COVID-19 early treatment: real-time analysis of 5,756 studies
COVID-19 involves the interplay of over 100 viral and host proteins and factors, providing many therapeutic targets.
c19early analyzes over 5,700 studies for 161 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.
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.
0.6% 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.
0.6% 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.
| Yadav | Ultrastructural examination of broncho-alveolar lavage from 79 intubated ARDS patients showing that prior HCQ prophylaxis correlated with markedly.. |
| Ohtani | 52 patients prophylaxis: 88% fewer cases (p=0.02) |
| Mousavi | Meta-analysis of 12 studies showing significantly lower vitamin D levels in COVID-19 patients compared to healthy controls. Children with moderate.. |
| Ito | Sufficiency: 5% more cases (p=0.89) |
| Li | Review of azvudine as a treatment for COVID-19, highlighting its pharmacological properties, clinical effectiveness, and safety profile. Azvudine, a.. |
| Sulistyani | 30 patients early treatment: 44% improved viral clearance (p=0.001) |
| Sulistyani | 30 patients early treatment: 54% improved viral clearance (p=0.001) |
| Emam | In Vitro study showing that curcumin, quercetin, gallic acid, and silymarin inhibit SARS-CoV-2 spike protein binding to the ACE2 receptor. Authors.. |
| Muthusamy | In Silico study identifying 32 anti-parisitic compounds effectively inhibiting the RBD of the SARS-CoV-2 spike protein, showing ivermectin and.. |
| Bess | In Silico study showing potential benefit of mebendazole and zinc against SARS-CoV-2 according to an AI platform, eVir, designed to identify.. |
| Agamah | In Silico study identifying potential drugs beneficial for COVID-19 by integrating transcriptomics, proteomics, metabolomics, lipidomics, and drug.. |
| Hamdan | In Silico study showing that H1RA antihistamines, including bilastine, fexofenadine, mizolastine, rupatadine, terfenadine, and the leukotriene.. |
Recent studies (see the individual treatment pages for all studies):
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 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. | ||
May 7 |
et al., American Journal of Respiratory and Critical Care Medicine, doi:10.1164/ajrccm.2025.211.Abstracts.A3027 | Early and Delayed Administration of Azvudine on Mortality of Adult Patients With COVID-19: A Retrospective Study |
| PSM retrospective 604 hospitalized COVID-19 patients showing lower mortality with azvudine. Detailed results are only provided for the subgroup of non-mild patients. | ||
May 6 |
et al., Clinical Nutrition ESPEN, doi:10.1016/j.clnesp.2025.05.007 | Serum Vitamin D and the Risk of SARS-CoV-2 and Seasonal Influenza Infection During the Twindemic Period |
| 5% more cases (p=0.89). Survey of 1,434 hospital staff members showing no significant difference in COVID-19 or influenza cases based on vitamin D sufficiency. | ||
May 3 |
et al., iScience, doi:10.1016/j.isci.2025.112575 | A pharmacokinetic study and critical reappraisal of curcumin formulations enhancing bioavailability |
| Crossover study of 9 healthy males comparing curcumin bioavailability from three commercial formulations (AOV, Longvida, NovaSOL). None of the three products tested contained the claimed amount of curcumin. Results showed plasma levels of.. | ||
May 2 |
et al., AAPS PharmSciTech, doi:10.1208/s12249-025-03113-8 | Enhancing Intracellular Uptake of Ivermectin through Liposomal Encapsulation |
| In Vitro study showing enhanced intracellular uptake of ivermectin through liposomal encapsulation in Vero E6 cells with reduced cytotoxicity. While free ivermectin showed a half-maximal cytotoxic concentration (CC50) of 10 μM, liposomal .. | ||
May 2 |
et al., medRxiv, doi:10.1101/2025.05.01.25326797 | A randomised-controlled Phase I de-escalation trial of Molnupiravir and Nirmatrelvir/Ritonavir combination for mild-moderate SARS-CoV-2 infection |
| 1% worse viral clearance (p=0.94). Randomized open-label phase I trial of 24 outpatients with mild-moderate COVID-19 showing safety and tolerability of combined molnupiravir and paxlovid therapy. The paper reports that the control group received standard of care and ".. | ||
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 30 |
et al., International Journal of Tokat Medical Sciences, 17:18-25 | COVİD-19 Pnömonisi Gelişen Hastalarda Vitamin D Düzeylerinin Hastane Yatış Süresi ve Mortalite ile İlişkisinin Değerlendirilmesi: Retrospektif Analiz |
| 60% lower mortality (p=0.07). Retrospective 178 hospitalized COVID-19 pneumonia patients showing higher mortality with lower vitamin D levels. | ||
Apr 30 |
et al., Dental and Medical Problems, doi:10.17219/dmp/192493 | Effects of chlorhexidine gluconate and povidone-iodine mouthwash on cycle threshold values in patients infected with SARS-CoV-2 |
| 54% improved viral clearance (p=0.001). Prospective study of 45 COVID-19 patients showing improved viral clearance with chlorhexidine gluconate and povidone-iodine mouthwash use. | ||
Apr 28 |
et al., ChemistrySelect, doi:10.1002/slct.202406035 | Phytochemical Inhibitors of SARS‐CoV‐2 Entry: Targeting the ACE2‐RBD Interaction with l‐Tartaric Acid, l‐Ascorbic Acid, and Curcuma longa Extract |
| In Vitro and In Silico study showing that l-tartaric acid, l-ascorbic acid, and Curcuma longa extract (curcumin, demethoxycurcumin, bisdemethoxycurcumin) inhibit the SARS-CoV-2 spike RBD interaction with human ACE2. Authors demonstrate by.. | ||
Apr 25 |
et al., Communications Medicine, doi:10.1038/s43856-025-00844-4 | Dissecting clinical features of COVID-19 in a cohort of 21,312 acute care patients |
| Retrospective 21,312 acute care COVID-19 patients in the USA showing that low albumin levels were one of the best predictors of disease severity, with hypoalbuminemia associated with higher rates of severe/critical disease trajectories an.. | ||
Apr 25 |
et al., Frontiers in Pharmacology, doi:10.3389/fphar.2025.1524072 | Advances in the effectiveness and safety of azvudine treatment: a comprehensive review |
| Review of azvudine as a treatment for COVID-19, highlighting its pharmacological properties, clinical effectiveness, and safety profile. Azvudine, a dual-target nucleoside drug initially developed for HIV, received conditional approval fr.. | ||
Apr 24 |
et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofaf246 | Aerosolized dornase alfa (DNase I) for the treatment of severe respiratory failure in COVID-19: a randomized controlled trial |
| 11% higher mortality (p=1) and 2% worse recovery (p=0.94). RCT 76 hospitalized COVID-19 patients showing no significant difference with inhaled dornase alfa (DNase I) for resolution of hypoxia or other clinical outcomes. | ||
Apr 22 |
et al., Authorea Inc., doi:10.22541/au.174532324.40343996/v1 | Zinc adjuvant treatment in SARS-CoV-2: a randomized clinical trial |
| 76% lower progression (p=0.05) and 40% improved recovery (p=0.08). RCT 71 hospitalized COVID-19 patients showing reduced disease progression with zinc treatment. In this open-label trial, patients were randomized to receive standard of care alone or with zinc acetate (90 mg/day) for 14 days. Disease prog.. | ||
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 5,756 studies,
2,734 present results comparing with a control group,
2,516 are treatment studies, and
218 analyze outcomes based on serum levels. There are
109 animal studies,
216 in silico studies,
406 in vitro studies,
450 reviews,
and 239 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.