COVID-19 early treatment: real-time analysis of 4,713 studies
Analysis of 94 COVID-19 early treatments,
approvals in 118 countries, database of
7,998 treatments
Mozaffari | Retrospective 788,238 hospitalized COVID-19 patients in the US, showing a very high prevalence of drug-drug interactions with paxlovid, with higher.. |
Ryu | In Vitro and mouse study showing that fibrin drives thromboinflammation and neuropathology in COVID-19. Fibrin binds to the SARS-CoV-2 spike protein.. |
Shah | 100 patients casirivimab/imdevimab late treatment: 14% higher mortality (p=1), no change in ventilation (p=1), 14% lower ICU admission (p=0.68), and 4% lower need for oxygen therapy (p=1) |
Winchester | 197 patient astodrimer sodium early treatment RCT: 19% improved recovery (p=0.41) and 24% improved viral clearance (p=0.3) |
Timeline for when studies showed efficacy - details and limitations.
0.6% of treatments show efficacy.
Top journals that accept positive studies for low cost treatments:
PLOS ONE,
Nutrients,
International Journal of Infectious Diseases,
Scientific Reports,
Journal of Clinical Medicine,
Frontiers in Pharmacology,
more...
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.
Mozaffari | Retrospective 788,238 hospitalized COVID-19 patients in the US, showing a very high prevalence of drug-drug interactions with paxlovid, with higher.. |
Low | 2,524 patients long COVID: 30% higher PASC (p=0.34) |
Ryu | In Vitro and mouse study showing that fibrin drives thromboinflammation and neuropathology in COVID-19. Fibrin binds to the SARS-CoV-2 spike protein.. |
Dai | Review of the interplay between airway cilia and coronavirus infection, and the implications for prevention and treatment of respiratory viral.. |
Shah | 100 patients late treatment: 14% higher mortality (p=1), no change in ventilation (p=1), 14% lower ICU admission (p=0.68), and 4% lower need for oxygen therapy (p=1) |
Winchester | 197 patient early treatment RCT: 19% improved recovery (p=0.41) and 24% improved viral clearance (p=0.3) |
Hobbs | 3,622 patient late treatment RCT: 86% lower mortality (p=0.11), 1% lower combined mortality/hospitalization (p=0.51), and 17% improved recovery (p=0.003) |
Shiraki | Reproductive toxicity analysis of antiviral drugs in C. elegans, showing increased incidence of arrested embryos with molnupiravir, favipiravir,.. |
Zengin | 75 patients late treatment: 14% lower mortality (p=1), 90% higher ICU admission (p=0.46), and 3% shorter hospitalization (p=0.81) |
Moon | 74,074 patients prophylaxis PSM: 33% lower severe cases (p=0.04) and 20% fewer cases (p<0.0001) |
Chen | Analysis of molnupiravir induced liver injury. Molnupiravir treatment may disrupt metabolic homeostasis and cause liver injury by increasing levels.. |
Shen | In Vitro and Ex Vivo study showing significant potential drug-drug interactions between remdesivir and molnupiravir. Author found that remdesivir.. |
Shiraki | Reproductive toxicity analysis of antiviral drugs in C. elegans, showing increased incidence of arrested embryos with molnupiravir, favipiravir,.. |
Shen | In Vitro and Ex Vivo study showing significant potential drug-drug interactions between remdesivir and molnupiravir. Author found that remdesivir.. |
Agafina | 166 patient late treatment RCT: 17% higher mortality (p=0.7), 2% lower progression (p=1), and 9% longer ventilation (p=0.62) |
Recent studies (see the individual treatment pages for all studies):
Sep 30 |
et al., Clinical Therapeutics, doi:10.1016/j.clinthera.2024.08.004 | Prevalence of Potential Drug Interactions With Direct-Acting Antivirals for COVID-19 Among Hospitalized Patients |
Retrospective 788,238 hospitalized COVID-19 patients in the US, showing a very high prevalence of drug-drug interactions with paxlovid, with higher prevalence for older patients, patients with more comorbidities, and patients at high-risk.. | ||
