COVID-19 early treatment: real-time analysis of 5,366 studies
| Hu | 926 patients ursodeoxycholic acid prophylaxis: 89% lower severe cases (p=0.02) and 25% fewer symptomatic cases (p<0.0001) |
| Luetkemeyer | 2,085 patient ensitrelvir early treatment RCT: 203% higher hospitalization (p=0.37), 5% faster recovery (p=0.14), and 19% improved viral clearance (p=0.02) |
| Sun | 2,924 patients azvudine late treatment PSM: 27% lower mortality (p=0.02) and 15% higher progression (p=0.16) |
Timeline for when studies showed efficacy - details and limitations.
0.5% of treatments show efficacy.
Top journals that accept positive studies for low cost treatments:
Nutrients,
PLOS ONE,
Cureus,
Journal of Clinical Medicine,
Scientific Reports,
International Journal of Infectious Diseases,
more...
Treatment cost times median NNT - details and limitations.
0.5% of treatments show efficacy.
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All clinical results for selected treatments. 0.5% 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. 0.5% 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. 0.5% 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. 0.5% 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. 0.5% 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. 0.5% 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. 0.5% of proposed treatments show efficacy in clinical studies. | |||||
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| Random effects meta-analysis of long covid results. 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. 0.5% of proposed treatments show efficacy in clinical studies. | |||||
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| Random effects meta-analysis of transmission results. 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. 0.5% 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.
| Hu | 926 patients prophylaxis: 89% lower severe cases (p=0.02) and 25% fewer symptomatic cases (p<0.0001) |
| Luetkemeyer | 2,085 patient early treatment RCT: 203% higher hospitalization (p=0.37), 5% faster recovery (p=0.14), and 19% improved viral clearance (p=0.02) |
| Sun | 2,924 patients late treatment PSM: 27% lower mortality (p=0.02) and 15% higher progression (p=0.16) |
| Wimalawansa | Systematic review examining the evidence for vitamin D deficiency as a causative factor in COVID-19 susceptibility, complications, and mortality,.. |
| Sümegi | 148 patients late treatment: 67% lower mortality (p=0.0002) |
| Rahman | In Vitro study showing potential genotoxic side effects of remdesivir and molnupiravir linked to DNA repair pathway deficiencies. Remdesivir.. |
| Rahman | In Vitro study showing potential genotoxic side effects of remdesivir and molnupiravir linked to DNA repair pathway deficiencies. Remdesivir.. |
| Kızılet | Cross-sectional study of 153 COVID-19 patients and 78 healthy controls showing significantly lower serum zinc levels in COVID-19 patients compared.. |
| Tassakos | Review of 15 studies examining associations between diet quality and COVID-19 severity and outcomes. Authors found that adherence to high-quality,.. |
| Su | In Vitro study showing that inhalable spray-dried dry powders combining ivermectin and niclosamide exhibit enhanced anti-SARS-CoV-2 activity.. |
Recent studies (see the individual treatment pages for all studies):
Feb 17 |
et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaf029 | Ensitrelvir for the Treatment of Nonhospitalized Adults with COVID-19: Results from the SCORPIO-HR, Phase 3, Randomized, Double-blind, Placebo-Controlled Trial |
| 203% higher hospitalization (p=0.37), 5% faster recovery (p=0.14), and 19% improved viral clearance (p=0.02). RCT 2,093 outpatients with mild-to-moderate COVID-19 showing improved viral clearance but no significant difference in time to symptom resolution with ensitrelvir. Participants were randomized to receive ensitrelvir or placebo within five.. | ||
Feb 15 |
et al., RPS Pharmacy and Pharmacology Reports, doi:10.1093/rpsppr/rqae028 | Potential drug interactions with nirmatrelvir/ritonavir in critically ill patients with COVID-19 – a retrospective observational study |
| Retrospective 500 critically ill COVID-19 patients in Germany showing potential drug-drug interactions with paxlovid in 48% of patients, with higher age and number of comorbidities significantly associated with drug-drug interactions. Aut.. | ||
Feb 6 |
, S., Nutrients, doi:10.3390/nu17030599 | Vitamin D Deficiency Meets Hill’s Criteria for Causation in SARS-CoV-2 Susceptibility, Complications, and Mortality: A Systematic Review |
| Systematic review examining the evidence for vitamin D deficiency as a causative factor in COVID-19 susceptibility, complications, and mortality, evaluated using Bradford Hill's criteria for causality. Author analyzed 294 studies, finding.. | ||
