COVID-19 early treatment: real-time analysis of 5,882 studies
| Alcântara | 131 patients curcumin early treatment: 37% improved recovery (p<0.0001) |
| Blázquez-Cabrera | 230 patients vitamin D late treatment: 52% lower mortality (p=0.05) |
COVID-19 involves the interplay of over 100 viral and host proteins and factors, providing many therapeutic targets.
c19early analyzes over 5,800 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.
| Blázquez-Cabrera | 230 patients late treatment: 52% lower mortality (p=0.05) |
Recent studies (see the individual treatment pages for all studies):
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 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 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.. | ||
May 31 |
et al., Clinical Nutrition Open Science, doi:10.1016/j.nutos.2025.05.007 | Exploring the association between vitamin D status and Corona Virus-19 infection in a cohort of adults aged 50 years and older |
| 74% fewer cases (p=0.01). Prospective study of 131 adults aged 50+ years showing lower vitamin D status was significantly associated with higher risk of COVID-19 infection and hospitalization. Adjusted results based on deficiency are only provided for cases (other.. | ||
May 31 |
et al., medRxiv, doi:10.1101/2025.05.30.25327809 | Risk of Post-COVID Conditions among adolescents and adults who received nirmatrelvir-ritonavir for acute COVID-19: a retrospective cohort study |
| Retrospective 291,433 paxlovid recipients matched 1:2 to 582,866 untreated COVID-19 outpatients in the USA reporting a modest reduction in long COVID in the primary model for patients 50+. Analysis requiring a positive laboratory test or .. | ||
May 31 |
et al., American Journal of Respiratory and Critical Care Medicine, doi:10.1164/ajrccm.2025.211.Abstracts.A1193 | Toxic as FK - A Case of Paxlovid-Induced Tacrolimus (FK506) Toxicity in a Kidney Transplant Recipient with COVID-19 |
| Case report of a 71-year-old kidney transplant recipient who developed fatal tacrolimus toxicity after being prescribed paxlovid for COVID-19. | ||
May 31 |
et al., Journal of Ayurveda and Integrative Medicine, doi:10.1016/j.jaim.2025.101135 | Ashwagandha, Withania somnifera (L.) Dunal, for the prophylaxis against SARS-CoV-2 infection: A multicentric randomized hydroxychloroquine controlled clinical trial in Indian health care workers |
| 61% fewer cases (p=0.28). RCT 400 healthcare workers in India comparing HCQ and withania somnifera (WS) for COVID-19 prophylaxis, showing 2 cases for HCQ and 5 for WS. Both treatments had comparable safety profiles, with mostly mild gastrointestinal adverse events. | ||
May 30 |
et al., Viruses, doi:10.3390/v17060792 | Antiviral Intervention of COVID-19: Linkage of Disease Severity with Genetic Markers FGB (rs1800790), NOS3 (rs2070744) and TMPRSS2 (rs12329760) |
| Genetic case-control study of 257 COVID-19 patients (197 moderate-severe, 60 mild) showing that carriers of the G-allele (especially GG genotype) of FGB gene rs1800790 and T-allele of TMPRSS2 gene rs12329760 had higher risk of developing.. | ||
May 29 |
et al., Journal of Cellular and Molecular Medicine, doi:10.1111/jcmm.70581 | Pathological Glucose Levels Enhance Entry Factor Expression and Hepatic SARS‐CoV‐2 Infection |
| Analysis of high glucose levels on SARS-CoV-2 infection, showing that hyperglycemia significantly increases expression of viral entry factors (ACE2, TMPRSS2, TMPRSS4, FURIN, NRP1) in liver cells but not in lung and pancreatic cells, which.. | ||
May 26 |
et al., Infectious Diseases, doi:10.1080/23744235.2025.2509011 | Dynamics of SARS-CoV-2 variants and mutations in Central Sweden between 2023 and 2024 and their potential implications on monoclonal antibodies pemivibart and sipavibart as PrEP in the region |
| Analysis of SARS-CoV-2 variants and mutations in central Sweden from October 2023 to October 2024, showing the rise of resistance mutations that likely render monoclonal antibodies sipavibart and pemivibart ineffective. | ||
May 22 |
et al., NCT04347226 | A Randomized Phase 2 Study of Anti-IL-8 Therapy Versus Standard of Care in the Treatment of Hospitalized Patients With Severe COVID-19 |
| 6% higher mortality (p=1), 100% higher ICU admission (p=0.59), and 107% slower improvement (p=0.08). RCT 43 hospitalized patients in the USA showing no significant benefit with HuMax-IL8 (BMS-986253) treatment. | ||
May 21 |
