COVID-19 early treatment: real-time analysis of 4,220 studies
Analysis of 72 COVID-19 early treatments,
approvals in 105 countries, database of
7,606 treatments
Zhang | In Silico and In Vitro study showing potential benefits of curcumin for severe COVID-19 by protecting mitochondrial function and reducing.. |
Hou | In Silico and In Vitro study showing metformin as a potential therapeutic for COVID-19/LUAD by regulating glucose metabolism. Authors identified.. |
Yang | Meta analysis of 19 RCTs with 2,435 total participants showing significantly lower ICU admission and mechanical ventilation with vitamin D treatment.. |
Bessi | In Vitro study showing that NHC, the active form of molnupiravir, can base pair with both G and A in two different tautomeric forms. This ambiguous.. |
Guan | 2,621 patients vitamin C prophylaxis: 31% fewer symptomatic cases (p=0.007) |
Timeline for when studies showed efficacy - details and limitations.
0.6% of treatments show efficacy.
Treatment cost times median NNT - details and limitations.
0.6% of treatments show efficacy.
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All clinical results for selected treatments. 0.6% of treatments show efficacy.
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Random effects meta-analysis of all studies (pooled effects, all stages). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all stages and outcomes depend on the distribution of stages and outcomes tested - for example late stage treatment may be less effective and if the majority of studies are late stage this may obscure the efficacy of early treatment. Please see the specific stage and outcome analyses. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.6% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of early treatment studies (pooled effects). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all outcomes are affected by the distribution of outcomes tested, please see detail pages for specific outcome analysis. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.6% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of all mortality results (all stages). Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Pooled results across all stages depend on the distribution of stages tested - for example late stage treatment may be less effective and if the majority of studies are late stage this may obscure the efficacy of early treatment. Please see the specific stage analyses. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.6% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of early treatment mortality results. Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.6% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of prophylaxis studies (pooled effects). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all outcomes are affected by the distribution of outcomes tested, please see detail pages for specific outcome analysis. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.6% of proposed treatments show efficacy in clinical studies. | |||||
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Random effects meta-analysis of prophylaxis mortality results. Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments. 0.6% of proposed treatments show efficacy in clinical studies. |
LATE TREATMENT | ||||||
Physician / Team | Location | Patients | HospitalizationHosp. | MortalityDeath | ||
Dr. David Uip (*) | Brazil | 2,200 | 38.6% (850) | Ref. | 2.5% (54) | Ref. |
EARLY TREATMENT - 40 physicians/teams | ||||||
Physician / Team | Location | Patients | HospitalizationHosp. | ImprovementImp. | MortalityDeath | ImprovementImp. |
