid19-the-idea-protocol-70290.html, https://c19p.org/carvallo

280 patient HCQ late treatment study: 15% lower mortality (p=1).
Retrospective 280 hospitalized patients in the Philippines, 25 treated with HCQ, not showing any significant differences in unadjusted results.

Nov 2021, Western Pacific Surveillance and Response J., https://ojs.wpro.who.int/ojs/index.php/wpsar/article/view/852, https://c19p.org/cortez

125 patient vitamin C ICU study: 10% lower mortality (p=0.56).
Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with vitamin C treatment in unadjusted results.

Mar 2022, Research Square, https://www.researchsquare.com/article/rs-1362678/v1, https://c19p.org/salehic

zinc prophylaxis study: 31% lower hospitalization (p=0.02).
Analysis of 1,957 older adults showing lower risk of COVID-19 hospitalization with higher dietary zinc intake. Each unit increase in zinc intake was associated with a 31% reduction in the risk of COVID-19 hospitalization after adjustments. A dynamical system model showed that consumption of zinc < 9.7mg per day was associated with a 1.5 times greater risk of COVID-19 infection.

Mar 2024, BMC Nutrition, https://bmcnutr.biomedcentral.com/articles/10.1186/s40795-024-00821-5, https://c19p.org/seifi

262 patient aspirin prophylaxis study: no change in mortality (p=1).
Retrospective 131 COVID-19 patients with aspirin use and 131 matched controls in Iran, showing no significant difference in outcomes, however age matching used only two categories, 40-60 and 60+, therefore matching may be very poor given the relationship between age and COVID-19 risk. The percentages given for the control group death/recovery outcomes do not match the reported counts.

Feb 2023, J. Nephropharmacology, https://www.jnephropharmacology.com/Inpress/npj-10506.pdf, https://c19p.org/azizi

HCQ prophylaxis study: 13% lower mortality (p=0.15), 3% lower hospitalization (p=0.63), and 9% fewer cases (p=0.02).
Retrospective database analysis of 374,229 patients in the USA, showing no significant difference with HCQ use, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri]. Authors compare with patients that never used HCQ and with patients that previously used HCQ. The comparison with patients previously using HCQ is more relevant because the matching of patients with systemic autoimmune disease is likely to be better.

Sep 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266922, https://c19p.org/fung

vitamin D prophylaxis study: 10% lower mortality (p=0.28).
Retrospective causal inference analysis of 4,091 COVID+ long-term care high risk patients in the USA, showing lower mortality with vitamin D, without statistical significance.

Nov 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.11.18.21266489, https://c19p.org/ahmed3

aspirin prophylaxis study: 22% lower progression (p=0.3) and 3% more cases (p=0.8).
Retrospective 2,736,091 individuals in the U.S., U.K., and Sweden, showing lower risk of hospital/clinic visits with aspirin use.

May 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.28.21256261, https://c19p.org/drew

metformin prophylaxis study: 1% fewer cases (p=0.45).
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of metformin.

Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenmf

famotidine prophylaxis study: 7% fewer cases (p=0.16).
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of famotidine.

Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenfm

vitamin B9 prophylaxis study: no change in cases (p=1).
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing no significant difference in cases with chronic use of vitamin B9.

Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenb9

89 patient favipiravir late treatment RCT: 15% lower mortality (p=1), 2% higher ICU admission (p=1), and 10% worse recovery (p=0.82).
Small 89 patient RCT comparing favipiravir and inhaled interferon with HCQ for moderate to severe COVID-19 pneumonia, not finding significant differences. There was no control group.

Nov 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220323195, https://c19p.org/khamisf

29 patient HCQ early treatment study: 2% faster recovery (p=0.96).
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups.

Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21252883v1, https://c19p.org/royh

famotidine prophylaxis study: no change in mortality (p=1), 6% lower hospitalization (p=0.0002), and 12% more cases (p<0.0001).
Retrospective database analysis of 374,229 patients in the USA, showing higher cases, lower hospitalizations, and no change in mortality with famotidine use.

Sep 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266922, https://c19p.org/fungfm

HCQ prophylaxis study: 8% higher mortality (p=0.64) and 18% lower hospitalization (p=0.03).
Retrospective database analysis case control study of rheumatic patients. When compared with other cDMARDs, HCQ users had significantly lower hospitalization, however there was no significant difference in mortality. Results differ significantly from previous studies, for example showing mortality OR 0.94 [0.83-1.06] for patients with rheumatic disease and mortality OR 0.88 [0.74-1.05] for patients with RA/SLE. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall.

Apr 2021, Rheumatology, https://academic.oup.com/rheumatology/advance-article/doi/10.1093/rheumatology/keab348/6226505?searchresult=1, https://c19p.org/alegiani

HCQ prophylaxis study: 6% fewer cases (p=0.75).
Comparison of CQ/HCQ users with the general population in a region of Italy, showing no significant difference in the probability of COVID-19. CQ/HCQ users were mostly systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].

Aug 2020, Arthritis & Rheumatology, https://onlinelibrary.wiley.com/doi/10.1002/art.41475, https://c19p.org/salvarani

29 patient ivermectin early treatment study: 6% faster recovery (p=0.87).
Retrospective database analysis of 56 mild COVID-19 patients, all treated with vitamin C, vitamin D, and zinc, comparing ivermectin + doxycycline (n=14), AZ (n=13), HCQ (n=14), and SOC (n=15), finding that all groups recover quickly, and there was no significant difference between the groups. Subject to the usual limitation of a database study, very small size, and limited evaluation of patients.

Mar 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.03.08.21252883v1, https://c19p.org/roy

875 patient ivermectin prophylaxis study: 73% fewer cases (p<0.0001).
Report on ivermectin prophylaxis in a hospital in Argentina showing lower cases for healthcare workers taking ivermectin. Results have been published in the press [lanacion.com.ar] (interim results), and a presentation posted online: [web.archive.org], however there is no formal publication to date. These results would be expected to receive priority publication due to the predicted impact on the pandemic and confirmation of previous prophylaxis studies. The lack of formal publication suggests a negative publication bias that may be due to politicization in the authors' location. Note that this prophylaxis study is different to the Vallejos early treatment trial.

Dec 2020, IVERCOR PREP, Preliminary Results, https://web.archive.org/web/20210226215453/https://twitter.com/Covid19Crusher/status/1365420061859717124, https://c19p.org/vallejos

600 patient ivermectin early treatment study: 92% lower mortality (p=0.03) and 93% lower hospitalization (p<0.0001).
Retrospective 600 PCR+ outpatients in Australia treated with ivermectin, zinc, and doxycycline, showing significantly lower mortality and hospitalization with treatment. This trial uses a synthetic control group, and the preliminary report provides minimal details. For discussion of the use of a synthetic control group, see [doyourownresearch.substack.com]. Notably, advantages include less-biased recruitment (patients do not opt-out if they feel they need treatment and don't want to risk placebo), trials are cheaper, there is less delay in treatment, and trials can be run where it is not ethical to give patients placebo.

Oct 2021, TrialSite News, https://www.trialsitenews.com/a/combination-therapy-for-covid-19-based-on-ivermectin-in-an-australian-population, https://c19p.org/borody

25 patient HCQ late treatment study: 38% improved viral clearance (p=0.17).
Early results from a very small trial, reported within the application for a later trial. Very minimal details are provided, but we include this as the earliest published results. For COVID-19 patients with pneumonia the viral negative conversion rate was 50% (5/10) with CQ versus 20% (3/15) with lopinavir/ritonavir.

Feb 2020, ChiCTR2000029741, http://www.chictr.org.cn/showproj.aspx?proj=49263, https://c19p.org/xia

160 patient vitamin C ICU study: 9% lower mortality (p=0.69) and 1% higher ventilation (p=1).
Retrospective 160 ICU patients, 32 with raised neutrophil/lymphocyte ratio treated with vitamin C, showing no significant differences.

Jul 2021, The European Research J., https://dergipark.org.tr/en/download/article-file/1774154, https://c19p.org/ozgunay

2,148 patient aspirin prophylaxis study: 4% lower hospitalization (p=0.08) and 18% higher severe cases (p=0.28).
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with aspirin prophylaxis.

Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimere

58,529 patient proton pump inhibitor prophylaxis study: 7% lower mortality (p=0.12) and 4% higher hospitalization (p=0.32).
Retrospective 433,609 COVID-19 patients in Croatia showing no significant difference in mortality or hospitalization risk with proton-pump inhibitor (PPI) use before COVID-19 diagnosis compared to matched controls with PPI-requiring morbidities but no PPI prescriptions. There was significantly higher hospitalization for users with 1-3 prescriptions which authors do not comment on. The classification of users and possible users may introduce confounding. Users required a PPI prescription, while possible users includes those with ≥3 NSAID prescriptions. Possible users may be OTC PPI users, and may differ significantly in NSAID use. NSAID use per group is not reported, and was not used in adjustments.

Oct 2022, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.15525, https://c19p.org/kodvanj

1,000 patient proton pump inhibitor prophylaxis study: 1% lower ICU admission (p=1) and 9% higher hospitalization (p=0.01).
Retrospective 1,000 hospitalized COVID-19 patients in New York City showing high rates of acute kidney injury, inpatient dialysis, prolonged intubation times, and length of stay compared to previous cohorts.

May 2020, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj.m1996, https://c19p.org/argenziano

40 patient saline early treatment RCT: 43% improved recovery (p=0.0004).
RCT with 20 saline and 20 control low risk patients in India, showing faster recovery with saline gargling, but no significant difference in viral clearance.

Jul 2022, Indian J. Community Medicine, https://journals.lww.com/ijcm/Fulltext/2022/47020/Impact_of_Steam_Inhalation,_Saline_Gargling,_and.12.aspx, https://c19p.org/chalagerisa

HCQ late treatment study: 52% higher mortality (p=0.58).
Retrospective hospitalized patients in Saudi Arabia showing higher mortality with most treatments although not reaching statistical significance. Confounding by indication, time, or other factors is likely (a 19x higher risk with lopinavir/ritonavir and 3.5x higher risk with azithromycin is not supported by other studies for example). The number of patients treated with HCQ is not provided.

Jul 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.07.13.21260428v1, https://c19p.org/alhamlan

75 patient montelukast late treatment study: 14% lower mortality (p=1), 90% higher ICU admission (p=0.46), and 3% shorter hospitalization (p=0.81).
Retrospective 75 hospitalized COVID-19 patients over 60 in Turkey showing no significant differences with montelukast treatment.

Aug 2024, Genel Tıp Dergisi, http://dergipark.org.tr/en/doi/10.54005/geneltip.1352153, https://c19p.org/zengin2

17 patient HCQ prophylaxis study: 43% higher ICU admission (p=1).
Retrospective 17 rheumatoid arthritis COVID-19+ patients, 7 on HCQ treatment, showing no significant differences. They study reports only including hospitalized patients, but the results include non-hospitalized patients. Results do not reflect potential difference in the probability that a case is serious enough to have been tested and identified. Few group details are provided (even the age of patients in each group is not specified).

Jul 2021, Research Square, https://www.researchsquare.com/article/rs-43812/v1, https://c19p.org/kucukakkas

aspirin prophylaxis study: 13% higher mortality (p=0.38), 3% lower hospitalization (p=0.64), no change in progression (p=0.98), and 8% fewer cases (p=0.02).
Population-based case-control study of 86,602 people in Spain, shower lower risk of COVID-19 cases with low-dose aspirin, but no significant difference for severity, hospitalization, or mortality.

Jan 2024, Revista Española de Cardiología, https://www.sciencedirect.com/science/article/pii/S1885585724000148, https://c19p.org/prietocampo

HCQ late treatment study: 8% higher mortality (p=0.13).
Retrospective database analysis of 64,781 hospitalized patients in the USA, showing lower mortality with vitamin C or vitamin D (authors do not distinguish between the two), and higher mortality with zinc and HCQ, statistically significant for zinc. Authors excluded hospital-based outpatient visits, without explanation. Confounding by indication is likely, adjustments do not appear to include any information on COVID-19 severity at baseline.

Dec 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2773971, https://c19p.org/rosenthal

zinc late treatment study: 16% higher mortality (p=0.003).
Retrospective database analysis of 64,781 hospitalized patients in the USA, showing lower mortality with vitamin C or vitamin D (authors do not distinguish between the two), and higher mortality with zinc and HCQ, statistically significant for zinc. Authors excluded hospital-based outpatient visits, without explanation. Confounding by indication is likely, adjustments do not appear to include any information on COVID-19 severity at baseline.

Dec 2020, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2773971, https://c19p.org/rosenthalz

acetaminophen early treatment study: 15% worse results (p=0.61).
Retrospective 1,824 hospitalized COVID-19 patients in South Korea, showing higher progression to combined death, ICU, ventilation, or sepsis (4% versus 0%, group sizes not provided) with paracetamol vs. NSAIDs. Treatment time may vary - exposure was defined as 7 days before and including cohort entry in hospitalized COVID-19 patients.

Jul 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/73/11/e4179/5876905, https://c19p.org/jeong

various antiandrogen prophylaxis study: 23% higher combined mortality/ICU admission (p=0.33).
Retrospective case-control study in Italy with 943 male COVID-19 patients, 45 on chronic 5ARI treatment (finasteride/dutasteride). There was significantly fewer COVID-19 patients >55 on 5ARI treatment compared to age-matched controls (5.57 vs. 8.14%, p=0.0083). The difference was greater for men aged >65 (7.14 vs. 12.31%, p=0.0001). There was no significant difference for ICU admission or death.

Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.04.20.20068056v2, https://c19p.org/lazzeri

1,811 patient alcohol study: 28% higher PASC (p=0.4).
Retrospective 1,811 COVID-19 patients in the UK, showing no significant difference in self-reported long COVID based on having ≤14 vs. >14 alcoholic drinks per week in the month before infection.

Apr 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.04.12.22273792, https://c19p.org/paulac

401 patient vitamin C late treatment RCT: 20% lower mortality (p=0.64), 200% higher ventilation (p=1), and 33% higher ICU admission (p=0.79).
RCT 401 hospitalized COVID-19 patients showing no significant differences with low-dose oral vitamin C (1000mg daily for 5 days).

Jul 2023, Disease and Diagnosis, https://ddj.hums.ac.ir/Article/ddj-500, https://c19p.org/mousaviasl

717 patient ivermectin early treatment study: 14% higher hospitalization (p=0.53).
Retrospective 717 patients in Brazil showing OR 1.17 [0.72-1.90] for ivermectin. This paper focuses on HCQ, event counts for ivermectin are not provided. With significant correlation between the variables used, including overlap in the prescription of multiple treatments that show efficacy alone, and limited data for the model size, the model used here may be inaccurate due to multicollinearity [statisticsbyjim.com].

Oct 2020, Travel Medicine and Infectious Disease, https://www.sciencedirect.com/science/article/abs/pii/S1477893920304026, https://c19p.org/fonsecai

aspirin prophylaxis PSM study: 31% higher mortality (p=0.04).
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.

Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatoroe

cannabidiol prophylaxis study: 24% more cases (p=0.009).
UK Biobank retrospective showing a higher risk of COVID-19 cases with a history of cannabis use.

Jun 2022, Chronic Diseases and Translational Medicine, https://onlinelibrary.wiley.com/doi/10.1002/cdt3.38, https://c19p.org/lehrer2

acetaminophen early treatment study: 15% higher combined mortality/hospitalization (p=0.22).
Retrospective paracetamol use with a primary care database in Italy, showing no significant difference in hospitalization/death for use 0-3 and 4-7 days from diagnosis, and significantly higher risk for use >7 days from diagnosis. Confounding by indication may have a greater effect on late usage.

Jul 2022, Internal and Emergency Medicine, https://link.springer.com/10.1007/s11739-022-03054-1, https://c19p.org/lapi

5,783 patient acetaminophen late treatment study: 27% higher mortality (p=0.1).
Retrospective 5,783 hospitalized patients in France, showing higher mortality with paracetamol use, without statistical significance.

Mar 2022, JMIR Medical Informatics, https://medinform.jmir.org/2022/3/e35190, https://c19p.org/lerner

acetaminophen prophylaxis study: 48% more cases (p<0.0001).
Retrospective 26,121 cases and 2,369,020 controls ≥65yo in Canada, showing higher cases with chronic use of acetaminophen.

Mar 2022, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofac156/6555707, https://c19p.org/macfaddenace

397,064 patient acetaminophen prophylaxis study: 23% more cases (p=0.009).
397,064 patient UK Biobank retrospective showing higher risk of COVID-19 with acetaminophen use.

Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241264, https://c19p.org/kolin

125 patient HCQ ICU study: 14% higher mortality (p=0.44).
Retrospective 125 mechanically ventilated ICU patients in Iran, showing no significant difference with HCQ treatment in unadjusted results.

Mar 2022, Research Square, https://www.researchsquare.com/article/rs-1362678/v1, https://c19p.org/salehih

186 patient HCQ late treatment study: 45% higher mortality (p=0.07).
Retrospective 186 hospitalized patients in Pakistan showing unadjusted HCQ mortality RR 1.45, p = 0.07. Confounding by indication is likely.

Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.28.20248920v1, https://c19p.org/sarfaraz

183 patient HCQ late treatment study: 39% higher mortality (p=0.51).
Retrospective 183 hospitalized pediatric COVID-19 patients in Iran, showing no significant difference in mortality with in unadjusted results.

Jul 2023, Canadian J. Infectious Diseases and Medical Microbiology, https://www.hindawi.com/journals/cjidmm/2023/5205188/, https://c19p.org/shamsih

538 patient favipiravir ICU study: 7% lower mortality (p=0.49), 9% higher ARDS (p=0.63), 34% longer ICU admission (p=0.001), and 37% longer hospitalization (p=0.001).
Retrospective 269 favipiravir ICU patients in Saudi Arabia and 269 matched controls receiving different treatments, showing no significant difference.

Feb 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034122000259, https://c19p.org/almutair

96 patient degarelix antiandrogen late treatment RCT: 18% lower mortality (p=0.66), 19% higher ventilation (p=0.7), 17% worse results (p=0.7), and 20% longer hospitalization (p=0.94).
Early terminated RCT with 62 very late stage (79% on oxygen) degarelix patients and 34 placebo patients, showing no significant differences with treatment. For discussion of many issues with this study see [twitter.com].

Apr 2022, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2791293, https://c19p.org/nickols

13,099 patient cannabidiol prophylaxis study: 181% higher mortality (p=0.04) and 19% fewer cases (p=0.0001).
UK Biobank retrospective with 13,099 cannabis users, showing a lower risk of COVID-19 infection, however regular users had a significantly higher risk of mortality.

Mar 2022, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2022.829715/abstract, https://c19p.org/huang2

154 patient proton pump inhibitor prophylaxis PSM study: 11% longer hospitalization (p=0.29), 6% higher hospital discharge (p=0.82), and 37% improved viral clearance (p=0.05).
Retrospective 154 hospitalized moderate COVID-19 patients in China showing no significant difference in viral clearance time or hospital stay duration with proton pump inhibitor (PPI) use. There was no association between PPI use and viral clearance or hospital stay duration in univariate or multivariate analysis. The same results were obtained after propensity score matching.

Feb 2021, J. Inflammation Research, https://www.dovepress.com/analysis-of-the-effect-of-proton-pump-inhibitors-on-the-course-of-covi-peer-reviewed-article-JIR, https://c19p.org/zhang30

446 patient HCQ late treatment PSM study: 17% lower mortality (p=1) and 75% higher combined mortality/intubation (p=0.24).
Retrospective analysis of acute care patients in Bahrain not showing a significant effect of HCQ. Confounding by indication is likely. Matching appears not to have matched for baseline severity. 17.5% of HCQ patients required oxygen while only 12.6% of control patients did.

Nov 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.11.25.20234914v1, https://c19p.org/abdulrahman

603 patient vitamin C prophylaxis study: 44% more cases (p=0.002).
Retrospective 603 patients in Iran, 34 taking vitamin C supplements, showing increased risk of COVID-19 cases in unadjusted results. IR.SHOUSHTAR.REC.1399.015.

Aug 2021, Nutrition & Food Science, https://www.emerald.com/insight/content/doi/10.1108/NFS-11-2020-0421/full/html, https://c19p.org/mohsenic

103 patient acetaminophen prophylaxis study: 47% higher mortality (p=0.42) and 23% lower severe cases (p=0.55).
Analysis of 103 elderly hospitalized COVID-19 patients in Spain, showing higher mortality with acetaminophen, without statistical significance.

Apr 2021, Gerontology, https://www.karger.com/Article/FullText/515159, https://c19p.org/galvezbarron

459 patient aspirin late treatment study: 28% higher mortality (p=0.52).
Retrospective 459 patients in Iran, 53 treated with aspirin, showing no significant difference with treatment.

Sep 2020, The Tohoku J. Experimental Medicine, https://www.jstage.jst.go.jp/article/tjem/252/1/252_73/_article/-char/ja/, https://c19p.org/alamdarie

60 patient vitamin C late treatment RCT: 25% higher ventilation (p=1) and 31% longer hospitalization (p=0.03).
Small late stage RCT for the addition of vitamin C to HCQ and lopinavir/ritonavir, with 30 treatment and 30 control patients, finding a significant reduction in temperature and a significant improvement in oxygenation after 3 days in the vitamin C group. However, hospitalization time was longer and there was no significant difference in mortality.

Jan 2021, Research Square, https://www.researchsquare.com/article/rs-139942/v1, https://c19p.org/jamalimoghadamsiahkali

proton pump inhibitor prophylaxis PSM study: 17% higher mortality (p=0.69) and 22% more cases (p=0.15).
PSM retrospective 9,469 UK Biobank participants tested for COVID-19, showing no significant association between proton pump inhibitor (PPI) or histamine-2 receptor antagonist (H2RA) use and risk of SARS-CoV-2 infection or COVID-19 mortality. Omeprazole was associated with higher risk of cases in patients with upper gastrointestinal diseases. The results for patients with upper gastrointestinal diseases should be more accurate due to reduced confounding and more accurate ascertainment of current use.

Jan 2021, Gastroenterology, https://www.sciencedirect.com/science/article/pii/S0016508520352094, https://c19p.org/fan4

299 patient HCQ late treatment RCT: 15% higher mortality (p=0.7) and 24% improved viral clearance (p=0.68).
Early terminated very late stage (95% on oxygen at baseline) DISCOVERY trial. 4% more patients were on ventilation at baseline in the HCQ group. This preprint presents more recent results than the earlier journal article.

Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2022.02.16.22271064, https://c19p.org/discovery

32 patient ivermectin late treatment RCT: 8% lower hospital discharge (p=1) and 8% worse viral clearance (p=1).
Small RCT of hospitalized patients in India with 19 ivermectin patients and 13 control patients, with all receiving SOC including HCQ, showing no significant differences. The patient population is biased because the study recruited patients that did not respond to standard treatment. Authors do not specify the treatment delay but it is likely relatively late because the patients had already undergone standard treatment. Criteria for discharge are not provided. The time of discharge status is not specified and may not have been an equal time since treatment initiation for all patients. Authors indicate 19 treatment and 16 control patients, but the results only show 13 control patients. Authors do not indicate why the other 3 are missing. Randomization in this small sample resulted in very large differences in the groups, with over twice as many in the ivermectin group with age >40, and the only 2 patients with age >60 both in the ivermectin group. Authors did not adjust for these..

Aug 2020, Paripex - Indian J. Research, https://www.worldwidejournals.com/paripex/recent_issues_pdf/2020/August/ivermectin-as-adjuvant-to-hydroxycholoroquine-in-patients-resistant-to-standard-treatment-for-sarscov2-results-of-an-openlabel-randomized-clinical-study_August_2020_1597492974_4801859.pdf, https://c19p.org/kishoria

32 patient vitamin C ICU PSM study: 11% higher mortality (p=1).
PSM retrospective 8 ICU patients treated with vitamin C and 24 matched controls, showing no significant difference. Authors note that "it is possible for the delayed timing of IV vitamin C to have blunted the beneficial effects as these patients may have already progressed to the late fibroproliferative phase or ARDS". IV vitamin C 1.5 grams every 6 hours.

Jun 2021, J. Pharmacy Practice, https://journals.sagepub.com/doi/10.1177/08971900211015052, https://c19p.org/li7

211 patient exercise study: 6% higher hospitalization (p=0.6) and 35% lower severe cases (p=0.3).
Retrospective 263 COVID+ patients, showing lower hospitalization with higher self-reported cardiorespiratory fitness, but no significant differences for physical activity. Participants in the study were healthier and more fit than the general population.

Jun 2021, J. Physical Activity and Health, https://journals.humankinetics.com/view/journals/jpah/18/7/article-p782.xml, https://c19p.org/brandenburg

9 patient HCQ prophylaxis study: 75% lower hospitalization (p=0.23).
Retrospective 9 COVID-19 patients with antiphospholipid syndrome in Turkey, showing no significant differences based on existing HCQ treatment.

Jan 2022, Bratislava Medical J., http://www.elis.sk/index.php?page=shop.product_details&flypage=flypage.tpl&product_id=7533&category_id=179&option=com_virtuemart&vmcchk=1&Itemid=1, https://c19p.org/erden

8,570 patient vitamin B9 prophylaxis study: 87% higher mortality (p<0.0001).
Retrospective 8,570 individuals in Spain and Italy, showing higher mortality with combined vitamin B9 and B12 supplementation. Adjustments only considered age.

