COVID-19 early treatment: real-time analysis of 4,870 studies
Tramontozzi | In Vitro study showing that indomethacin inhibits the replication of human seasonal coronaviruses HCoV-229E (alpha-coronavirus) and HCoV-OC43 (beta.. |
García-Zendejas | Vitamin D sufficiency: 65% lower mortality (p=0.18), 64% lower ICU admission (p=0.15), 84% lower hospitalization (p=0.02), and 58% fewer cases (p=0.26) |
Planas | In Vitro study showing significant escape of SARS-CoV-2 variants KP.1.1, LB.1, and KP.3.3 with monoclonal antibodies pemivibart (VYD222) and.. |
Nguyen | Analysis of payments by drug and medical device manufacturers to US physician peer reviewers of 4 major medical journals from 2020-2022. Authors.. |
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:
PLOS ONE,
Nutrients,
International Journal of Infectious Diseases,
Scientific Reports,
Journal of Clinical Medicine,
Cureus,
more...
Treatment cost times median NNT - details and limitations.
0.6% of treatments show efficacy.
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All clinical results for selected treatments. 0.6% of treatments show efficacy.
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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. | |||||
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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. | |||||
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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. | |||||
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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. | |||||
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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. | |||||
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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. | |||||
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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. |
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.
Tramontozzi | In Vitro study showing that indomethacin inhibits the replication of human seasonal coronaviruses HCoV-229E (alpha-coronavirus) and HCoV-OC43 (beta.. |
García-Zendejas | Sufficiency: 65% lower mortality (p=0.18), 64% lower ICU admission (p=0.15), 84% lower hospitalization (p=0.02), and 58% fewer cases (p=0.26) |
Santa | Comparative analysis of COVID-19 responses in Japan and Africa, focusing on diet, phytochemicals, vitamin D, and gut microbiota in reducing.. |
Zhang | Meta analysis: 28% lower mortality (p=0.02), 22% lower ventilation (p=0.14), and 42% lower ICU admission (p=0.01) |
Karcıoğlu Batur | Genetic association study of 56 adult COVID-19 patients showing an association between vitamin D deficiency, vitamin D-binding protein (VDBP) gene.. |
Sajinadiyasa | Analysis of 68 COVID-19 patients in Indonesia showing higher vitamin D levels associated with lower COVID-19 severity. |
Planas | In Vitro study showing significant escape of SARS-CoV-2 variants KP.1.1, LB.1, and KP.3.3 with monoclonal antibodies pemivibart (VYD222) and.. |
Planas | In Vitro study showing significant escape of SARS-CoV-2 variants KP.1.1, LB.1, and KP.3.3 with monoclonal antibodies pemivibart (VYD222) and.. |
Nguyen | Analysis of payments by drug and medical device manufacturers to US physician peer reviewers of 4 major medical journals from 2020-2022. Authors.. |
Vashisht | Review of the neurological complications of COVID-19 and their pathophysiological underpinnings and therapeutic implications. Authors note that SARS.. |
Zhang | In Silico and In Vitro study showing that andrographolide inhibits SARS-CoV-2 pseudovirus entry and replication and suppresses proinflammatory.. |
Pfizer | 436 patient late treatment RCT: 8% improved recovery (p=0.52) and 18% improved viral clearance (p=0.0004) |
Tamura | Prospective study of 156 outpatients showing emergent nirmatrelvir resistance mutations with nirmatrelvir treatment, especially in immunosuppressed.. |