Dr. Roberto Alfonso Accinelli 0/360 deaths for treatment within 3 days |
Peru | 1,265 | 0.6% (7) | 77.5% | ||
Dr. Mohammed Tarek Alam patients up to 84 years old |
Bangladesh | 100 | 0.0% (0) | 100.0% | ||
Dr. Oluwagbenga Alonge | Nigeria | 310 | 0.0% (0) | 100.0% | ||
Dr. Raja Bhattacharya up to 88yo, 81% comorbidities |
India | 148 | 1.4% (2) | 44.9% | ||
Dr. Flavio Cadegiani | Brazil | 3,450 | 0.1% (4) | 99.7% | 0.0% (0) | 100.0% |
Dr. Alessandro Capucci | Italy | 350 | 4.6% (16) | 88.2% | ||
Dr. Shankara Chetty | South Africa | 8,000 | 0.0% (0) | 100.0% | ||
Dr. Deborah Chisholm | USA | 100 | 0.0% (0) | 100.0% | ||
Dr. Ryan Cole | USA | 400 | 0.0% (0) | 100.0% | 0.0% (0) | 100.0% |
Dr. Marco Cosentino vs. 3-3.8% mortality during period; earlier treatment better |
Italy | 392 | 6.4% (25) | 83.5% | 0.3% (1) | 89.6% |
Dr. Jeff Davis | USA | 6,000 | 0.0% (0) | 100.0% | ||
Dr. Dhanajay | India | 500 | 0.0% (0) | 100.0% | ||
Dr. Bryan Tyson & Dr. George Fareed | USA | 20,000 | 0.0% (6) | 99.9% | 0.0% (4) | 99.2% |
Dr. Raphael Furtado | Brazil | 170 | 0.6% (1) | 98.5% | 0.0% (0) | 100.0% |
Rabbi Yehoshua Gerzi | Israel | 860 | 0.1% (1) | 99.7% | 0.0% (0) | 100.0% |
Dr. Heather Gessling | USA | 1,500 | 0.1% (1) | 97.3% | ||
Dr. Ellen Guimarães | Brazil | 500 | 1.6% (8) | 95.9% | 0.4% (2) | 83.7% |
Dr. Syed Haider | USA | 4,000 | 0.1% (5) | 99.7% | 0.0% (0) | 100.0% |
Dr. Mark Hancock | USA | 24 | 0.0% (0) | 100.0% | ||
Dr. Sabine Hazan | USA | 1,000 | 0.0% (0) | 100.0% | ||
Dr. Mollie James | USA | 3,500 | 1.1% (40) | 97.0% | 0.0% (1) | 98.8% |
Dr. Roberta Lacerda | Brazil | 550 | 1.5% (8) | 96.2% | 0.4% (2) | 85.2% |
Dr. Katarina Lindley | USA | 100 | 5.0% (5) | 87.1% | 0.0% (0) | 100.0% |
Dr. Ben Marble | USA | 150,000 | 0.0% (4) | 99.9% | ||
Dr. Edimilson Migowski | Brazil | 2,000 | 0.3% (7) | 99.1% | 0.1% (2) | 95.9% |
Dr. Abdulrahman Mohana | Saudi Arabia | 2,733 | 0.0% (0) | 100.0% | ||
Dr. Carlos Nigro | Brazil | 5,000 | 0.9% (45) | 97.7% | 0.5% (23) | 81.3% |
Dr. Benoit Ochs | Luxembourg | 800 | 0.0% (0) | 100.0% | ||
Dr. Ortore | Italy | 240 | 1.2% (3) | 96.8% | 0.0% (0) | 100.0% |
Dr. Valerio Pascua one death for a patient presenting on the 5th day in need of supplemental oxygen |
Honduras | 415 | 6.3% (26) | 83.8% | 0.2% (1) | 90.2% |
Dr. Sebastian Pop | Romania | 300 | 0.0% (0) | 100.0% | ||
Dr. Brian Proctor | USA | 869 | 2.3% (20) | 94.0% | 0.2% (2) | 90.6% |
Dr. Anastacio Queiroz | Brazil | 700 | 0.0% (0) | 100.0% | ||
Dr. Didier Raoult | France | 8,315 | 2.6% (214) | 93.3% | 0.1% (5) | 97.6% |
Dr. Karin Ried up to 99yo, 73% comorbidities, av. age 63 |
Turkey | 237 | 0.4% (1) | 82.8% | ||
Dr. Roman Rozencwaig patients up to 86 years old |
Canada | 80 | 0.0% (0) | 100.0% | ||
Dr. Vipul Shah | India | 8,000 | 0.1% (5) | 97.5% | ||
Dr. Silvestre Sobrinho | Brazil | 116 | 8.6% (10) | 77.7% | 0.0% (0) | 100.0% |
Dr. Unknown | Brazil | 957 | 1.7% (16) | 95.7% | 0.2% (2) | 91.5% |
Dr. Vladimir Zelenko | USA | 2,200 | 0.5% (12) | 98.6% | 0.1% (2) | 96.3% |
Mean improvement with early treatment protocols | 238,381 | HospitalizationHosp. | 94.4% | MortalityDeath | 94.9% |
Physician results with early treatment protocols compared to
no early treatment. These results are subject to selection and ascertainment
bias and more accurate analysis requires details of the patient populations
and followup, however results are consistently better across many teams, and consistent
with the extensive controlled trial evidence that shows a significant
reduction in risk with many early treatments, and improved results with the
use of multiple treatments in combination.