Nov 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/22/11786, https://c19p.org/bliekbuenob9

85 patient HCQ late treatment study: 21% slower viral clearance (p=0.05).
Retrospective 65 HCQ+AZ, 20 control patients, showing median time to negative PCR of 23 days for HCQ+AZ vs. 19 days for control. Confounding by indication. 100% of non-HCQ group had mild disease vs. 63% of the HCQ+AZ group. More comorbidities and symptoms in the HCQ+AZ group.

Aug 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.05.20151027v1, https://c19p.org/saleemi

colchicine prophylaxis study: 37% higher mortality (p=0.57) and 137% higher hospitalization (p=0.2).
Retrospective 9,379 patients attending a rheumatology outpatient clinic in Spain, showing higher mortality and hospitalization with colchicine use, without statistical significance.

Jan 2021, Therapeutic Advances in Musculoskeletal Disease, http://journals.sagepub.com/doi/10.1177/1759720X211002684, https://c19p.org/madridgarcia

43 patient vitamin C ICU study: 5% higher mortality (p=1).
Retrospective 43 ICU patients in Turkey, 21 treated with vitamin C, showing no significant difference in mortality and increased renal failure. Treatment included stage 1 AKI patients. Vitamin C 45-50 g/day for 5 days.

Sep 2022, Kastamonu Medical J., https://www.kastamonumedicaljournal.com/index.php/kmj/article/view/59, https://c19p.org/ozgultekin

5,413 patient ivermectin late treatment RCT: 36% lower long COVID and 16% faster recovery despite very late treatment, low-risk patients, and poor administration. Probability of superiority > 0.999.
Significantly improved recovery and significantly lower risk of long COVID with ivermectin, despite very late treatment, low-risk patients, and poor administration. 36% lower ongoing persistent COVID-19 specific symptoms, p 0.999), missing from the abstract (details below). The p values for sustained recovery, early sustained recovery, alleviation of all symptoms, and sustained alleviation are all The efficacy seen for ivermectin here is despite the trial being the most clearly designed to fail trial, with major bias in design, operation, analysis, and reporting. This trial is a great example of bias in clinical trials which will be covered in detail in the future. c19 early .org Molnupiravir PANORAMIC [ Gbinigie , isrctn.com ] Ivermectin PRINCIPLE [ isrctn.com (B) ] Investigator Prof. Chris Butler Prof. Chris Butler Delay ≤5 days from onset median 2 days ≤14 days from onset median unknown Population 50+ or 18+ w/comorbidities 18+ (mid-trial change) Treatment 5 days, 2x per day 3..

Feb 2024, J. Infection, https://www.sciencedirect.com/science/article/pii/S0163445324000641, https://c19p.org/principleivm

598 patient favipiravir late treatment study: 263% higher mortality (p=0.04), 41% lower need for oxygen therapy (p<0.0001), and 40% longer hospitalization (p=0.03).
Prospective observational study of 598 hospitalized patients in Saudi Arabia, showing higher risk of mortality and longer hospitalization time with favipiravir.

Mar 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.826247/full, https://c19p.org/almuhsen

188 patient ivermectin late treatment study: 9% higher mortality (p=1) and 8% longer hospitalization (p=0.4).
Retrospective 188 hospitalized patients in Pakistan, 90 treated with ivermectin, showing no significant differences with treatment. The ivermectin group had more severe disease (66% vs 58%, with 6x higher risk for severe disease patients), and more male patients (70% vs. 65%). Higher use of remdesivir and steroids in the ivermectin group also suggests that ivermectin was more likely to be given to patients in more severe condition. There were no side effects seen with ivermectin. Authors note that significantly improved ferritin levels were seen with treatment. Authors state that ivermectin patients received 2 12mg doses, 24 hours apart, but later state that the dosage was not standardized.

Jan 2022, Monaldi Archives for Chest Disease, https://monaldi-archives.org/index.php/macd/article/download/2062/1397, https://c19p.org/zubair

favipiravir early treatment study: 227% higher progression (p=0.005).
Retrospective 514 patients in Thailand, showing higher risk of progression with favipiravir treatment.

Sep 2022, Tropical Medicine and Infectious Disease, https://www.mdpi.com/2414-6366/7/9/238, https://c19p.org/bruminhent

35 patient budesonide late treatment RCT: 7% higher mortality (p=1) and 20% shorter hospitalization.
Small RCT 49 severe condition hospitalized patients in Syria, showing lower mortality with colchicine and shorter hospitalization time with both colchicine and budesonide (all of these are not statistically significant).

Dec 2021, Interdisciplinary Perspectives on Infectious Diseases, https://www.hindawi.com/journals/ipid/2021/2129006/, https://c19p.org/alsultan

430 patient aspirin late treatment study: 70% higher mortality (p=0.02).
Retrospective 430 hospitalized COVID-19 patients with type 2 diabetes in Poland showing lower mortality with metformin and higher mortality with remdesivir, convalescent plasma, and aspirin in univariable analysis. These results were not statistically significant except for aspirin, and no baseline information per treatment is provided to assess confounding.

Mar 2024, Biomedicines, https://www.mdpi.com/2227-9059/12/3/605, https://c19p.org/lewandowski2e

vitamin B9 prophylaxis PSM study: 132% higher mortality (p=0.003).
PSM retrospective 3,712 hospitalized patients in Spain, showing lower mortality with existing use of azithromycin, bemiparine, budesonide-formoterol fumarate, cefuroxime, colchicine, enoxaparin, ipratropium bromide, loratadine, mepyramine theophylline acetate, oral rehydration salts, and salbutamol sulphate, and higher mortality with acetylsalicylic acid, digoxin, folic acid, mirtazapine, linagliptin, enalapril, atorvastatin, and allopurinol.

Jan 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/1/78, https://c19p.org/monserratvillatorob9

1,357 patient proton pump inhibitor prophylaxis study: 124% higher mortality (p<0.0001).
In Vitro study showing lower pH increased ACE2 expression and viral load on SARS-CoV-2 infection, and retrospective study showing proton pump inhibitor use, which is correlated with low gastric pH-related diseases, was associated with higher mortality.

Aug 2021, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2021.637885/full, https://c19p.org/jimenez2ppi

67 patient aspirin late treatment study: 8% higher ventilation (p=0.93).
Retrospective 225 hospitalized patients in Egypt, showing significantly lower thromboembolic events with aspirin treatment, but no significant difference in the need for mechanical ventilation.

Jul 2021, Clinical Drug Investigation, https://link.springer.com/article/10.1007/s40261-021-01061-2, https://c19p.org/abdelwahab

48 patient HCQ late treatment study: 2% higher mortality (p=0.99).
Analysis of hospitalized lung cancer patients with 35 of 48 taking HCQ, mortality OR 1.03, p = 0.99.

Jun 2020, Annals of Oncology, 1386-1396, https://www.annalsofoncology.org/article/S0923-7534(20)39894-X/fulltext, https://c19p.org/luo

74 patient HCQ late treatment PSM study: 400% higher mortality (p=0.49), 43% shorter hospitalization (p=0.63), and 29% higher hospital discharge (p=0.74).
Retrospective 200 hospitalized COVID-19 patients in Saudi Arabia, showing no significant difference in outcomes between HCQ and favipiravir.

Nov 2022, Pharmaceuticals, https://www.mdpi.com/1424-8247/15/12/1456, https://c19p.org/alosaimi

56 patient HCQ ICU study: 11% higher mortality (p=1).
Small retrospective study of 56 ICU patients in Mexico showing HCQ RR 1.1, p = 1.0.

Jun 2020, Cir Cir. 2020, 569-575, https://cirugiaycirujanos.com/frame_esp.php?id=358, https://c19p.org/sosagarcia

134 patient colchicine late treatment study: 7% higher mortality (p=0.83).
Retrospective 134 hospitalized COVID-19 patients in India, showing no significant difference with colchicine treatment in unadjusted results.

Dec 2020, Indian J. Critical Care Medicine, https://www.ijccm.org/doi/pdf/10.5005/jp-journals-10071-23599, https://c19p.org/mahale

166 patient azvudine late treatment study: 13% higher mortality (p=0.85).
Retrospective 166 hospitalized NSCLC patients with COVID-19 showing no significant difference in mortality with paxlovid or azvudine in univariate analysis.

Jan 2024, Technology in Cancer Research & Treatment, https://journals.sagepub.com/doi/10.1177/15330338241248573, https://c19p.org/peng4azv

543 patient vitamin D late treatment RCT: 44% higher mortality (p=0.31), 5% higher ICU admission (p=0.82), and 5% longer hospitalization.
RCT 274 very late stage (>80% pulmonary involvement at baseline) hospitalized COVID-19 patients treated with a single dose of cholecalciferol, and 269 control patients, showing no significant differences. High serum calcidiol levels at admission were associated with lower pulmonary involvement, shorter hospitalization, and lower ICU admission. Serum levels increased in the treatment group, however average levels were still insufficient at discharge. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more successful, especially with this very late stage usage. 100,000IU cholecalciferol.

Feb 2022, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-022-02290-8, https://c19p.org/cannataandia

149 patient aspirin ICU study: 10% higher mortality (p=0.43).
Retrospective 149 patients under invasive mechanical ventilation in Germany showing no significant difference in mortality with aspirin prophylaxis in unadjusted results.

Mar 2023, Scientific Reports, https://www.nature.com/articles/s41598-023-31944-7, https://c19p.org/aweimere

643 patient HCQ late treatment study: 18% higher mortality (p=0.17).
Retrospective database analysis of 7,816 Veterans Affairs hospitalized patients analyzing progression to ARDS and 30-day mortality from ARDS. Confounding by indication is likely. Chronological bias is likely, with HCQ more likely to be used earlier on, before significant improvements in overall treatment. No results are provided for HCQ for progression to ARDS.

Oct 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.10.16.20214130v1, https://c19p.org/solh

5,338 patient various antiandrogen prophylaxis study: 2% lower mortality (p=0.94), 28% higher ICU admission (p=0.28), and 23% higher hospitalization (p=0.09).
Retrospective 7,894 COVID+ prostate cancer patients, analyzing patients on antiandrogen treatment, ADT, and ADT + abiraterone acetate or enzalutamide, showing mixed results and higher mortality for ADT + abiraterone acetate or enzalutamide. This paper also includes a small RCT which is listed separately, and an In Vitro HBEC study showing no significant differences (p = 0.084). The supplementary data is not currently available. NCT04475601. For discussion of issues with this study see [sciencedirect.com, sciencedirect.com, sciencedirect.com, sciencedirect.com].

Dec 2021, European Urology, https://www.europeanurology.com/article/S0302-2838(21)02224-7/fulltext, https://c19p.org/welen2

2,468 patient aspirin late treatment study: 32% higher mortality (p=0.04).
Prospective study of 2,468 hospitalized COVID-19 patients in Iran, showing higher mortality with aspirin treatment. IR.MUQ.REC.1399.013.

May 2021, Research Square, https://www.researchsquare.com/article/rs-365321/v2, https://c19p.org/pourhoseingholie

106 patient vitamin D prophylaxis study: 25% more cases (p=0.56).
Analysis of vitamin D and zinc levels in 53 PCR+ outpatients and 53 matched controls, showing lower zinc levels in COVID-19 patients, and increased risk of cases and symptoms with vitamin D deficiency. There was no significant difference in the use of supplements between cases and controls. IR.ABADANUMS.REC.1399.073.

Aug 2021, Nutrients, https://www.mdpi.com/2072-6643/13/10/3368, https://c19p.org/golabi2

283 patient zinc late treatment study: 41% higher mortality (p=0.33).
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments.

Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiyaz

271 patient HCQ late treatment study: 5% higher mortality (p=0.89).
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments. Time based confounding is likely because HCQ became increasingly controversial and less used over the time covered (March 1 to May 31, 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved.

Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiya

281 patient vitamin C late treatment study: 1% higher mortality (p=0.99).
Retrospective 283 patients in the USA showing higher mortality with all treatments (not statistically significant). Confounding by indication is likely. In the supplementary appendix, authors note that the treatments were usually given for patients that required oxygen therapy. Oxygen therapy and ICU admission (possibly, the paper includes ICU admission for model 2 in some places but not others) were the only variables indicating severity used in adjustments.

Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042549.info, https://c19p.org/gadhiyac

84 patient HCQ late treatment PSM study: 200% higher mortality (p=1), 67% lower ICU admission (p=1), and 10% shorter hospitalization (p=0.9).
PSM retrospective 260 late stage hospitalized COVID-19 pneumonia patients in Turkey, showing no significant difference between favipiravir and HCQ.

Mar 2022, Acta Medica, https://actamedica.org/index.php/actamedica/article/view/719, https://c19p.org/uyaroglu

vitamin C early treatment study: 135% higher progression (p=0.18) and 34% slower improvement (p=0.04).
Retrospective 616 patients in China showing increased risk of disease progression with vitamin C treatment.

Dec 2020, BioScience Trends, https://www.jstage.jst.go.jp/article/bst/advpub/0/advpub_2020.03340/_article/-char/ja/, https://c19p.org/suc

37 patient HCQ late treatment study: 40% slower viral clearance (p=0.06).
Small retrospective database analysis of 37 late stage patients hospitalized in an intensive care center in China, not finding a significant difference in viral shedding. Pateints were all in serious condition. There was only one death however the group is not specified. Confounding by indication is likely.

Jan 2021, Research Square, https://www.researchsquare.com/article/rs-119202/v1, https://c19p.org/li2

313 patient HCQ late treatment study: 6% higher mortality (p=0.77).
Retrospective 313 patients, mostly critical stage and mostly requiring respiratory support, showing unadjusted RR 1.06, p = 0.77. Confounding by indication likely.

Nov 2020, Mayo Clinic Proceedings: Innovations, Quality & Outcomes, https://www.sciencedirect.com/science/article/pii/S2542454820302071, https://c19p.org/rodrigueznava

190 patient N-acetylcysteine ICU study: 13% higher mortality (p=0.47), 20% higher ventilation (p=0.25), 12% shorter ICU admission (p=0.58), and 13% shorter hospitalization (p=0.09).
Retrospective 190 critical COVID-19 patients in Turkey, showing no significant differences with N-acetylcysteine treatment in unadjusted results with no baseline details. NAC 2400mg/day.

Oct 2022, Aksaray Üniversitesi Tıp Bilimleri Dergisi, https://dergipark.org.tr/en/pub/asujms/issue/73171/1062868, https://c19p.org/cavus

60,334 patient HCQ prophylaxis study: 44% higher hospitalization (p=0.25) and 10% fewer cases (p=0.23).
Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for example saying that "currently, no obvious connection exists between a known rheumatological disorder and the risk of contracting SARS-CoV-2". Many papers show that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, e.g., Ferri et al. show OR 4.42, p<0.001 [Ferri]. Supplementary data is not currently available.

May 2021, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971221004781, https://c19p.org/kamstrup

27 patient vitamin A late treatment study: 282% higher mortality (p=0.001).
Retrospective 27 severe COVID-19 patients and 23 non-COVID-19 patients, showing significantly lower vitamin A levels in COVID-19 patients (0.37mg/L vs. 0.52 mg/L, p<0.001). 10 of 27 COVID-19 patients received vitamin A, with higher mortality. Group details are not provided but authors note that 8 of 10 had comorbidities.

Jan 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.01.30.21250844v1, https://c19p.org/sarohan

175 patient HCQ late treatment study: 15% higher mortality (p=0.72).
Retrospective 175 hospitalized COVID-19 patients in the USA, showing no significant difference in mortality with HCQ. Authors note that "patients treated with HCQ in our cohort were more likely to be sicker at baseline".

Nov 2020, HCA Healthcare J. Medicine, https://scholarlycommons.hcahealthcare.com/hcahealthcarejournal/vol1/iss0/20, https://c19p.org/aboulenain

1,215 patient HCQ late treatment study: 24% higher mortality (p=0.32).
Retrospective 1,215 hospitalized patients in the Phillipines, showing no significant difference in outcomes with remdesivir or HCQ use in unadjusted results subject to confounding by indication.

Jul 2022, IJID Regions, https://www.sciencedirect.com/science/article/pii/S2772707622000935, https://c19p.org/malundo

903 patient HCQ late treatment study: 37% higher mortality (p=0.28).
Convalescent plasma study also showing mortality based on HCQ treatment, unadjusted hazard ratio uHR 1.37, p = 0.28. Confounding by indication is likely.

Nov 2020, The American J. Pathology, https://www.sciencedirect.com/science/article/pii/S0002944020304892, https://c19p.org/salazar

36 patient HCQ late treatment study: 25% worse viral load (p=0.45).
Small late stage (7-10 days post symptoms) study of nasal swab RNA with 12 control and 33 patients, showing no significant differences (significant reduction in viral load is seen in both groups). The groups are not comparable, with significant differences seen between hospitalized and non-hospitalized patients. 9 of 10 hospitalized patients were in the HCQ group and only one in the control group. 2 additional control patients were added between the first and second version of this preprint (including the only hospitalized control patient).

Jun 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.06.30.20143289v1, https://c19p.org/komissarov

89 patient budesonide late treatment RCT: 23% higher mortality (p=1) and 39% lower progression (p=0.69).
Small early-terminated RCT with 40 inhaled budesonide and 49 control patients, showing no significant differences. 400µg/12h via Pulmicort Turbuhaler.

Feb 2022, European Respiratory J., https://erj.ersjournals.com/content/early/2022/01/13/13993003.03036-2021, https://c19p.org/agusti2

689 patient aspirin prophylaxis study: 34% higher combined mortality/ICU admission (p=0.09).
Retrospective 689 hospitalized COVID-19 patients in Denmark, showing higher risk of ICU/death with aspirin use in unadjusted results subject to confounding by indication.

May 2020, J. Hypertension, https://journals.lww.com/10.1097/HJH.0000000000002515, https://c19p.org/holt2e

49 patient camostat early treatment RCT: 35% improved recovery (p=0.24), 86% improvement (p=0.11), and 41% improved viral clearance (p=0.24).
RCT 49 outpatients in the USA, showing no significant differences with camostat treatment.

May 2021, NCT04524663, https://clinicaltrials.gov/study/NCT04524663, https://c19p.org/parsonnet

185 patient budesonide late treatment study: 11% higher mortality (p=0.85).
Retrospective 185 hospitalized COVID-19 patients in China, showing no significant difference in mortality with budesonide use in unadjusted results.

Aug 2022, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2022-0569/html, https://c19p.org/yang3

165 patient HCQ prophylaxis study: 50% more cases (p=0.59).
Survey of 165 SLE patients, 127 on HCQ. 8 patients with suspected COVID-19 and 4 confirmed cases. No mortality, one ICU case. 7 patients had no symptoms despite contact with a COVID-19 patient. No adjustment for concomitant medications or severity of SLE. Confounding by indication.

May 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/05/23/annrheumdis-2020-217717.info, https://c19p.org/cassione

171 patient HCQ ICU study: 39% higher mortality (p=0.52).
Retrospective 171 ICU patients in Saudi Arabia showing no significant difference for HCQ treatment in unadjusted results.

Aug 2021, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016421001559, https://c19p.org/alghamdi2

176 patient HCQ late treatment study: 38% higher mortality (p=0.54).
Retrospective 176 hospitalized patients (144 HCQ, 32 control) showing no significant differences with HCQ or TCZ. Confounding by indication.

Aug 2020, J. Medical Internet Research, https://www.jmir.org/2020/9/e21758/, https://c19p.org/roomi

24 patient povidone-iodine late treatment RCT: 27% worse recovery (p=1) and no change in viral clearance (p=1).
Very late treatment (7 days from onset) RCT comparing 11 & 13 PVP-I (0.5% and 2%), and 11 saline spray patients in the USA, showing no significant differences. There was no control group (saline is likely not a placebo, showing efficacy in other trials). There are large unadjusted differences between groups, e.g. 7.1 days from onset for PVP-I versus 4.8 for saline. Baseline Ct was higher for PVP-I, providing less room for improvement. Authors note that they cannot determine if earlier use is more beneficial.

Oct 2021, Laryngoscope, https://onlinelibrary.wiley.com/doi/abs/10.1002/lary.29935, https://c19p.org/zarabanda

324 patient azvudine late treatment study: 42% higher mortality (p=0.64).
Retrospective 324 hospitalized kidney transplant recipients with COVID-19 showing no significant benefit with molnupiravir, paxlovid, or azvudine. The study was conducted during the omicron wave in China between December 2022 and January 2023. Adjusted results are only provided for all antivirals combined, however the results are similar before and after adjustment. Multivariable Cox regression analysis for all antivirals combined showed an adjusted hazard ratio for mortality of 6.06, p=0.099. While adjustment includes factors related to baseline severity, there may be residual confounding by indication.

Jun 2024, J. Zhejiang University - SCIENCE B (Biomedicine & Biotechnology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199089/, https://c19p.org/lv3azv

397 patient vitamin C late treatment PSM study: 157% higher mortality (p=0.33) and 35% worse improvement (p=0.17).
Retrospective 397 severe COVID-19 patients in China, showing worse outcomes with vitamin C treatment, without statistical significance. IV vitamin C 2-4g/day. Subject to confounding by indication and immortal time bias. Exclusion criteria were (a) the duration of hospitalization was less than 3 days; (b) vitamin C treatment started before admission; and (c) the length of vitamin C use was less than 3 days. Includes vitamin C use started at any time during hospitalization, for many patients this was >15 days later (Figure A2). Duration of treatment varied widely (Figure A1). Treatment was determined by clinicians according to the condition of each patient.

Sep 2021, Open Medicine, https://www.degruyter.com/document/doi/10.1515/med-2021-0361/html, https://c19p.org/zheng

63 patient HCQ late treatment study: 147% higher mortality (p=0.58).
Small retrospective study with 63 patients (32 treated with HCQ), showing no effectiveness, however the baseline state of each arm significantly differs. This preprint was submitted to NEJM but has not been published several months later.

Apr 2020, Preprint, https://www.sefq.es/_pdfs/NEJM_Hydroxychlorquine.pdf, https://c19p.org/barbosa

100 patient colchicine early treatment RCT: 40% higher hospitalization (p=0.76) and 4% improved recovery (p=1).
RCT 150 patients in Egypt showing no significant difference in outcomes with colchicine. SOC included vitamin C, D, and zinc. Colchicine 0.5mg tid days 1-3, bid days 4-7.

Jun 2023, Research Square, https://www.researchsquare.com/article/rs-3049708/v1, https://c19p.org/hassano

31 patient acetaminophen late treatment study: 56% higher mortality (p=0.64).
Retrospective 31 hospitalized patients ≤19 with pre-existing inborn errors of immunity, showing no significant difference in mortality with acetaminophen. Only 6 patients were treated with acetaminophen.

Sep 2022, J. Allergy and Clinical Immunology, https://www.sciencedirect.com/science/article/pii/S009167492201185X, https://c19p.org/abolhassani

928 patient HCQ late treatment study: 5% higher mortality (p=0.88).
Retrospective 928 cancer patients, showing higher mortality with HCQ+AZ. The relative risks of different treatments suggest significant confounding by indication. Authors note that HCQ+AZ might not be the cause of increased mortality, but instead was given to patients with more severe COVID-19.

May 2020, Lancet, June 20, 2020, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext, https://c19p.org/kuderer

928 patient azithromycin late treatment study: 27% higher mortality (p=0.46).
Retrospective 928 cancer patients, showing higher mortality with HCQ+AZ. The relative risks of different treatments suggest significant confounding by indication. Authors note that HCQ+AZ might not be the cause of increased mortality, but instead was given to patients with more severe COVID-19.

May 2020, Lancet, June 20, 2020, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31187-9/fulltext, https://c19p.org/kudererazaz

600 patient acetaminophen early treatment study: 23% higher hospitalization (p=0.11).
Retrospective 416 non-hospitalized and 184 hospitalized COVID-19 patients in Bangladesh, showing higher acetaminophen and lower vitamin C usage for hospitalized patients. Confounding may be significant and baseline details per treatment group are not provided, however fever and symptomatic patients were more common in the non-hospitalized group. Note there is an alignment mismatch in Table 1.

Nov 2023, Molecular Mechanism Research, https://ojs.as-pub.com/index.php/MMR/article/view/133, https://c19p.org/rahman5ace

465 patient vitamin C ICU study: 12% higher mortality (p=0.15).
Prospective study of 465 COVID-19 ICU patients in Libya showing no significant differences with treatment.

Apr 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251085, https://c19p.org/elhadic

259 patient aspirin late treatment PSM study: 34% lower mortality (p=0.22), 102% higher ventilation (p=0.16), and 91% higher ICU admission (p=0.36).
Retrospective database analysis of 22,660 patients tested for COVID-19 in South Korea. There was no significant difference in cases according to aspirin use. Aspirin use before COVID-19 was related to an increased death rate and aspirin use after COVID-19 was related to a higher risk of oxygen therapy. Results for prophylaxis are listed separately [Kim].

Sep 2021, Medicina, https://www.mdpi.com/1648-9144/57/9/931, https://c19p.org/kim2b

478 patient aspirin late treatment study: 123% higher mortality (p=0.008).
Retrospective 478 moderate to severe hospitalized patients in Iran, showing higher mortality with aspirin treatment. Authors note confounding by indication for aspirin treatment.

