COVID-19 early treatment: real-time analysis of 5,559 studies
COVID-19 involves the interplay of over 100 viral and host proteins and factors, providing many therapeutic targets.
c19early analyzes over 5,500 studies for 121 treatments—over 17 million hours of research.
US authorities believe only three high-profit early treatments
reduce risk (remdesivir, paxlovid, molnupiravir). In reality, many treatments reduce risk,
and 25 low-cost treatments have been approved across 163 countries.
0.5% of 8,000+ proposed treatments show reduced risk.
Direct treatment to the primary source of initial infection reduces progression and transmission.
Many low-cost agents are widely available.
Exercise, sunlight, a healthy diet, and good sleep all reduce risk.
Vitamins A, C, D, and zinc show reduced risk, as with other viruses.
Methods for increasing internal body temperature reduce risk, comparable to natural fever, enhancing immune system function.
Many systemic agents reduce risk, and may be required when infection progresses beyond the upper respiratory tract.
High-profit systemic agents are also effective, but have greater access and cost barriers.
Highly effective for matching variants but rarely used, with high cost, variant dependence, and IV/subcutaneous administration.
Acetaminophen increases the risk of severe outcomes and mortality.
Antiviral efficacy is offset by serious side effects, resulting in increased mortality with longer followup.
c19early.org
We do not provide medical advice. No treatment is 100% effective, and all may have side effects. Protocols combine multiple treatments. Consult a qualified physician for personalized risk/benefit analysis.
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.
All clinical results for selected treatments. 0.5% of treatments show efficacy.
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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.
| Reis | In Vitro and Ex Vivo study showing that BromAc (bromelain and N-acetylcysteine) exhibits antiviral activity against SARS-CoV-2 Omicron variant... |
| Bath | Discussion of a planned COVID-19 platform trial (PROTECT-CH) in care homes that failed to start recruitment. The trial was designed to test.. |
| Ilyas | In Silico study showing that intrinsically disordered regions (IDRs) in SARS-CoV-2 proteins are promising targets for small-molecule drug discovery. |
| Bajaj | High-throughput screen of 2,640 acrylamide-based compounds, identifying 10 covalent inhibitors of SARS-CoV-2 Nsp15 with IC₅₀ values under 5 μM... |
| Baazim | In Vitro and animal study showing that inhibiting Fatty Acid-Binding Protein 4 (FABP4) reduces SARS-CoV-2 infection, viral replication, and lung.. |
| Yu | 4,192 patients late treatment PSM: 38% lower mortality (p<0.0001) and 21% lower progression (p=0.03) |
| Liu | Meta-analysis of 6 studies examining vitamin K status in COVID-19 patients showing that infected patients have significantly higher levels of.. |
| Zhao | In Vitro and clinical study showing potent antiviral activity of simnotrelvir against SARS-CoV-2 variants with a high resistance barrier. Authors.. |
| Qin | Meta-analysis of 3 RCTs (451 patients) showing significantly lower in-hospital mortality with melatonin treatment in severe-to-critical COVID-19.. |
| Kuntzman | 10 patient late treatment RCT: 77% lower mortality (p=0.3), 57% lower ICU admission (p=1), and 22% shorter hospitalization (p=0.61) |
| Drysdale | 629,172 patients early treatment: 4% lower PASC (p=0.002) |
Recent studies (see the individual treatment pages for all studies):
Apr 30 |
et al., Health Technology Assessment, doi:10.3310/MTRS8833 | Lessons from the PROTECT-CH COVID-19 platform trial in care homes |
| Discussion of a planned COVID-19 platform trial (PROTECT-CH) in care homes that failed to start recruitment. The trial was designed to test prophylactic antiviral interventions (initially ciclesonide and niclosamide) to reduce SARS-CoV-2 .. | ||
Apr 11 |
et al., NCT04590547 | Safety, Tolerability and Efficacy and Dose Response of GLS-1027 in the Prevention of Severe Pneumonitis Caused by SARS-CoV-2 Infection |
| 200% higher mortality (p=0.34), 1% worse recovery (p=0.99), and 1% shorter hospitalization (p=0.87). RCT 132 hospitalized COVID-19 patients showing no significant difference in outcomes with zenuzolac (GLS-1027) treatment. | ||
Apr 11 |
et al., JMIR Formative Research, doi:10.2196/66509 | Oxidative Stress Markers and Prediction of Severity With a Machine Learning Approach in Hospitalized Patients With COVID-19 and Severe Lung Disease: Observational, Retrospective, Single-Center Feasibility Study |
