COVID-19 early treatment: real-time analysis of 5,007 studies
Leavy | Retrospective 1,888 patients hospitalized with COVID-19 in the UK showing no significant difference in health-related quality of life or other.. |
Qu | 121 patients amubarvimab ICU PSM: 46% lower mortality (p=0.06) and 4% improved viral clearance (p=0.89) |
Tamil Selvan | In Silico study showing that the flavonoid compounds hesperidin, narirutin, and isoquercetin may have potential as antiviral agents against SARS-CoV.. |
Sánchez-García | In Vitro study showing that nitric oxide (NO) inhibits SARS-CoV-2 spike protein binding to ACE2 and reduces ACE2 enzymatic activity. Authors showed.. |
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.
Leavy | Retrospective 1,888 patients hospitalized with COVID-19 in the UK showing no significant difference in health-related quality of life or other.. |
Qu | 121 patients ICU PSM: 46% lower mortality (p=0.06) and 4% improved viral clearance (p=0.89) |
Tamil Selvan | In Silico study showing that the flavonoid compounds hesperidin, narirutin, and isoquercetin may have potential as antiviral agents against SARS-CoV.. |
Sánchez-García | In Vitro study showing that nitric oxide (NO) inhibits SARS-CoV-2 spike protein binding to ACE2 and reduces ACE2 enzymatic activity. Authors showed.. |
Mitev | Retrospective 125 outpatients showing reduced COVID-19 infection rates with prophylactic bromhexine hydrochloride (BRH) use during 2021-2022 COVID.. |
Recent studies (see the individual treatment pages for all studies):
Oct 26 |
et al., Antioxidants, doi:10.3390/antiox13111301 | Potential Beneficial Role of Nitric Oxide in SARS-CoV-2 Infection: Beyond Spike-Binding Inhibition |
In Vitro study showing that nitric oxide (NO) inhibits SARS-CoV-2 spike protein binding to ACE2 and reduces ACE2 enzymatic activity. Authors showed that NO donors DETA-NONOate (DETA-NO) and S-nitrosoglutathione (GSNO) significantly decrea.. | ||
Oct 25 |
et al., Preprints.org, doi:10.20944/preprints202410.1998.v1 | COVID-19 Prophylactic Effect of Bromhexine Hydrochloride |
Retrospective 125 outpatients showing reduced COVID-19 infection rates with prophylactic bromhexine hydrochloride (BRH) use during 2021-2022 COVID waves in Bulgaria. Prior to BRH prophylaxis, 62% of participants reported confirmed COVID-1.. | ||
Oct 25 |
et al., Cureus, doi:10.7759/cureus.72385 | Association Between the Use of Proton Pump Inhibitors and Severe Clinical Outcomes in COVID-19 Patients: A Retrospective Observational Study |
57% higher hospitalization (p=0.15). Retrospective 506 outpatients in Oman showing no significant association between proton pump inhibitor (PPI) use and COVID-19 hospitalization in unadjusted results. | ||
Oct 20 |
et al., Cureus, doi:10.7759/cureus.71952 | Short-Term Outcomes in Patients With Coexistence of COVID-19 Infection and Vitamin D Deficiency: A Large Cohort Study |
6% lower mortality (p=0.42), 5% lower progression (p=0.02), and 1% lower hospitalization (p=0.8). PSM retrospective 68,814 COVID-19 patients showing vitamin D deficiency associated with significantly increased risk of requiring critical care services, and non-significant higher all-cause mortality. Mortality for COVID-19 was less like.. | ||
Oct 19 |
et al., bioRxiv, doi:10.1101/2024.10.18.619137 | Nirmatrelvir-Resistant Mutations in SARS-CoV-2 Mpro Enhance Host Immune Evasion via Cleavage of NF-κB Essential Modulator |
In Vitro study showing that paxlovid use may promote the emergence of SARS-CoV-2 variants that can weaken host immunity and potentially contribute to long COVID. Authors show that SARS-CoV-2 main protease (Mpro) mutations that confer resi.. | ||
Oct 17 |
et al., Research Square, doi:10.21203/rs.3.rs-4973191/v1 | A descriptive analysis of drug related problems identified when prescribing the COVID-19 antiviral drug Paxlovid® |
Retrospective 140 hospitalized COVID-19 patients in Austria showing that pharmacist review identified a high rate of drug-related problems (DRPs) with paxlovid prescribing, including drug-drug interactions (DDIs) and inappropriate dosing .. | ||
Oct 17 |
et al., Frontiers in Immunology, doi:10.3389/fimmu.2024.1456634 | Immunomodulatory effect of bovine lactoferrin during SARS-CoV-2 infection |
In Silico, In Vitro, and mouse study showing immunomodulatory effects of bovine lactoferrin (bLf) during SARS-CoV-2 infection. In Silico analysis showed bLf strongly binds to TLR4 and NF-kB. In Vitro, bLf modulated frequencies of NK and T.. | ||
Oct 16 |
et al., International Journal of General Medicine, doi:10.2147/IJGM.S476578 | Association Between Serum Zinc Concentration Levels And Severity Of Coronavirus Disease 2019 (Covid-19) In Japanese Inpatients |