Feb 6 |
et al., Frontiers in Medicine, doi:10.3389/fmed.2025.1494248 | Ursodeoxycholic acid relieves clinical severity of COVID-19 in patients with chronic liver diseases |
| 89% lower severe cases (p=0.02) and 25% fewer symptomatic cases (p<0.0001). Retrospective 926 outpatients with chronic liver diseases in China showing lower incidence of symptomatic COVID-19 and milder symptoms with ursodeoxycholic acid (UDCA) treatment. | ||
Feb 5 |
et al., VIEW, doi:10.1002/VIW.20240133 | Antiviral effectiveness and safety of azvudine in hospitalized SARS‐CoV‐2 patients with pre‐existing chronic respiratory diseases: A multicenter, retrospective cohort study |
| 27% lower mortality (p=0.02) and 15% higher progression (p=0.16). Retrospective 2,924 hospitalized COVID-19 patients with chronic respiratory diseases in China, showing lower all-cause mortality with azvudine, but no significant difference in composite disease progression. | ||
Feb 4 |
et al., BMJ Open Diabetes Research & Care, doi:10.1136/bmjdrc-2024-004536 | Association of glycemic control with Long COVID in patients with type 2 diabetes: findings from the National COVID Cohort Collaborative (N3C) |
| 18% lower PASC (p=0.001). Retrospective 7,430 COVID-positive patients with type 2 diabetes showing lower risk of long COVID or death with metformin use, and higher risk with insulin use. | ||
Feb 1 |
et al., Internal Medicine, doi:10.2169/internalmedicine.4856-24 | Use of Ursodeoxycholic Acid and the Risk of Severe Coronavirus Disease 2019 in Elderly Patients with Viral Hepatitis |
| 72% higher mortality (p=0.03), 57% higher ventilation (p=0.48), 3% higher need for oxygen therapy (p=0.83), and 4% higher hospitalization (p=0.52). Retrospective 6,413 elderly patients with viral hepatitis in Japan showing increased mortality with ursodeoxycholic acid (UDCA) use in COVID-19 patients. There was no significant difference in hospitalization or oxygen therapy. | ||
Feb 1 |
et al., Current Nutrition Reports, doi:10.1007/s13668-025-00618-3 | The Impact of Diet Quality on COVID-19 Severity and Outcomes—A Scoping Review |
| Review of 15 studies examining associations between diet quality and COVID-19 severity and outcomes. Authors found that adherence to high-quality, anti-inflammatory diets like the Mediterranean and DASH diets was generally associated with.. | ||
Jan 31 |
et al., Biophysica, doi:10.3390/biophysica5010004 | Investigation of Interactions Between the Protein MPro and the Vanadium Complex VO(metf)2∙H2O: A Computational Approach for COVID-19 Treatment |
| In Silico study showing that the vanadium complex VO(metf)2∙H2O (VC) and metformin (MF) may be beneficial for COVID-19 treatment by interacting with the main protease (Mpro) of SARS-CoV-2. Using docking simulations, authors found that VC .. | ||
Jan 31 |
et al., Cureus, doi:10.7759/cureus.78291 | Impact of Vitamin D Levels on Clinical Outcomes in SARS-CoV-2 Infections |
| 53% fewer symptomatic cases (p=0.002). Cross-sectional study of 100 COVID-19 patients showing low vitamin D levels associated with increased symptom severity. | ||
Jan 30 |
et al., International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2025.125302 | Inhalable spray-dried dry powders combining ivermectin and niclosamide to inhibit SARS-CoV-2 infection in vitro |
| In Vitro study showing that inhalable spray-dried dry powders combining ivermectin and niclosamide exhibit enhanced anti-SARS-CoV-2 activity compared to the individual drugs. Authors developed stable, amorphous powders with aerodynamic pr.. | ||
Jan 30 |
et al., Nutrients, doi:10.3390/nu17030507 | Effect of Moderately High-Dose Vitamin D3 Supplementation on Mortality in Patients Hospitalized for COVID-19 Infection |
| 67% lower mortality (p=0.0002). Retrospective 148 hospitalized COVID-19 patients showing significantly lower mortality (67% reduction) with moderately high-dose vitamin D3 treatment (30,000 IU for 3 days or 12,000 IU for 7 days followed by 3,000 IU daily), regardless of.. | ||
Jan 29 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofae631.016 | Metformin reduces the risk of Long COVID or Death over 6 months in an Emulated Target Trial of Primarily Omicron-infected Adults without Diabetes or Prediabetes: a New-User, Active-Comparator Analysis Using the National COVID Cohort Collaborative (N3C) Electronic Health Record Database. This research was supported in part by the Intramural/Extramural research program of the National Center for Advancing Translational Science, NIH |
| Emulated target trial of Omicron-infected outpatients without diabetes or prediabetes, showing significantly lower long COVID or death with metformin treatment. | ||
Jan 29 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofae631.2172 | Evaluating the use of Monoclonal Antibodies - Sotrovimab, Casirivimab/Imedvimab (REGEN-COV) and Tixagevimab/Cilgavimab (EVUSHELD) for COVID-19 Treatment in Singapore |