Oct 2022, J. Pharmaceutical Care, https://publish.kne-publishing.com/index.php/JPC/article/view/10790, https://c19p.org/karimpourrazkenari2e

168 patient favipiravir early treatment RCT: 39% faster recovery (p=0.007) and 22% improved viral clearance (p=0.16).
RCT 168 patients, 112 receiving favipiravir and 56 SOC, showing shorter time to clinical improvement and faster viral clearance with favipiravir.

Oct 2020, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3696907, https://c19p.org/ruzhentsova

311 patient probiotics late treatment study: 12% lower hospital discharge (p=0.68) and 35% slower viral clearance (p=0.001).
Retrospective 311 severe condition hospitalized patients in China, 123 treated with probiotics, showing slower viral clearance and recovery with treatment. Authors note that probiotics were able to moderate immunity and decrease the incidence of secondary infections.

Mar 2021, Int. Immunopharmacology, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934664/, https://c19p.org/li10

15,227 patient metformin prophylaxis study: 27% more cases (p=0.42).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtmf

811 patient HCQ late treatment study: 35% higher mortality (p=0.46).
Retrospective 811 hospitalized COVID+ patients in Saudi Arabia, showing higher mortality with HCQ treatment in unadjusted results subject to confounding by indication.

Feb 2022, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S187603412200034X, https://c19p.org/albanghali

1,505 patient favipiravir late treatment study: 3% slower viral clearance (p=0.09).
Retrospective hospitalized patients in the United Arab Emirates, showing no significant difference in viral clearance with different combinations of HCQ, AZ, favipiravir, and lopinavir/ritonavir.

Apr 2022, Antibiotics, https://www.mdpi.com/2079-6382/11/4/498, https://c19p.org/hafeza

1,418 patient ivermectin late treatment study: 41% higher mortality (p=0.001).
Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing higher mortality with ivermectin. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22% for SpO2 >95%. The more extreme Cox result compared to the event counts also supports this. There may also be significant confounding by time with SOC changing substantially over the first few months of the pandemic. Patients may overlap with those in [Soto-Becerra]. The results in the table and text do not match.

Mar 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264789, https://c19p.org/soto

75 patient HCQ late treatment study: 70% higher mortality (p=0.69).
HCQ+AZ early in the epidemic had a fairly good success rate with few complications, 86% of HCQ patients survived and 92% of HCQ+AZ patients. Patients not receiving either had 93% survival but were not considered comparable because the treated groups were significantly more ill (100% hypoxic at admission vs. 59%) and this study does not adjust for the differences. Transition from an early intubation strategy to aggressive utilization of high flow nasal cannula and noninvasive ventilation (i.e, BiPAP) was successful in freeing up ICU resources.

Jul 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.07.17.20156521v1, https://c19p.org/mcgrail

395 patient HCQ late treatment study: 46% higher mortality (p=0.22).
Retrospective 395 hospitalized patients in Brazil, showing higher mortality with HCQ treatment, without statistical significance.

May 2022, Frontiers in Cellular and Infection Microbiology, https://www.frontiersin.org/articles/10.3389/fcimb.2022.899702/full, https://c19p.org/silva3

775 patient HCQ late treatment study: 7% higher mortality (p=0.88).
Retrospective 775 hospitalized patients in Saudi Arabia showing no significant difference. There was no adjustment for severity or comorbidities. Confounding by indication is likely.

Mar 2021, Antibiotics, https://www.mdpi.com/2079-6382/10/4/365, https://c19p.org/alghamdi

1,418 patient HCQ late treatment study: 6% higher mortality (p=0.46).
Retrospective 1,418 very late stage (46% mortality) patients in Peru, showing no significant difference with HCQ. There is strong confounding by indication, for example 48% of patients with baseline SpO2 <70% were treated compared with 22% for SpO2 >95%. There may also be significant confounding by time with SOC changing substantially over the first few months of the pandemic.

Mar 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0264789, https://c19p.org/sotoh

952 patient famotidine prophylaxis study: 34% higher severe cases (p=0.72).
Retrospective 952 COVID-19 patients in Hong Kong, showing no significant difference in severe disease with famotidine use or PPI use.

Apr 2021, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34940-4/fulltext, https://c19p.org/cheung

80 patient acetaminophen late treatment study: 19% higher PASC (p=0.62).
Retrospective 80 mild COVID-19 patients in Italy, showing no significant difference in long COVID with acetaminophen use during infection.

Apr 2023, Int. J. Molecular Sciences, https://www.mdpi.com/1422-0067/24/8/7445, https://c19p.org/stufano

831 patient aspirin late treatment study: 97% higher mortality (p=0.002).
Retrospective 831 hospitalized COVID-19 patients showing higher mortality with aspirin treatment in unadjusted results.

Aug 2024, Cureus, https://www.cureus.com/articles/263779-anticoagulant-use-in-covid-19-patients-a-longitudinal-study-from-zanjan-iran, https://c19p.org/azimipirsaraei

1,402 patient HCQ late treatment study: 22% slower viral clearance (p=0.0001).
Health insurance database analysis failing to adjust for disease severity and not finding a significant difference in time to PCR- for LPV/r and HCQ. There are large differences in severity across groups. Authors did PSM but chose not to prioritize severity, resulting in incomparable groups, e.g., baseline pneumonia of 44% in the HCQ group and 15% in the control group (after PSM). Authors note this but offer no explanation for not correcting for severity: "However, the disease severity and proportion of accompanying pneumonia were still significantly higher in the LPV/r and HCQ-group".

Oct 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220322669, https://c19p.org/choi

3,219 patient vitamin C late treatment study: 32% higher mortality (p=0.01).
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.

Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhemc

1,446 patient HCQ late treatment study: 4% higher combined mortality/intubation (p=0.76).
Before propensity matching, 38 control patients had hypertension. After propensity matching, 146 patients had hypertension (Table 1). Even if all propensity matched control patients had hypertension, the control prevalence would only be 14% compared to 49% for treatment. Since patients with hypertension are at much greater risk of mortality (HR 2.12, see [academic.oup.com]), this appears to invalidate the results. Observational study of 1,446 hospitalized patients showing no significant effect on a combined intubation/death outcome for late treatment. However, secondary analysis shows the success of HCQ was hidden by combining intubation and death - death / (combined death/intubation) for HCQ was 60% vs. control 89%, for details see: [twitter.com]. RCT recommended. No AZ or Zinc. HCQ group much sicker - patients already in mild/moderate ARDS, most of the control group not in ARDS. Control cases received other therapeutics.

May 2020, NEJM, May 7, 2020, https://www.nejm.org/doi/full/10.1056/NEJMoa2012410, https://c19p.org/geleris

1,039 patient metformin prophylaxis study: 3% more cases (p=0.87).
Retrospective 1,039 diabetes patients in Jordan, showing no significant difference in COVID-19 cases with metformin use in unadjusted results. Severity outcomes are not provided for metformin.

Sep 2023, J. Int. Medical Research, http://journals.sagepub.com/doi/10.1177/03000605231198413, https://c19p.org/farah

397 patient azithromycin late treatment RCT: 8% higher mortality (p=0.63) and 30% improvement (p=0.08).
Small RCT comparing the addition of AZ for very late stage patients on ventilation or oxygen. One notable result is that even within this extremely late stage population, results suggest increased efficacy with the addition of AZ for patients with earlier use of AZ/HCQ, OR 0.71 [0.25-2.03] (Figure S4). Patients received 8g of HCQ over 10 days, approaching the high levels used in the RECOVERY trial (9.2g over 10 days), showing significantly more adverse events than typical trials. 50% of patients were on mechanical ventilation at baseline. More than the increase in mortality at day 29 occurred on day 0, and more than 3x the increase occurred by day 2.

Sep 2020, The Lancet, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31862-6/fulltext, https://c19p.org/furtadoazaz

37 patient HCQ late treatment study: 29% worse viral clearance (p=0.7).
2 very small studies with hospitalized patients in Taiwan. RCT with 21 treatment and 12 SOC patients. No mortality, or serious adverse effects. Median time to negative RNA 5 days versus 10 days SOC, p=0.4. Risk of PCR+ at day 14, RR 0.76, p = 0.71. Small retrospective study with 12 of 28 HCQ patients and 5 of 9 in the control group being PCR- at day 14, RR 1.29, p = 0.7. The RCT and retrospective study are listed separately [Chen, Chen].

Jul 2020, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242763, https://c19p.org/chen26

1,375 patient HCQ prophylaxis study: 43% more cases (p=0.15).
Analysis of autoimmune disease patients on HCQ, compared to a control group from the general population (matched on age and sex, but not adjusted for autoimmune disease), showing non-significant differences between groups. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the mortality result becomes RR 0.35, p=0.23, suggesting a substantial benefit for HCQ treatment (as shown in other studies).

Sep 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.08.31.20185314v1, https://c19p.org/delaiglesia

57 patient nitazoxanide late treatment RCT: 11% worse recovery (p=0.73) and 5% improved viral clearance (p=0.92).
Small RCT in Nigeria with 31 nitazoxanide and atazanavir/ritonavir patients, and 26 control patients, showing no significant differences with treatment. 4 treatment group patients discontinued treatment due to the size of the tablets. Time from onset is not provided, only time from diagnosis. NACOVID. 14-day course of nitazoxanide (1000 mg b.i.d.) and atazanavir/ritonavir (300/100 mg od). NCT04459286.

Feb 2022, medRxiv, https://www.medrxiv.org/content/10.1101/2022.02.03.22270152, https://c19p.org/fowotade

44,046 patient camostat prophylaxis study: 14% more cases (p=0.84).
Retrospective database analysis showing no significant differences with camostat use.

Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2cm

102 patient ivermectin late treatment study: 54% higher combined mortality/intubation (p=0.37).
Retrospective 230 hospitalized patients in Brazil showing no significant difference with ivermectin treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors note that they do not know if treatment was started before or after ICU admission and intubation. Baseline total chest CT opacities were higher for ivermectin (20% vs. 15%). 25% of control patients were admitted within 3 days, compared to 5 days for ivermectin. Only 38% of patients in the ivermectin arm were treated within 7 days, compared to 61% for HCQ. These are consistent with ivermectin being used for more severe patients. Dosage is unknown.

Nov 2021, Revista da Associação Médica Brasileira, https://www.scielo.br/j/ramb/a/kzbmDvJqjJdQR9GfqK65CZs/, https://c19p.org/ferreira2

465 patient antiandrogen prophylaxis study: 16% higher mortality (p=0.59), 19% lower ventilation (p=0.73), 3% higher severe cases (p=0.91), and 4% lower hospitalization (p=0.9).
Retrospective 465 prostate cancer patients, showing no significant difference in COVID-19 outcomes with ADT.

May 2022, JNCI Cancer Spectrum, https://academic.oup.com/jncics/article/6/3/pkac035/6584832, https://c19p.org/shah3

481 patient azvudine early treatment study: 1% slower recovery (p=0.9).
Retrospective 481 low-risk COVID-19 patients in China showing no significant difference in recovery or symptomatic severity with azvudine, but slightly lower total viral load.

Feb 2024, J. Clinical Pharmacology and Therapeutics, https://www.medtextpublications.com/open-access/effects-of-azvudine-on-the-low-risk-patients-infected-with-covid-19-1584.pdf, https://c19p.org/jin

1,213 patient colchicine prophylaxis study: 28% higher mortality (p=0.54) and 8% lower hospitalization (p=0.83).
Retrospective 1,213 rheumatic disease patients in France, showing no significant difference with colchicine use in univariate analysis.

Mar 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1152587/full, https://c19p.org/chevaliero

3,219 patient aspirin prophylaxis study: 14% higher mortality (p=0.21).
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.

Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulheme

3,256 patient HCQ late treatment study: 48% higher mortality (p<0.0001).
Retrospective very late stage hospitalized patients in New York during the first wave, showing no significant relationship between HCQ levels and outcomes. Authors note that the patients with data were the sickest patients.

Aug 2022, British J. Clinical Pharmacology, https://onlinelibrary.wiley.com/doi/10.1111/bcp.15489, https://c19p.org/lyashchenko

15,227 patient vitamin C prophylaxis study: 3% more cases (p=0.86).
Prospective survey-based study with 15,227 people in the UK, showing lower risk of COVID-19 cases with vitamin A, vitamin D, zinc, selenium, probiotics, and inhaled corticosteroids; and higher risk with metformin and vitamin C. Statistical significance was not reached for any of these. Except for vitamin D, the results for treatments we follow were only adjusted for age, sex, duration of participation, and test frequency. NCT04330599. COVIDENCE UK.

Mar 2021, Thorax, https://thorax.bmj.com/content/early/2021/11/02/thoraxjnl-2021-217487, https://c19p.org/holtc

1,949 patient HCQ late treatment study: 9% higher mortality (p=0.57).
Retrospective study of HCQ use in 9 hospitals in the Netherlands, showing no significant difference in mortality with HCQ/CQ. Late stage (admitted to hospital with positive test or CT scan abnormalities). 4 of 7 hospitals started treatment only after further deterioration. Short cutoff (21 days) - other studies have shown treated patient cases resolved faster and more control patients remaining in hospital at this time. In the preprint, 58 of 341 control patients died. In the journal version, 53 of 353 control patients died. Significant differences between hospitals - HCQ hospitals had significantly older patients with significantly more comorbidities. Non-HCQ hospitals were "tertiary academic centres" whereas HCQ hospitals were "secondary care hospitals". Residual confounding likely. This study compares overcrowded regular hospitals with undercrowded academic hospitals. A subset of patients were excluded due to transfer to other hospitals. This introduces bias..

Aug 2020, Clinical Microbiology and Infection, https://www.clinicalmicrobiologyandinfection.com/article/S1198-743X(20)30615-7/fulltext, https://c19p.org/peters

2,215 patient HCQ late treatment study: 6% higher mortality (p=0.41).
Analysis of 2,215 intensive care unit patients showing no significant differences with this very late stage use of HCQ.

Jul 2020, JAMA Intern. Med., https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2768602, https://c19p.org/gupta

30 patient vitamin A late treatment RCT: 76% slower improvement (p=0.21) and 8% longer hospitalization (p=0.49).
RCT 30 hospitalized patients in Iran, showing no significant difference with vitamin A treatment. All patients received HCQ. 50,000 IU/day intramuscular vitamin A for up to 2 weeks.

Oct 2022, Nutrition and Health, http://journals.sagepub.com/doi/10.1177/02601060221129144, https://c19p.org/somi

40 patient curcumin late treatment RCT: 46% worse recovery (p=0.9).
Small RCT with 40 low risk patients in Iran, 20 treated with nano-curcumin, showing no significant difference in outcomes with treatment. Authors note that treatment can improve peripheral blood inflammatory indices and modulate immune response by decreasing Th1 and Th17 responses, increasing T regulatory responses, further reducing IL-17 and IFN-γ, and increasing suppressive cytokines TGF-β and IL-4.

Sep 2021, Phytotherapy Research, https://onlinelibrary.wiley.com/doi/full/10.1002/ptr.7294, https://c19p.org/hassaniazad

459 patient HCQ prophylaxis study: 2% higher hospitalization (p=1) and 3% more cases (p=0.96).
Retrospective 459 SLE, RA, SjS, or PsA patients in France, showing no significant difference with HCQ treatment. However, the statistical analysis shows significant mismatches with prior research, which may be due to overfitting with the limited data and very small number of events. For example, the analysis estimates lower risk OR 0.72 for age, and shows very different relative risks of SLE, RA, SjS, or PsA compared to other research. We note the very different distribution of diseases in the groups, for example there is a much higher prevalence of PsA in the no HCQ group. The inaccurate estimations of risk for the different diseases and for age likely makes the adjusted analysis very inaccurate.

Sep 2021, Rheumatology and Therapy, https://link.springer.com/10.1007/s40744-021-00373-1, https://c19p.org/guillaume

790 patient aspirin prophylaxis study: 29% higher mortality (p=0.02).
Retrospective 790 hospitalized type 2 diabetes patients ≥80 years old in Spain, showing higher mortality with existing aspirin use.

Dec 2020, Research Square, https://www.researchsquare.com/article/rs-133358/v1, https://c19p.org/ramosrincone

3,219 patient HCQ late treatment study: 28% higher mortality (p=0.1).
Retrospective database analysis of 3,219 hospitalized patients in the USA. Very different results in the time period analysis (Table S2), and results significantly different to other studies for the same medications (e.g., heparin OR 3.06 [2.44-3.83]) suggest significant confounding by indication and confounding by time.

Apr 2021, BMJ Open, https://bmjopen.bmj.com/content/11/4/e042042.info, https://c19p.org/mulhem

146 patient favipiravir ICU PSM study: 17% higher mortality (p=0.51), 47% longer ventilation (p=0.008), and 50% longer ICU admission (p=0.01).
PSM retrospective 1,218 COVID-19 ICU patients in Saudi Arabia, showing no significant difference in mortality, and longer ICU/MV time with favipiravir treatment.

Jun 2023, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034123002162, https://c19p.org/sulaiman2

200 patient colchicine ICU study: 33% higher mortality (p=0.33).
Retrospective 200 patients with ARDS due to COVID-19 on invasive mechanical ventilation, showing no significant difference in mortality with colchicine treatment. The Cox proportional hazards result is from [journals.plos.org].

Dec 2022, PeerJ, https://peerj.com/articles/14290, https://c19p.org/huedazavaleta2

815 patient nitric oxide ICU study: 40% higher mortality (p=0.1).
Retrospective 815 COVID-19 ICU patients in Saudi Arabia, showing significant improvement in oxygenation. There was no significant difference in mortality, and ICU and hospitalization time was longer.

Oct 2022, Critical Care, https://ccforum.biomedcentral.com/articles/10.1186/s13054-022-04158-y, https://c19p.org/alsulaiman4

188 patient HCQ late treatment study: 299% higher mortality (p=0.04).
Retrospective 188 hospitalized patients in Brazil, showing higher risk of mortality with HCQ. Relatively few patients received HCQ. The results are likely subject to confounding by indication with treatment more likely for severe cases, and severity was not used in adjustments. Confounding by time is likely, with declining use of HCQ and improving SOC over the study period.

Jul 2021, Diabetology & Metabolic Syndrome, https://dmsjournal.biomedcentral.com/articles/10.1186/s13098-021-00695-8, https://c19p.org/tamurah

1,476 patient fluvoxamine early treatment RCT: 12% lower hospitalization (p=1) and 50% lower progression (p=0.04).
Low-risk (1% hospitalization) outpatient RCT with 738 fluvoxamine + budesonide patients and 738 placebo patients, showing significantly lower hospitalization/ER visits with treatment.

Apr 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/epdf/10.7326/M22-3305, https://c19p.org/reis10

1,476 patient budesonide early treatment RCT: 12% lower hospitalization (p=1) and 50% lower progression (p=0.04).
Low-risk (1% hospitalization) outpatient RCT with 738 fluvoxamine + budesonide patients and 738 placebo patients, showing significantly lower hospitalization/ER visits with treatment.

Apr 2023, Annals of Internal Medicine, https://www.acpjournals.org/doi/epdf/10.7326/M22-3305, https://c19p.org/reis10u

481 patient vitamin C late treatment study: 48% higher mortality (p=0.54).
Retrospective COVID+ hospitalized patients in Uganda, 385 patients receiving vitamin C treatment, showing higher mortality with treatment, without statistical significance.

Dec 2021, Research Square, https://www.researchsquare.com/article/rs-1193578/v1, https://c19p.org/bagumac

11,721 patient HCQ late treatment study: 27% higher mortality (p=0.001).
Database analysis of 11,721 hospitalized patients, 4,232 on HCQ. Strong evidence for confounding by indication and compassionate use of HCQ. 24.9% of HCQ patients were on mechanical ventilation versus 12.2% control. Ventilation mortality was 70.5% versus 11.6%. This study does not adjust for the differences in comorbid conditions and disease severity, and therefore does not make a conclusion. Unadjusted HCQ mortality was 24.8% versus control 19.6%. Adjusting for ventilation only gives us 17.7% HCQ versus 19.6% control (adjusting the HCQ group to have the same proportion of ventilation patients), RR 0.90. Hopefully authors can do a full adjustment analysis. Comorbidities may favor control, while patients remaining in the hospital (5.3%) may favor HCQ (other studies show faster resolution for HCQ patients). Data inconsistencies have been found in this study, for example 99.4% of patients treated with HCQ were treated in urban hospitals, compared to 65% of untreated patients ..

Aug 2020, Clinical Infectious Disease, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1268/5898276, https://c19p.org/fried

134 patient acetaminophen early treatment study: 473% higher mortality (p=0.3) and 534% higher need for oxygen therapy (p=0.06).
Retrospective 89 febrile COVID-19 patients in Israel taking paracetamol and 49 taking ibuprofen, showing higher need for respiratory support with paracetamol. Although not statistically significant, patients in the paracetamol group were older.

Sep 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20303438, https://c19p.org/rinottace

202 patient HCQ late treatment study: 25% higher mortality (p=0.76), 41% higher ventilation (p=0.34), and 17% higher ICU admission (p=0.53).
Retrospective 202 patients in Saudi Arabia not showing significant differences with treatment. No information is provided on how patients were selected for treatment, there may be significant confounding by indication. Time varying confounding is also likely as HCQ became controversial during the period studied, therefore HCQ use was likely more frequent toward the beginning of the period, a time when overall treatment protocols were significantly worse.

Dec 2020, Turk. Thorac. J., https://turkthoracj.org/en/use-of-hydroxychloroquine-in-patients-with-covid-19-a-retrospective-observational-study-131729, https://c19p.org/lotfy

254 patient HCQ late treatment RCT: 4% lower mortality (p=0.91), 8% higher ventilation (p=0.78), 31% higher ICU admission (p=0.24), and 29% slower recovery (p=0.29).
RCT 254 very late stage (93% on oxygen, 17% in ICU at baseline) hospitalized patients in Saudi Arabia not showing significant differences with HCQ+favipiravir treatment. Only SaO2 < 94% patients were eligible, however the actual SaO2 of enrolled patients is not provided.

Apr 2021, Infect. Dis. Ther., https://link.springer.com/epdf/10.1007/s40121-021-00496-6, https://c19p.org/bosaeed

288 patient vitamin D ICU study: 22% higher mortality (p=0.25), 27% higher ventilation (p=0.05), 17% higher ICU admission (p=0.07), and no change in hospitalization (p=1).
Retrospective 1,435 ICU patients in Saudi Arabia, showing no significant difference in mortality, and longer mechanical ventilation with treatment. Vitamin D patients had higher Q1, median, and Q3 SOFA scores after propensity score matching. 98% of patients were treated with cholecalciferol.

Aug 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1237903/full, https://c19p.org/alsulaiman5

150 patient HCQ late treatment study: 105% higher mortality (p=0.69).
Retrospective 150 patients in the Dominican Republic, 132 treated with HCQ, showing higher mortality with treatment in unadjusted results. Confounding by indication is likely.

Dec 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.12.11.20247437v1, https://c19p.org/deluna

365 patient various antiandrogen prophylaxis study: 229% higher hospitalization (p=0.2) and 29% fewer cases (p=0.32).
Retrospective 365 prostate cancer patients in Turkey, 138 treated with ADT, showing no significant differences with treatment.

Oct 2021, Türk Üroloji Dergisi/Turkish J. Urology, https://turkishjournalofurology.com/en/the-clinical-impact-of-androgen-deprivation-therapy-on-sars-cov-2-infection-rates-and-disease-severity-133775, https://c19p.org/kazan

13,585 patient aspirin prophylaxis PSM study: 8% lower mortality (p=0.52), 1% higher ventilation (p=0.96), 12% higher ICU admission (p=0.36), and 18% higher hospitalization (p=0.04).
Retrospective 13,585 COVID+ patients in the USA, showing higher hospitalization with aspirin use, and no significant difference for mortality, ventilation, and ICU admission.

Oct 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0275787, https://c19p.org/morrisone

689 patient spironolactone antiandrogen prophylaxis study: 129% higher combined mortality/ICU admission (p=0.0007).
Retrospective 689 hospitalized COVID-19 patients in Denmark, showing higher risk of ICU/death with spironolactone use in unadjusted results subject to confounding by indication.

May 2020, J. Hypertension, https://journals.lww.com/10.1097/HJH.0000000000002515, https://c19p.org/holt2

689 patient spironolactone prophylaxis study: 129% higher combined mortality/ICU admission (p=0.0007).
Retrospective 689 hospitalized COVID-19 patients in Denmark, showing higher risk of ICU/death with spironolactone use in unadjusted results subject to confounding by indication.

May 2020, J. Hypertension, https://journals.lww.com/10.1097/HJH.0000000000002515, https://c19p.org/holt2sp

173 patient HCQ late treatment study: 20% higher mortality (p=0.75).
Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HCQ. Power of study appears too low to support conclusions [bmj.com]. None of the 15 patients receiving HCQ+AZ were transferred to intensive care or died compared to 23% overall.

May 2020, BMJ 2020, https://www.bmj.com/content/369/bmj.m1844, https://c19p.org/mahevas

1,620 patient proton pump inhibitor prophylaxis PSM study: 34% higher combined mortality/intubation (p=0.01).
PSM retrospective 1,620 hospitalized patients in the USA, showing higher risk of combined death/intubation with PPI treatment.