Zabek | Ex Vivo study showing placental transfer of molnupiravir (NHC) and nirmatrelvir in human placentas. Author used a placental perfusion model to.. |
Santa | Comparative analysis of COVID-19 responses in Japan and Africa, focusing on diet, phytochemicals, vitamin D, and gut microbiota in reducing.. |
Santa | Comparative analysis of COVID-19 responses in Japan and Africa, focusing on diet, phytochemicals, vitamin D, and gut microbiota in reducing.. |
Maria | 81 patients early treatment: 72% lower mortality (p=0.15) and 77% lower progression (p=0.03) |
Gong | Review of natural and socio-environmental factors impacting the transmission of COVID-19. Authors summarized epidemiological and mechanistic.. |
Zabek | Ex Vivo study showing placental transfer of molnupiravir (NHC) and nirmatrelvir in human placentas. Author used a placental perfusion model to.. |
Sakamaki | 650,317 patients prophylaxis: 79% higher severe cases (p<0.0001) |
Recent studies (see the individual treatment pages for all studies):
Oct 8 |
, NCT05567952 | A Study to Learn About a Repeat 5-Day Treatment With the Study Medicines (Called Nirmatrelvir/Ritonavir) in People 12 Years Old or Older With Return of COVID-19 Symptoms and SARS-CoV-2 Positivity After Finishing Treatment With Nirmatrelvir/Ritonavir |
8% improved recovery (p=0.52) and 18% improved viral clearance (p=0.0004). RCT 436 patients with post-paxlovid rebound showing improved viral load at day 5 but no significant difference in recovery time or viral clearance with repeated paxlovid treatment vs. placebo/ritonavir. | ||
Oct 7 |
et al., Natural Product Communications, doi:10.1177/1934578X241288428 | Effects and Mechanisms of Andrographolide for COVID-19: A Network Pharmacology-Based and Experimentally Validated Study |
In Silico and In Vitro study showing that andrographolide inhibits SARS-CoV-2 pseudovirus entry and replication and suppresses proinflammatory cytokine expression in BEAS-2B bronchial epithelial cells. Network pharmacology analysis identi.. | ||
Oct 6 |
et al., Frontiers in Nutrition, doi:10.3389/fnut.2024.1465324 | Comparative analysis of COVID-19 responses in Japan and Africa: diet, phytochemicals, vitamin D, and gut microbiota in reducing mortality—A systematic review and meta-analysis |
Comparative analysis of COVID-19 responses in Japan and Africa, focusing on diet, phytochemicals, vitamin D, and gut microbiota in reducing mortality. Authors conducted a systematic review and meta-analysis to investigate the unexpectedly.. | ||
Oct 4 |
et al., European Journal of Medical Research, doi:10.1186/s40001-024-02062-5 | Does early combination vs. Monotherapy improve clinical outcomes of clinically extremely vulnerable patients with COVID-19? Results from a retrospective propensity-weighted analysis |
72% lower mortality (p=0.15) and 77% lower progression (p=0.03). Retrospective 81 severely immunocompromised COVID-19 outpatients in Italy showing improved composite outcome of death, hospitalization, and emergency department encounters with early combination therapy of an antiviral plus sotrovimab com.. | ||
Sep 30 |
et al., Pathogens and Immunity, doi:10.20411/pai.v10i1.752 | Escape of SARS-CoV-2 Variants KP.1.1, LB.1, and KP.3.3 From Approved Monoclonal Antibodies |
In Vitro study showing significant escape of SARS-CoV-2 variants KP.1.1, LB.1, and KP.3.3 with monoclonal antibodies pemivibart (VYD222) and sipavibart (AZD3152). Sipavibart lost antiviral efficacy, while pemivibart maintained reduced act.. | ||
Sep 27 |
, M., Electronic Thesis and Dissertation Repository, 10427 | The Transfer of Molnupiravir and Nirmatrelvir Across the Human Placenta and Prediction of Drug Safety in Pregnancy |
Ex Vivo study showing placental transfer of molnupiravir (NHC) and nirmatrelvir in human placentas. Author used a placental perfusion model to assess drug transfer across the human placental barrier. Both compounds readily crossed the pla.. | ||