et al., medRxiv, doi:10.1101/2025.05.18.25327861 | Antiviral efficacy of oral ensitrelvir versus oral ritonavir-boosted nirmatrelvir in COVID-19 |
| 8% faster recovery (p=0.006) and 49% improved viral clearance (p<0.0001). RCT 604 low-risk adults with early COVID-19 symptoms showing significantly improved SARS-CoV-2 viral clearance with both ensitrelvir and paxlovid. Inclusion criteria selected for low-risk patients with high viral loads which may not gener.. | ||
May 21 |
et al., Scientific Reports, doi:10.1038/s41598-025-02240-3 | Dose-dependent impact of tixagevimab–cilgavimab as primary prevention against SARS-CoV-2 in immunocompromised individuals |
| 70% more cases (p=0.08). Retrospective 597 immunocompromised individuals showing no significant difference in infection rates over the entire study period. However, when truncating data to November 1, 2022 (before resistant variants dominated), effectiveness incr.. | ||
May 20 |
et al., PLOS One, doi:10.1371/journal.pone.0323910 | Hospitalised children with COVID-19 display an aberrant intestinal microbiota and a shift in faecal compounds related with the metabolism of vitamins and lipids |
| Analysis of 16 children hospitalized with COVID-19 and 20 age-matched healthy controls showing altered gut microbiota and faecal metabolomic profiles in infected children. COVID-19 patients had higher abundance of opportunistic bacteria a.. | ||
May 19 |
et al., Journal of Infection, doi:10.1016/j.jinf.2025.106510 | Monitoring the emergence of resistance with sotrovimab in immunocompromised patients with COVID-19: LUNAR study |
| Prospective study of 217 mostly immunocompromised COVID-19 outpatients in the UK showing viral clearance in 84% by day 28 after sotrovimab treatment, and treatment-emergent substitutions in the sotrovimab epitope in 30% of patients with p.. | ||
May 19 |
et al., British Journal of Clinical Pharmacology, doi:10.1002/bcp.70099 | Association between ramelteon and 30-day mortality in ICU patients with COVID-19: A retrospective analysis of the MIMIC-IV database |
| 47% lower mortality (p=0.005). PSM retrospective 1,066 ICU patients in China, showing significantly lower mortality with ramelteon treatment. | ||
May 18 |
et al., American Journal of Respiratory and Critical Care Medicine, doi:10.1164/ajrccm.2025.211.Abstracts.A2672 | Ultrastructural Alteration of Bronchoalveolar Lavage of COVID19 Induced Acute Respiratory Distress Syndrome Patients Reveals the Selective Cellular Infectivity, Impact of Hydroxy-Chloroquine, and Syncytial Formation in the Lung |
| Ultrastructural examination of broncho-alveolar lavage from 79 intubated ARDS patients showing that prior HCQ prophylaxis correlated with markedly fewer intracellular virions, preserved airway cilia, and granulocytes packed with degrading.. | ||
May 14 |
et al., Infection and Drug Resistance, doi:10.2147/IDR.S499371 | Clinical Characteristics and Mortality Trends Among COVID-19 Patients During the First Four Waves in Ngaliema Clinic, Democratic Republic of the Congo |
| 76% lower mortality (p=0.01). Retrospective 410 hospitalized COVID-19 patients in the Democratic Republic of Congo showing significantly lower mortality with vitamin C treatment. | ||
May 13 |
et al., Frontiers in Pediatrics, doi:10.3389/fped.2025.1436633 | Vitamin D status in children with mild, moderate, or severe confirmed COVID-19: systematic-review and meta-analysis |
| Meta-analysis of 12 studies showing significantly lower vitamin D levels in COVID-19 patients compared to healthy controls. Children with moderate COVID-19 had 3.6 times higher odds of vitamin D deficiency compared to aymptomatic patients.. | ||
May 13 |
et al., Research Square, doi:10.21203/rs.3.rs-6582593/v1 | Clinical efficacy of casirivimab and imdevimab in preventing COVID-19 in the Omicron BA.5 subvariant epidemic: a retrospective study |
| 88% fewer cases (p=0.02). Retrospective study of 52 hospitalized patients showing significantly lower COVID-19 incidence with casirivimab/imdevimab for post-exposure prophylaxis during a period when Omicron BA.5 was dominant. | ||
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 5,882 studies,
2,824 present results comparing with a control group,
2,605 are treatment studies, and
219 analyze outcomes based on serum levels. There are
111 animal studies,
219 in silico studies,
412 in vitro studies,
451 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.