May 2020, Gastroenterology, https://www.gastrojournal.org/article/S0016-5085(20)34706-5/fulltext, https://c19p.org/freedbergppi

11 patient HCQ ICU study: 140% higher mortality (p=0.55), 157% longer ICU admission, and 125% worse recovery.
Retrospective 11 critically ill COVID-19 ICU patients with organ failure treated with camostat mesylate (6 patients) or HCQ (5 patients). Over an 8 day period, the severity of COVID-19 decreased in the camostat group as measured by a decline in the SOFA score, inflammatory markers, and improvement in oxygenation. A similar effect was not seen in the HCQ group.

Nov 2020, Critical Care Explorations, https://journals.lww.com/10.1097/CCE.0000000000000284, https://c19p.org/hofmannwinklerh

670 patient proton pump inhibitor prophylaxis study: 81% higher severe cases (p=0.05) and 78% higher mortality (p=0.21).
Retrospective 670 COVID-19 patients in Iran showing significantly higher COVID-19 severity scores and more symptomatic presentation in patients with a history of proton pump inhibitor (PPI) use. Adjusted results are only provided for severity. Several values in Table 4 are likely misreported raising concern for the reliability of the main result.

Mar 2023, Annales Pharmaceutiques Françaises, https://www.sciencedirect.com/science/article/pii/S0003450922001122, https://c19p.org/shokri

175 patient HCQ late treatment study: 399% higher mortality (p=0.003).
Retrospective 340 patients with hematological malignancy in Turkey, showing higher mortality with HCQ treatment. Confounding by time is likely because more HCQ patients were earlier in time when overall treatment protocols were significantly worse.

Sep 2021, Turk. J. Haematol., https://pubmed.ncbi.nlm.nih.gov/34521187/, https://c19p.org/civrizbozdag

11,474 patient ibuprofen prophylaxis PSM study: 9% lower mortality (p=0.65) and 303% higher severe cases (p<0.0001).
N3C retrospective 250,533 patients showing higher COVID-19 severity with ibuprofen use. Note that results for individual treatments are not included in the journal version or v2 of this preprint.

Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reeseib

388 patient aspirin prophylaxis study: 21% higher ICU admission (p=0.52).
Retrospective 388 hospitalized COVID-19 patients in Italy showing higher use of aspirin in ICU patients, without statistical significance.

Jul 2020, Thrombosis Research, https://www.sciencedirect.com/science/article/pii/S0049384820301407, https://c19p.org/lodigiani

927 patient HCQ prophylaxis study: 49% more cases (p=0.02).
Observational study of 927 low-risk healthcare workers in India, 731 volunteering for weekly HCQ prophylaxis, showing higher cases with treatment in unadjusted results. Clinical outcome was in the protocol, however no information on which patients were symptomatic is provided. There were no adverse events and no hospitalizations or deaths. Adherence was very low, decreasing weekly, with almost all participants discontinuing by week 11. The majority of infections occurred in later weeks when adherence was very low, and there was no per protocol analysis. #ECR/206/Inst/GJ/2013/RR-20.

Aug 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.08.02.21260750v1, https://c19p.org/bhatt

103 patient metformin prophylaxis study: 16% higher mortality (p=0.46) and 16% higher severe cases (p=0.46).
Analysis of 103 elderly hospitalized COVID-19 patients in Spain, showing higher mortality with metformin, without statistical significance.

Apr 2021, Gerontology, https://www.karger.com/Article/FullText/515159, https://c19p.org/galvezbarronmf

32,758 patient HCQ prophylaxis study: 9% more cases (p=0.62).
Comparison of the percentage of SLE/RA patients on immunosuppressants that were taking HCQ, for COVID-19 diagnosis versus other infections or outpatient visits, finding a similar percentage in each case. No mortality of severity information is provided to determine if HCQ treated patients fared better. No adjustment for concomitant medications or severity.

Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/content/early/2020/08/19/annrheumdis-2020-218500, https://c19p.org/singer

132 patient favipiravir late treatment study: 168% higher mortality (p=0.06).
Retrospective 132 hospitalized COVID-19 patients over age 65 in Japan during the Alpha variant surge, showing higher mortality with favipiravir in unadjusted results, without statistical significance.

Jan 2024, Infection Prevention in Practice, https://www.sciencedirect.com/science/article/pii/S2590088924000052, https://c19p.org/saito2

629 patient ursodeoxycholic acid prophylaxis study: 7% higher mortality (p=0.77).
PSM retrospective 629 hospitalized COVID-19 patients showing no significant difference in survival between 108 patients taking UDCA prior to infection compared to 521 matched controls not taking the drug. The lack of observed benefit in this retrospective inpatient cohort does not preclude potential protective effects of UDCA against infection or illness severe enough to require hospitalization.

Sep 2023, Liver Int., https://onlinelibrary.wiley.com/doi/10.1111/liv.15736, https://c19p.org/marrone

217 patient HCQ late treatment study: 3% higher mortality (p=1).
Retrospective 217 critically ill patients, 114 receiving HCQ, showing no significant difference in mortality.

Apr 2020, Critical Care Medicine, https://journals.lww.com/ccmjournal/Fulltext/2020/09000/ICU_and_Ventilator_Mortality_Among_Critically_Ill.35.aspx, https://c19p.org/auld

559 patient HCQ ICU study: 1% higher mortality (p=0.91).
Retrospective 559 COVID-19 ICU patients in Indonesia, showing no difference in mortality with HCQ in unadjusted results.

Sep 2023, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0290964, https://c19p.org/burhan

2,148 patient selenium prophylaxis study: 26% higher hospitalization (p=0.48) and 9% higher severe cases (p=0.8).
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with selenium prophylaxis.

Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerse

689 patient vitamin C prophylaxis study: 26% higher IgG positivity (p=0.49).
Retrospective 689 healthcare workers in India, showing no significant difference in IgG positivity with vitamin C prophylaxis.

Feb 2021, American J. Blood Research, https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8010601/, https://c19p.org/mahtoc

390 patient aspirin prophylaxis study: 13% higher mortality (p=0.0003).
Retrospective 390 hospitalized patients in Israel, showing higher risk of mortality with prior aspirin use. Details of the analysis are not provided.

Oct 2021, Metabolites, https://www.mdpi.com/2218-1989/11/10/679, https://c19p.org/basheer

104 patient HCQ late treatment PSM study: 125% higher combined mortality/intubation (p=0.23).
203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding.

Jun 2021, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252388, https://c19p.org/saib

67 patient HCQ late treatment study: 63% higher mortality (p=0.52).
Retrospective 67 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended during the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.

Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S330/6057008, https://c19p.org/psevdos

226 patient ursodeoxycholic acid prophylaxis study: 2% more cases (p=0.88).
Retrospective 280 Chinese families with children previously seen in a liver clinic assessing whether ursodeoxycholic acid (UDCA) reduced SARS-CoV-2 infection risk. Among infected families, the study found no significant difference in confirmed or suspected SARS-CoV-2 infections between children taking UDCA (80.9%) and those not taking it (77.6%) (p=0.843).

Jun 2023, Liver Int., https://onlinelibrary.wiley.com/doi/10.1111/liv.15660, https://c19p.org/liu12

917,198 patient colchicine late treatment study: 13% higher mortality (p<0.0001).
Retrospective study of 917,198 hospitalized COVID-19 cases covered by the Iran Health Insurance Organization over 26 months showing that antithrombotics, corticosteroids, and antivirals reduced mortality while diuretics, antibiotics, and antidiabetics increased it. Confounding makes some results very unreliable. For example, diuretics like furosemide are often used to treat fluid overload, which is more likely in ICU or advanced disease requiring aggressive fluid resuscitation. Hospitalization length has increased risk of significant confounding, for example longer hospitalization increases the chance of receiving a medication, and death may result in shorter hospitalization. Mortality results may be more reliable. Confounding by indication is likely to be significant for many medications. Authors adjustments have very limited severity information (admission type refers to ward vs. ER department on initial arrival). We can estimate the impact of confounding from typical usage..

Dec 2023, Frontiers in Public Health, https://www.frontiersin.org/articles/10.3389/fpubh.2023.1280434/full, https://c19p.org/mehrizio

59 patient colchicine late treatment RCT: 4% higher hospitalization (p=0.98), 5% higher need for oxygen therapy (p=0.97), 40% improvement (p=0.97), and 11% improved viral clearance (p=0.77).
Early terminated RCT with 14 colchicine, 13 edoxaban, 16 colchicine+edoxaban, and 16 control patients, showing no significant difference in outcomes with treatment up to 7 days after PCR diagnosis.

May 2024, J. Cardiovascular Medicine, https://journals.lww.com/10.2459/JCM.0000000000001639, https://c19p.org/landi

763 patient aspirin prophylaxis study: 49% higher mortality (p=0.0001).
Retrospective 770 COVID-19 patients with cancer, showing increased mortality with aspirin use in unadjusted results.

Oct 2021, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S238702062100485X, https://c19p.org/perezsegura

17,190 patient acetaminophen prophylaxis PSM study: 18% higher mortality (p=0.35) and 27% more cases (p=0.17).
Retrospective 12,457 patients prescribed paracetamol with codeine/dihydrocodeine and 13,202 prescribed NSAIDs, showing no significant differences in cases and mortality. Patients prescribed codeine/dihydrocodeine may have different susceptibility to COVID-19.

Apr 2021, Arthritis & Rheumatology, https://onlinelibrary.wiley.com/doi/10.1002/art.41593, https://c19p.org/chandan

14,958 patient proton pump inhibitor prophylaxis study: 3% lower mortality (p=0.66), 21% higher ventilation (p=0.06), 13% higher ICU admission (p=0.06), and 5% higher hospitalization (p=0.26).
Retrospective 14,958 US veterans who tested positive for SARS-CoV-2, showing no significant difference in severe COVID-19 outcomes (mechanical ventilation, death, ICU admission, or hospitalization) with proton pump inhibitor (PPI) use compared to non-use in a propensity score weighted analysis.

Oct 2021, Gut, https://gut.bmj.com/lookup/doi/10.1136/gutjnl-2021-325701, https://c19p.org/shah8

108 patient zinc early treatment RCT: 44% higher hospitalization (p=0.72) and 12% faster recovery (p=0.38).
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. Study performed in the USA where zinc deficiency is relatively uncommon. The zinc dosage is relatively low, 50mg zinc gluconate (7mg elemental zinc), one tenth of that shown to reduce the duration of colds in other studies [patrickholford.com].

Feb 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305, https://c19p.org/thomas

1,370,600 patient acetaminophen prophylaxis study: 5% higher hospitalization (p=0.83) and 3% fewer cases (p=0.82).
PSM retrospective 1,370,600 osteoarthritis or back pain patients in the US, showing no significant differences in COVID-19 cases and hospitalization for paracetamol vs. ibuprofen.

Jul 2022, Drugs, https://link.springer.com/article/10.1007/s40265-022-01822-z, https://c19p.org/xie

118 patient zinc ICU study: 81% higher mortality (p=0.44).
Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.

Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiriz

194,637 patient HCQ prophylaxis study: 3% higher mortality (p=0.83).
Observational database study of RA/SLE patients in the UK, 194,637 RA/SLE patients with 30,569 having >= 2 HCQ prescriptions in the prior 6 months, HCQ HR 1.03 [0.80-1.33] (HR 0.78 before adjustments). 70 patients with HCQ prescriptions died. One major problem is that there is no knowlege of medication adherence for these 70 - for example, it is possible that they were part of the expected percentage of patients that did not take the medication as prescribed, invalidating the result. Other limitations include confounding by use of bDMARDs and confounding by severity of rheumatological disease.

Sep 2020, The Lancet Rheumatology, https://www.sciencedirect.com/science/article/pii/S2665991320303787, https://c19p.org/rentsch

506 patient HCQ late treatment study: 2% higher mortality (p=0.92).
Retrospective cancer patients, showing adjusted OR 1.03 [0.62-1.73] for HCQ. The study reports the number of HCQ+AZ patients but they do not provide results for HCQ+AZ (only HCQ + any other treatment). Significant confounding by indication and compassionate use is likely.

Jul 2020, Cancer Discovery, https://cancerdiscovery.aacrjournals.org/content/early/2020/09/12/2159-8290.CD-20-0941, https://c19p.org/rivera

161 patient HCQ late treatment study: 79% higher mortality (p=0.1).
Retrospective 161 hospitalized patients in the USA showing non-statistically significant unadjusted increased mortality with HCQ. Confounding by indication is likely. Time varying confounding is likely. HCQ became controversial and was suspended towards the end of the period studied, therefore HCQ use was likely more frequent toward the beginning of the study period, a time when overall treatment protocols were significantly worse.

Dec 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/7/Supplement_1/S251/6058327, https://c19p.org/teixeira

118 patient favipiravir ICU study: 79% higher mortality (p=0.5).
Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.

Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiria

44,046 patient HCQ prophylaxis study: 97% higher progression (p=0.11) and 6% fewer cases (p=0.82).
Retrospective database analysis with 17 cases for existing HCQ users and 5 severe cases, showing no significant difference for cases and higher risk for severe cases. However, HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].

Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2

91 patient N-acetylcysteine late treatment study: 135% higher mortality (p=0.68).
Prospective study with 75 NAC patients and 16 control patients, showing no significant difference in mortality.

Dec 2021, Indonesian J. Tropical and Infectious Disease, https://www.e-journal.unair.ac.id/IJTID/article/view/30874, https://c19p.org/ramadhan

354 patient acetaminophen long COVID study: 32% higher PASC (p=0.07).
Prospective study of 494 COVID-19 patients showing higher risk of PASC with acetaminophen use in unadjusted results, without reaching statistical significance (p=0.07). Higher risk is also seen for dexamethasone and remdesivir (statistically significant for dexamethasone), however confounding by indication may be significant for these treatments, with increased use for more severe patients. While details of treatment timing and dose are not available, the result for acetaminophen can be compared with ibuprofen, with comparable indication for use. Notably there is no increased risk with ibuprofen, suggesting higher risk with acetaminophen, consistent with the higher risk seen in meta analysis.

Oct 2023, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2023.1227883/full, https://c19p.org/chen12

498 patient metformin prophylaxis PSM study: 10% higher mortality (p=0.48).
Retrospective 2,666 type 2 diabetes COVID-19 patients in Spain, showing higher mortality with existing metformin use (not statistically significant).

Nov 2020, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-020-01832-2, https://c19p.org/perezbelmonte

134 patient HCQ late treatment study: 143% higher mortality (p=0.03).
Retrospective 82 hospitalized patients HCQ/AZ, 52 SOC, not finding statistically significant differences. Confounding by indication - authors note that the HCQ/AZ patients were more severely ill, and do not attempt to adjust for confounders.

Jul 2020, British J. Clinical Pharmacology, https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bcp.14482, https://c19p.org/kelly

262 patient HCQ prophylaxis study: 17% higher mortality (p=0.8), 78% higher combined mortality/ICU admission (p=0.21), and 45% higher hospitalization (p=0.12).
Retrospective 71 chronic HCQ patients compared with 191 matched controls, analyzing only those with a highly suspected or confirmed diagnosis of COVID-19. No significant difference was found in outcomes, however matching failed with extreme confounding - 77.5% of HCQ patients with systemic autoimmune diseases vs. 21.5% of control patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].

Jan 2021, Revue du Rhumatisme, https://www.sciencedirect.com/science/article/abs/pii/S1169833021002489, https://c19p.org/trefond

738 patient vitamin D prophylaxis study: 49% higher hospitalization (p=0.002).
Retrospective survey-based analysis of 738 COVID-19 patients in Saudi Arabia, showing lower hospitalization with vitamin C, turmeric, zinc, and nigella sativa, and higher hospitalization with vitamin D. For vitamin D, most patients continued prophylactic use. For vitamin C, the majority of patients continued prophylactic use. For nigella sativa, the majority of patients started use during infection. Authors do not specify the fraction of prophylactic use for turmeric and zinc.

May 2021, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/18/10/5086, https://c19p.org/aldwihid

118 patient vitamin D ICU study: 66% higher mortality (p=0.6).
Retrospective 118 ICU patients in Saudi Arabia showing no significant differences in unadjusted results with zinc, vitamin D, and favipiravir treatment.

Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002495, https://c19p.org/assiri

44,046 patient metformin prophylaxis study: 1% higher progression (p=0.11) and 4% fewer cases (p=0.82).
Retrospective database analysis showing no significant differences with pre-existing metformin use.

Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2mf

325 patient HCQ late treatment study: 890% higher progression (p=0.03).
Retrospective 325 hospitalized COVID-19 patients in Malaysia, showing higher progression with HCQ, however the groups are not comparable. 17 HCQ vs. 3 control patients had severity category ≥3 at baseline (7 vs. 0 for severity ≥4).

Mar 2023, Malaysian J. Medicine and Health Sciences, https://medic.upm.edu.my/upload/dokumen/2023032211275502_MJMHS_0551.pdf, https://c19p.org/ho2

72 patient ibuprofen prophylaxis PSM study: 240% higher progression (p=0.26).
Retrospective 293 patients in South Korea, showing higher risk of progression with ibuprofen use, without statistical significance.

Jun 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/6/1959, https://c19p.org/choi2

10,000 patient vitamin B9 prophylaxis study: 18% more cases (p=0.29).
Retrospective 10,000 adults in Qatar, showing higher risk of COVID-19 cases with vitamin B9 supplementation, without statistical significance. Authors do not analyze COVID-19 severity.

Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2b9

144 patient HCQ late treatment study: 53% higher mortality (p=0.17).
Analysis of 144 hospitalized kidney transplant patients showing HCQ mortality HR 1.53, p = 0.17. Subject to confounding by indication.

Jul 2020, American J. Transplantation, https://onlinelibrary.wiley.com/doi/full/10.1111/ajt.16185, https://c19p.org/cravedi

518 patient proton pump inhibitor prophylaxis study: 57% higher hospitalization (p=0.15).
Retrospective 506 outpatients in Oman showing no significant association between proton pump inhibitor (PPI) use and COVID-19 hospitalization in unadjusted results.

Oct 2024, Cureus, https://www.cureus.com/articles/310267-association-between-the-use-of-proton-pump-inhibitors-and-severe-clinical-outcomes-in-covid-19-patients-a-retrospective-observational-study, https://c19p.org/pinto2

605 patient andrographolide late treatment study: 26% higher progression (p=0.4).
Retrospective 605 hospitalized patients in Thailand, showing higher progression with andrographis, without statistical significance.

Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.947373/full, https://c19p.org/tanwettiyanont

72 patient metformin prophylaxis PSM study: 120% higher progression (p=0.26).
Retrospective 293 patients in South Korea, showing higher risk of progression with metformin use, without statistical significance.

Jun 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/6/1959, https://c19p.org/choi2mf

7,944 patient famotidine prophylaxis study: 11% higher mortality (p=0.33).
Retrospective 9,532 hospitalized COVID+ veterans in the USA, showing no significant difference in mortality with famotidine use. The study provides results for use before, after, and before+after. Before+after should more accurately represent prophylaxis up to COVID-19 infection (and continued use). Before included use up to 2 years before, and after included use up to 60 days later.

Dec 2021, BMJ Open, https://bmjopen.bmj.com/content/11/12/e050051.info, https://c19p.org/wallacefm

61 patient ivermectin early treatment RCT: 20% improved viral clearance (p=0.59).
Early terminated 89 patient RCT with 29 high dose and 32 very high dose ivermectin patients, showing dose dependent viral load reduction, although not reaching statistical significance due to early termination. Since most patients have low viral load at day 7, there is little room for improvement with a treatment at day 7. Intermediate results may show significantly greater improvement, but are not provided. Authors note that ivermectin remained safe even at the very high dose used, although tolerability was reduced. Adherence was very low in the very high dose arm (~60%). The paper reports 4 SAEs, all resolved, with 3 patients hospitalized in the very high dose ivermectin arm, 1 in the high dose arm, and 0 in the control arm. However, the supplementary data is contradictory, showing 2 grade 3 events in both ivermectin arms (2 infections and infestations, and 2 COVID-19 pneumonia). While this result is not statistically significant, it may be in part due to randomization failure..

Sep 2021, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857921013571, https://c19p.org/buonfrate

328 patient HCQ late treatment PSM study: 240% higher mortality (p=0.002).
Retrospective 1,108 hospitalized patients in New York showing significantly higher mortality with HCQ treatment. Time based confounding is very likely because HCQ became increasingly controversial and less used over the time covered (Mar - Jun 2020), while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. Authors note that for every week or month later that a person was admitted, their risk of death dropped by 16% and 49%, respectively, yet they do not consider time based confounding.

May 2021, PLOS One, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251262, https://c19p.org/sammartino

168 patient proton pump inhibitor prophylaxis study: 240% higher severe cases (p<0.0001).
Retrospective 168 hospitalized COVID-19 patients in China showing higher risk of severe cases with acid suppression drugs.

Mar 2020, medRxiv, https://www.medrxiv.org/content/10.1101/2020.03.19.20038539, https://c19p.org/yan6

104 patient favipiravir late treatment RCT: 87% higher mortality (p=0.26).
RCT 156 COVID-19 patients showing higher mortality with favipiravir and remdesivir overall. Favipiravir and remdesivir were more effective when started earlier, however note that Table 10 compares earlier favipiravir/remdesivir+standard care with standard care at any time, which will exaggerate the benefits/harms of earlier/later treatment. The confidence intervals for the Cox results are unusually narrow suggesting a possible error in calculation.

Jan 2024, Infectious Diseases in Clinical Practice, https://journals.lww.com/10.1097/IPC.0000000000001336, https://c19p.org/alsaraja

11,157 patient HCQ late treatment study: 28% higher mortality (p=0.03) and 29% higher ventilation (p=0.09).
Retrospective analysis of seven databases in the USA, showing higher mortality with treatment. Results contradict strong evidence from the RECOVERY/SOLIDARITY trials, suggesting substantial confounding by indication. Time based confounding is very likely because HCQ became highly controversial and usage dramatically declined over the time covered, while overall treatment protocols during this period improved dramatically, i.e., more control patients likely come later in the period when treatment protocols were greatly improved. This study includes anyone PCR+ during or prior to their visit, and anyone with ICD-10 COVID-19 codes which includes asymptomatic PCR+ patients, therefore some patients in the control groups may be asymptomatic with regards to SARS-CoV-2, but in the hospital for another reason. Authors do not mention the possibility of any of these likely confounding factors.

Mar 2021, PLoS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248128, https://c19p.org/stewart

324 patient acetaminophen prophylaxis PSM study: 71% higher mortality (p=0.34), 14% higher ventilation (p=1), 40% lower ICU admission (p=0.72), and 9% higher need for oxygen therapy (p=0.87).
PSM retrospective in South Korea, showing no significant differences in outcomes with acetaminophen use vs. NSAID use. Adherence and dosage are unknown.

Feb 2023, Int. J. Environmental Research and Public Health, https://www.mdpi.com/1660-4601/20/5/3832, https://c19p.org/kim7

437 patient HCQ late treatment study: 134% higher mortality (p=0.05).
Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. May be subject to significant confounding by indication and confounding by time.

Sep 2021, Int. J. General Medicine, https://www.dovepress.com/getfile.php?fileID=73585, https://c19p.org/alotaibi

1,483 patient HCQ late treatment study: 35% higher mortality (p=0.31).
Retrospective observational late stage study showing no significant differences but calling for clinical trials. Zervos et al. [ijidonline.com] point out serious limitations that they say should be corrected on the record: patients receiving HCQ with or without AZ were overall sicker on presentation and had multiple other risk factors including much higher risk based on ethnicity; patients receiving HCQ were more likely to be obese, diabetic, have chronic lung disease, and cardiovascular conditions; yet these sicker patients had approximately the same mortality rates compared to patients with a milder course of the disease and less risk factors. However, the authors conclude that "there are no significant benefits." It is noteworthy that HCQ was associated with a significant survival benefit in a larger cohort of patients from New York City as reported by [Mikami]. See also [worldtribune.com].

May 2020, JAMA, May 11, 2020, https://jamanetwork.com/journals/jama/fullarticle/2766117, https://c19p.org/rosenberg

20,238 patient HCQ prophylaxis study: 46% higher hospitalization (p=0.1) and 8% more cases (p=0.5).
Retrospective database analysis of chronic HCQ users and matched control patients, failing to match or adjust for the very different baseline risk for systemic autoimmune disease patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri].

Mar 2021, Eurosurveillance, https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2021.26.9.2001202, https://c19p.org/vivancohidalgo

848 patient azithromycin ICU study: 22% higher mortality (p=0.08).
Retrospective 848 ICU patients in Saudi Arabia, showing higher mortality with azithromycin in unadjusted results.

May 2023, Clinical Infection in Practice, https://www.sciencedirect.com/science/article/pii/S2590170223000122, https://c19p.org/alqadheebazaz

30 patient zinc late treatment RCT: 14% higher ventilation (p=1), 14% higher ICU admission (p=1), and 14% higher hospitalization (p=1).
Small RCT of zinc plus resveratrol in COVID-19+ outpatients, showing no significant differences in viral clearance or symptoms. Although the treatment group was older (46.3 vs. 38.5) and had more severe baseline symptoms, they had similar symptomatic recovery by the second week.

Sep 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3934228, https://c19p.org/kaplan

30 patient resveratrol late treatment RCT: 14% higher ventilation (p=1), 14% higher ICU admission (p=1), and 14% higher hospitalization (p=1).
Small RCT of zinc plus resveratrol in COVID-19+ outpatients, showing no significant differences in viral clearance or symptoms. Although the treatment group was older (46.3 vs. 38.5) and had more severe baseline symptoms, they had similar symptomatic recovery by the second week.

