COVID-19 early treatment: real-time analysis of 6,020 studies
| Hobbs | PRINCIPLE RCT 413 outpatients patients showing significantly faster recovery with HCQ. Publication was delayed over 5 years. Treatment was very late.. |
| Wimalawansa | Review of food, drug, and nutraceutical regulations and their impact on public health and healthcare costs. Author argues that the current.. |
COVID-19 involves the interplay of over 200 viral and host proteins and factors, providing many therapeutic targets.
c19early analyzes over 6,000 studies for 175 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 26 low-cost treatments have been approved across 163 countries.
0.6% of 9,000+ proposed treatments show reduced risk.
Direct treatment to the primary source of initial infection reduces progression and transmission.
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, 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/SC administration.
Acetaminophen increases the risk of severe outcomes and mortality.
Studies show 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,
Scientific Reports,
PLOS ONE,
International Journal of Infectious Diseases,
Frontiers in Medicine,
Cureus,
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.
(*) Dr. Uip reportedly prescribed early treatment for himself, but not for patients.
| Hobbs | PRINCIPLE RCT 413 outpatients patients showing significantly faster recovery with HCQ. Publication was delayed over 5 years. Treatment was very late.. |
| Wimalawansa | Review of food, drug, and nutraceutical regulations and their impact on public health and healthcare costs. Author argues that the current.. |
Recent studies (see the individual treatment pages for all studies):
Jul 26 |
et al. | The Association Between Metformin Use and Outcomes of Hospitalized COVID-19 Patients |
| 33% lower mortality (p=0.76) and 45% higher ventilation (p=0.52). Retrospective 285 hospitalized COVID-19 patients in Taiwan with 41 treated with metformin, showing no significant difference in mortality with metformin use. Authors note higher ventilation with use ≥17.5 days, however this requires hospi.. | ||
Jul 26 |
et al., Phytomedicine Plus, doi:10.1016/j.phyplu.2025.100850 | Potential of diterpenoid andrographolide in COVID-19 therapy: an insight on its antiviral-, immunomodulatory-, anti-inflammatory-, antioxidant- and antithrombotic- properties |
| Review of andrographolide's potential for COVID-19, examining its antiviral, immunomodulatory, anti-inflammatory, antioxidant, and antithrombotic properties. Authors describe how andrographolide, a diterpenoid from Andrographis paniculata.. | ||
Jul 25 |
et al., NCT04615949 | Study to Evaluate the Efficacy and Safety of CardiolRx™ in Patients With COVID-19 and Cardiovascular Disease or Risk Factors A Double-blind, Placebo-controlled Trial |
| 80% lower mortality (p=0.49). Early terminated RCT showing lower mortality with cannabidiol treatment, without statistical significance. | ||
Jul 23 |
et al., Research Square, doi:10.21203/rs.3.rs-7146347/v1 | Vitamin D blood levels and vitamin D receptor polymorphisms contribute to post-acute sequelae of severe acute respiratory syndrome coronavirus 2 severity in the pediatric patients |
| Analysis of 123 pediatric patients with post-acute sequelae of SARS-CoV-2 (PASC) showing that both low vitamin D levels and VDR genetic variants contribute to increased symptom severity. | ||
Jul 22 |
et al., Toxicological Sciences, doi:10.1093/toxsci/kfaf093 | Detection of developmental toxicity of the anti-COVID-19 drug molnupiravir using gastruloid-based in vitro assays |
| In Vitro study showing developmental toxicity with N4-hydroxycytidine (NHC), the active metabolite of molnupiravir, in mouse and human gastruloid models. Authors exposed P19C5 mouse embryonic-stem-cell gastruloids to 20 µM NHC, which seve.. | ||
Jul 22 |
et al., BMC Pulmonary Medicine, doi:10.1186/s12890-025-03824-5 | Efficacy and safety of combined nebulization of unfractionated heparin, acetylcysteine, budesonide and ipratropium bromide in hospitalised patients with COVID-19 pneumonia: a randomized controlled clinical trial |