Zhang | In Silico and In Vitro study showing potential benefits of curcumin for severe COVID-19 by protecting mitochondrial function and reducing.. |
Hou | In Silico and In Vitro study showing metformin as a potential therapeutic for COVID-19/LUAD by regulating glucose metabolism. Authors identified.. |
Yang | Meta analysis of 19 RCTs with 2,435 total participants showing significantly lower ICU admission and mechanical ventilation with vitamin D treatment.. |
Bessi | In Vitro study showing that NHC, the active form of molnupiravir, can base pair with both G and A in two different tautomeric forms. This ambiguous.. |
Horby | 923 patient late treatment RCT: 11% higher mortality (p=0.55), 43% higher ventilation (p=0.59), 9% lower hospital discharge (p=0.46), and 12% improved viral clearance (p<0.0001) |
Zhang | Retrospective 440 counties/districts across 7 countries in the Americas, showing solar radiation exhibited an overall negative association with.. |
Guan | 2,621 patients prophylaxis: 31% fewer symptomatic cases (p=0.007) |
Hemilä | Reanalysis of the REMAP-CAP and LOVIT-COVID vitamin C RCTs- showing that the poor results may be explained by a rebound effect due to the abrupt.. |
Horby | 137 patient early treatment RCT: 1% higher mortality (p=1), 35% lower hospital discharge (p=0.33), and 19% improved viral clearance (p<0.0001) |
Naggie | Partial correction to ACTIV-6 600 confirming that 16% of patients were missing in the analysis. It's not clear how the trial could have such a large.. |
Rothman | 1,250 patient late treatment RCT: 1% fewer combined hospitalization/ER visits (p=1), 32% lower progression (p=0.29), and 2% improved recovery (p=0.71) |
Gaweł | Analysis of 69 lactating mothers showing higher colostrum lactoferrin concentrations in mothers with a history of COVID-19 infection during.. |
Recent studies (see the individual treatment pages for all studies):
May 31 |
et al., Heliyon, doi:10.1016/j.heliyon.2024.e31160 | Non-linear effects of meteorological factors on COVID-19: An analysis of 440 counties in the americas |
Retrospective 440 counties/districts across 7 countries in the Americas, showing solar radiation exhibited an overall negative association with daily new COVID-19 cases. The study used generalized additive models (GAM) and distributed lag.. | ||
May 27 |
et al., Frontiers in Pharmacology, doi:10.3389/fphar.2024.1367686 | Therapeutic effects of vitamin D supplementation on COVID-19 aggravation: a systematic review and meta-analysis of randomized controlled trials |
Meta analysis of 19 RCTs with 2,435 total participants showing significantly lower ICU admission and mechanical ventilation with vitamin D treatment. Results were better for moderate to severe COVID-19 patients, and with multiple dose ver.. | ||
May 24 |
et al., medRxiv, doi:10.1101/2024.05.23.24307731 | Molnupiravir or nirmatrelvir-ritonavir versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial |
11% higher mortality (p=0.55), 43% higher ventilation (p=0.59), 9% lower hospital discharge (p=0.46), and 12% improved viral clearance (p<0.0001). RECOVERY RCT showing no significant differences in mortality, ventilation, or discharge with either molnupiravir (923 patients) or paxlovid (137 patients). Viral load was improved with treatment but did not translate into clinical benefit.. | ||
May 23 |
et al., Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfae069.1573 | Effectiveness of regdanvimab on clinical outcomes in COVID-19 infected patients on hemodialysis |
59% lower mortality (p=0.002). Retrospective 230 hemodialysis patients with COVID-19, showing lower mortality with regdanvimab. Details of the adjusted results are not provided. | ||
May 22 |
et al., The American Journal of the Medical Sciences, doi:10.1016/j.amjms.2024.05.005 | High-dose Vitamin C Intake and COVID-19 Related Symptoms During the SARS-CoV-2 Pandemic |
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 21 |
et al., Frontiers in Medicine, doi:10.3389/fmed.2024.1391346 | Rebound effect explains the divergence in survival after 5 days in a controlled trial on vitamin C for COVID-19 patients |
Reanalysis of the REMAP-CAP and LOVIT-COVID vitamin C RCTs [Adhikari] showing that the poor results may be explained by a rebound effect due to the abrupt termination of vitamin C treatment after 4 days. Authors describe a rebound effect .. | ||
May 18 |
et al., medRxiv, doi:10.1101/2024.05.16.24307115 | Effect of Montelukast vs Placebo on Time to Sustained Recovery in Outpatients with COVID-19: The ACTIV-6 Randomized Clinical Trial |