| Retrospective 28 hospitalized COVID-19 patients showing an association between oxidative stress biomarkers and disease severity. Lower zinc and thiol levels, higher Cu/Zn ratios, and increased high-sensitivity C-reactive protein (hs-CRP) .. | ||
Apr 9 |
et al., VIEW, doi:10.1002/VIW.20240075 | The effectiveness and safety of azvudine treatment in COVID‐19 patients with kidney disease based on a multicenter retrospective cohort study |
| 38% lower mortality (p<0.0001) and 21% lower progression (p=0.03). PSM retrospective 4,192 hospitalized COVID-19 patients with kidney disease showing significantly reduced all-cause mortality and disease progression with azvudine. | ||
Apr 8 |
et al., Clinical and Translational Medicine, doi:10.1002/ctm2.70275 | Severe SARS‐CoV‐2 infection in diabetes was rescued in mice supplemented with metformin and/or αKG, and patients taking metformin, via HIF1α‐IFN axis |
| In Vitro and mouse study showing that metformin and/or alpha-ketoglutarate (αKG) supplementation reduces SARS-CoV-2 infection severity in diabetic mice by modulating the HIF1α–interferon axis. Diabetic mice exhibited elevated viral loads,.. | ||
Apr 7 |
et al., Frontiers in Nutrition, doi:10.3389/fnut.2025.1476622 | Low vitamin K status is a potential risk factor for COVID-19 infected patients: a systematic review and meta-analysis |
| Meta-analysis of 6 studies examining vitamin K status in COVID-19 patients showing that infected patients have significantly higher levels of dephosphorylated-uncarboxylated Matrix Gla Protein (dp-ucMGP), indicating lower vitamin K status.. | ||
Apr 7 |
et al., Scientific Reports, doi:10.1038/s41598-025-92242-y | Antiviral effect of Bromelain combined with acetylcysteine against SARS-CoV-2 Omicron variant |
| In Vitro and Ex Vivo study showing that BromAc (bromelain and N-acetylcysteine) exhibits antiviral activity against SARS-CoV-2 Omicron variant. Authors demonstrate that BromAc at 250 μg/mL significantly reduces infectious viral particles .. | ||
Apr 6 |
et al., Talanta, doi:10.1016/j.talanta.2025.128084 | Does Favipiravir interact with DNA? Design of electrochemical DNA nanobiosensor to investigate the interaction between DNA and Favipiravir used in the treatment of COVID-19 |
| Favipiravir exhibits a direct interaction with DNA, as detected by a novel electrochemical nanobiosensor. Authors observed a decrease in guanine oxidation signals that suggests favipiravir may bind to or alter DNA structure, raising conce.. | ||
Apr 4 |
et al., Food Chemistry Advances, doi:10.1016/j.focha.2025.100969 | Novel dietary herbal preparations with inhibitory activities against multiple SARS-CoV-2 targets: A multidisciplinary investigation into antiviral activities |
| In Vitro and In Silico study showing potent inhibition of SARS-CoV-2 main protease (3CLpro) by novel polyherbal dietary preparations. Curcumin was used as a positive control and inhibited protease activity by >95% at 50 μM. | ||
Apr 4 |
et al., Biomedical Research, doi:10.2220/biomedres.46.37 | Possible involvement of neuropeptide Y sub-receptor 1 (NPY-Y1) in the anti-viral response of SARS-CoV-2 infection in Syrian hamster |
| Animal study showing that molnupiravir and remdesivir co-administration reduces SARS-CoV-2 viral load and inflammatory responses in Syrian hamsters, with involvement of neuropeptide Y sub-receptor 1 (NPY-Y1). Authors found that SARS-CoV-2.. | ||
Apr 2 |
et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/aac.01556-24 | Potent antiviral activity of simnotrelvir against key epidemic SARS-CoV-2 variants with a high resistance barrier |
| In Vitro and clinical study showing potent antiviral activity of simnotrelvir against SARS-CoV-2 variants with a high resistance barrier. Authors demonstrated simnotrelvir's efficacy against multiple Omicron variants including BA.1, BA.4,.. | ||
Apr 1 |
et al., National Journal of Medical Research, doi:10.55489/njmr.150220251070 | A Study on Serum Vitamin D3 Level in Patients with Covid-19: A Cross-Sectional Study in Kolkata |
| 58% lower severe cases (p=0.002). Analysis of 100 hospitalized COVID-19 patients in India showing strong association between vitamin D deficiency and COVID-19 severity. | ||
Mar 31 |
et al., Saudi Journal of Medicine, doi:10.36348/sjm.2025.v10i03.00X | Phase-II RCT Convalescent Plasma Transfusion in Severe COVID-19 Patients -Evaluation of Efficacy and Tolerability |
| no change in mortality (p=1). RCT 60 severe COVID-19 patients showing no benefit with convalescent plasma. | ||
Mar 31 |