| RCT 74 hospitalized COVID-19 pneumonia patients showing improved lung lesion absorption and oxygenation with combined nebulization of unfractionated heparin, acetylcysteine, budesonide, and ipratropium bromide. The treatment group demonst.. | ||
Jul 22 |
et al., ISPRS International Journal of Geo-Information, doi:10.3390/ijgi14080283 | Spatial and Temporal Correlations of COVID-19 Mortality in Europe with Atmospheric Cloudiness and Solar Radiation |
| Analysis of 37 European countries showing that COVID-19 mortality was significantly negatively correlated with solar radiation in the previous month and positively correlated with cloudiness in both the current month and previous month, a.. | ||
Jul 22 |
, C., Zenodo, doi:10.5281/zenodo.16325841 | Micronutrientes esenciales en la evolución clínica del SARS-CoV-2 en pacientes hospitalizados |
| Observational study of 15 hospitalized COVID-19 patients in Peru showing significant inverse correlations between the intake of zinc, selenium, and vitamin C with both lung damage and oxygen requirements. | ||
Jul 21 |
et al., International Journal of Molecular Sciences, doi:10.3390/ijms26147002 | Afucosylated IgG Promote Thrombosis in Mouse Injected with SARS-CoV-2 Spike Expressing Megakaryocytes |
| Mouse study showing that SARS-CoV-2 spike-expressing megakaryocytes induce afucosylated IgG antibodies leading to thrombosis, and identifying potential therapeutic targets. Inhibitors targeting FcγRIIa receptor, serotonin transporter.. | ||
Jul 18 |
et al., PLoS One, doi:10.1371/journal.pone.0328232 | Effects of vitamin D on COVID-19 risk and hospitalisation in the UK biobank |
| 26% lower hospitalization (p<0.0001) and 5% more cases (p=0.03). Case-control analysis of 151,543 UK Biobank participants showing higher odds of COVID-19 hospitalisation for those with low baseline serum vitamin D, and slightly lower risk of cases. Vitamin D measurements were taken a decade before the .. | ||
Jul 17 |
et al., Redox Biology, doi:10.1016/j.redox.2025.103766 | Viral mitochondriopathy in COVID-19 |
| Discussion of the role of mitochondrial dysfunction in COVID-19 pathogenesis. Authors describe how SARS-CoV-2 viral proteins disrupt mitochondrial function through multiple mechanisms, including impairing bioenergetics, altering calcium h.. | ||
Jul 16 |
et al., Phytotherapy Research, doi:10.1002/ptr.70046 | Oral Administration of Water-Soluble Curcumin Complex Prevents ARDS With the Potential for COVID-19 Treatment |
| Mouse and In Vitro study showing that orally administered water-soluble cyclodextrin-curcumin complex (CDC) protected C57BL/6 mice from Klebsiella or LPS-induced acute lung injury and down-regulated COVID-19 relevant pathways: treated ani.. | ||
Jul 16 |
et al., Scientific Reports, doi:10.1038/s41598-025-07170-8 | Serum melatonin as a potential biomarker for COVID-19 severity |
| Retrospective 145 COVID-19 patients in South Korea showing significantly lower serum melatonin levels in patients with severe disease and in non-survivors compared to survivors. | ||
Jul 15 |
et al., Biomedicine & Pharmacotherapy, doi:10.1016/j.biopha.2025.118346 | Do vitamins halt the COVID-19-evoked pro-inflammatory cytokines involved in the development of neuropathic pain? |
| Review of vitamin supplementation for COVID-19-evoked pro-inflammatory cytokines involved in neuropathic pain development. Authors examine how certain vitamins may help prevent post-COVID neuropathic pain by modulating pro-inflammatory cy.. | ||
Jul 11 |
, D., Nature Communications, doi:10.1038/s41467-025-60478-x | On meta-analytic models and the effect of hydroxychloroquine use in COVID-19 |
| Meta-analytic re-analysis of randomized COVID-19 trials (mortality in inpatients; hospitalization in outpatients) showing that hydroxychloroquine (HCQ) does not significantly increase inpatient mortality once Hartung-Knapp scale factors a.. | ||
Jul 8 |
et al., bioRxiv, doi:10.1101/2025.07.07.663218 | Shedding of mitochondrial Voltage-Dependent Anion Channel-1 (VDAC1) Reflects COVID-19 Severity and Reveals Macrophage Dysfunction |