Sep 27 |
et al., Discover Public Health, doi:10.1186/s12982-024-00225-7 | Insights from a multicenter nationwide cohort analysis in Japan on the association of underlying conditions and pharmacological interventions with COVID-19 disease severity |
23% lower severe cases (p<0.0001). Retrospective 650,317 COVID-19 patients in Japan showing lower risk of severe COVID-19 with metformin use. | ||
Sep 25 |
et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2024.35431 | Emerging SARS-CoV-2 Resistance After Antiviral Treatment |
Prospective study of 156 outpatients showing emergent nirmatrelvir resistance mutations with nirmatrelvir treatment, especially in immunosuppressed individuals. Results support the use of combination antiviral therapy and host-directed tr.. | ||
Sep 25 |
et al., Frontiers in Nutrition, doi:10.3389/fnut.2024.1441847 | The impact of supplementing vitamin D through different methods on the prognosis of COVID-19 patients: a systematic review and meta-analysis |
28% lower mortality (p=0.02), 22% lower ventilation (p=0.14), and 42% lower ICU admission (p=0.01). Systematic review and meta analysis of 21 studies with 4,553 COVID-19 patients showing significantly lower mortality and ICU admission rates with vitamin D supplementation. Improved results were seen with continuous dosing, total doses le.. | ||
Sep 24 |
et al., Nutrients, doi:10.3390/nu16193225 | Patterns of Dietary Supplement Use during the COVID-19 Pandemic in Poland: Focus on Vitamin D and Magnesium |
Survey of 926 Polish pharmacy patients showing a high prevalence of dietary supplemention during the COVID-19 pandemic, with vitamin D and magnesium being the most commonly used. Supplement use was significantly higher among women, those .. | ||
Sep 21 |
et al., Cells, doi:10.3390/cells13181591 | The Nucleolus and Its Interactions with Viral Proteins Required for Successful Infection |
Review of the interaction between viral proteins and the nucleolus during infection. The nucleolus is a crucial site for regulating cellular functions and viral proteins can interact with nucleolar components to facilitate viral replicati.. | ||
Sep 19 |
et al., Brownstone Journal | Those Published “17,000 Hydroxychloroquine Deaths” Never Happened |
Review of a retracted study that claimed hydroxychloroquine (HCQ) for COVID-19 caused 17,000 deaths. Author highlights that the study was based on unreliable data and contradicted the well-established safety profile of HCQ. The article cr.. | ||
Sep 19 |
et al., Journal of General Internal Medicine, doi:10.1007/s11606-024-08864-x | Preadmission Metformin Use Is Associated with Reduced Mortality in Patients with Diabetes Mellitus Hospitalized with COVID-19 |
18% lower mortality (p<0.0001). Retrospective 11,993 hospitalized COVID-19 patients with diabetes mellitus but without chronic kidney disease or need for hemodialysis, showing lower mortality with metformin use. | ||
Sep 19 |
et al., Antiviral Research, doi:10.1016/j.antiviral.2024.106006 | Identification of antibody-resistant SARS-CoV-2 mutants via N4-Hydroxycytidine mutagenesis |
In Vitro selection study identifying SARS-CoV-2 spike mutations that confer resistance to therapeutic antibodies. Using a Wuhan-like strain and omicron B.1.1.529, the authors used sequential mutagenesis with the molnupiravir active compou.. | ||
Sep 18 |
, A., Journal of Translational Medicine, doi:10.1186/s12967-024-05587-9 | Nutraceuticals and pharmacological to balance the transitional microbiome to extend immunity during COVID-19 and other viral infections |
Review of nutraceuticals and pharmacological interventions to balance the microbiome and boost immunity during COVID-19 and other viral infections. Authors propose that optimal usage of probiotics, dietary fibers, vitamins, minerals, omeg.. | ||
Sep 17 |
et al., Diabetes Care, doi:10.2337/DCa24-0032 | Prevalent Metformin Use in Adults With Diabetes and the Incidence of Long COVID: An EHR-Based Cohort Study From the RECOVER Program |
