COVID-19 early treatment: real-time analysis of 5,420 studies
| He | 53,030 patients HCQ late treatment PSM: 66% lower mortality (p<0.0001), 25% lower ventilation (p=0.05), 41% lower progression (p=0.21), and 31% improvement (p=0.005) |
| Hewison | Review of vitamin D's role in immune function with a focus on COVID-19. Author outlines how vitamin D influences both innate and adaptive immunity.. |
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,
Frontiers in Medicine,
Cureus,
Journal of Clinical Medicine,
Scientific Reports,
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.
| He | 53,030 patients late treatment PSM: 66% lower mortality (p<0.0001), 25% lower ventilation (p=0.05), 41% lower progression (p=0.21), and 31% improvement (p=0.005) |
| Hewison | Review of vitamin D's role in immune function with a focus on COVID-19. Author outlines how vitamin D influences both innate and adaptive immunity.. |
| Vasconcelos | 126 patients ICU: 73% lower mortality (p=0.02) |
| Mori | In Vitro study showing that molnupiravir may have cytotoxic and mutagenic effects in host cells via hydroxylamine production from N4-hydroxycytidine.. |
| Zhou | 2,834 patients late treatment PSM: 26% lower mortality (p=0.02) and 9% lower progression (p=0.36) |
| Hu | 926 patients prophylaxis: 89% lower severe cases (p=0.02) and 25% fewer symptomatic cases (p<0.0001) |
Recent studies (see the individual treatment pages for all studies):
Mar 4 |
et al., Frontiers of Medicine, doi:10.1007/s11684-025-1123-9 | Low dose of hydroxychloroquine is associated with reduced COVID-19 mortality: a multicenter study in China |
| 66% lower mortality (p<0.0001), 25% lower ventilation (p=0.05), 41% lower progression (p=0.21), and 31% improvement (p=0.005). PSM retrospective 53,030 hospitalized patients in China showing low dose HCQ treatment associated with significantly lower all-cause mortality, mechanical ventilation, acute heart injury, and acute kidney injury, with benefits consistent .. | ||
Mar 4 |
et al., medRxiv, doi:10.1101/2025.02.28.25323075 | Identifying DNA Methylation Patterns in Post COVID-19 Condition: Insights from a One-Year Prospective Cohort Study |
| Prospective cohort study with 22 Post COVID-19 condition (PCC+) patients and 22 matched COVID-19 convalescents (PCC-), showing distinct DNA methylation patterns diminishing over time. The study identified TXNRD1 methylation changes associ.. | ||
Feb 26 |
et al., Expert Opinion on Drug Safety, doi:10.1080/14740338.2025.2471509 | Effects of Nirmatrelvir/ritonavir (paxlovid) on the nervous system: analysis on adverse events released by FDA |
| Adverse event disproportionality analysis for COVID-19 drugs showing significantly higher risk of neurological adverse events with paxlovid. | ||
Feb 26 |
et al., Safety and Risk of Pharmacotherapy, doi:10.30895/2312-7821-2025-458 | The Effect of Potentially Hepatotoxic Medicinal Products on Alanine Transaminase Levels in COVID-19 Patients: A Case–Control Study |
| Case-control study of 1,296 hospitalized COVID-19 patients showing remdesivir associated with significantly increased ALT levels (OR 4.38, p<0.001). | ||
Feb 25 |
et al., BMC Infectious Diseases, doi:10.1186/s12879-025-10643-w | Real-world effectiveness and safety of oral Azvudine versus Paxlovid for COVID-19 in patients with kidney disease: a multicenter, retrospective, cohort study |
| Retrospective 657 hospitalized COVID-19 patients with kidney disease showing no significant difference in all-cause mortality or disease progression between azvudine and paxlovid. Subgroup analysis showed lower disease progression with az.. | ||
Feb 20 |
, M., The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2025.106710 | COVID-19 and our understanding of vitamin D and immune function |
| Review of vitamin D's role in immune function with a focus on COVID-19. Author outlines how vitamin D influences both innate and adaptive immunity through multiple mechanisms that could impact viral infections including SARS-CoV-2. The re.. | ||
Feb 20 |
et al., Free Radical Research, doi:10.1080/10715762.2025.2469738 | Reactive oxygen species-mediated cytotoxic and DNA-damaging mechanism of N4-hydroxycytidine, a metabolite of the COVID-19 therapeutic drug molnupiravir |
| In Vitro study showing that molnupiravir may have cytotoxic and mutagenic effects in host cells via hydroxylamine production from N4-hydroxycytidine (NHC) by cytidine deaminase (CDA). Molnupiravir metabolite NHC may induce cytotoxicity an.. | ||
Feb 19 |
et al., Nutrition in Clinical Practice, doi:10.1002/ncp.11277 | High-dose vitamin D supplementation in patients with severe acute respiratory syndrome coronavirus 2 pneumonia hospitalized in a polyvalent intensive care unit: A retrospective cohort study |
| 73% lower mortality (p=0.02). Retrospective ICU patients in Portugal, showing significantly lower mortality with vitamin D treatment. | ||
Feb 18 |
et al., Frontiers in Endocrinology, doi:10.3389/fendo.2025.1467303 | A multicenter, real-world cohort study: effectiveness and safety of Azvudine in hospitalized COVID-19 patients with pre-existing diabetes |
| 26% lower mortality (p=0.02) and 9% lower progression (p=0.36). PSM retrospective 2,834 hospitalized COVID-19 patients with pre-existing diabetes in China showing lower all-cause mortality with azvudine, but no significant difference in composite disease progression. | ||
Feb 18 |
et al., Emerging Microbes & Infections, doi:10.1080/22221751.2025.2469648 | Effectiveness of nirmatrelvir/ritonavir and molnupiravir on post-COVID-19 outcomes among outpatients: a target trial emulation investigation |
| 3% lower mortality (p=0.77) and 8% higher hospitalization (p=0.001). Retrospective target trial emulation of outpatients in Hong Kong showing reduced post-acute mortality and hospitalization with paxlovid, but no significant long-term benefit with molnupiravir. Figure 1 shows only 0.08% of patients were ex.. | ||
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 14 |
et al., Frontiers in Pediatrics, doi:10.3389/fped.2025.1507169 | Vitamin D status in children with COVID-19: does it affect the development of long COVID and its symptoms? |
| 54% lower PASC (p=0.03). Prospective study of 162 hospitalized children in Ukraine showing increased risk of developing long COVID in children with vitamin D deficiency/insufficiency, especially neurological and musculoskeletal symptoms. | ||
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., PLOS ONE, doi:10.1371/journal.pone.0316700 | Over-the-counter carrageenan-based sprays may interfere with PCR testing of nasopharyngeal swabs to detect SARS-CoV-2 |
| In Vitro study showing that carrageenan may interfere with PCR testing for SARS-CoV-2 on nasopharyngeal swabs, potentially leading to false negative results. Seegene STARlet was most affected, frequently returning invalid results, while q.. | ||
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. | ||
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 5,420 studies,
2,577 present results comparing with a control group,
2,363 are treatment studies, and
214 analyze outcomes based on serum levels. There are
101 animal studies,
199 in silico studies,
364 in vitro studies,
423 reviews,
and 235 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.