1% fewer combined hospitalization/ER visits (p=1), 32% lower progression (p=0.29), and 2% improved recovery (p=0.71). RCT 1,250 outpatients with mild to moderate COVID-19 showing no significant difference in time to sustained recovery with montelukast treatment. There were no deaths and only 2 hospitalizations in each group. Notably, results were better .. | ||
May 17 |
et al., Molecular Biomedicine, doi:10.1186/s43556-024-00183-1 | Effects of different treatments for type 2 diabetes mellitus on mortality of coronavirus disease from 2019 to 2021 in China: a multi-institutional retrospective 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 17 |
et al., Biomedicines, doi:10.3390/biomedicines12051120 | Colostrum Lactoferrin Following Active and Recovered SARS-CoV-2 Infections during Pregnancy |
Analysis of 69 lactating mothers showing higher colostrum lactoferrin concentrations in mothers with a history of COVID-19 infection during pregnancy or delivery compared to pre-pandemic controls. The highest lactoferrin concentrations we.. | ||
May 16 |
et al., Journal of Dentistry, doi:10.1016/j.jdent.2024.105082 | Satisfaction with Government Recommended Pre-Procedural Mouth Rinses in the Mitigation of Covid-19 in Hong Kong SAR: A Triple Blind Randomized Controlled Clinical Trial |
RCT 228 dental patients showing high satisfaction and acceptability of three pre-procedural mouthrinses (povidone-iodine, hydrogen peroxide, and chlorhexidine digluconate) recommended by the Hong Kong government for mitigating COVID-19 tr.. | ||
May 16 |
et al., PLOS ONE, doi:10.1371/journal.pone.0300512 | The efficacy and safety of fluvoxamine in patients with COVID-19: A systematic review and meta-analysis from randomized controlled trials |
Meta analysis of 6 RCTs with 4,711 total participants showing significantly lower clinical deterioration and hospitalization with fluvoxamine treatment for COVID-19. Fluvoxamine doses ≥200mg daily were more effective than lower doses. The.. | ||
May 16 |
, S., JAMA, doi:10.1001/jama.2024.8723 | Error in the Exclusion of Participants From Analysis in the ACTIV-6 Platform Randomized Clinical Trial |
Partial correction to ACTIV-6 600 confirming that 16% of patients were missing in the analysis. It's not clear how the trial could have such a large error for the number of patients randomized, why the correction took over a year, or why .. | ||
May 15 |
et al., BMC Infectious Diseases, doi:10.1186/s12879-024-09387-w | Phytoconstituents of Artemisia Annua as potential inhibitors of SARS CoV2 main protease: an in silico study |
In Silico study showing that quercetin binds strongly to the SARS-CoV-2 main protease (Mpro) and may be a potential inhibitor of viral replication. Authors screened 25 compounds from Artemisia annua and found that quercetin had one of the.. | ||
May 15 |
et al., Cell Biochemistry and Function, doi:10.1002/cbf.4039 | 1,25‐Dihydroxyvitamin D3 attenuates platelet aggregation potentiated by SARS‐CoV‐2 spike protein via inhibiting integrin αIIbβ3 outside‐in signaling |
In Vitro study showing that calcitriol minimizes platelet aggregation mediated by SARS-CoV-2 spike protein via inhibiting integrin αIIbβ3 outside-in signaling. Authors find that calcitriol reduces platelet aggregation and Src-mediated sig.. | ||
May 15 |
et al., Cureus, doi:10.7759/cureus.60364 | Colchicine and/or Naltrexone for Hospitalized COVID-19 Patients Not Requiring High Levels of Ventilatory Support (COLTREXONE): A Prospective, Randomized, Open-Label Trial |
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 numbe.. | ||
May 13 |
et al., ASPET 2024 Annual Meeting Abstract - Toxicology, doi:10.1124/jpet.212.937140 | Molnupiravir Active Metabolite–N4 hydroxycytidine causes Cytotoxicity to Mammalian Cells In Vitro |
In Vitro study showing cytotoxicity of N4-hydroxycytidine (NHC), the active metabolite of molnupiravir, at concentrations relevant to therapeutic doses of molnupiravir in COR-L23 and HepG2 cancer cell lines, and compared with cytotoxicity.. | ||
May 10 |
et al., Scientific Reports, doi:10.1038/s41598-024-61662-7 | Antiviral, anti-inflammatory and antioxidant effects of curcumin and curcuminoids in SH-SY5Y cells infected by SARS-CoV-2 |
In Vitro study showing antiviral, anti-inflammatory, and antioxidant effects of curcumin and curcuminoids in SARS-CoV-2 infected SH-SY5Y human neuroblastoma cells. Authors found that the curcuminoid Me23 significantly decreased expression.. | ||
May 10 |
et al., International Journal of Molecular Sciences, doi:10.3390/ijms25105190 | Anti-Inflammatory Potential of the Anti-Diabetic Drug Metformin in the Prevention of Inflammatory Complications and Infectious Diseases Including COVID-19: A Narrative Review |