Sep 2021, SSRN, https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3934228, https://c19p.org/kaplanrsv

529 patient metformin prophylaxis study: 1% higher mortality (p=0.98), 4% higher ventilation (p=0.87), and 8% lower ICU admission (p=0.72).
Retrospective 529 hospitalized COVID-19 patients with type 2 diabetes, showing no significant difference in outcomes with metformin use. This does not account for the different risk of being hospitalized based on metformin use. Authors note that "there is a lower-than-expected proportion of metformin prescription in our population (28%) compared to the general US population", without noting that this may reflect the lower risk of being hospitalized for metformin patients, as shown in other studies [c19early.org].

Jun 2023, Endocrine Practice, https://www.sciencedirect.com/science/article/pii/S1530891X23004299, https://c19p.org/obiriyeboah

69 patient ivermectin late treatment RCT: 32% faster recovery (p=0.05) and 15% shorter hospitalization (p=0.02).
RCT in Iran showing shorter time to recovery and shorter hospitalization time with ivermectin. There were no adverse effects. There was one death in the treatment group, the patient was in critical condition at baseline and died within 24 hours of admission. Also see [sciencedirect.com] and the author response [clinicaltherapeutics.com].

Jan 2021, Clinical Therapeutics, https://www.sciencedirect.com/science/article/abs/pii/S0149291821002010, https://c19p.org/shahbaznejad

1,346 patient HCQ late treatment study: 5% higher mortality (p=0.68), 21% higher ventilation (p=0.08), 9% higher ICU admission (p=0.31), and 12% longer hospitalization (p=0.03).
Retrospective 7,580 hospitalized patients in Brazil, showing longer hospitalization, and no significant difference in mortality, mechanical ventilation, and ICU admission with HCQ treatment. Authors note confounding by indication due to selected use in a compassionate use context. Authors match only on age, sex, cardiovascular comorbidities, and in-hospital use of corticosteroid, and only 10% of patients received HCQ/CQ, therefore confounding by indication is likely to be significant. A different matching list is included in the text, but neither includes COVID-19 severity. In the first line of the abstract authors falsely state that there is no evidence of benefit for HCQ treatment. While misrepresenting prior research is common, this is an extreme case and raises concern for validity of the analysis. In reality controlled studies show statistically significant positive results for one or more outcomes (including RCTs). Authors discussion of prior research shows similar bias.

Sep 2023, Arquivos Brasileiros de Cardiologia, https://abccardiol.org/article/dados-de-vida-real-sobre-o-uso-da-hidroxicloroquina-ou-da-cloroquina-combinadas-ou-nao-a-azitromicina-em-pacientes-com-covid-19-uma-analise-retrospectiva-no-brasil/, https://c19p.org/souzasilva

5,772 patient antihistamine H1RA prophylaxis study: 7% higher mortality (p=0.5).
Retrospective 72,105 COVID+ hospitalized patients in France, showing no significant difference in mortality with antihistamine H1RAs desloratadine and hydroxyzine.

Aug 2023, Pharmaceuticals, https://www.mdpi.com/1424-8247/16/8/1107, https://c19p.org/hoertel5h1

501 patient ivermectin early treatment RCT: 33% lower hospitalization (p=0.23) and 5% worse viral clearance (p=0.55).
RCT with 501 relatively low-risk outpatients in Argentina showing hospitalization OR 0.65 [0.32-1.31]. With only 7% hospitalization, this trial is underpowered. The trial primarily includes low-risk patients that recover quickly without treatment, leaving minimal room for improvement with treatment. 74 patients had symptoms for >= 7 days. Among the 7 patients requiring ventilation, authors note that the earlier requirement in the ivermectin group may be due to those patients having higher severity at baseline. However, authors know the answer to this - it is unclear why it is not reported. There were more adverse events in the placebo group than the ivermectin group, suggesting a possible issue with dispensing or non-trial medication usage. 25+% of patients were hospitalized within 2/3 days for the placebo/treatment groups (Figure S2). The companion prophylaxis study [ IVERCOR PREP ] has reported results in the press and an online presentation [ lanacion.com.ar , web.archive.org (M) ..

Jul 2021, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-021-06348-5, https://c19p.org/vallejos2

2,148 patient zinc prophylaxis study: 25% higher hospitalization (p=0.21) and 13% higher severe cases (p=0.46).
Retrospective 2,148 COVID-19 recovered patients in Jordan, showing no significant differences in the risk of severity and hospitalization with zinc prophylaxis.

Feb 2022, Bosnian J. Basic Medical Sciences, https://www.bjbms.org/ojs/index.php/bjbms/article/view/7009, https://c19p.org/nimerz

524 patient nitric oxide early treatment RCT: 1% higher progression (p=1) and 11% faster recovery (p=0.3).
RCT 524 outpatients in the USA for a nitric oxide generating lozenge, showing no significant difference in combined hospitalization, ICU admission, intubation, dialysis, and death. There were only 3 events in each arm, all occuring in 2020, with zero events in 2021 or 2022. Recovery was 11% faster with treatment, without statistical significance. Authors note that a higher dose may have been more effective. Trials showing greater efficacy have used a nasal spray.

Jun 2023, The American J. Medicine, https://www.sciencedirect.com/science/article/pii/S0002934323003911, https://c19p.org/bryan

250,655 patient proton pump inhibitor prophylaxis PSM study: 47% higher severe cases (p=0.32) and 8% fewer cases (p=0.06).
Retrospective 255,355 adults in Israel showing no significant association between proton pump inhibitor (PPI) use and SARS-CoV-2 positivity or COVID-19 severity.

Feb 2022, Frontiers in Pharmacology, https://www.frontiersin.org/articles/10.3389/fphar.2022.791074/full, https://c19p.org/shafrir

1,360 patient ursodeoxycholic acid prophylaxis study: 7% higher mortality (p=0.67), 4% lower ICU admission (p=0.96), 6% higher hospitalization (p=0.66), and 3% fewer cases (p=0.77).
Retrospective cohort study of 9,617 patients with liver disease in Italy, divided into UDCA users and non-users. UDCA exposure was not associated with reduced SARS-CoV-2 infection or improved COVID-19 outcomes including death, hospitalization, and ICU admission in this unvaccinated cohort. The large sample size provides power, but administrative data limitations include lack of important confounders like BMI and hypertension.

Aug 2023, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13711, https://c19p.org/ojedafernandez2

44,046 patient azithromycin prophylaxis study: 54% higher progression (p=0.33) and 42% fewer cases (p=0.1).
Retrospective database analysis showing no significant differences with azithromycin use.

Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325650, https://c19p.org/huh2azaz

905 patient nitazoxanide early treatment RCT: 188% higher progression (p=0.04).
RCT with 462 nitazoxanide/ciclesonide and 443 paracetamol patients, up to 7 days from onset, showing no significant difference in progression. Minimal details, with the primary mortality outcome and treatment delay not being reported.

Feb 2022, ANTICOV, News, https://www.isglobal.org/en/new/-/asset_publisher/JZ9fGljXnWpI/content/ensayo-anticov-halla-combinacion-nitazoxanida-ciclesonida-no-reduce-riesgo-hospitalizacion-pacientes-covid-19-leve, https://c19p.org/anticovn

638 patient HCQ prophylaxis study: 56% more cases (p=0.24).
Survey of 319 autoimmune disease patients taking CQ/HCQ with 5.3% COVID-19 incidence, compared to a control group from the general population (matched on age, sex, and region, but not adjusted for autoimmune disease), with 3.4% incidence. It not clear why authors did not compare with autoimmune patients not on CQ/HCQ. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.001 [Ferri], which is the observed real-world risk, taking into account factors such as these patients potentially being more careful to avoid exposure. If we adjust for the different baseline risk, the result becomes RR 0.36, p<0.001, suggesting a substantial benefit for HCQ/CQ treatment (as shown in other studies). There may also be significant survey bias - those experiencing COVID-19 may be more likely to respond to the survey. Authors note that they "could not eliminate completely the possibility of some bias due to the..

Sep 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243598, https://c19p.org/laplana

179 patient acetaminophen prophylaxis study: 51% more cases (p=0.19).
Retrospective 179 elderly patients in France, showing higher risk of COVID-19 cases with acetaminophen use, without statistical significance.

May 2020, Preprints, https://www.preprints.org/manuscript/202005.0016/v1, https://c19p.org/blanc2

1,500 patient HCQ late treatment study: 4% higher mortality (p=0.97).
Retrospective 1,500 hospitalized late stage (median SaO2 87.7) patients in Turkey, showing no significant difference with HCQ treatment.

Apr 2021, Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S0954611121001396, https://c19p.org/kokturk

503 patient acetaminophen early treatment study: 77% higher mortality (p=0.74).
Retrospective COVID-19 patients in Bangladesh, showing higher mortality with acetaminophen use in unadjusted results.

Nov 2022, Nutrients, https://www.mdpi.com/2072-6643/14/23/5029, https://c19p.org/shariface

72,501 patient cannabidiol prophylaxis study: 3% lower mortality (p=0.73), 27% higher ICU admission (p<0.0001), and 80% higher hospitalization (p<0.0001).
Retrospective 72,501 COVID-19 patients in the USA showing cannabis use associated with higher risk of hospitalization and ICU admission.

Jun 2024, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2820235, https://c19p.org/griffith

397 patient ibuprofen early treatment study: 170% higher mortality (p=0.35), 45% higher need for oxygen therapy (p=0.64), 18% higher hospitalization (p=0.64), and 85% higher severe cases (p=0.42).
Prospective study of 503 COVID-19 cases in Saudi Arabia, 40 using ibuprofen during infection, and 357 not using NSAIDs, showing no significant differences in outcomes. Results are subject to confounding by indication.

Nov 2020, Infectious Diseases and Therapy, http://link.springer.com/10.1007/s40121-020-00363-w, https://c19p.org/abuesba

3,345 patient HCQ late treatment study: 81% higher mortality (p=0.007).
Retrospective 3,345 hospitalized patients in India, 11.5% treated with HCQ, showing unadjusted higher mortality with treatment. Confounding by indication and time based confounding (due to declining use over the period when overall treatment protocols improved dramatically) are likely.

Apr 2021, Clinical Epidemiology and Global Health, https://www.sciencedirect.com/science/article/pii/S2213398421000555, https://c19p.org/mohandas

1,996 patient exercise study: 42% more cases (p=0.55).
Retrospective survey of 1,997 college students in the USA, showing no significant difference in COVID-19 cases with exercise in unadjusted results.

Feb 2022, JMIR Mental Health, https://mental.jmir.org/2022/2/e34645, https://c19p.org/gilley

22,385 patient acetaminophen prophylaxis study: 1% higher mortality (p=0.43).
Retrospective 28,856 COVID-19 patients in the USA, showing no significant difference in mortality for chronic acetaminophen use vs. sporadic NSAID use. Since acetaminophen is available OTC and authors only tracked prescriptions, many patients classified as sporadic users may have been chronic users.

May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267462, https://c19p.org/campbell2ace

8,426 patient zinc prophylaxis study: 12% more cases (p=0.58).
Retrospective 8,426 patients in the USA, showing no significant difference in cases with zinc prophylaxis. Severity results were not reported due to the small number of events.

Oct 2022, Cureus, https://www.cureus.com/articles/119536-does-prophylactic-oral-zinc-reduce-the-risk-of-contracting-covid-19, https://c19p.org/adrean

158,835 patient vitamin D late treatment study: 9% higher mortality (p<0.0001) and 41% higher ventilation (p<0.0001).
N3C retrospective showing higher risk with vitamin D treatment for hospitalized patients. As noted by authors, confounding by indication may be significant. The more extreme ventilation result, which is a significant outlier among all studies, is consistent with such confounding. Timing, dose, and duration of treatment were not used.

Jul 2022, Nutrients, https://www.mdpi.com/2072-6643/14/15/3073, https://c19p.org/fairfield

7,910 patient proton pump inhibitor prophylaxis PSM study: 5% lower mortality (p=0.7), 8% higher ventilation (p=0.73), 5% higher ICU admission (p=0.8), and 22% higher hospitalization (p=0.005).
Retrospective 83,224 SARS-CoV-2 cases and 332,799 controls in Denmark showing increased risk of infection and hospital admission with proton pump inhibitor (PPI) use, but no significant association with ICU admission or mortality.

Sep 2021, Clinical Gastroenterology and Hepatology, https://www.sciencedirect.com/science/article/pii/S1542356521005140, https://c19p.org/israelsen

96 patient camostat early treatment RCT: 36% higher hospitalization (p=1) and 8% improved recovery (p=0.84).
RCT 90 outpatients showing no significant difference in viral load or time to clinical improvement with camostat mesylate. The trial was discontinued early and did not reach the intended sample size. Authors note that combining camostat with a cathepsin inhibitor may improve efficacy.

Sep 2022, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971222003885, https://c19p.org/tobback

36,160 patient antihistamine H1RA prophylaxis study: 30% higher severe cases (p=0.0004).
Retrospective 4,251 severe COVID-19 cases and 36,738 matched controls in Scotland showing increased risk of severe COVID-19 with PPI use and antihistamine H1RA use. Adjusted results are only provided for the patients not in care homes (2,357 cases and 33,803 controls).

Feb 2021, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-01907-8, https://c19p.org/mckeigueh1

549 patient ivermectin early treatment RCT: 9% higher ICU admission (p=0.95), 36% higher hospitalization (p=0.41), 2% worse recovery (p=0.49), and 23% worse viral clearance (p=0.16).
RCT 549 low risk outpatients in Iran. Reported outcomes are very different from the pre-specified outcomes [irct.ir]. The inpatient trial is listed separately. The pre-specified primary clinical outcome was not reported. The reported components of this outcome are both positive. Pre-specified outcomes (3 not reported) [irct.ir]: - reduction in persistent cough and tachypnea and O2 saturation above 94% - not reported - negative PCR - reported - main complaints recovery time - not reported (only individual symptoms) - hospitalization - reported - time to hospitalization - not reported - mortality - reported - side effects - reported in only one patient (anomalous) A new outcome "relative recovery" is reported but not mentioned in the trial registration. The reported percentages and RR do not match. Authors include a researcher caught on video admitting that conclusions on ivermectin research were influenced by a funder [c19ivm.org]. Most/many patients were also treated with..

Jun 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.919708/full, https://c19p.org/rezai3

34 patient HCQ late treatment study: 203% slower viral clearance (p=0.02).
Very small retrospective analysis of 34 patients finding slower binary PCR viral clearance with HCQ. No information on severity for treatment versus control is provided. No deaths, ICU admission, or mechanical ventilation. Binary PCR does not distinguish replication-competence. HCQ treatment started very late for many patients with >= 9 days for 25%.

May 2020, Medicine, https://journals.lww.com/md-journal/Fulltext/2020/12240/Hydroxychloroquine_is_associated_with_slower_viral.34.aspx, https://c19p.org/mallat

144 patient acetaminophen late treatment PSM study: 2700% higher need for oxygen therapy (p<0.0001) and 75% slower recovery (p<0.0001).
PSM retrospective 72 indomethacin and 72 paracetamol patients in India, showing higher progression and worse recovery with acetaminophen.

Jul 2021, J. the Indian Medical Association, https://sapiensfoundation.org/wp-content/uploads/2021/08/Use-of-Indomethacin-in-Covid-19-patients-JIMA-2021.pdf, https://c19p.org/ravichandran2ace

336 patient HCQ late treatment study: 19% higher mortality (p=0.6), 461% higher ventilation (p<0.0001), and 463% higher ICU admission (p<0.0001).
This paper has inconsistent values - the number of treatment and control patients differs in the text and Table 1, we have used treatment 188 and control 148. Retrospective 336 hospitalized patients in the USA showing higher mortality, ICU admission, and intubation with treatment. Confounding by indication is likely. Time varying confounding is also likely due to declining usage over the early period when overall treatment protocols were also improving dramatically. Authors and reviewers appear to be unfamiliar with either of these.

Feb 2021, American J. Health-System Pharmacy, https://academic.oup.com/ajhp/advance-article/doi/10.1093/ajhp/zxab056/6144083, https://c19p.org/awad

762 patient aspirin prophylaxis study: 13% higher mortality (p=0.63) and 2% higher combined mortality/intubation (p=0.93).
Retrospective 762 COVID+ hospitalized patients in the USA, 239 on antiplatelet medication (199 aspirin), showing no significant differences in outcomes. For more discussion see [sciencedirect.com].

May 2021, Heart & Lung, https://www.heartandlung.org/article/S0147-9563(21)00175-8/fulltext, https://c19p.org/pan

403 patient ibuprofen early treatment study: 21% higher mortality (p=0.73), 12% higher ventilation (p=0.77), and 40% higher ICU admission (p=0.56).
Retrospective 403 COVID-19 cases in Israel, showing no significant difference in outcomes with ibuprofen use. Patients were asked about ibuprofen use starting a week before diagnosis of COVID-19 - treatment time may have been early, late, or prophylactic.

Sep 2020, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X20303438, https://c19p.org/rinott

901 patient N-acetylcysteine late treatment study: 19% higher mortality (p=0.33), 34% higher ICU admission (p=0.08), and 1% higher hospital discharge (p=0.94).
Retrospective 1,083 consecutive hospitalized COVID patients in Italy, showing no significant differences with NAC treatment. The number of patients transferred to another facility exceeds the number of deaths, which may significantly affect results.

Dec 2021, ERJ Open Research, https://openres.ersjournals.com/content/8/1/00542-2021, https://c19p.org/faverio

373 patient favipiravir late treatment RCT: 19% higher mortality (p=0.54), 53% higher ventilation (p=0.15), and 19% higher ICU admission (p=0.56).
RCT late stage patients (median SpO2 89), 193 treated with favipiravir, 187 with lopinavir/ritonavir, showing no significant differences in mortality, intubation, or ICU admission.

Mar 2021, Int. Immunopharmacology, https://www.sciencedirect.com/science/article/pii/S1567576921001582, https://c19p.org/solaymanidodaran

158 patient ibuprofen prophylaxis study: 100% higher mortality (p=0.001), 428% higher severe cases (p=0.0007), and 13% higher progression (p=0.04).
Retrospective 158 COVID-19 patients in Iran, showing higher risk of mortality with ibuprofen use.

Jul 2020, Archives of Clinical Infectious Diseases, https://brief.land/archcid/articles/106847.html, https://c19p.org/samimagham2

1,853 patient HCQ late treatment RCT: 19% higher mortality (p=0.23).
WHO SOLIDARITY open-label trial with 954 very late stage (64% on oxygen/ventilation) HCQ patients, mortality relative risk RR 1.19 [0.89-1.59], p=0.23. HCQ dosage very high as in RECOVERY, 1.6g in the first 24 hours, 9.6g total over 10 days, only 25% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors state they do not know the weight or obesity status of patients to analyze toxicity (since they do not adjust dosage based on patient weight, toxicity may be higher in patients of lower weight). KM curves show a spike in HCQ mortality days 5-7, corresponding to ~90% of the total excess seen at day 28 (a similar spike is seen in the RECOVERY trial). Almost all excess mortality is from ventilated patients. Authors refer to a lack of excess mortality in the first few days to suggest a lack of toxicity, but they are ignoring the very long half-life of HCQ and the dosing regimen - much higher levels of HCQ will be reached later. Increased..

Oct 2020, SOLIDARITY Trial Consortium, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2023184, https://c19p.org/solidarity

1,669 patient HCQ late treatment study: 70% higher mortality (p=0.01).
Retrospective database analysis of 1,669 patients in the US showing OR 1.81, p = 0.01. Confounding by indication is likely. COVID-19 was determined via PCR+ results, therefore authors include patients asymptomatic for COVID-19, but in the hospital for other reasons. While authors adjust for severity, the method used is very poor. 93.5% of patients are classified as "mild", which is patients with no documented care in a critical care unit within 8 hours of admission. Therefore almost all patients are in the same category, and those in a different category may be due to symptoms unrelated to COVID-19. Lower bias toward male patients in the control group also agrees with the hypothesis that the control group is made up of more people that were in hospital for another reason. Since the analysis covers the initial period of the pandemic in the USA, it is likely that HCQ was used more often earlier in the analysis period when treatment protocols were considerably worse. It's..

Dec 2020, Int. J. Infectious Diseases, https://www.sciencedirect.com/science/article/pii/S1201971220325832, https://c19p.org/sands

24,174 patient antiandrogen prophylaxis study: 25% higher mortality (p=0.11).
Case control study with 474 patients that died of COVID-19 in Sweden, showing higher risk with ADT, without statistical significance.

Dec 2021, Scandinavian J. Urology, https://www.tandfonline.com/doi/pdf/10.1080/21681805.2021.2019304, https://c19p.org/gedeborg

14,849 patient vitamin D prophylaxis study: 42% higher mortality (p=0.35) and 146% more cases (p<0.0001).
Retrospective 15,440 patients with hepatobiliary and pancreatic diseases in the United Kingdom, 226 with confirmed COVID-19, showing higher risk with vitamin D supplementation. Results are likely confounded by impaired vitamin D processing and propensity to prescribe supplementation based on specifics of each patient's disease and vitamin D levels. Adjustments used broad age ranges, likely adding to residual confounding.

Mar 2021, Pancreatology, https://www.sciencedirect.com/science/article/abs/pii/S1424390320307298, https://c19p.org/ullah2

379 patient nitazoxanide early treatment RCT: 79% lower hospitalization (p=0.22), 85% lower severe cases (p=0.07), and 7% slower recovery (p=0.88).
RCT with 184 outpatients treated with an extended release formulation of nitazoxanide, and 195 controls, showing lower hospitalization and progression to severe disease with treatment. There was one COVID-19 related death in the treatment arm. 600mg twice daily for five days.

Apr 2021, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00040-2/fulltext, https://c19p.org/rossignol

404,109 patient vitamin D prophylaxis study: 1% higher mortality (p=0.91) and 1% fewer cases (p=0.65).
Retrospective study of cholecalciferol and calcitriol supplementation in Catalonia showing a small but significant lower risk of cases with cholecalciferol, but no significant difference for mortality, or for calcitriol supplementation. Significant benefit was found for cases, severity, and mortality in patients achieving serum vitamin D levels ≥30ng/ml.

Jul 2021, J. Endocrinological Investigation, https://link.springer.com/article/10.1007/s40618-021-01639-9, https://c19p.org/oristrell2

108 patient HCQ late treatment study: 67% higher mortality (p=0.57).
Small retrospective database analysis of 36 patients receiving HCQ not showing significant differences. Confounding by indication is likely.

Aug 2020, J. Global Antimicrobial Resistance, https://www.sciencedirect.com/science/article/pii/S2213716520301934, https://c19p.org/kalligeros

70 patient favipiravir early treatment RCT: 40% worse improvement (p=0.57).
Preliminary report for an RCT in Nepal with 38 favipiravir patients and 32 control patients, showing no significant differences. There were no serious side effects.

Feb 2022, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(21)01001-8/fulltext, https://c19p.org/adhikari

99,890 patient acetaminophen prophylaxis study: 29% higher hospitalization (p<0.0001).
Aanlysis of prescriptions in multiple databases showing higher risk of COVID-19 hospitalization with acetaminophen use for COPD patients. Acetaminophen use was more prevalent in hospitalized patients compared to diagnosed patients (data from tables 1, 5, and S3).

Jan 2022, Wellcome Open Research, https://wellcomeopenresearch.org/articles/7-22/v3, https://c19p.org/morenomartos

34,936 patient proton pump inhibitor prophylaxis study: 9% more cases (p=0.58).
Retrospective 34,936 hypertensive outpatients in Spain showing no significant difference in COVID-19 cases with PPIs and antihistamine H1RAs.

Jul 2020, The J. Clinical Hypertension, https://onlinelibrary.wiley.com/doi/10.1111/jch.13948, https://c19p.org/vilacorcoles2

36,160 patient proton pump inhibitor prophylaxis study: 44% higher severe cases (p<0.0001).
Retrospective 4,251 severe COVID-19 cases and 36,738 matched controls in Scotland showing increased risk of severe COVID-19 with PPI use and antihistamine H1RA use. Adjusted results are only provided for the patients not in care homes (2,357 cases and 33,803 controls).

Feb 2021, BMC Medicine, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-01907-8, https://c19p.org/mckeigue

314 patient melatonin prophylaxis RCT: 108% more cases (p=0.26).
PrEP RCT healthcare workers in Spain, showing no significant difference in cases with melatonin prophylaxis. Most cases were asymptomatic or paucisymtomatic, there were two symptomatic cases, no moderate/severe cases, and no hospitalization. The registered primary outcome is symptomatic cases. Authors report on all cases due to the small number of symptomatic cases. They did not include the original primary outcome results in the paper, but have provided the results via email to a contributor. The dosage in this trial is very low, 2mg daily. Meta regression suggests higher doses are much more effective. EudraCT 2020-001530-35.

Feb 2022, J. Clinical Medicine, https://www.mdpi.com/2077-0383/11/4/1139, https://c19p.org/garciagarcia

10,147 patient ursodeoxycholic acid prophylaxis study: 19% lower ICU admission (p=1) and 40% lower hospitalization (p=0.17).
Retrospective cohort study of 10,147 chronic liver disease patients in France, with 1,322 exposed to ursodeoxycholic acid (UDCA), showing lower risk of hospitalization for COVID-19 with UDCA exposure, without statistical significance (adjusted OR 0.48, 95% CI 0.20-1.19). A case-control analysis of 88 hospitalized patients and 840 matched controls showed no significant difference, and there was no significant difference for ICU admission and mortality. The study is underpowered due to the low number of COVID-19 hospitalizations.