Sep 6 |
et al., Pharmaceutics, doi:10.3390/pharmaceutics16091173 | Astodrimer Sodium Nasal Spray versus Placebo in Non-Hospitalised Patients with COVID-19: A Randomised, Double-Blinded, Placebo-Controlled Trial |
19% improved recovery (p=0.41) and 24% improved viral clearance (p=0.3). RCT 222 non-hospitalized low risk COVID-19 patients showing lower SARS-CoV-2 viral load, faster viral clearance, and improvements in symptoms, particularly anosmia, with astodrimer sodium nasal spray compared to placebo. The reduction in .. | ||
Sep 3 |
et al., Inflammopharmacology, doi:10.1007/s10787-024-01564-2 | The impact of vitamin D administration on mortality in COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials |
28% lower mortality (p=0.04). Systematic review and meta analysis of 19 RCTs with 2,495 patients, showing significantly lower mortality with vitamin D treatment. | ||
Sep 2 |
et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00421-3 | Effect of timing of casirivimab and imdevimab administration relative to mRNA-1273 COVID-19 vaccination on vaccine-induced SARS-CoV-2 neutralising antibody responses: a prospective, open-label, phase 2, randomised controlled trial |
37% more symptomatic cases (p=0.65). RCT 293 healthy adults focusing on the timing of casirivimab and imdevimab administration relative to mRNA-1273, but also showing the incidence of COVID-19 for each group, with higher incidence in the casirivimab and imdevimab groups (wit.. | ||
Sep 1 |
et al., Journal of the Association of Physicians of India, doi:10.59556/japi.72.0646 | A Retrospective Cohort Observational Study to Assess the Efficacy of Monoclonal Antibody in Coronavirus Disease 2019 Patients |
14% higher mortality (p=1), no change in ventilation (p=1), 14% lower ICU admission (p=0.68), and 4% lower need for oxygen therapy (p=1). PSM retrospective 100 hospitalized COVID-19 patients in India showing no benefit with casirivimab/imdevimab treatment. There were no significant differences between groups in need for oxygen therapy, high-flow nasal cannula, noninvasive v.. | ||
Aug 31 |
et al., Journal of Infection, doi:10.1016/j.jinf.2024.106248 | Favipiravir for COVID-19 in adults in the community in PRINCIPLE, an open-label, randomised, controlled, adaptive platform trial of short- and longer-term outcomes |
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.. | ||
Aug 27 |
et al., Virology Journal, doi:10.1186/s12985-024-02464-1 | Association between ursodeoxycholic acid use and COVID-19 in individuals with chronic liver disease: a nationwide case-control study in South Korea |
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 ben.. | ||
Aug 23 |
et al., Biomedical Chromatography, doi:10.1002/bmc.5996 | Mass spectrometry‐based metabolomics reveals metabolism of molnupiravir may lead to metabolic disorders and hepatotoxicity |
Analysis of molnupiravir induced liver injury. Molnupiravir treatment may disrupt metabolic homeostasis and cause liver injury by increasing levels of certain metabolites and activating inflammatory pathways. | ||
Aug 15 |
et al., Pathogens and Immunity, 10.20411/pai.v9i2.715 | Comparison Study of the Bio-Plex and Meso Scale Multiplexed SARS-CoV-2 Serology Assays Reveals Evidence of Diminished Host Antibody Responses to SARS-CoV-2 after Monoclonal Antibody Treatment |
Comparison of two multiplex serology assays for detecting SARS-CoV-2 antibodies in 455 samples from 304 participants in the ACTIV-2/A5401 trial of bamlanivimab for non-hospitalized COVID-19 patients. Authors found diminished host antibody.. | ||
Aug 14 |
et al., Age and Ageing, doi:10.1093/ageing/afae180 | Efficacy of COVID-19 Oral antivirals in hospitalised oldest-old with high morbidity burden: a target trial emulation study |