Review of the potential of metformin for preventing inflammatory complications and infectious diseases including COVID-19. Authors discuss evidence from preclinical and clinical studies suggesting metformin may help prevent symptoms of CO.. | ||
May 9 |
et al., Frontiers in Pharmacology, doi:10.3389/fphar.2024.1388348 | Vitamin D level in COVID-19 patients has positive correlations with autophagy and negative correlations with disease severity |
Retrospective 52 COVID-19 patients showing that patients with severe/critical disease had lower levels of vitamin D and autophagy markers ATG7 and BECN1 compared to those with mild or moderate disease. Vitamin D levels had a significant n.. | ||
May 7 |
et al., Nutrients, doi:10.3390/nu16101402 | Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials |
44% lower mortality (p=0.02), 27% lower ICU admission (p=0.02), and 21% lower need for oxygen therapy (p=0.07). Meta analysis of 13 RCTs for severe COVID-19 showing lower ICU admission and lower COVID-19 mortality with vitamin D treatment. Other outcomes show lower risk with treatment but without statistical significance. Authors conclude that it i.. | ||
May 6 |
et al., Journal of Medical Virology, doi:10.1002/jmv.29642 | Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study |
Analysis of 38 COVID-19 outpatients treated with molnupiravir showing significantly increased SARS-CoV-2 genetic diversity and complexity compared to 17 patients treated with tixagevimab/cilgavimab. Molnupiravir increased the mutation rat.. | ||
May 4 |
et al., Global Journal of Medical, Pharmaceutical, and Biomedical Update, doi:10.25259/GJMPBU_78_2023 | Curcumin as a Promising Therapy for COVID-19: A Review |
Review of curcumin for COVID-19. Authors discuss the molecular mechanisms of COVID-19 pathogenesis and the properties and mechanisms of action of curcumin. Curcumin exhibits antiviral activity against SARS-CoV-2 by interfering with viral .. | ||
May 3 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofae233 | The DARPin antiviral ensovibep for non-hospitalized patients with COVID-19: Results from EMPATHY, a randomized, placebo-controlled Phase 2 study |
89% lower mortality (p=0.06), 78% fewer combined hospitalization/ER visits (p=0.02), 87% lower hospitalization (p=0.01), and 87% improvement (p=0.01). RCT 407 mild to moderate COVID-19 outpatients showing faster viral clearance, lower risk of hospitalization/ER visits, and shorter time to sustained recovery with ensovibep treatment (75/225/600mg single infusion). There were 2 COVID-19 r.. | ||
May 3 |
et al., Scientific Reports, doi:10.1038/s41598-024-57424-0 | Comparing vitamin D receptor gene polymorphisms in rs11568820, rs7970314, rs4334089 between COVID-19 patients with mild and severe symptoms: a case control study |
Case control study of 176 COVID-19 patients showing the TT genotype of the rs11568820 vitamin D receptor (VDR) polymorphism was associated with a lower risk of severe COVID-19 requiring hospitalization. No significant differences were fou.. |
We aim to cover the most promising early treatments for
COVID-19. We use pre-specified effect extraction criteria that prioritizes
more serious outcomes, for details see methods. For specific
outcomes and different treatment stages see the individual pages. Not all
treatments are covered here, effectiveness has been reported for many other treatments in studies.
Of the 4,220 studies,
2,190 present results comparing with a control group,
1,994 are treatment studies, and
196 analyze outcomes based on serum levels. There are
67 animal studies,
145 in silico studies,
243 in vitro studies,
263 reviews,
and 189 meta analyses.
Please send us corrections, updates, or comments.
c19early involves the extraction of 100,000+ datapoints from
thousands of papers. Community updates
help ensure high accuracy.
Treatments and other interventions are complementary.
All practical, effective, and safe
means should be used based on risk/benefit analysis.
No treatment or intervention is 100% available and effective for all current
and future variants.
We do not provide medical advice. Before taking any medication,
consult a qualified physician who can provide personalized advice and details
of risks and benefits based on your medical history and situation. FLCCC and WCH
provide treatment protocols.
Thanks for your feedback! Please search before submitting papers and note
that studies are listed under the date they were first available, which may be
the date of an earlier preprint.