| PSM retrospective 366 hospitalized COVID-19 patients in Singapore showing no statistically significant reduction in severe outcomes with monoclonal antibodies (mAbs), except for lower oxygen use in patients treated with sotrovimab during .. | ||
Jan 29 |
et al., Clinical Kidney Journal, doi:10.1093/ckj/sfaf030 | COVID-19 among Kidney Transplant Recipients: Evaluating Risk Factors During the Initial Phase of the Pandemic |
| 58% higher combined mortality/hospitalization (p=0.0002). Retrospective 5,824 kidney transplant recipients in Sweden showing proton pump inhibitor use associated with higher risk of severe COVID-19. | ||
Jan 29 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofae631.2173 | Nirmatrelvir-ritonavir and molnupiravir for the outpatient treatment of Covid-19: a population-based cohort study |
| 27% higher mortality (p=0.5) and 1% higher hospitalization (p=0.93). Retrospective 113,399 outpatients in Austria showing lower hospitalization and mortality with paxlovid treatment in patients over 60, but no significant differences with molnupiravir. Viral rebound was observed after treatment with both a.. | ||
Jan 29 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofae631.2185 | Results from a Phase 1 First in Human Study of Pemivibart: An Extended Half-Life Monoclonal Antibody (mAb) |
| Phase 1 RCT with 30 healthy participants showing pemivibart was well-tolerated at doses up to 4500 mg, with no serious adverse events or adverse events leading to drug discontinuation reported. Pemivibart demonstrated linear and dose-prop.. | ||
Jan 29 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofae631.2191 | Pharmacokinetics (PK) and Serum Virus Neutralizing Antibody (sVNA) Titers Following the 2nd dose of Pemivibart in the Phase 3 CANOPY Trial |
| Pharmacokinetics (PK) and Serum Virus Neutralizing Antibody (sVNA) analysis for the CANOPY trial showing a second dose boosted serum virus neutralizing antibody titers by 17% compared to the first dose. A population pharmacokinetic model .. | ||
Jan 27 |
et al., medRxiv, doi:10.1101/2025.01.24.25321081 | Sotrovimab versus usual care in patients admitted to hospital with COVID-19: a randomised, controlled, open-label, platform trial (RECOVERY) |
| 5% lower mortality (p=0.64), 4% lower hospital discharge (p=0.51), and 2% lower combined mortality/ICU admission (p=0.82). RCT 1,723 hospitalized COVID-19 patients showing lower 28-day mortality with sotrovimab in patients with high serum nucleocapsid antigen levels, but no significant benefit in the overall population. Sotrovimab reduced mortality from 29% t.. | ||
Jan 27 |
et al., bioRxiv, doi:10.1101/2025.01.24.634813 | Molecular Mechanisms of Drug Resistance and Compensation in SARS-CoV-2 Main Protease: The Interplay Between E166 and L50 |
| In Vitro study showing that mutations at position E166 in the SARS-CoV-2 main protease (Mpro) confer resistance to nirmatrelvir, the active component of paxlovid, while preserving substrate cleavage. Authors found that E166A and E166V mut.. | ||
Jan 24 |
et al., PLOS ONE, doi:10.1371/journal.pone.0313616 | Secondary metabolites of Alternaria alternate appraisal of their SARS-CoV-2 inhibitory and anti-inflammatory potentials |
| In Silico and In Vitro study showing that compounds isolated from the fungus Alternaria alternate inhibit SARS-CoV-2 infection by blocking the ACE2-Spike protein interaction and reducing ACE2 expression and inflammatory cytokines. Quercet.. | ||
Jan 24 |
et al., Chemistry & Biodiversity, doi:10.1002/cbdv.202403202 | Amphibian‐Derived Peptides as Natural Inhibitors of SARS‐CoV‐2 Main Protease (Mpro): A Combined In Vitro and In Silico Approach |
| In Vitro and In Silico study showing that amphibian-derived peptides inhibit SARS-CoV-2 main protease (Mpro). Authors tested 23 peptides from Hylidae and Leptodactylidae amphibians and found five with significant Mpro inhibition, with IC5.. | ||
Jan 20 |
et al., Frontiers in Immunology, doi:10.3389/fimmu.2024.1490478 | TLR10 overexpression modulates immune response in A549 lung epithelial cells challenged with SARS-CoV-2 S and N proteins |
| In Vitro study showing that overexpression of TLR10 in A549 lung epithelial cells immunostimulated with SARS-CoV-2 S and N proteins mainly downregulated proinflammatory cytokines and interferons and affected gene expression in cocultured .. | ||
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 5,366 studies,
2,560 present results comparing with a control group,
2,348 are treatment studies, and
212 analyze outcomes based on serum levels. There are
100 animal studies,
196 in silico studies,
362 in vitro studies,
419 reviews,
and 234 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.