COVID-19 early treatment: real-time analysis of 5,923 studies
| Hobbs | PRINCIPLE RCT 413 outpatients patients showing significantly faster recovery with HCQ. Publication was delayed over 5 years. Treatment was very late.. |
COVID-19 involves the interplay of over 100 viral and host proteins and factors, providing many therapeutic targets.
c19early analyzes over 5,900 studies for 172 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.
0.6% 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.
0.6% of treatments show efficacy.
Top journals that accept positive studies for low cost treatments:
Nutrients,
PLOS ONE,
Scientific Reports,
International Journal of Infectious Diseases,
Frontiers in Medicine,
Cureus,
more...
Treatment cost times median NNT - details and limitations.
0.6% of treatments show efficacy.
All clinical results for selected treatments. 0.6% 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. 0.6% 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. 0.6% 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. 0.6% 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. 0.6% 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. 0.6% 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. 0.6% 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. 0.6% 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. 0.6% 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.
(*) 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.. |
| Negru | Pharmacovigilance analysis of 64,776 adverse event reports from EudraVigilance comparing safety profiles of COVID-19 antivirals, showing remdesivir.. |
| Chen | 90,552 patients sufficiency: 61% lower mortality (p=0.007) |
| Blázquez-Cabrera | 230 patients late treatment: 52% lower mortality (p=0.05) |
| Negru | Pharmacovigilance analysis of 64,776 adverse event reports from EudraVigilance comparing safety profiles of COVID-19 antivirals, showing remdesivir.. |
| Rowland | RCT 24 hospitalized COVID-19 patients (16 treatment, 8 standard of care) evaluating safety and pharmacokinetics of intravenous favipiravir at.. |
| Tate | 302 patient early treatment RCT: 34% lower hospitalization (p=0.68), 21% improved 7-point scale results (p=0.61), 3% improved recovery (p=0.82), and 12% improved viral clearance (p=0.68) |
Recent studies (see the individual treatment pages for all studies):
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.. | ||
Jun 27 |
et al., COVID, doi:10.3390/covid5070097 | Vitamin D Status and SARS-CoV-2 Positivity in Lebanon Among Adults: A Cross-Sectional Study in South Lebanon |
| 34% fewer cases (p=0.15). Cross-sectional study of 384 adults showing no significant association between vitamin D levels and test positivity. | ||
Jun 24 |
et al., Journal of Inflammation Research, doi:10.2147/JIR.S522566 | Association Between Vitamin A and D Status and the Risk of COVID-19 in the Elderly Population: A Single-Center Experience |
| 99% fewer cases (p=0.002). Prospective study of 32 elderly COVID-19 patients and 30 healthy controls in China showing significantly lower vitamin A and D levels in COVID-19 patients. In multivariable analysis, vitamin A deficiency was associated with significantly .. | ||
Jun 24 |
et al., Antimicrobial Agents and Chemotherapy, doi:10.1128/aac.00054-25 | Clinical effectiveness, safety, and viral mutagenicity of oral favipiravir for COVID-19: results from a community-based, open-label, randomized Phase III trial |
| 34% lower hospitalization (p=0.68), 21% improved 7-point scale results (p=0.61), 3% improved recovery (p=0.82), and 12% improved viral clearance (p=0.68). RCT 302 outpatients with mild COVID-19 showing no significant difference in outcomes with favipiravir treatment. The study population was relatively young and had few comorbidities, resulting in a low incidence of severe disease. Favipira.. | ||
Jun 18 |
et al., npj Metabolic Health and Disease, doi:10.1038/s44324-025-00072-3 | Aspirin reduces the risk of type 2 diabetes associated with COVID-19 |
| Retrospective 35,525 adults followed from 2018 to 2022, showing that daily low-dose aspirin (100 mg) significantly reduced the risk of new-onset type 2 diabetes (T2D). After propensity score matching, aspirin users had a 52% overall reduc.. | ||
Jun 18 |
et al., Frontiers in Nutrition, doi:10.3389/fnut.2025.1583276 | Association between vitamin D deficiency and clinical outcome in patients with COVID-19 in the post-Omicron phase |
| 61% lower mortality (p=0.007). TriNetX PSM retrospective showing that vitamin D deficiency was significantly associated with increased 30-day mortality and adverse outcomes in COVID-19 patients, although the magnitude of this association decreased in the post-Omicron p.. | ||
Jun 18 |
et al., Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2025.1584261 | Effectiveness and safety of azvudine in the treatment of COVID-19 patients: a retrospective cohort study using propensity score matching |
| 20% shorter hospitalization (p=0.001) and no change in viral clearance (p=1). Retrospective 192 COVID-19 patients in China showing significantly shorter hospitalization with azvudine treatment, but no significant difference for viral clearance. | ||
Jun 17 |
et al., Journal of Health, Population and Nutrition, doi:10.1186/s41043-025-00958-4 | Dietary glycemic index, glycemic load, and risk of COVID-19: a prospective cohort study |
| 84% fewer cases (p<0.0001). Prospective cohort study of 3,319 participants showing higher risk of COVID-19 infection associated with higher dietary glycemic index (GI) and glycemic load (GL). Authors suggest that diets with high GI/GL may increase COVID-19 susceptib.. | ||
