COVID-19 early treatment: real-time analysis of 5,189 studies
| Yip | Review of the role of inflammatory gene polymorphisms in severe COVID-19. Authors explore how genetic variations in key inflammatory genes.. |
| You | 198 patients vitamin D sufficiency: 82% lower mortality (p=0.15) and 96% lower severe cases (p=0.01) |
| Puigdellívol-Sánchez | Retrospective 140,681 patients in Spain showing lower COVID-19 infection, hospitalization, and mortality with chronic antihistamine treatment, with.. |
Timeline for when studies showed efficacy - details and limitations.
0.5% of treatments show efficacy.
Top journals that accept positive studies for low cost treatments:
Nutrients,
PLOS ONE,
Journal of Clinical Medicine,
International Journal of Infectious Diseases,
Scientific Reports,
Cureus,
more...
Treatment cost times median NNT - details and limitations.
0.5% of treatments show efficacy.
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All clinical results for selected treatments. 0.5% 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. 0.5% 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. 0.5% 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. 0.5% 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. 0.5% 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. 0.5% 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. 0.5% 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. 0.5% of proposed treatments show efficacy in clinical studies. | |||||
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| 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. 0.5% 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.
| Yip | Review of the role of inflammatory gene polymorphisms in severe COVID-19. Authors explore how genetic variations in key inflammatory genes.. |
| Wu | Review of the mechanism of SARS-CoV-2 protein translation and potential therapeutic strategies targeting viral RNA for inhibition. Protein.. |
| Kuderer | 928 patients late treatment: 27% higher mortality (p=0.46) |
| Rong | Postmortem analysis of COVID-19 patients and SARS-CoV-2 infected mice showing persistence of spike protein in the skull, meninges, and brain, which.. |
| You | 198 patients sufficiency: 82% lower mortality (p=0.15) and 96% lower severe cases (p=0.01) |
| Mogire | Analysis of 187 countries showing higher latitude and lower vitamin D levels associated with increased COVID-19 prevalence, mortality, and case.. |
| Puigdellívol-Sánchez | Retrospective 140,681 patients in Spain showing lower COVID-19 infection, hospitalization, and mortality with chronic antihistamine treatment, with.. |
| Eissa | In Silico study showing potential SARS-CoV-2 helicase inhibition by aspirin and eight other compounds. Authors screened 3,009 clinical and FDA.. |
| Zhu | 3,998 patients late treatment PSM: 22% lower mortality (p=0.001), 13% higher hospital discharge (p=0.05), 1% shorter hospitalization (p=0.43), and 10% faster viral clearance (p<0.0001) |
| Siripongboonsitti | 2,006 patients early treatment: 25% lower transmission (p=0.05) |
| Mikhail | 2,773 patients early treatment: no change in progression (p=0.97) and 33% lower hospitalization (p=0.14) |
| Yu | 130 patients early treatment: 9% lower mortality (p=0.92) and 34% improved recovery (p=0.04) |
| Eker | Review of the potential of lactoferrin as an antiviral and immune-modulating agent against various viruses, with a focus on SARS-CoV-2. Authors.. |
| Metwaly | In Silico and In Vitro study showing quercetin as a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Computational analyses.. |
Recent studies (see the individual treatment pages for all studies):
Dec 22 |
et al., Hemodialysis International, doi:10.1111/hdi.13194 | Associations of vitamin D levels and clinical parameters with COVID‐19 infection, severity and mortality in hemodialysis patients: A cohort study |
| 82% lower mortality (p=0.15) and 96% lower severe cases (p=0.01). Retrospective 198 hemodialysis patients in China showing vitamin D deficiency associated with an increased risk of COVID‐19 severity. | ||
Dec 13 |
et al., Microorganisms, doi:10.3390/microorganisms12122589 | COVID-19 in Relation to Chronic Antihistamine Prescription |
