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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

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 control group. No serious adverse events were reported. All patients had mild COVID-19 and the paper indicates early treatment, however time from onset is not reported and minimal baseline information is provided.

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

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

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

36 patient HCQ early treatment study: 66% improved viral clearance (p=0.001).
HCQ was significantly associated with reduction / elimination of viral load, which was enhanced with AZ. Updated 8/13: responses to this paper have raised methodological issues [sciencedirect.com, sciencedirect.com, sciencedirect.com]. Despite the limitations, this early observational study was a milestone in the discovery process, including detailed daily evolution of PCR positivity. This study should be viewed in the context of the series of studies from this group. An update to this paper, including originally excluded patients, confirms the effectiveness of HCQ+AZ on viral clearance and early discharge [sciencedirect.com]. Also see [sciencedirect.com] and the response from the authors [sciencedirect.com].

Mar 2020, Int. J. Antimicrobial Agents, https://www.sciencedirect.com/science/article/abs/pii/S0924857920300996, https://c19p.org/gautretjaa

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

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