Jun 12 |
et al., Virology, doi:10.1016/j.virol.2025.110607 | SARS-CoV-2 host-pathogen interactome: insights into more players during pathogenesis |
| Review of SARS-CoV-2 host-pathogen interactions during viral pathogenesis, focusing on protein-protein interactions that facilitate viral entry, replication, immune evasion, assembly, and release. Authors comprehensively analyze how SARS-.. | ||
Jun 10 |
et al., Japanese Dental Science Review, doi:10.1016/j.jdsr.2025.05.001 | Antiseptics as effective virucidal agents against SARS-CoV-2: Systematic review and Bayesian network meta-analysis |
| Bayesian network meta-analysis of 26 studies evaluating the effectiveness of oral and nasal antiseptics against SARS-CoV-2 viral load, finding that povidone-iodine was the most effective. Hydrogen peroxide and chlorhexidine also showed si.. | ||
Jun 10 |
et al., Nutrients, doi:10.3390/nu17121968 | ALBACOVIDIOL Study: Effect of Calcifediol Treatment on Mortality in Patients Hospitalized for COVID-19: A Retrospective Analysis |
| 52% lower mortality (p=0.05). Retrospective 230 hospitalized COVID‑19 patients in Spain, showing lower mortality with calcifediol treatment (p = 0.053). | ||
Jun 9 |
et al., medRxiv, doi:10.1101/2025.06.09.25329141 | Optimal dose and safety of intravenous favipiravir in hospitalised patients with SARS-CoV-2 infection: a Phase Ib, open-label, dose-escalating, randomised controlled study |
| RCT 24 hospitalized COVID-19 patients (16 treatment, 8 standard of care) evaluating safety and pharmacokinetics of intravenous favipiravir at escalating doses. The study found that IV favipiravir was safe and well-tolerated up to 2400mg t.. | ||
Jun 5 |
et al., Frontiers in Medicine, doi:10.3389/fmed.2025.1565069 | Povidone-iodine nasal spray (Nasodine®) for the common cold: a randomized, controlled, double-blind, Phase III clinical trial |
| Non-COVID-19 RCT of 260 outpatients with early common-cold symptoms comparing 0.5% povidone-iodine (PVP-I) nasal spray and saline spray four-times daily for five days. PVP-I showed lower Global Severity Score (GSS) and improved quality-of.. | ||
Jun 5 |
et al., Biomedicines, doi:10.3390/biomedicines13061387 | Comparative Pharmacovigilance Analysis of Approved and Repurposed Antivirals for COVID-19: Insights from EudraVigilance Data |
| Pharmacovigilance analysis of 64,776 adverse event reports from EudraVigilance comparing safety profiles of COVID-19 antivirals, showing remdesivir associated with more serious adverse events compared to paxlovid. Remdesivir showed consis.. | ||
Jun 5 |
et al., Research Square, doi:10.21203/rs.3.rs-6819274/v1 | INP-Guided Network Pharmacology Discloses Multi-Target Therapeutic Strategy Against Cytokine and IgE Storms in the SARS-CoV-2 NB.1.8.1 Variant |
| Computational modeling study presenting a multi-target therapeutic approach against the SARS-CoV-2 NB.1.8.1 variant using Intrinsic Network Pharmacology (INP) and network pharmacology tools. The researchers identified ZINC000014930714, a .. | ||
Jun 4 |
et al., NCT04481685 | A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19 |
| no change in mortality (p=1) and 25% higher progression (p=1). RCT 20 hospitalized patients showing no significant difference in outcomes with ATI-450 (zunsemetinib). | ||
Jun 4 |
et al., PLOS One, doi:10.1371/journal.pone.0324903 | In-hospital mortality outcomes of favipiravir in patients with moderate to severe COVID-19 infection: An emulated target trial using real-world data from the largest field hospital in Thailand |
| 4% improved survival (p=0.004). Retrospective 3,193 moderate to severe COVID-19 patients in Thailand showing modest survival benefits with favipiravir. This emulated target trial found that favipiravir alone increased restricted mean survival time by 1.32 days (p=0.042).. | ||
Jun 4 |
et al., Authorea Inc., doi:10.22541/au.174904567.74543434/v1 | Earlier clinical improvement in mild-moderate acute COVID patients treated with pharmacological-grade Curcumin |
| 37% improved recovery (p<0.0001). Prospective study of 131 mild-moderate COVID-19 patients showing significant reduction in time to symptom relief and complete recovery with pharmaceutical-grade curcumin. | ||
Jun 4 |
et al., Frontiers in Pharmacology, doi:10.3389/fphar.2025.1558054 | Real-world data of Azvudine-induced hepatotoxicity among hospitalized COVID-19 patients in China: a retrospective case-control study |
| Retrospective case-control study of 669 hospitalized COVID-19 patients in China showing significant hepatotoxicity associated with azvudine treatment. | ||
Jun 3 |
et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiaf294 | Functional and structural characterization of treatment-emergent nirmatrelvir resistance mutations at low frequencies in the main protease (Mpro) reveals a unique evolutionary route for SARS-CoV-2 to gain resistance |
| In Vitro and In Silico study showing that novel SARS-CoV-2 main protease (Mpro) mutations confer resistance to paxlovid. Authors identified new Mpro clinical variants, including D48D/L58F/P132H and D48D/L67V/K90R/P132H, in patients who re.. | ||
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 5,923 studies,
2,834 present results comparing with a control group,
2,612 are treatment studies, and
222 analyze outcomes based on serum levels. There are
111 animal studies,
222 in silico studies,
414 in vitro studies,
452 reviews,
and 247 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.