Jan 2024, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.29418, https://c19p.org/corpechot

86,692 patient colchicine prophylaxis study: 8% higher hospitalization (p=0.68) and 12% more cases (p=0.68).
Retrospective 86,652 patients in Spain, showing no significant difference in cases and hospitalization with colchicine use. The different risk for patients prescribed colchicine may not be fully adjusted for. See [onlinelibrary.wiley.com].

Jan 2023, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.28496, https://c19p.org/saenzaldea

650 patient HCQ prophylaxis study: 215% higher hospitalization (p=0.36), 40% more symptomatic cases (p=0.44), and 5% more cases (p=0.88).
Retrospective 317 HCQ users and 333 household contacts, showing higher risk with HCQ.

Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27731, https://c19p.org/oztas

4,716 patient HCQ late treatment RCT: 9% higher mortality (p=0.15) and 15% higher ventilation (p=0.19).
RECOVERY trial finds no significant benefit for very late stage (9 days after symptom onset) very sick patients. Results may be due to the unusually high dosage used (9.2g total over 10 days) [twitter.com, twitter.com]. The overall dosage used is only 23% less than the high dosage that Borba et al. show greatly increases risk (OR 2.8) [Borba]. Authors do not report results based on weight, BMI, or related conditions such as diabetes, which may provide additional evidence of toxic dosages. Authors do not adjust dosage based on patient weight, so toxicity may be higher in patients of lower weight. KM curves show a spike in HCQ mortality days 5-8, corresponding to ~85% of the total excess seen at day 28 (a similar spike is seen in the SOLIDARITY trial). Authors note: "we did not observe excess mortality in the first 2 days of treatment ... when early effects of dose-dependent toxicity might be expected", but they are ignoring the very long half-life of HCQ and the dosing..

Jun 2020, RECOVERY Collaborative Group, NEJM, https://www.nejm.org/doi/full/10.1056/NEJMoa2022926, https://c19p.org/recovery

653 patient fluvoxamine early treatment RCT: 11% higher combined mortality/hospitalization (p=0.88), 16% higher progression (p=0.68), and 2% lower hospitalization (p=1).
COVID-OUT remotely operated RCT, showing no significant difference in outcomes. Results for other treatments are listed separately - metformin , ivermectin . The "control" group includes patients receiving metformin, which is known to be beneficial for COVID-19 [ c19early.org ] . Authors note that the dosage used in the trial is lower than that of other trials [ twitter.com (H) ] . Control arm results are very different between treatments, for example considering hospitalization/death, this was 1.0% for ivermectin vs. 2.7% for overall control, however it was 1.3% for the ivermectin-specific control. 394 control patients are shared. The rate for the non-shared 261 metformin control patients is 5%, compared to 1.3% for ivermectin control patients. The metformin arm started earlier, however it is unclear why the difference in outcomes is so large. Results were delayed for 6 months with no explanation, with followup ending Feb 14, 2022. Multiple outcomes are missing, for example time to..

Aug 2022, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2201662, https://c19p.org/covidoutf

2,119 patient aspirin late treatment RCT: 5% higher mortality (p=0.66) and 8% lower progression (p=0.32).
RCT very late stage (baseline SpO2 77%) patients, showing no significant differences with rivaroxaban and aspirin treatment.

Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002983, https://c19p.org/eikelboome

1,697,522 patient ibuprofen prophylaxis study: 12% higher hospitalization (p=0.26) and 8% more cases (p=0.25).
PSM retrospective 1,697,522 osteoarthritis or back pain patients in the US, showing no significant differences in COVID-19 cases and hospitalization for ibuprofen vs. other NSAIDs.

Jul 2022, Drugs, https://link.springer.com/article/10.1007/s40265-022-01822-z, https://c19p.org/xieib

197 patient vitamin D prophylaxis study: 73% higher mortality (p=0.14) and 17% higher hospitalization (p=0.68).
Retrospective 105 Parkinson's disease patients, 92 caregivers, and 127 hospital inpatients, showing higher, but not statistically significant mortality and hospitalization with treatment. Supplementation was defined as >=25,000IU/month for at least 3 months.

Nov 2020, Nutrition, https://www.sciencedirect.com/science/article/pii/S0899900720303385, https://c19p.org/cereda2

44,866 patient acetaminophen prophylaxis study: 21% higher mortality (p<0.0001).
Retrospective 44,866 hospitalized COVID-19 patients in Sweden, showing higher mortality with vitamin D deficiency and with acetaminophen use. The study focuses on cardiorenal disease, finding higher risk of mortality with CRD. Authors also show that COVID-19 mortality was about 1.5x higher when compared with influenza in the first two pandemic waves, but there was no significant difference in the third wave (HR 1.53 [1.45-1.62] and 1.52 [1.44-1.61] in the first two waves and 1.07 [0.99-1.14] in the third).

Apr 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-069037, https://c19p.org/ritsinger

110 patient metformin prophylaxis study: 225% higher progression (p=0.05).
Retrospective 110 hospitalized COVID-19 patients with diabetes in China, showing increased risk of severity with metformin.

Oct 2020, Clinical and Translational Science, https://ascpt.onlinelibrary.wiley.com/doi/10.1111/cts.12897, https://c19p.org/gao4

2,200 patient HCQ prophylaxis study: 142% higher severe cases (p=0.59) and 6% more cases (p=0.67).
Retrospective 2,200 healthcare workers in India, 996 taking HCQ prophylaxis, showing no significant differences. There were large differences in the occupation of participants and therefore exposure, and the authors make no adjustments.

Jan 2022, J. Basic and Clinical Physiology and Pharmacology, https://www.degruyter.com/document/doi/10.1515/jbcpp-2021-0221/html, https://c19p.org/juneja

650,317 patient aspirin prophylaxis study: 37% higher severe cases (p<0.0001).
Retrospective 650,317 COVID-19 patients in Japan showing higher risk of severe COVID-19 with low-dose apirin use. Although cardiovascular disease should have been adjusted for (details of adjustments are not provided), there may be significant residual confounding because aspirin use might indicate more severe or complex cardiovascular issues not fully captured by the adjustment.

Sep 2024, Discover Public Health, https://ete-online.biomedcentral.com/articles/10.1186/s12982-024-00225-7, https://c19p.org/sakamakie

304 patient azithromycin early treatment RCT: 33% higher hospitalization (p=1), 67% lower progression (p=0.62), 100% worse recovery (p=0.5), and 4% worse viral clearance (p=0.63).
Low risk patient RCT for HCQ+AZ and HCQ vs. control, not showing any significant differences. Authors note that the results are not applicable to higher risk patients, that positive PCR may simply reflect detection of inactive (non-infectious) viral remnants, that an alternative dosage regimen may be more effective, and that medication adherence was unknown. HCQ dosing was 600mg/day for 1 week, therapeutic levels may not be reached for several days. There were no deaths or serious adverse events. Viral load was already very high at baseline.

Nov 2020, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537020303898, https://c19p.org/omraniazaz

309 patient proton pump inhibitor prophylaxis study: 17% higher mortality (p=0.49), 25% higher ICU admission (p=0.05), 126% higher progression (p=0.14), and 19% shorter hospitalization (p=0.18).
Retrospective 309 hospitalized patients showing higher risk of severe cases (ASA≥3) with PPI use.

Nov 2023, Academic J. Gastroenterology & Hepatology, https://www.researchgate.net/publication/375801185_Effect_of_Preadmission_Proton_Pump_Inhibitor_PPI_on_the_clinical_outcome_of_Covid-19_Hospitalised_Patients_during_the_Pandemic_Academic_Journal_of, https://c19p.org/elkanzi

1,977,972 patient ibuprofen prophylaxis study: 23% higher mortality (p=0.19).
Retrospective 2,463,707 people in the UK, showing no significant difference in COVID-19 mortality with NSAID use. Current NSAID users were defined as those ever prescribed an NSAID in the 4 months prior to study start, and non-users were those with no record of NSAID prescription in the same time period.

Jan 2021, Annals of the Rheumatic Diseases, https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2020-219517, https://c19p.org/wong4ib

266 patient ivermectin ICU study: 53% higher mortality (p=0.13).
Retrospective 266 COVID-19 ICU patients in India, showing significantly lower mortality with PVP-I oral gargling and topical nasal use, and non-statistically significant higher mortality with ivermectin and lower mortality with remdesivir.

Dec 2021, Cureus, https://www.cureus.com/articles/73667-determinants-of-outcome-among-critically-ill-police-personnel-with-covid-19-a-retrospective-observational-study-from-andhra-pradesh-india, https://c19p.org/jamir

106 patient favipiravir late treatment RCT: 76% lower ICU admission (p=0.2), 42% worse recovery (p=0.51), and 43% improved viral clearance (p=0.21).
RCT with 54 favipiravir, 51 HCQ, and 52 SOC hospitalized patients in Bahrain, showing no significant differences. Viral clearance improved with both treatments, but did not reach statistical significance with the small sample size.

Mar 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-08794-w, https://c19p.org/alqahtani2a

804 patient ivermectin early treatment RCT: 61% lower hospitalization for ivermectin vs. placebo (not reported in the paper which uses a control group including metformin), despite very late treatment, low-risk patients, and poor administration. ER results do not match symptoms.
COVID-OUT remote RCT, showing no significant differences compared to a combined metformin/placebo "control" group. Results for other treatments are listed separately - metformin , fluvoxamine . Authors include metformin patients in the control group, allowing details of adjustments to affect results. Using standard treatment vs. placebo analysis shows 61% lower hospitalization, or 75% lower for patients with onset ≤5 days (not statistically significant with only 7 and 5 events). These results are not reported in the paper or the supplementary appendix, readers need to request the data. Authors note that "hospitalization is perhaps the most accurate and well-documented end point". There are many major issues as detailed below. We provide more detailed analysis of this study due to widespread incorrect press. Submit Updates or Corrections Severity Issue CRITICAL 1. Ivermectin vs. placebo analysis - 61% lower hospitalization CRITICAL 2. Severity mismatch for ivermectin treatment but not..

Aug 2022, NEJM, https://www.nejm.org/doi/10.1056/NEJMoa2201662, https://c19p.org/covidoutivm

28,636 patient famotidine late treatment study: 3% higher mortality (p=0.67) and 3% higher combined mortality/ICU admission (p=0.62).
Retrospective 1,816 famotidine users and 26,820 non-users hospitalized for COVID-19 in the USA, showing no significant differences with treatment.

Sep 2020, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000001153, https://c19p.org/shoaibif

86,602 patient fluvoxamine prophylaxis study: 395% higher ICU admission (p=0.24), 40% lower hospitalization (p=0.39), and 12% fewer cases (p=0.6).
Retrospective 86,602 patients in Spain, showing lower COVID-19 risk SSRIs citalopram and paroxetine. There were no significant difference for fluvoxamine, which few patients were taking.

Apr 2023, European Neuropsychopharmacology, https://www.sciencedirect.com/science/article/pii/S0924977X23000639, https://c19p.org/visosvarela

77 patient favipiravir early treatment RCT: 105% higher hospitalization (p=0.43).
RCT 77 outpatients in Iran, showing increased hospitalization with treatment, without statistical significance. Favipiravir 1600mg daily for five days. 21% of favipiravir patients did not complete treatment.

Jan 2023, Advances in Respiratory Medicine, https://www.mdpi.com/2543-6031/91/1/4, https://c19p.org/vaezi

248 patient favipiravir early treatment RCT: 6% worse viral clearance (p=0.42).
High conflict of interest RCT with very low risk patients, high existing immunity, and a post-hoc change to exclude patients more likely to benefit. There was no significant difference in viral clearance with favipiravir among patients with high viral load at baseline. Patients in both arms had very short viral clearance half-life times. With rapid viral clearance and very low risk patients, infection is less likely to spread to other tissues. Systemic treatment is less applicable, and has less time to reach therapeutic concentrations before self-recovery. Treatment administered directly to the respiratory tract, e.g. as in [Yildiz Pekoz], may be more effective for COVID-19 in general, and extend applicability to fast-resolving cases with infection primarily localized to the respiratory tract. Authors note that "all-cause hospitalisation for clinical deterioration (until day 28) was a secondary endpoint", but do not provide the result. For more discussion of the post-hoc..

Apr 2023, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-023-08835-3, https://c19p.org/luvira

441 patient smoking prophylaxis study: 270% more cases (p<0.0001).
Case control analysis with 149 multiple sclerosis patients and 292 matched controls in Italy, showing lower risk of COVID-19 cases with smoking.

Feb 2023, J. Neurology, https://link.springer.com/10.1007/s00415-023-11618-0, https://c19p.org/montinism

650,317 patient ursodeoxycholic acid prophylaxis study: 79% higher severe cases (p<0.0001).
Retrospective 650,317 COVID-19 patients in Japan showing higher risk of severe COVID-19 with UDCA use. There may be significant residual confounding because authors do not appear to have adjusted for liver diseases (details of adjustments are not provided), and UDCA use is a strong indicator of certain liver conditions.

Sep 2024, Discover Public Health, https://ete-online.biomedcentral.com/articles/10.1186/s12982-024-00225-7, https://c19p.org/sakamakiudca

152 patient colchicine late treatment RCT: 36% higher mortality (p=0.77), 7% higher progression (p=1), 76% lower ICU admission (p=0.21), and 4% shorter hospitalization (p=0.69).
RCT 152 hospitalized patients in Italy, showing no significant difference in outcomes with colchicine treatment. Table 2 shows 13% of patients treated with antivirals in the colchicine arm, however 16.9% were treated with one specific antiviral (HCQ).

Oct 2022, European J. Internal Medicine, https://www.sciencedirect.com/science/article/pii/S0953620522003739, https://c19p.org/perricone

315 patient exercise study: 105% more cases (p=0.0003).
Case control study in China with 105 cases and 210 matched controls, showing COVID-19 cases associated with physical activity ≥5 times per week. Authors note that people may choose gyms for exercise in winter, leading to higher exposure risk.

Nov 2020, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241540, https://c19p.org/gao5

226 patient favipiravir late treatment study: 42% higher mortality (p=0.1), 90% higher ICU admission (p=0.02), and 11% slower recovery (p=0.17).
Retrospective 226 COVID-19 pneumonia patients, 110 treated with favipiravir, showing higher mortality (p=0.1) and ICU admission (p=0.02) with treatment in multivariate analysis.

Aug 2021, J. Infection and Public Health, https://www.sciencedirect.com/science/article/pii/S1876034121002410, https://c19p.org/almoosa

468,569 patient diet study: 3% higher mortality (p=0.85).
Retrospective 468,569 adults in the UK, showing no significant difference in COVID-19 mortality based on diet quality, however significantly lower mortality was seen with higher diet quality for pneumonia and infectious diseases.

Aug 2021, Brain, Behavior, and Immunity, https://www.sciencedirect.com/science/article/pii/S088915912100180X, https://c19p.org/ahmadi2dt

180 patient acetaminophen late treatment RCT: 110% higher ICU admission (p=0.05), 110% higher need for oxygen therapy (p=0.05), and 36% longer hospitalization (p=0.01).
RCT 180 moderate hospitalized COVID-19 patients in Egypt, showing higher ICU admission and longer hospitalization with acetaminophen compared with ibuprofen.

Apr 2023, The Open Anesthesia J., https://openanesthesiajournal.com/VOLUME/17/ELOCATOR/e258964582303020/, https://c19p.org/sobhyace

56 patient ivermectin early treatment RCT: 15% worse recovery (p=0.58) and 2% improved viral clearance (p=0.64).
Small low-risk patient RCT with 30 low-dose ivermectin and 26 control patients, with no primary outcome events in either arm. Viral load was significantly better with ivermectin on day 5, while there was no significant difference on day 1 or day 14. There was no significant difference in combined symptoms, however authors include cough which was the most frequent symptom and may persist long after infection has been cleared. Ivermectin patients were 4 years older with a higher standard deviation, had higher prevalence of obesity, diabetes, hypertension, and cardiovascular disease, and lower prevalence of hepatic and kidney disease. SOC included acetaminophen, which has . The slow viral clearance seen may be in part due to acetaminophen use. Authors conclude that "ivermectin is not effective to prevent progression to a severe state", however there was no progression to severe in either group. Authors report 92.9% of ivermectin patients compliant with the symptom diary,..

May 2022, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-022-07890-6, https://c19p.org/delarocha

290 patient HCQ late treatment study: 59% higher mortality (p=0.12).
290 patient observational trial in the USA, not showing a significant difference with HCQ treatment overall, but showing significantly lower mortality in a subgroup of patients where HCQ is expected to be beneficial based on a machine learning algorithm.

Nov 2020, J. Clinical Medicine, https://www.mdpi.com/2077-0383/9/12/3834, https://c19p.org/burdick

272 patient nitric oxide late treatment study: 54% higher mortality (p=0.25) and 27% higher ventilation (p=0.26).
Retrospective 272 acute respiratory failure patients in the USA treated with high-flow nasal cannula, 66 treated with inhaled nitric oxide, showing increased mortality with inhaled nitric oxide. There were significant differences in the usage of several other treatments between the groups.

Jan 2021, Clinical Medicine Insights: Circulatory, Respiratory and Pulmonary Medicine, http://journals.sagepub.com/doi/10.1177/11795484211047065, https://c19p.org/chandel

1,779 patient various antiandrogen prophylaxis study: 124% higher mortality (p=0.12) and 7% fewer cases (p=0.8).
Retrospective 1,779 prostate cancer patients, showing no significant differences in COVID-19 outcomes with ADT.

Jan 2021, J. Urology, https://www.auajournals.org/doi/10.1097/JU.0000000000001338, https://c19p.org/klein

228 patient HCQ late treatment study: 126% higher severe cases (p=0.002).
Retrospective 228 rheumatic disease and 228 non-rheumatic disease hospitalized COVID-19 patients in Spain, showing higher risk of severe COVID-19 with HCQ treatment.

Aug 2020, Annals of the Rheumatic Diseases, https://ard.bmj.com/lookup/doi/10.1136/annrheumdis-2020-218296, https://c19p.org/pablos

34,601 patient vitamin D prophylaxis RCT: 11% lower hospitalization (p=1), 20% higher severe cases (p=0.17), and no change in cases (p=0.98).
RCT 17,278 low-risk patients (zero mortality) treated with 5mL/day cod liver oil (~400IU vitamin D) and 17,323 placebo patients in Norway with, showing no significant differences with treatment. The placebo group had higher vitamin D at baseline, and both groups had comparable vitamin D during treatment (74 vs. 63 nmol/L). 23% of control patients took vitamin D supplements and 62% consumed fatty fish (typically a good source of vitamin D). Adherence was low (<70% for "strict" compliance, which only required >0.5L consumed, or treatment for > "2-3" months).

Sep 2022, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj-2022-071245, https://c19p.org/brunvoll

606 patient azvudine late treatment study: 32% higher mortality (p=0.2), 62% higher ventilation (p=0.22), 7% higher ICU admission (p=0.89), and 9% shorter hospitalization (p=0.05).
PSM retrospective 303 hospitalized patients treated with azvudine and 303 matched controls in China, showing shorter hospital stay and higher lymphocyte improvement rate, particularly for non-severe patients, however there were no significant differences for mortality, ICU admission, or mechanical ventilation.

Oct 2024, Infection and Drug Resistance, https://www.dovepress.com/efficacy-of-azvudine-therapy-in-patients-with-severe-and-non-severe-co-peer-reviewed-fulltext-article-IDR, https://c19p.org/zhang35

1,278 patient colchicine prophylaxis study: 406% higher hospitalization (p=0.12), 73% more symptomatic cases (p=0.07), and 24% more cases (p=0.35).
Retrospective 635 HCQ users and 643 household contacts, showing higher risk with colchicine in unadjusted results. Patients with conditions leading to the use of colchicine may have significantly different baseline risk, e.g. [Topless].

Mar 2022, J. Medical Virology, https://onlinelibrary.wiley.com/doi/10.1002/jmv.27731, https://c19p.org/oztaso

1,302 patient favipiravir late treatment study: 184% higher ventilation (p=0.01), 181% higher ICU admission (p=0.001), and 100% longer hospitalization (p=0.001).
Retrospective 1,472 hospitalized patients in Turkey, showing a higher ICU admission and ventilation with favipiravir. Results may be subject to confounding by indication.

Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full, https://c19p.org/babayigit

218 patient vitamin D late treatment RCT: 25% lower ventilation (p=0.85), 27% lower ICU admission (p=0.62), and 3% lower progression (p=0.82).
Late stage RCT with 115 patients treated with a single dose of 500,000IU cholecalciferol and 103 placebo patients, showing no significant differences. Authors do not explain why they did very late treatment with cholecalciferol instead of calcifediol or calcitriol, which would avoid several days delay in conversion. Baseline vitamin D levels were relatively high, limiting the potential benefit.

May 2022, PLOS ONE, https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0267918https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0267918&type=printable, https://c19p.org/mariani

2,611 patient colchicine late treatment RCT: 8% higher mortality (p=0.38) and 4% higher progression (p=0.58).
RCT very late stage (baseline SpO2 80%) patients, showing no significant differences with colchicine treatment.

Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002983, https://c19p.org/eikelboom

365 patient proton pump inhibitor late treatment study: 204% higher mortality (p=0.02).
Retrospective hospitalized COVID-19 patients in Indonesia showing higher mortality with high dose proton pump inhibitor (PPI) use compared to low dose.

Aug 2022, J. Of The Indonesian Medical Association, https://mki-ojs.idionline.org/jurnal/article/view/802, https://c19p.org/liwang

686 patient proton pump inhibitor prophylaxis study: 127% higher mortality (p=0.001).
Prospective study showing COVID- PPI users had higher salivary ACE2 expression, and retrospective analysis of 694 hospitalized COVID-19 patients, showing higher mortality with PPI use.

May 2021, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000001311, https://c19p.org/liu22

336 patient HCQ prophylaxis study: 88% more cases (p=0.09).
Retrospective 230 low risk healthcare workers taking HCQ prophylaxis, and 106 that declined, showing higher cases without statistical significance. No case severity information is provided. The point estimate favored HCQ when excluding the first 14 days and including participants that worked for at least 16 days. Authors note a significant dose response relationship.

Dec 2022, Life, https://www.mdpi.com/2075-1729/12/12/2047, https://c19p.org/shahrin

1,199 patient HCQ late treatment study: 22% higher mortality (p=0.18) and 55% higher ventilation (p=0.02).
Retrospective 1,769 hospitalized patients in the USA showing no significant differences for HCQ, and higher intubation for HCQ+AZ.

Jun 2021, American J. Epidemiology, https://academic.oup.com/aje/advance-article/doi/10.1093/aje/kwab183/6308675, https://c19p.org/gerlovin

1,087 patient proton pump inhibitor prophylaxis study: 37% higher combined mortality/ICU admission (p=0.09) and 96% worse results (p=0.0001).
Retrospective 1,087 hospitalized COVID-19 patients showing significantly increased risk of secondary bacterial infections (SBIs) and secondary bacterial sepsis (SBS) sepsis with pre-admission proton pump inhibitor (PPI) use. Combined ICU admission/mortality was higher but without statistical significance.

Oct 2024, Annals of Medicine, https://www.tandfonline.com/doi/full/10.1080/07853890.2024.2399761, https://c19p.org/bianconi2

672 patient dexamethasone early treatment study: 130% higher mortality (p<0.0001).
Retrospective 672 COVID-19 patients in Zimbabwe, showing higher mortality with dexamethasone treatment.

Mar 2023, Pan African Medical J., https://www.panafrican-med-journal.com/content/article/44/142/full, https://c19p.org/madamombedxdex

98 patient vitamin C early treatment RCT: 18% faster recovery (p=0.15).
Small 214 low-risk outpatient RCT showing non-statistically significant faster recovery with zinc and with vitamin C. A secondary analysis concludes that vitamin C increases recovery rate by 71% (p = 0.036) [pubpeer.com]. See also [patrickholford.com].

Feb 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2776305, https://c19p.org/thomasc

1,000 patient smoking early treatment study: 134% more cases (p<0.0001).
Retrospective 1,000 frontline healthcare workers in South Africa showing higher risk of COVID-19 for non-smokers.

Mar 2024, Vaccines, https://www.mdpi.com/2076-393X/12/3/329, https://c19p.org/mockeliunas

192 patient HCQ late treatment study: 151% higher mortality (p=0.03) and 46% higher combined mortality/intubation (p=0.23).
Retrospective 230 hospitalized patients in Brazil showing higher mortality with HCQ treatment. Authors note that the treatments were more likely to be offered to sicker patients. Authors note that they do not know if treatment was started before or after ICU admission and intubation. Dosage is unknown.

Nov 2021, Revista da Associação Médica Brasileira, https://www.scielo.br/j/ramb/a/kzbmDvJqjJdQR9GfqK65CZs/, https://c19p.org/ferreira2h

253 patient proton pump inhibitor prophylaxis study: 100% higher mortality (p=0.39), 48% higher ventilation (p=0.54), and 25% higher ICU admission (p=0.64).
Retrospective 254 hospitalized COVID-19 patients in Jordan showing higher rates of gastrointestinal symptoms such as abdominal pain and diarrhea with proton pump inhibitor (PPI) use. There were no significant differences for mortality, ventilation, and ICU admission. Authors hypothesize that PPIs may facilitate SARS-CoV-2 survival and invasion in the gastrointestinal tract.