72% lower severe cases (p=0.002). Retrospective 467 hospitalized COVID-19 patients in Japan showing significantly higher risk of severe cases with zinc deficiency. | ||
Oct 16 |
et al., Cureus, doi:10.7759/cureus.71609 | Zinc Deficiency and Post-acute Outcomes in Patients With COVID-19: A Six-Month Retrospective Cohort Analysis of 3,726 Patients |
42% lower mortality (p=0.05) and 24% lower hospitalization (p<0.0001). TriNetX PSM retrospective 3,726 post-acute COVID-19 patients showing significantly higher 6-month all-cause hospitalization and mortality with zinc deficiency. Zinc levels were measured in the three months before COVID-19 diagnosis. | ||
Oct 16 |
et al., Scientific Reports, doi:10.1038/s41598-024-75338-9 | SARS-CoV-2 infection causes a decline in renal megalin expression and affects vitamin D metabolism in the kidney of K18-hACE2 mice |
Mouse study showing that SARS-CoV-2 infection decreases renal megalin expression and affects vitamin D metabolism in K18-hACE2 mice. Authors found that infected mice experienced acute kidney injury, suppressed megalin protein levels in pr.. | ||
Oct 16 |
, S., Biology, doi:10.3390/biology13100831 | Unveiling the Interplay—Vitamin D and ACE-2 Molecular Interactions in Mitigating Complications and Deaths from SARS-CoV-2 |
Review of the interplay between vitamin D and angiotensin-converting enzyme-2 (ACE2) in mitigating complications and deaths from SARS-CoV-2. Author reports that over 300 clinical studies have shown that proper doses of vitamin D effective.. | ||
Oct 11 |
et al., Heliyon, doi:10.1016/j.heliyon.2024.e39167 | Decoding the mechanism of Qingjie formula in the prevention of COVID-19 based on network pharmacology and molecular docking |
In Silico study showing potential benefits of quercetin for COVID-19 prevention through network pharmacology and molecular docking. Authors identified quercetin as one of the key active ingredients in Qingjie formula (QJF). Quercetin was .. | ||
Oct 10 |
et al., JMIR Bioinformatics and Biotechnology, doi:10.2196/58018 | Comparison of the Neutralization Power of Sotrovimab Against SARS-CoV-2 Variants: Development of a Rapid Computational Method |
In Silico computational method developed to predict the neutralization power of monoclonal antibodies against new SARS-CoV-2 variants. The method evaluates binding affinity of antibodies based on molecular interactions and Gibbs free ener.. | ||
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., Infection and Drug Resistance, doi:10.2147/IDR.S481591 | Efficacy of Azvudine Therapy in Patients with Severe and Non-Severe COVID‐19: A Propensity Score-Matched Analysis |
32% higher mortality (p=0.2), 62% higher ventilation (p=0.22), 7% higher ICU admission (p=0.89), and 9% shorter hospitalization (p=0.05). PSM retrospective 303 hospitalized patients treated with azvudine and 303 matched controls in China, showing shorter hospital stay and higher lymphocyte improvement rate, particularly for non-severe patients, however there were no signifi.. | ||
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.. | ||
Oct 1 |
et al., Tasman Medical Journal, 6:4 | Use of hydroxychloroquine in multidrug protocols for SARS-CoV-2 |
Review of the use of HCQ in multidrug protocols for SARS-CoV-2 treatment. Authors report that HCQ played an important role in preventing hospitalizations and deaths due to COVID-19, particularly in 2020 with more virulent strains. They di.. | ||
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 30 |
et al., Journal of Virus Eradication, doi:10.1016/j.jve.2024.100387 | Indomethacin inhibits human seasonal coronaviruses at late stages of viral replication in lung cells: Impact on virus-induced COX-2 expression |
In Vitro study showing that indomethacin inhibits the replication of human seasonal coronaviruses HCoV-229E (alpha-coronavirus) and HCoV-OC43 (beta-coronavirus) in lung-derived MRC-5 cells. Indomethacin acts at late stages of the viral li.. | ||
Sep 30 |
et al., Heliyon, doi:10.1016/j.heliyon.2024.e37663 | Effect of amubarvimab-romlusevimab for treatment of severe COVID-19 in intensive care units: A retrospective cohort study |
46% lower mortality (p=0.06) and 4% improved viral clearance (p=0.89). Retrospective 121 severe ICU COVID-19 patients in China showing lower 28-day mortality and ICU mortality with amubarvimab-romlusevimab treatment compared to no antiviral treatment. No significant differences were found in viral conversion.. |
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 5,007 studies,
2,449 present results comparing with a control group,
2,242 are treatment studies, and
207 analyze outcomes based on serum levels. There are
92 animal studies,
174 in silico studies,
326 in vitro studies,
373 reviews,
and 226 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.