et al., Scientific Reports, doi:10.1038/s41598-025-85677-w | Efficacy and safety of azvudine versus nirmatrelvir/ritonavir in cancer patients with COVID-19 |
| PSM retrospective 596 cancer patients with COVID-19 showing that azvudine significantly reduced all-cause mortality and composite disease progression compared to paxlovid. | ||
Mar 28 |
et al., Medical Hypotheses, doi:10.1016/j.mehy.2025.111613 | Cholinergic eubiosis: A hypothesis on Ivermectin-upregulated Bifidobacterium |
| Hypothesis that ivermectin may increase beneficial Bifidobacterium populations in the gut through a "cholinergic eubiosis" mechanism. Authors theorize that ivermectin acts as a positive allosteric regulator of alpha-7 nicotinic.. | ||
Mar 26 |
et al., PLOS ONE, doi:10.1371/journal.pone.0320415 | Integration of metabolomics and chemometrics with in-silico and in-vitro approaches to unravel SARS-Cov-2 inhibitors from South African plants |
| In Silico and In Vitro study showing that quercetin derivatives from South African plants effectively inhibit SARS-CoV-2 main protease (3CLpro). Authors integrated metabolomics and chemometrics with computational approaches to identify bi.. | ||
Mar 25 |
et al., NCT04478071 | Vadadustat for the Prevention and Treatment of Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Patients With Coronavirus Disease 2019 (COVID-19) |
| 3% higher mortality (p=1), 16% lower progression (p=0.36), and 8% improved recovery (p=0.6). RCT 448 hospitalized COVID-19 patients in the USA showing no significant differences with vadadustat. | ||
Mar 25 |
et al., Frontiers in Nutrition, doi:10.3389/fnut.2025.1566505 | Association of zinc deficiency and clinical symptoms, inflammatory markers, severity of COVID-19 in hospitalized children |
| 280% higher severe cases (p=1). Prospective study of 140 hospitalized children with COVID-19 in Ukraine showing that zinc deficiency associated with higher inflammatory markers. While there was a trend toward more frequent fever (p=0.0654) with deficiency, there was no .. | ||
Mar 25 |
et al., The Japanese Journal of Antibiotics, doi:10.11553/antibiotics.78.1_35 | Critical appraisal of multidrug therapy in the ambulatory management of patients with COVID-19 and hypoxemia Part II: Causal inference using the Bradford Hill criteria |
| Critical appraisal of three case series totaling 119 COVID-19 patients with hypoxemia treated with ivermectin-based multidrug protocols in the United States, Zimbabwe, and Nigeria, showing reduced hospitalization and mortality. Authors ap.. | ||
Mar 22 |
et al., Infection, doi:10.1007/s15010-025-02505-z | Impact of treatment of COVID-19 with sotrovimab on post-acute sequelae of COVID-19 (PASC): an analysis of National COVID Cohort Collaborative (N3C) data |
| 4% lower PASC (p=0.002). N3C retrospective 9,504 sotrovimab-treated high-risk COVID-19 patients versus 619,668 untreated high-risk controls showing reduced risk of post-acute sequelae of COVID-19 (PASC) with treatment. ATT weighting failed to adjust for "hea.. | ||
Mar 21 |
et al., Journal of Health Sciences and Medicine, doi:10.32322/jhsm.1625339 | Can hydroxychloroquine and azithromycin combination cause cardiac rhythm disturbances in children with COVID-19 pneumonia? |
| Retrospective 24 pediatric COVID-19 pneumonia patients showing no cardiac rhythm disturbances or QTc prolongation with hydroxychloroquine and azithromycin combination therapy. | ||
Mar 18 |
et al., PNAS Nexus, doi:10.1093/pnasnexus/pgaf085 | Clinical and molecular landscape of prolonged SARS-CoV-2 infection with resistance to remdesivir in immunocompromised patients |
| Clinical and virological study of 3 immunocompromised B-cell lymphoma patients with prolonged SARS-CoV-2 infection showing development of remdesivir and sotrovimab resistance. Through serial viral genome sequencing, authors identified NSP.. | ||
Mar 17 |
et al., JACC: Case Reports, doi:10.1016/j.jaccas.2025.103238 | Complete Heart Block Triggered by Nirmatrelvir-Ritonavir and Verapamil |
| Case report of a 58-year-old woman who developed complete heart block and shock due to a drug-drug interaction between paxlovid and verapamil, exacerbated by acute kidney injury and liver dysfunction. This case highlights potentially leth.. | ||
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 5,559 studies,
2,623 present results comparing with a control group,
2,407 are treatment studies, and
216 analyze outcomes based on serum levels. There are
106 animal studies,
201 in silico studies,
384 in vitro studies,
442 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. IMA 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.