Jun 2024, Annals of Medicine, https://www.tandfonline.com/doi/full/10.1080/07853890.2024.2355581, https://c19p.org/almomani

86 patient favipiravir early treatment RCT: 16% higher need for oxygen therapy (p=0.73) and 16% worse viral clearance (p=0.66).
Early terminated RCT 84 patients in Japan, showing no significant difference in outcomes with favipiravir treatment. There was a trend for improved efficacy for patients enrolled within 48 hours of symptom onset.

Oct 2023, J. Infection and Chemotherapy, https://www.sciencedirect.com/science/article/pii/S1341321X23002556, https://c19p.org/iwata

295 patient proton pump inhibitor prophylaxis study: 92% higher mortality (p=0.02) and 80% higher progression (p=0.02).
Retrospective 295 hospitalized COVID-19 patients showing higher mortality and acute respiratory distress syndrome (ARDS) with pre-hospitalization proton pump inhibitor (PPI) use. Authors hypothesize that hypochlorhydria caused by PPIs may allow SARS-CoV-2 to more easily infect the gastrointestinal tract.

Nov 2021, European J. Gastroenterology & Hepatology, https://journals.lww.com/10.1097/MEG.0000000000002013, https://c19p.org/ramachandran

92 patient vitamin D prophylaxis study: 70% higher mortality (p=0.52), 10% higher ventilation (p=0.89), and 30% higher ICU admission (p=0.61).
Retrospective 92 hospitalized patients not showing significant differences in outcomes based on vitamin D status or supplementation.

Aug 2021, J. Primary Care & Community Health , https://journals.sagepub.com/doi/full/10.1177/21501327211041206, https://c19p.org/pecina

41 patient ivermectin early treatment RCT: 66% improved viral load (p=0.09).
Proof of concept RCT with 30 ivermectin patients and 15 control patients, showing a concentration dependent antiviral activity, but no significant difference in clinical outcomes. There was no significant difference in viral load reduction between groups overall, but a significant difference was found in patients with higher median plasma ivermectin levels (72% vs. 42%, p=0.004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r=0.47, p=0.02). The change in viral load is provided for the <160ng/mL and >160ng/mL groups, but not the overall treatment group. The corrigendum provides individual viral decay rates for computing the overall treatment group viral decay rate. Authors published a corrigendum: [sciencedirect.com].

Jun 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S258953702100239X, https://c19p.org/krolewiecki

60 patient HCQ late treatment RCT: 55% lower hospital discharge (p=0.2) and 10% improved viral clearance (p=0.78).
Small RCT with 61 patients in Nigeria, all patients treated with ivermectin, zinc, and vitamin C, showing no significant improvements in recovery with the addition of HCQ+AZ.

Sep 2021, J. Infectious Diseases and Epidemiology, https://www.clinmedjournals.org/articles/jide/journal-of-infectious-diseases-and-epidemiology-jide-7-233.php?jid=jide, https://c19p.org/babalola2h

2,539 patient favipiravir late treatment PSM study: 14% higher mortality (p=0.13), 2% higher progression (p=0.83), 19% longer ICU admission (p=0.005), and 29% longer hospitalization (p=0.001).
PSM retrospective 29 hospitals in Saudi Arabia, showing higher mortality with favipiravir treatment, without statistical significance.

Feb 2023, Saudi Pharmaceutical J., https://www.sciencedirect.com/science/article/pii/S1319016423000348, https://c19p.org/alshamrania

1,047 patient aspirin prophylaxis study: 10% higher mortality (p=0.52), 110% higher ICU admission (p=0.007), and 10% longer hospitalization (p=0.02).
Retrospective 1,047 pneumonia patients in 5 COVID-19 geriatric units in France and Switzerland, significantly higher ICU admission and longer hospital stays with existing aspirin treatment. Numbers in this study appear to be inconsistent, for example the abstract says 147 of 301 aspirin patients died, shown as 34.3%, while Table 1 shows 104 of 301 (34.6%).

Jan 2022, GeroScience, https://link.springer.com/article/10.1007%2Fs11357-021-00499-8, https://c19p.org/sullerot

20,641 patient aspirin prophylaxis PSM study: 3% higher mortality (p=0.48), 3% higher ventilation (p=0.75), and 4% higher ICU admission (p=0.65).
Retrospective 20,641 hospitalized patients in Spain, showing no significant difference in outcomes with existing aspirin use.

Nov 2021, Internal and Emergency Medicine, https://link.springer.com/10.1007/s11739-021-02870-1, https://c19p.org/formiga2

113 patient proton pump inhibitor prophylaxis study: 228% higher mortality (p=0.008) and 392% higher ICU admission (p=0.02).
Retrospective 113 hospitalized COVID-19 patients in Spain showing higher mortality and ICU admission with PPI use.

Sep 2020, Frontiers in Pharmacology, https://www.frontiersin.org/article/10.3389/fphar.2020.570721/full, https://c19p.org/garciamenaya

834 patient proton pump inhibitor prophylaxis study: 59% higher severe cases (p=0.002).
Retrospective 834 elderly patients in France showing higher risk of severe COVID-19 with PPI use, and increasing risk with increasing dosage.

Apr 2024, Age and Ageing, https://academic.oup.com/ageing/article/doi/10.1093/ageing/afae082/7645558, https://c19p.org/gramont

210 patient acetaminophen late treatment RCT: 43% worse recovery (p=0.002), 3925% higher progression (p<0.0001), and 20% worse viral clearance (p=0.19).
RCT with 107 paracetamol and 103 indomethacin patients, showing higher progression and worse recovery with paracetamol.

Apr 2022, Scientific Reports, https://www.nature.com/articles/s41598-022-10370-1, https://c19p.org/ravichandranace

295 patient camostat early treatment RCT: 152% higher mortality (p=1), 13% lower progression (p=0.79), and 16% improved viral clearance (p=0.36).
RCT 295 outpatients in the USA, showing no significant differences with camostat.

Mar 2021, Sagent Pharmaceuticals, NCT04583592, https://clinicaltrials.gov/study/NCT04583592, https://c19p.org/sagent

205 patient losartan late treatment RCT: 3% higher mortality (p=1), 27% higher ventilation (p=0.47), and 3% lower need for oxygen therapy (p=0.66).
RCT 205 hospitalized COVID-19 patients showing no significant difference in lung injury (PaO2:FiO2 ratio) at day 7 with losartan treatment, and no difference in clinical outcomes including mortality. Losartan was associated with more adverse events including acute kidney injury and need for vasopressors. Results suggest losartan is not beneficial and may cause harm in this setting.

Mar 2022, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2790162, https://c19p.org/puskarich2

414 patient HCQ prophylaxis RCT: 196% higher progression (p=1), 52% lower hospitalization (p=0.62), and 14% fewer cases (p=0.73).
Low-dose prophylaxis RCT with low-risk healthcare workers in India, showing no significant differences. Symptomatic case results are not provided. Followup was over 6 months, however treatment ended after 3 months. 21% of patients discontinued treatment before 3 months (Table S2).

May 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2021-059540, https://c19p.org/tirupakuzhi

3,114 patient famotidine late treatment PSM study: 84% higher severe cases (p=0.0001).
Retrospective 4,445 COVID+ patients in China, showing higher risk of combined death/intubation/ICU with famotidine and with PPIs.

Dec 2020, Gut, https://gut.bmj.com/content/70/10/2012.full, https://c19p.org/zhou3

3,144 patient proton pump inhibitor late treatment PSM study: 165% higher severe cases (p=0.0001).
Retrospective 4,445 COVID+ patients in China, showing higher risk of combined death/intubation/ICU with famotidine and with PPIs.

Dec 2020, Gut, https://gut.bmj.com/content/70/10/2012.full, https://c19p.org/zhou3ppi

34 patient nitric oxide late treatment RCT: 179% higher ventilation (p=1), 21% lower hospitalization (p=1), and 38% worse results (p=0.72).
Early terminated RCT with 47 ER patients in the USA, less than 12 days of symptoms, showing no significant difference in outcomes with a single high-dose administration of inhaled nitric oxide by mask, 250ppm for 30 min.

May 2022, The American J. Emergency Medicine, https://www.sciencedirect.com/science/article/pii/S0735675722002832, https://c19p.org/strickland

2,196 patient dexamethasone early treatment study: 103% higher mortality (p=0.0002).
Retrospective 2,196 COVID-19 patients in Taiwan (49% mild cases, 44% moderate, 7% severe) showing significantly higher mortality with dexamethasone. Authors report that all infected patients were hospitalized at the time of the study in Taiwan.

Aug 2024, BMC Infectious Diseases, https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-024-09654-w, https://c19p.org/yen2dexdex

76 patient favipiravir early treatment RCT: 13% higher progression (p=0.89), 23% slower recovery (p=0.42), and 67% worse viral clearance (p=0.13).
Very high COI low-risk patient RCT in South Africa, showing no significant differences with favipiravir plus nitazoxanide. There were no deaths and no COVID-19 hospitalizations for favipiravir plus nitazoxanide. More patients were seropositive at baseline in the treatment arm (28% vs 22%). Favipiravir 1600mg 12-hourly for 1 day, then 600mg 12-hourly for 6 days. Nitazoxanide 1000mg 12-hourly for 7 days.

Oct 2022, eBioMedicine, https://www.sciencedirect.com/science/article/pii/S2352396422005047, https://c19p.org/chandiwana

76 patient nitazoxanide early treatment RCT: 13% higher progression (p=0.89), 23% slower recovery (p=0.42), and 67% worse viral clearance (p=0.13).
Very high COI low-risk patient RCT in South Africa, showing no significant differences with favipiravir plus nitazoxanide. There were no deaths and no COVID-19 hospitalizations for favipiravir plus nitazoxanide. More patients were seropositive at baseline in the treatment arm (28% vs 22%). Favipiravir 1600mg 12-hourly for 1 day, then 600mg 12-hourly for 6 days. Nitazoxanide 1000mg 12-hourly for 7 days.

Oct 2022, eBioMedicine, https://www.sciencedirect.com/science/article/pii/S2352396422005047, https://c19p.org/chandiwanan

477 patient HCQ late treatment PSM study: 333% higher mortality (p=0.0001) and 613% higher severe cases (p<0.0001).
Retrospective 1,106 prostate cancer patients, showing higher mortality with HCQ treatment.

Nov 2021, JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2786026, https://c19p.org/schmidth

1,213 patient metformin prophylaxis PSM study: 65% higher mortality (p=0.25).
Retrospective 1,213 hospitalized diabetic COVID-19 patients in China, showing no significant difference in mortality with pre-existing metformin use.

Aug 2021, Cell Metabolism, https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30426-5, https://c19p.org/cheng2

128 patient HCQ late treatment RCT: 6% higher mortality (p=1) and 173% higher ICU admission (p=0.13).
Small RCT on very late stage use of HCQ, with 48% on oxygen at baseline. 67 HCQ patients, 61 control. Baseline states were not comparable - 82% more HCQ patients had the highest severity at baseline, there was 32% more male HCQ patients, and 44% more control patients used AZ. The HCQ group also had significantly more patients with cerebrovascular disease, cardiovascular disease (non-hypertension), renal disease (non-dialysis), and a history of organ transplants.

Sep 2020, Open Forum Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofaa446/5910201, https://c19p.org/ulrich

3,024 patient proton pump inhibitor late treatment study: 600% higher severe cases (p<0.0001).
Retrospective 3,024 hospitalized COVID-19 patients in China showing increased risk of the composite outcome of ICU admission, mechanical ventilation, or death with proton pump inhibitor (PPI) use. Intravenous administration was significantly worse than oral. Authors hypothesize that PPIs may lead to worse COVID-19 outcomes by increasing the risk of secondary infections, cardiac damage, renal damage, and liver complications.

Jan 2022, Therapeutic Advances in Gastroenterology, http://journals.sagepub.com/doi/10.1177/17562848221104365, https://c19p.org/yao3

135 patient N-acetylcysteine late treatment RCT: 3% higher mortality (p=0.94), 16% higher ventilation (p=0.64), 9% lower ICU admission (p=0.65), and 10% longer hospitalization (p=0.87).
RCT 135 severe stage patients in Brazil, showing no significant differences. NAC 21g (~300mg/kg) for 20 hours. U1111-1250-356 [ensaiosclinicos.gov.br].

Sep 2020, Clinical Infectious Diseases, https://academic.oup.com/cid/article/72/11/e736/5910353, https://c19p.org/dealencar

160,923 patient proton pump inhibitor prophylaxis study: 46% higher mortality (p=0.02), 33% higher severe cases (p=0.004), and 8% more cases (p=0.1).
UK Biobank retrospective with 160,923 patients showing increased risks of influenza, pneumonia, COVID-19 severity, and COVID-19 mortality with proton pump inhibitor (PPI) use.

Jul 2024, eLife, https://elifesciences.org/articles/94973, https://c19p.org/zeng2

19 patient favipiravir late treatment RCT: 422% higher ICU admission (p=0.21), 11% improved recovery (p=1), and 422% worse viral clearance (p=0.21).
Small late stage RCT with 10 favipiravir, 10 baloxavir marboxil, and 10 control patients in China, showing no significant differences.

Oct 2020, European J. Pharmaceutical Sciences, https://www.sciencedirect.com/science/article/pii/S092809872030419X, https://c19p.org/lou

1,126 patient spirulina early treatment RCT: 21% higher progression (p=0.29).
RCT 1,126 patients in Brazil showing no significant differences with low dose spirulina. The dose used was 7.6 times lower than the dose used by [Aghasadeghi] which shows significantly lower mortality. eFigure 1 shows 12 events in the treatment group before the first event in the placebo group. The probability of this happening is very low, ~ 0.001. One possible cause would be if some process resulted in patients expected to visit the ER soon being more likely to be placed in the treatment group. (Another possibility is treatment side effects causing ER visits, however the were fewer adverse events and fewer severe adverse events in the treatment group).

Aug 2024, The American J. Clinical Nutrition, https://www.sciencedirect.com/science/article/pii/S0002916524005884, https://c19p.org/reis13spi

197 patient astodrimer sodium early treatment RCT: 19% improved recovery (p=0.41) and 24% improved viral clearance (p=0.3).
RCT 222 non-hospitalized low risk COVID-19 patients showing lower SARS-CoV-2 viral load, faster viral clearance, and improvements in symptoms, particularly anosmia, with astodrimer sodium nasal spray compared to placebo. The reduction in viral load and benefits were statistically significant in patients aged 45 years and older, with greater effects in older age groups. There was only one hospitalization event. Treatment delay is not specified and may be relatively late - authors suggest that patients were "already at or past the time of peak viral load, and the infection was already in its decline phase".

Sep 2024, Pharmaceutics, https://www.mdpi.com/1999-4923/16/9/1173, https://c19p.org/winchester2

44 patient HCQ late treatment study: 215% higher mortality (p=0.38), 652% higher ventilation (p=0.15), 145% higher ICU admission (p<0.0001), and 107% longer hospitalization (p=0.007).
Planned RCT of HCQ vs. HCQ+nitazoxanide which was aborted due to the retracted Surgisphere paper. Authors retrospectively analyze a small set of HCQ vs. nitazoxanide patients (which were protocol deviations in the planned RCT), showing reduced hospitalization time and ICU admission with nitazoxanide.

Nov 2021, PAMJ - Clinical Medicine, https://www.clinical-medicine.panafrican-med-journal.com/content/article/7/15/full/, https://c19p.org/calderon2h

244 patient colchicine prophylaxis study: 150% higher need for oxygen therapy (p=1), 150% higher hospitalization (p=1), 7% improved recovery (p=1), and 1% fewer cases (p=1).
Retrospective 244 Behçet disease patients in Spain, showing no significant difference in outcomes with colchicine treatment. Confounding by indication may significantly affect results - colchicine may be prescribed more often for more serious cases, which may have a higher baseline risk for COVID-19.

Sep 2022, Medicina Clínica, https://www.sciencedirect.com/science/article/pii/S238702062200417X, https://c19p.org/correarodriguez

800 patient cannabidiol prophylaxis study: 212% more symptomatic cases (p<0.0001) and 3% more cases (p=0.33).
Retrospective 800 e-cigarette users in the USA, showing higher risk of COVID-19 diagnosis and symptoms with cannabis use.

Mar 2022, Addictive Behaviors, https://www.sciencedirect.com/science/article/pii/S0306460321003555, https://c19p.org/merianos

489 patient famotidine late treatment study: 519% higher mortality (p=0.001) and 2390% higher ICU admission (p=0.001).
Retrospective 489 COVID+ hospitalized patients in the USA, showing higher mortality with famotidine treatment.

Oct 2021, American J. Gastroenterology, https://journals.lww.com/ajg/Fulltext/2021/10001/S1301_A_Retrospective_Review__Famotidine_Use_Is.1305.aspx, https://c19p.org/stolow

367 patient HCQ late treatment RCT: 73% higher hospitalization (p=0.54), 20% improved recovery (p=0.19), and 17% improved viral clearance (p=0.19).
Delayed publication of an early terminated late treatment RCT with low-risk (no mortality) outpatients in the USA, showing no significant differences with HCQ. Authors do not provide symptom onset data, but the subgroup analysis suggests that more patients may have been in the 5+ days group (the estimate for the 5+ days group has a smaller confidence interval, and the overall mean/median for HCQ is much closer to the 5+ days group). Treatment was started one day after enrollment according to Table S1 (authors report "commonly 1 day after randomization" in the text). This suggests that most patients were treated 6+ days after onset. Subgroup analysis for <5, ≥5 days is provided only for viral shedding duration, and shows improved results for earlier treatment. Adherence was only 66% (Figure 1). Publication was 21 months after the trial ended. Registered outcomes were modified November 2022, December 2022, and January 2023, all over a year after completion of the trial. For..

Mar 2023, Microbiology Spectrum, https://journals.asm.org/doi/10.1128/spectrum.04674-22, https://c19p.org/spivak

250 patient colchicine late treatment RCT: 75% higher mortality (p=0.54), 200% higher ventilation (p=0.28), and 46% higher severe cases (p=0.34).
RCT 250 late stage (80% on oxygen) hospitalized patients in the USA, showing no significant differences with combined colchicine/rosuvastatin treatment. There was a trend towards increased risk, which authors note may be due to chance because the patients enrolled in the treatment arm were in more serious condition, for example, patients in the treatment arm were more frequently on oxygen, more frequently on HFNC/NIV, and had higher mean SOFA scores. Colchicine 0.6mg two times daily for 3 days followed by 0.6mg daily, and high-intensity rosuvastatin 40mg daily.

Feb 2023, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-067910, https://c19p.org/shah6

10,000 patient smoking prophylaxis study: 82% more cases (p<0.0001).
Retrospective 10,000 adults in Qatar, showing lower risk of COVID-19 cases with smoking. Authors do not analyze COVID-19 severity.

Nov 2023, Nutrients, https://www.mdpi.com/2072-6643/16/7/1037, https://c19p.org/akbar2sm

353 patient favipiravir late treatment RCT: 29% higher mortality (p=0.54), 33% higher ventilation (p=0.54), 2% higher ICU admission (p=0.54), and 1% slower recovery (p=0.94).
Late stage RCT with 353 hospitalized patients, showing no significant differences with favipiravir treatment overall, however a trend towards benefit was seen within patients treated relatively early, including a statistically significant shorter time to discharge with treatment.

Nov 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.11.08.21265884v1, https://c19p.org/shenoy

101 patient HCQ prophylaxis RCT: 60% more symptomatic cases (p=0.41) and 92% more cases (p=0.12).
Small PrEP RCT of low risk healthcare workers, showing no significant differences. Authors report that there was no hospitalization, ICU care, or death from COVID-19, however table 3 of the preprint shows severe events labeled as "requiring hospitalization". Symptomatology and disease severity results in tables 3 and 4 appear inconsistent. NCT04359537.

May 2021, Cureus, https://www.cureus.com/articles/77806-pre-exposure-prophylaxis-with-various-doses-of-hydroxychloroquine-among-healthcare-personnel-with-high-risk-exposure-to-covid-19-a-randomized-controlled-trial, https://c19p.org/syed

152 patient proton pump inhibitor prophylaxis study: 248% higher mortality (p=0.02), 124% higher ARDS (p=0.02), and 86% worse results (p=0.03).
Retrospective 152 hospitalized COVID-19 patients showing increased risk of secondary infections, ARDS, and mortality with proton pump inhibitor (PPI) use. Authors hypothesize that reduced gastric acid production from PPIs leads to bacterial overgrowth and microaspiration, increasing the risk of secondary lung infections. PPIs may also have immunomodulatory effects.

Jul 2020, J. Internal Medicine, https://onlinelibrary.wiley.com/doi/10.1111/joim.13121, https://c19p.org/luxenburger

27,746 patient proton pump inhibitor prophylaxis PSM study: 79% higher severe cases (p=0.009) and 10% fewer cases (p=0.11).
PSM retrospective 132,316 patients in South Korea, showing significantly higher risk of severe COVID-19 with PPI use, but no significant difference in cases.

Jul 2020, Gut, https://gut.bmj.com/lookup/doi/10.1136/gutjnl-2020-322248, https://c19p.org/lee15

327 patient fluvoxamine early treatment RCT: 2% higher need for oxygen therapy (p=1) and 22% higher hospitalization (p=0.77).
RCT 327 outpatients in Thailand, showing no significant difference with 50mg fluvoxamine bid added to favipiravir. Authors note that trials showing benefit mostly used 100mg bid.

Jun 2023, Int. J. Infectious Diseases, https://www.ijidonline.com/article/S1201-9712(23)00641-0/fulltext, https://c19p.org/siripongboonsitti2

6,556 patient famotidine prophylaxis study: 107% higher progression (p=0.06) and 109% higher need for oxygen therapy (p=0.07).
PSM retrospective 6,556 COVID-19 patients in South Korea, showing higher risk of poor outcomes with famotidine vs. other H2-blocker use.

May 2023, Heliyon, https://www.sciencedirect.com/science/article/pii/S2405844023033789, https://c19p.org/kwon2

5,197 patient smoking prophylaxis study: 72% more cases (p=0.02).
Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity, depression, anxiety, stress, and poor health-related quality of life.

Nov 2023, Diseases, https://www.mdpi.com/2079-9721/11/4/165, https://c19p.org/pavlidousm

477 patient HCQ late treatment RCT: 6% higher mortality (p=0.85) and 3% worse 7-point scale results (p=0.87).
Early terminated very late stage (65% on supplemental oxygen) RCT with 242 HCQ and 237 control patients showing no significant difference in outcomes. For the subgroup not on supplemental oxygen at baseline (relatively early treatment), the odds ratio for the 7 point outcome scale is: aOR 0.61 [0.34-1.08]. Dosage may be too low: Dose in first 24 hours - 1g (compare to Boulware et al. 2g) Dose in 5 days - 2.4g (compare to Boulware et al. 3.8g) Dosage note: Boulware 2g within 24 hours includes the second day dose. Note two important differences with the RECOVERY/SOLIDARITY dosage which is believed to be dangerously high - in RECOVERY/SOLIDARITY the total dose is much higher, which is problematic because the half-life of HCQ is very long, and it is given to patients that are already in very serious condition. Note the paper reports primary outcome values with OR>1 favoring HCQ, we have converted to OR<1 favoring HCQ. Subgroup analysis is in the supplemental appendix.

Nov 2020, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2772922, https://c19p.org/self

272 patient aspirin prophylaxis PSM study: 700% higher mortality (p=0.03), 433% higher ventilation (p=0.14), 433% higher ICU admission (p=0.14), and 33% fewer cases (p=0.29).
Retrospective database analysis of 22,660 patients tested for COVID-19 in South Korea. There was no significant difference in cases according to aspirin use. Aspirin use before COVID-19 was related to an increased death rate and aspirin use after COVID-19 was related to a higher risk of oxygen therapy. Results for late treatment are listed separately [Kim].

Sep 2021, Medicina, https://www.mdpi.com/1648-9144/57/9/931, https://c19p.org/kim2

4,634 patient proton pump inhibitor prophylaxis study: 197% higher mortality (p=0.0004) and 10% worse viral clearance (p=0.02).
Retrospective 4,634 hospitalized COVID-19 patients in China, showing higher mortality and slower viral clearance with proton pump inhibitor (PPI) use. Authors hypothesize that PPIs may increase susceptibility to COVID-19 by increasing ACE2 expression.

Feb 2022, J. Global Health, http://jogh.org/documents/2022/jogh-12-05005.pdf, https://c19p.org/wu12

50 patient favipiravir late treatment RCT: 20% longer hospitalization, 58% improved recovery (p=0.08), and 47% faster viral clearance (p=0.04).
Small very late treatment RCT in the USA, with 25 favipiravir and 25 control patients, showing faster viral clearance with treatment. The benefit was only seen in patients <8 days from symptom onset. There were no significant differences in clinical outcomes. The death in the favipiravir group occurred after discharge and was believed to be unrelated to COVID-19 or favipiravir.