10% lower mortality (p=0.007). Target trial emulation study of 13,642 (molnupiravir) and 9,553 (paxlovid) elderly hospitalized patients in Hong Kong showing lower mortality with treatment. | ||
Aug 14 |
et al., JMIR Public Health and Surveillance, doi:10.2196/59274 | Ursodeoxycholic acid is associated with better clinical outcomes in COVID-19 patients: A population-based cohort study (Preprint) |
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 13 |
et al., Journal of Chromatography A, doi:10.1016/j.chroma.2024.465265 | Countercurrent chromatography isolation of green propolis biomarkers: potential blockers of SARS-CoV-2 RBD and ACE2 interaction |
In Vitro study showing potential inhibition of SARS-CoV-2 spike protein and ACE2 interaction by artepillin C and baccharin from Brazilian green propolis. Artepillin C showed 67.3% inhibition of Spike:ACE2 interaction at 10 μM, while bacch.. | ||
Aug 13 |
et al., bioRxiv, doi:10.1101/2024.08.12.607496 | Pemivibart is less active against recent SARS-CoV-2 JN.1 sublineages |
In Vitro study showing pemivibart has reduced neutralizing activity against recent SARS-CoV-2 JN.1 sublineages, particularly KP.3.1.1 which had a 32.7-fold higher IC50 compared to the original JN.1. Structural analyses suggest the Q493E m.. | ||
Aug 13 |
et al., European Journal of Medical Research, doi:10.1186/s40001-024-02008-x | Efficacy and safety of trimodulin in patients with severe COVID-19: results from a randomised, placebo-controlled, double-blind, multicentre, phase II trial (ESsCOVID) |
17% higher mortality (p=0.7), 2% lower progression (p=1), and 9% longer ventilation (p=0.62). RCT 166 severe COVID-19 patients on non-invasive ventilation or high-flow oxygen showing no significant difference in clinical deterioration or mortality with trimodulin treatment compared to placebo. In a post hoc analysis of a subgroup .. | ||
Aug 12 |
et al., Journal of Infection and Public Health, doi:10.1016/j.jiph.2024.102512 | Sotrovimab lost neutralization efficacy against SARS-CoV-2 subvariants but remained clinically effective: Were monoclonal antibodies against COVID-19 rejected too early? |
Retrospective 14 outpatients treated with sotrovimab showing that while sotrovimab lost in vitro neutralization efficacy against omicron subvariants BA.1 and BA.2, it remained clinically effective in reducing viral load in patients who di.. | ||
Aug 12 |
et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiae385 | Persistence of an infectious form of SARS-CoV-2 post protease inhibitor treatment of permissive cells in vitro |
In Vitro study showing the persistence of an infectious form of SARS-CoV-2 after treatment with 3CLpro inhibitors nirmatrelvir and ensitrelvir, which may explain the rebound often seen with paxlovid. 3CLpro is crucial for processing viral.. | ||
Aug 11 |
et al., Cells, doi:10.3390/cells13161331 | Spike Protein of SARS-CoV-2 Activates Cardiac Fibrogenesis through NLRP3 Inflammasomes and NF-κB Signaling |
In Vitro study showing that the SARS-CoV-2 spike protein can activate cardiac fibroblasts through ACE2-dependent mechanisms, leading to cardiac fibrosis via the NLRP3 inflammasome and NF-κB signaling pathways. The results suggest that COV.. | ||
Aug 11 |
, D., Current Topics in Microbiology and Immunology, doi:10.1007/82_2024_268 | Monoclonal Antibody Therapies Against SARS-CoV-2: Promises and Realities |
Review of monoclonal antibodies for SARS-CoV-2. Author notes that the omicron variant has reset achievements to date. |
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 4,713 studies,
2,380 present results comparing with a control group,
2,178 are treatment studies, and
202 analyze outcomes based on serum levels. There are
86 animal studies,
167 in silico studies,
283 in vitro studies,
323 reviews,
and 217 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.