| In Vitro, Ex Vivo, and retrospective observational study showing that VDAC1 (Voltage-Dependent Anion Channel-1) levels reflect COVID-19 severity and that VDAC1 inhibitors (VBIT-4, metformin, and VDAC1-specific antibody) restore macrophage.. | ||
Jul 6 |
et al., Biomacromolecules, doi:10.1021/acs.biomac.5c00576 | Controlling the Sulfation Density of Glycosaminoglycan Glycopolymer Mimetics Enables High Antiviral Activity against SARS-CoV-2 and Reduces Anticoagulant Activity |
| In Vitro study showing the efficacy of carrageenan (used as a positive control) in inhibiting SARS-CoV-2 infection. Authors preincubated SARS-CoV-2 pseudovirus (PsV) with carrageenan before infecting Vero cells. Carrageenan reduced viral .. | ||
Jul 6 |
et al., Scientific Reports, doi:10.1038/s41598-025-08638-3 | Tocilizumab as a targeted immunomodulatory therapy in the management of severe respiratory illnesses: a multicenter cohort study of COVID-19 patients |
| 16% lower mortality (p=0.002). Retrospective 1,470 critically ill COVID-19 patients in Saudi Arabia showing significantly lower mortality with tocilizumab treatment. | ||
Jul 6 |
et al., Nutrition in Clinical Practice, doi:10.1002/ncp.11349 | Vitamin D and COVID‐19: How much more evidence do we need? |
| Discussion of clinical evidence supporting vitamin D treatment for COVID-19. Authors highlight [Vasconcelos] showing reduced all-cause mortality, and cite their own systematic review and meta-analysis of 19 RCTs that found a significant .. | ||
Jul 4 |
et al., Scientific Reports, doi:10.1038/s41598-025-09275-6 | The PRINCIPLE randomised controlled open label platform trial of hydroxychloroquine for treating COVID19 in community based patients at high risk |
| PRINCIPLE RCT 413 outpatients patients showing significantly faster recovery with HCQ. Publication was delayed over 5 years. Treatment was very late, with 25% of patients ≥10 days from onset. There was no significant difference for hospit.. | ||
Jul 1 |
et al., Scientific Reports, doi:10.1038/s41598-025-05381-7 | Impact of early and delayed azvudine administration on COVID-19 mortality: a retrospective study |
| 45% lower mortality (p=0.05). PSM retrospective 604 COVID-19 patients (302 receiving azvudine, 302 controls) showing reduced mortality with azvudine treatment when administered within 8 days of symptom onset. | ||
Jul 1 |
et al., Scientific Reports, doi:10.1038/s41598-025-05683-w | Antiviral and anti-inflammatory efficacy of nanoencapsulated brazilian green propolis against SARS-CoV-2 |
| In Vitro and Ex Vivo study showing that microencapsulated Brazilian green propolis (ME-GP) inhibits SARS-CoV-2 infection and reduces inflammatory responses. Authors created a microemulsion containing 11% Brazilian green propolis extract w.. | ||
Jul 1 |
et al., BMC Infectious Diseases, doi:10.1186/s12879-025-11195-9 | Real-world effectiveness of simnotrelvir-ritonavir versus nirmatrelvir-ritonavir in hospitalized patients with COVID-19 during the omicron wave in China: a retrospective cohort study |
| Retrospective 585 hospitalized COVID-19 patients in China showing that xiannuoxin provided better clinical improvement than paxlovid. There were no significant differences for progression, mortality, or respiratory support. | ||
Jun 30 |
et al., International Journal of Molecular Sciences, doi:10.3390/ijms26136332 | A Mathematical Model of Metformin Action on COVID-19 Risk Infection in Cardiovascular Diabetic Patients Studied by FTIR Spectroscopy |
| Ex vivo Fourier-transform infrared (FTIR) spectroscopy of coronary-artery tissue and fractional-calculus risk modelling showing that metformin use is associated with lower predicted COVID-19 infection and mortality than insulin or thiazol.. | ||
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 6,020 studies,
2,850 present results comparing with a control group,
2,627 are treatment studies, and
223 analyze outcomes based on serum levels. There are
117 animal studies,
223 in silico studies,
424 in vitro studies,
473 reviews,
and 248 meta analyses.
Please send us corrections, updates, or comments.
c19early involves the extraction of 200,000+ 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.