N3C/PCORnet retrospective adults with type 2 diabetes in the USA showing lower incidence of mortality or long COVID with metformin use. | ||
Sep 17 |
et al., The American Journal of Tropical Medicine and Hygiene, doi:10.4269/ajtmh.23-0710 | Circulation of COVID-19-Related Medicines on Japanese Websites during the COVID-19 Pandemic and Their Quality and Authenticity |
Investigation of the circulation and quality of COVID-19-related medicines sold online in Japan showing poor-quality ivermectin and dexamethasone. Four dexamethasone samples and two ivermectin samples failed quantitative analysis, and thr.. | ||
Sep 16 |
et al., Journal of Agriculture and Food Research, doi:10.1016/j.jafr.2024.101422 | Anti-inflammatory and Nutritional Interventions Against SARS-CoV-2: A Comprehensive Review |
Review of anti-inflammatory and nutritional interventions against SARS-CoV-2. Authors emphasize the importance of a healthy immune response in reducing the severity of COVID-19, especially in high-risk groups like the elderly and those wi.. | ||
Sep 16 |
et al., AMB Express, doi:10.1186/s13568-024-01739-8 | Establishment of in-house assay for screening of anti-SARS-CoV-2 protein inhibitors |
In Vitro study showing that curcumin, quercetin, gallic acid, and silymarin inhibit SARS-CoV-2 spike protein binding to the ACE2 receptor. Authors developed a novel immunofluorescent assay to screen potential inhibitors of the spike-ACE2 .. | ||
Sep 13 |
et al., The Laryngoscope, doi:10.1002/lary.31761 | Washing Illness Away: A Systematic Review of the Impact of Nasal Irrigation and Spray on COVID‐19 |
Review of the efficacy of nasal irrigation with saline, povidone-iodine (PVP-I), and intranasal corticosteroids (INCS) at reducing SARS-CoV-2 nasopharyngeal viral load (NVL) and transmissibility. Saline nasal irrigation (SNI) showed the g.. | ||
Sep 13 |
et al., Medicine, doi:10.1097/MD.0000000000039252 | Adequate serum 25-hydroxy-vitamin D levels are correlated with low anti-PF4 levels in mild COVID-19 Patients: An observational study |
52% lower severe cases (p=0.37). Retrospective 160 COVID-19 patients in Indonesia showing a significant negative correlation between vitamin D levels and anti-PF4 antibodies in mild COVID-19 patients. Severe COVID-19 patients were more likely to have vitamin D deficiency.. | ||
Sep 12 |
et al., PLOS Medicine, doi:10.1371/journal.pmed.1004428 | Evaluation of hydroxychloroquine or chloroquine for the prevention of COVID-19 (COPCOV): A double-blind, randomised, placebo-controlled trial |
57% fewer symptomatic cases (p=0.0002). RCT 4,652 low-risk participants, published days after completion, showing significantly lower PCR+ COVID-19 cases with HCQ/CQ prophylaxis, p = 0.0004. Authors include a meta-analysis of this and 11 other RCTs confirming significantly low.. | ||
Sep 12 |
et al., BMC Infectious Diseases, doi:10.1186/s12879-024-09886-w | Nebulized inhalation of plasma-activated water in the treatment of progressive moderate COVID-19 patients with antiviral treatment failure: a randomized controlled pilot trial |
9% higher progression (p=1), 73% greater improvement (p=0.04), 28% shorter hospitalization (p=0.16), and 30% higher hospital discharge (p=0.24). RCT 23 moderate COVID-19 patients with antiviral treatment failure, showing nebulized plasma-activated water (PAW) improved chest CT and accelerated cough resolution compared to saline control, however there was no significant difference .. |
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 4,870 studies,
2,420 present results comparing with a control group,
2,215 are treatment studies, and
205 analyze outcomes based on serum levels. There are
89 animal studies,
168 in silico studies,
301 in vitro studies,
350 reviews,
and 223 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. FLCCC 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.