Dec 2021, Open Forum Infectious Diseases, https://academic.oup.com/ofid/article/8/12/ofab563/6455602, https://c19p.org/finberg

84 patient HCQ early treatment RCT: 14% improved viral clearance (p=0.15).
RCT 84 low risk patients, 42 treated with HCQ/AZ, showing no significant differences. There was only one hospitalization which was in the treatment arm.

Aug 2021, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/pii/S0924857921002065, https://c19p.org/rodrigues

31,072,642 patient aspirin prophylaxis study: 4% higher combined mortality/intubation (p=0.18) and 3% higher hospitalization (p=0.05).
Retrospective 31 million people without cardiovascular disease in France, showing no significant difference in hospitalization or combined intubation/death with low dose aspirin prophylaxis.

Jun 2022, Research and Practice in Thrombosis and Haemostasis, https://onlinelibrary.wiley.com/doi/10.1002/rth2.12743, https://c19p.org/botton

1,029 patient ivermectin early treatment RCT: 205% higher progression (p=0.49), 4% worse improvement (p=0.62), and 4% improved recovery (p=0.72).
RCT very low risk patients (mean age 35.7, SpO2 97.4) showing no significant differences with rapid recovery and almost no progression in both groups. The groups were unbalanced. There were 41% more patients with dyspnea at baseline in the treatment group. Similarly, at baseline patients with 4+ symptoms scored 2+ were more common in the treatment group - 7% for ivermectin vs. 4% for placebo. Table S8 shows only one case of COVID-19 pneumonia. Authors report 3 and 1 cases of progression, this matches the 3 and 1 cases of the adverse event "COVID-19" in Table S8. It's unclear how the COVID-19 adverse events were defined since all patients are meant to have COVID-19. Authors definition of progression includes "use of COVID-19 therapeutic agents" and therefore the significance for progression of disease is not clear. The study is designed to produce a null result with very low risk patients, administration on an empty stomach, the primary outcome including symptoms..

Sep 2022, J. Infection and Chemotherapy, https://www.sciencedirect.com/science/article/pii/S1341321X23003161, https://c19p.org/mikamo

51,973 patient proton pump inhibitor prophylaxis study: 179% more cases (p=0.0001).
Survey of 53,130 individuals with a history of GI symptoms showing increased risk of COVID-19 positivity with proton pump inhibitor (PPI) use, especially twice-daily PPI use. There was a dose-response relationship between PPI use and COVID-19 risk. Those taking PPIs twice daily had 3.67 times higher odds of testing positive compared to those not taking PPIs. The authors hypothesize that PPI-induced hypochlorhydria may impair the body's defense against ingested pathogens like SARS-CoV-2.

Aug 2020, American J. Gastroenterology, https://journals.lww.com/10.14309/ajg.0000000000000798, https://c19p.org/almario

9,842 patient aspirin prophylaxis PSM study: 61% higher mortality (p<0.0001) and 309% higher severe cases (p<0.0001).
N3C retrospective 250,533 patients showing significantly higher mortality with aspirin use. Note that aspirin results were not included in the journal version or v2 of this preprint.

Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reesee

12 patient losartan late treatment RCT: 533% higher mortality (p=0.49) and 160% longer hospitalization (p=0.3).
RCT 15 hospitalized COVID-19 patients showing no significant differences with losartan treatment. The study was terminated early due to low enrollment.

Oct 2022, Contemporary Clinical Trials Communications, https://www.sciencedirect.com/science/article/pii/S2451865422000850, https://c19p.org/freilich

11,340 patient colchicine late treatment RCT: 1% higher mortality (p=0.77), 18% higher ventilation (p=0.06), 2% higher combined mortality/intubation (p=0.47), and 2% lower hospital discharge (p=0.44).
RCT with 5,610 colchicine and 5,730 control patients showing mortality RR 1.01 [0.93-1.10]. Very late stage treatment, median 9 days after symptom onset, baseline 32% ventilation (5% invasive). ISRCTN 50189673. Dose frequency was halved for patients receiving a moderate CYP3A4 inhibitor, patients with an estimated glomerular filtration rate of less than 30 mL/min per 1·73m², and those with an estimated bodyweight of less than 70kg.

May 2021, Recovery Collaborative Group, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260021004355, https://c19p.org/recoveryc

829 patient HCQ prophylaxis RCT: 27% more cases (p=0.33).
Early terminated PEP RCT comparing HCQ and vitamin C with 781 low-risk patients (83% household contacts), reporting no significant differences. Different results were reported at IDWeek from the AIM results. The study enrolled people with their last exposure within 4 days, i.e., if someone was exposed for 30 days in a row, they could be enrolled anywhere from day 1 to day 34. Therefore many were likely infected earlier than the enrollment date. Note that PCR has a very high false negative rates, e.g., 100% on day 1 and 67% on day 4 here [ncbi.nlm.nih.gov]. 50% of infections were detected by day 4. With the PCR false negatives and treatment delays it is likely that a majority of infections happened before enrollment or before HCQ can reach therapeutic levels. Significantly more cases were caught at baseline in the control group (54 vs. 29 for HCQ) and excluded from analysis. The early presentation stated that therapy started one day after enrollment and study supplies were sent to the..

Dec 2020, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M20-6519, https://c19p.org/barnabas

68 patient HCQ prophylaxis RCT: 69% more cases (p=0.46).
Early terminated healthcare worker PrEP RCT with only 68 patients and 8 cases, showing no significant difference with HCQ. No information on symptoms per group, case severity, or the timing of cases is provided.

Feb 2023, BMC Research Notes, https://bmcresnotes.biomedcentral.com/articles/10.1186/s13104-023-06281-7, https://c19p.org/llanoscuentas

156 patient lactoferrin early treatment RCT: 26% improved recovery (p=0.24), 11% worse viral clearance (p=0.36), and 8% lower PASC (p=0.84).
RCT 156 mild/moderate COVID-19 patients, 77 treated with hen egg white and bovine colostrum, showing faster recovery of severe symptoms with treatment. There were no significant differences in overall symptom duration, viral clearance, or post-COVID symptoms. Only one participant progressed to severe COVID-19.

Jul 2023, Future Science OA, https://www.future-science.com/doi/10.2144/fsoa-2023-0024, https://c19p.org/mann

352 patient HCQ ICU RCT: 51% higher mortality (p=0.06).
Long-term followup for the REMAP-CAP very late stage ICU trial, showing higher risk with HCQ, not quite reaching statistical significance.

Dec 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2799870, https://c19p.org/higgins

874 patient proton pump inhibitor prophylaxis PSM study: 28% higher mortality (p=0.63), 75% higher ventilation (p=0.37), 150% higher ICU admission (p=0.11), and 21% higher progression (p=0.6).
PSM retrospective in South Korea, showing lower risk of COVID-19 cases with H2RA (including famotidine) and PPI use, but no significant difference in severe outcomes (results provided for the combined groups only).

Mar 2023, J. Korean Medical Science, https://jkms.org/DOIx.php?id=10.3346/jkms.2023.38.e99, https://c19p.org/kim11ppi

93 patient HCQ late treatment RCT: 120% higher mortality (p=0.35).
Small RCT in Norway showing no significant differences with HCQ treatment. Add-on trial to WHO Solidarity.

Jul 2021, Annals of Internal Medicine, https://www.acpjournals.org/doi/10.7326/M21-0653, https://c19p.org/barratdue

218 patient lactoferrin late treatment RCT: 12% higher mortality (p=0.85), 45% higher ventilation (p=0.39), 6% higher combined mortality/ICU admission (p=0.87), and 34% worse recovery (p=0.12).
RCT 218 hospitalized patients in Italy, showing no significant differences with lactoferrin treatment. Authors note that in several previous studies showing clinical improvement, lactoferrin was given at an earlier stage of disease. Authors also note that potential benefits with the late treatment in this study could be masked by other SOC medications - corticosteroids may have masked immunomodulatory effects of lactoferrin, and there may be heparin-dependent reduction in lactoferrin antiviral activity. 800mg oral bovine lactoferrin daily.

Mar 2023, Nutrients, https://www.mdpi.com/2072-6643/15/5/1285, https://c19p.org/matino

44 patient favipiravir late treatment RCT: 383% higher mortality (p=0.49), 37% higher ventilation (p=1), no change in improvement (p=0.45), and 17% improved recovery (p=0.64).
Underpowered RCT with 44 hospitalized patients in Spain, showing no significant difference with favipiravir treatment in the primary outcome of time to clinical improvement, or in the secondary efficacy outcomes. Adverse events were more frequent in the favipiravir group (68%) compared to placebo (32%), but most were mild.

Aug 2023, Pneumonia, https://pneumonia.biomedcentral.com/articles/10.1186/s41479-023-00124-6, https://c19p.org/horcajada

439,154 patient proton pump inhibitor prophylaxis study: 49% higher mortality (p=0.005), 36% higher severe cases (p=0.27), 20% higher hospitalization (p=0.0003), and 9% more cases (p<0.0001).
Retrospective 627,514 patients in Hong Kong showing slightly higher risk of COVID-19 with pre-vaccination proton pump inhibitor (PPI) use in two-dose or three-dose vaccine recipients, and higher risk of hospitalization and severe outcomes only in two-dose recipients.

May 2024, J. Gastroenterology and Hepatology, https://onlinelibrary.wiley.com/doi/10.1111/jgh.16601, https://c19p.org/cheung2

119 patient favipiravir early treatment RCT: 28% improved viral clearance (p=0.03).
240 patient RCT comparing favipiravir, favipiravir + LPV/r, LPV/r, and placebo, showing improved viral clearance with favipiravir. Efficacy was lower in the combined favipiravir + LPV/r arm, where plasma levels of favipiravir were lower. Favipiravir 1800mg twice daily on day 1 followed by 400mg four times daily on days 2-7.

Feb 2022, PLOS Medicine, https://journals.plos.org/plosone/article?id=10.1371/journal.pmed.1004120, https://c19p.org/lowe

199 patient favipiravir early treatment RCT: 1% higher need for oxygen therapy (p=1) and 56% higher hospitalization (p=0.38).
RCT with 99 favipiravir and 100 placebo patients in Australia, all except one being outpatients, showing no significant differences with treatment.

Jun 2022, eClinicalMedicine, https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00433-3/fulltext, https://c19p.org/mcmahon

41,652 patient acetaminophen prophylaxis PSM study: 61% higher mortality (p<0.0001) and 816% higher severe cases (p<0.0001).
N3C retrospective 250,533 patients showing significantly higher mortality with acetaminophen use. Note that acetaminophen results were not included in the journal version or v2 of this preprint, which focuses on NSAID analysis.

Apr 2021, medRxiv, https://www.medrxiv.org/content/10.1101/2021.04.13.21255438v1, https://c19p.org/reese

198 patient probiotics prophylaxis RCT: 2% higher mortality (p=1), 38% slower recovery (p=0.56), 28% higher severe cases (p=0.75), and 2% more symptomatic cases (p=1).
RCT 200 nursing home residents over 60 years old in Spain showing Loigolactobacillus coryniformis K8 probiotic administration enhanced IgG antibody response in subjects previously infected with SARS-CoV-2 and tended to improve IgA antibody response in those over 85 years old not previously infected, in the context of COVID-19 vaccination. There was no significant difference in incidence of COVID-19 infection between the probiotic and placebo groups during the study. The probiotic group had a higher percentage of asymptomatic COVID-19 cases compared to placebo, without statistical significance.

Jan 2022, Nutrients, https://www.mdpi.com/2072-6643/14/1/228, https://c19p.org/fernandezferreiro

40 patient vitamin K late treatment RCT: 200% higher mortality (p=1), 200% higher ICU admission (p=0.6), and 17% shorter hospitalization (p=0.52).
RCT 40 hospitalized COVID-19 patients showing vitamin K2 supplementation was well-tolerated and reduced dp-ucMGP levels, reflecting improved vitamin K status, but did not affect desmosine, a marker of elastic fiber degradation. The study was not powered to assess effects on clinical outcomes. Authors suggest that the dose may have been insufficient to fully correct the vitamin K deficiency seen in COVID-19, and that higher doses might be required to achieve potential protective effects against inflammation or lung damage.

Jun 2024, J. Clinical Medicine, https://www.mdpi.com/2077-0383/13/12/3476, https://c19p.org/visser

117 patient losartan early treatment RCT: 2% higher ICU admission (p=1), 205% higher hospitalization (p=0.36), and 27% higher progression (p=0.74).
RCT 117 symptomatic outpatients showing no significant difference in hospitalization, functional status, dyspnea, or viral load with losartan treatment. The trial was terminated early due to low event rates. Losartan 25mg twice daily for 10 days.

Jul 2021, eClinicalMedicine, https://www.sciencedirect.com/science/article/pii/S2589537021002376, https://c19p.org/puskarich

547 patient fluvoxamine early treatment RCT: 201% higher need for oxygen therapy (p=0.5), 9% lower hospitalization (p=1), and 12% lower progression (p=0.85).
Remote RCT 547 outpatients a median of 5 days from onset, showing no significant differences with fluvoxamine. The trial was stopped early and underpowered due to low event rates. The trial does not report outcomes that may not be underpowered like time to recovery. Authors note that treatment may have been too late.

Aug 2021, Open Forurm Infectious Diseases, https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofad419/7238414, https://c19p.org/reiersen

2,206 patient vitamin C late treatment RCT: 19% higher mortality (p=0.08) and 35% higher ventilation (p=0.04).
Very late stage (APACHE II 8 and 12 for non-critical and critical) RCT with publication delayed over a year showing higher ventilation and no significant difference in mortality with vitamin C. Authors have combined what was to be two separate trials into one trial, however there are very large differences between the trials. The results for each source trial are shown separately here [Adhikari, Adhikari]. eTable 15 shows that results in LOVIT-COVID were substantially better than those in REMAP-CAP. eTable 13 shows improved survival for LOVIT-COVID and worse survival for REMAP-CAP (authors provide mortality breakdown only for hospital survival): LOVIT-COVID shows 85% and 82% probability of superiority of vitamin C (critical and non-critical). REMAP-CAP shows 12% and 7% probability of superiority of vitamin C. Notably, LOVIT-COVID patients were blinded, while REMAP-CAP was open-label, introducing additional opportunity for bias on this highly politicized treatment. REMAP-CAP had more..

Oct 2023, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2811212, https://c19p.org/adhikari2

91 patient cannabidiol late treatment RCT: 557% higher hospitalization (p=0.25) and 33% slower recovery (p=0.21).
RCT 105 patients recruited in an ER in Brazil, 49 treated with CBD, showing no significant differences with treatment. 300mg CBD for 14 days. For discussion see [liebertpub.com].

Oct 2021, Cannabis and Cannabinoid Research, https://www.liebertpub.com/doi/full/10.1089/can.2021.0093, https://c19p.org/crippa

1,472 patient HCQ late treatment study: 112% higher ventilation (p=0.21), 53% higher ICU admission (p=0.33), and 17% longer hospitalization (p=0.05).
Retrospective 1,472 hospitalized patients in Turkey, showing a higher risk of ICU admission and ventilation with HCQ, without statistical significance.

Aug 2022, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2022.894126/full, https://c19p.org/babayigith

524 patient acetaminophen late treatment study: 220% higher mortality (p=0.001), 434% higher ventilation (p=0.001), 244% higher progression (p=0.005), and 100% longer hospitalization (p=0.001).
Retrospective 524 hospitalized patients in the USA, showing higher mortality and progression with acetaminophen use.

Oct 2021, Chest, https://www.sciencedirect.com/science/article/pii/S0012369221024430, https://c19p.org/manjani

19,915 patient proton pump inhibitor prophylaxis study: 48% higher mortality (p<0.0001), 119% higher ARDS (p<0.0001), 88% worse results (p<0.0001), and 73% higher need for oxygen therapy (p<0.0001).
Retrospective 19,915 hospitalized COVID-19 patients with gastrointestinal symptoms, showing that use of proton pump inhibitors or H2 receptor antagonists was associated with higher mortality, ARDS, sepsis, and ventilator or oxygen requirement among patients

Dec 2023, Gastro Hep Advances, https://www.sciencedirect.com/science/article/pii/S277257232200142X, https://c19p.org/patil3

245 patient PPE prophylaxis RCT: 164% worse results (p=0.08).
RCT 245 people in South Africa, showing no significant difference in COVID-19 cases with PPE use.

Oct 2021, NCT05119348, https://clinicaltrials.gov/study/NCT05119348, https://c19p.org/bekker

216 patient camostat late treatment RCT: 198% higher mortality (p=1), 18% higher hospitalization (p=1), and no change in recovery (p=0.99).
RCT 216 patients, 55% >5 days from symptom onset, showing no significant difference with camostat treatment.

Jun 2023, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciad342/7190261, https://c19p.org/jilg

3,881 patient colchicine late treatment RCT: 9% higher mortality (p=0.84), 2% higher combined mortality/hospitalization (p=0.93), and 2% higher hospitalization (p=0.92).
Late (5.4 days) outpatient RCT showing no significant difference in outcomes with colchicine treatment. Authors include a meta analysis of 6 colchicine RCTs, however there were 19 RCTs as of the publication date [c19colchicine.com].

Oct 2022, The Lancet Respiratory Medicine, https://www.sciencedirect.com/science/article/pii/S2213260022002995, https://c19p.org/eikelboom2

209 patient lactoferrin prophylaxis RCT: 59% more symptomatic cases (p=0.34) and 23% more cases (p=0.65).
Early terminated low-risk patient prophylaxis RCT in Peru, showing no significant difference in cases with lactoferrin. There were no moderate or severe cases.

Dec 2022, BioMetals, https://link.springer.com/10.1007/s10534-022-00477-3, https://c19p.org/navarro

376,254 patient vitamin B9 prophylaxis study: 164% higher mortality (p<0.0001) and 51% more cases (p<0.0001).
UK Biobank retrospective showing higher cases and mortality with folic acid supplementation.

Aug 2022, BMJ Open, https://bmjopen.bmj.com/lookup/doi/10.1136/bmjopen-2022-062945, https://c19p.org/topless2

392 patient nitazoxanide early treatment RCT: 404% higher ICU admission (p=0.24), 2% higher hospitalization (p=1), 16% worse recovery (p=0.37), and 12% improved viral clearance (p=0.006).
RCT 392 patients, median treatment delay 5 days, showing improved viral recovery at 5 days. Symptom recovery was no different at 5 days, and the treatment arm had two ICU admissions compared to zero for control. There were no serious adverse events.

Oct 2020, European Respiratory J., https://erj.ersjournals.com/content/early/2020/12/17/13993003.03725-2020, https://c19p.org/rocco

60 patient favipiravir late treatment RCT: 46% improved viral clearance (p=0.03) and 67% lower hospital discharge (p=0.51).
Interim results for a small RCT with 40 favipiravir and 20 control patients showing faster viral clearance with favipiravir. There is limited data in this report to evaluate the results. 75% of the control group received HCQ/CQ.

Aug 2020, Clinical Infectious Diseases, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454388/, https://c19p.org/ivashchenko

105 patient colchicine late treatment RCT: 7% improved recovery (p=0.21).
RCT 122 hospitalized patients in India, showing improved recovery with colchicine treatment. All patients received aspirin. There was one death and higher progression in the colchicine arm, however 3 patients in the colchicine arm had baseline ordinal scores ≥5, while no patients in the control arm did.

Jan 2023, Contemporary Clinical Trials Communications, https://www.sciencedirect.com/science/article/pii/S2451865423000169, https://c19p.org/sunilnaik

179 patient HCQ late treatment RCT: 37% improved recovery (p=0.15).
Small early terminated late treatment RCT showing no significant differences. The HCQ group was a median of 7 days from symptom onset at baseline, which may not include the delay delivering the medication. From the 4 HCQ hospitalizations, only one is in the per-protocol analysis, and that patient was hospitalized one day after randomization (authors do not specify if the patient received and took any HCQ before the hospitalization). The trial was terminated early due to the fraudulent Lancet article (wording here is notably different between the submitted and published versions). Per-protocol analysis, the submitted version, and the peer-review comments (two reviewers, only one with substantial feedback) are in the supplementary material. Long-term recovery results are reported in [Ganesh]. When a patient reported a symptom, they were asked whether they were still experiencing that symptom, and to choose between these three options when comparing the symptom to their pre-COVID-19..

Jun 2021, CMAJ Open, http://cmajopen.ca/content/9/2/E693.full, https://c19p.org/schwartz2

126 patient dexamethasone late treatment RCT: 134% higher ventilation (p=0.41), 217% higher ICU admission (p=0.46), 17% higher ARDS (p=0.81), and 3% shorter hospitalization (p=0.88).
RCT 126 hospitalized COVID-19 pneumonia patients not requiring oxygen at admission, showing no significant difference in outcomes with dexamethasone treatment.

Jul 2024, Frontiers in Medicine, https://www.frontiersin.org/articles/10.3389/fmed.2024.1385833/full, https://c19p.org/francomorenodexdex

317 patient ivermectin late treatment RCT: 104% higher ICU admission (p=0.62), 104% worse improvement (p=0.62), and 4% faster recovery (p=0.63).
RCT low risk hospitalized patients in Thailand showing no significant difference with the addition of ivermectin to favipiravir based SOC. Only the abstract is currently available. The trial was registered retrospectively [thaiclinicaltrials.org]. The primary outcome was WHO-category ordinal scale improvement of 2 points at days 3, 7, 14, 21, for which only a single unspecified time point (when almost all patients have recovered) is provided in the abstract (details may be in the full paper). The registration indicates that the intervention was only provided "after laboratory result", without explanation.

Dec 2022, Infection & Chemotherapy, https://icjournal.org/DOIx.php?id=10.3947/ic.2022.0127, https://c19p.org/sarojvisut

105 patient HCQ late treatment RCT: 57% higher mortality (p=0.2), 115% higher ventilation (p=0.03), and 147% worse recovery (p=0.02).
Early terminated very late stage (99% on oxygen, 81% in ICU, 18% on mechanical ventilation at baseline) RCT with 24 CQ patients, 29 HCQ, and 52 control patients, showing worse clinical outcomes with treatment. NCT04420247.

Apr 2021, Scientific Reports, https://www.nature.com/articles/s41598-021-88509-9, https://c19p.org/reanato

500 patient favipiravir late treatment RCT: 1154% higher mortality (p=0.08), 20% higher ventilation (p=0.76), and 9% higher ICU admission (p=0.84).
RCT 500 hospitalized patients in Malaysia, showing no significant differences with favipiravir treatment.

Nov 2021, Clinical Infectious Diseases, https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab962/6432025, https://c19p.org/chuah

231 patient favipiravir early treatment RCT: 619% higher ICU admission (p=0.11), 219% higher hospitalization (p=0.16), 12% slower recovery (p=0.51), and 15% slower viral clearance (p=0.51).
RCT with 112 favipiravir and 119 control patients showing no significant differences in outcomes. Viral clearance and clinical recovery for patients treated within 48 hours was better than those treated later. NCT04464408.

Jan 2022, Clinical Microbiology and Infection, https://www.sciencedirect.com/science/article/pii/S1198743X21007345, https://c19p.org/bosaeed2

1,591 patient ivermectin late treatment RCT: 99%, 98%, 97% posterior probability of efficacy for mean time unwell and clinical progression @14 and 7 days, despite very late treatment, low-risk patients, and poor administration. All exceed the pre-specified threshold for superiority. Clinical progression results were changed without explanation in a later version.
RCT low-risk outpatients with very late treatment (median 6 days, 25% ≥8 days) in the USA, showing 98% probability of efficacy for clinical progression at day 14, a treatment delay-response relationship, and significant efficacy for patients with severe symptoms at baseline. The posterior probability ivermectin is effective was 99%, 98%, 97% for mean time unwell and clinical progression @14 and 7 days. All exceed the pre-specified threshold for superiority [ fnih.org ] . Note that the clinical progression results exceeding the superiority threshold in the preprint [ medrxiv.org (C) ] changed in the journal version for the 400µg/kg arm, with no explanation for over 700 days). The 600µg/kg arm was reported separately [ Naggie ] . When not specified, comments refer to the 400µg/kg arm. We provide more detailed analysis of this study due to widespread incorrect press. There was one death reported in each of the 400µg/kg and 600µg/kg ivermectin arms. For 400µg/kg, the patient did not take..

Jun 2022, JAMA, https://jamanetwork.com/journals/jama/fullarticle/2797483, https://c19p.org/activ6ivm

4,464 patient vitamin D prophylaxis RCT: 41% higher hospitalization (p=0.16) and 9% more cases (p=0.55).
RCT 5,979 low risk patients (0 COVID-19 deaths) in the UK, showing no significant differences with vitamin D prophylaxis. CORONAVIT. NCT04579640. For more discussion see [ reddit.com , twitter.com (I) ] . 51% of confirmed COVID-19 cases were hospitalized in the control arm which is 7 times the median rate in other studies reporting both cases and hospitalization as of Sep 2022 (7.2%), suggesting possible issues with the data or major differences between the study population and the general population. Authors do not provide exact start/end dates (month only) or specify when infections occurred, however based on cases in the UK, most infections may have been closer to the start of the trial when vitamin D levels may still have been relatively low. Reportedly, authors do not plan to analyze this issue, and have declined to allow one of the funders access to the data. [ Villasis-Keever ] present an RCT showing conflicting results, 78% lower cases with vitamin D prophylaxis. In..

Mar 2022, BMJ, https://www.bmj.com/lookup/doi/10.1136/bmj-2022-071230, https://c19p.org/jolliffe2
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