| Retrospective 140,681 patients in Spain showing lower COVID-19 infection, hospitalization, and mortality with chronic antihistamine treatment, with a greater protective effect for patients taking 2-7 chronic treatments. Results are provid.. | ||
Dec 12 |
et al., Acta Pharmaceutica Sinica B, doi:10.1016/j.apsb.2024.12.004 | Real-world efficacy and safety of azvudine in hospitalized older patients with COVID-19 during the omicron wave in China: A retrospective cohort study |
| 22% lower mortality (p=0.001), 13% higher hospital discharge (p=0.05), 1% shorter hospitalization (p=0.43), and 10% faster viral clearance (p<0.0001). PSM retrospective 3,998 hospitalized COVID-19 patients aged 60 years and older in China showing lower all-cause mortality, higher rate of discharge, and shorter time to viral clearance with azvudine treatment. | ||
Dec 12 |
et al., Journal of Virus Eradication, doi:10.1016/j.jve.2024.100576 | Assessing Favipiravir's Impact on SARS-CoV-2 Transmission within Households: Insights from a Multi-center Study (FaviPrev) |
| 25% lower transmission (p=0.05). Retrospective 976 mild to moderate COVID-19 outpatients in Thailand showing significantly lower household transmission with favipiravir treatment of index cases. | ||
Dec 12 |
et al., American Journal of Gastroenterology, doi:10.14309/01.ajg.0001082744.48729.45 | Efficacy of Nirmatrelvir/Ritonavir (Paxlovid) for COVID-19 in Vaccinated Patients With Inflammatory Bowel Disease |
| no change in progression (p=0.97) and 33% lower hospitalization (p=0.14). PSM retrospective 2,773 IBD patients showing no significant difference in hospitalization or the composite outcome of ICU admission, intubation, or mortality with paxlovid treatment. Authors do not specify exclusion of contraindicated pat.. | ||
Dec 9 |
et al., JDR Clinical & Translational Research, doi:10.1177/23800844241296840 | A Cetylpyridinium Chloride Oral Rinse Reduces Salivary Viral Load in Randomized Controlled Trials |
| 72% improved viral clearance (p=0.71). Two RCTs with a total of 247 recently diagnosed COVID-19 patients showing a significant reduction in salivary SARS-CoV-2 viral load 30 minutes after rinsing with a cetylpyridinium chloride (CPC) mouthwash compared to rinsing with saline o.. | ||
Dec 6 |
et al., Wiadomości Lekarskie, doi:10.36740/WLek/191875 | Effectiveness of the quercetin use in patients with COVID-19 with concomitant type 2 diabetes mellitus |
| 15% shorter hospitalization (p<0.0001). RCT 60 hospitalized COVID-19 patients with type 2 diabetes showing quercetin treatment decreased levels of inflammatory markers (interleukin-6, CRP, ferritin), reduced length of hospital stay, and improved capillaroscopy measures compared.. | ||
Dec 3 |
et al., PLOS ONE, doi:10.1371/journal.pone.0312866 | Integrated study of Quercetin as a potent SARS-CoV-2 RdRp inhibitor: Binding interactions, MD simulations, and In vitro assays |
| In Silico and In Vitro study showing quercetin as a potent inhibitor of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). Computational analyses reveal quercetin binds similarly to remdesivir in the RdRp active site and outperforms it i.. | ||
Dec 2 |
, NCT05705167 | A Multicentre, Open Label, Randomised, Controlled, Basket, Pragmatic, Phase II, Clinical and Translational Study to Determine the Efficacy and Safety of Plitidepsin Versus Control in Immunocompromised Adult Patients With Symptomatic COVID-19 Requiring Hospital Care |
| 36% higher mortality (p=1). RCT 37 hospitalized immunocompromised patients, showing no significant benefit with plitidepsin treatment. | ||
Dec 1 |
, R., medRxiv, doi:10.1101/2024.11.29.24318208 | Early Pandemic Associations of Latitude, Sunshine Duration, and Vitamin D Status with COVID-19 Incidence and Fatalities: A Global Analysis of 187 Countries |
| Analysis of 187 countries showing higher latitude and lower vitamin D levels associated with increased COVID-19 prevalence, mortality, and case fatality rates during the early months of the pandemic. | ||
Nov 30 |
et al., IJC Heart & Vasculature, doi:10.1016/j.ijcha.2024.101574 | Clinical characteristics and risk factors for in-hospital mortality of COVID-19 patients in Hubei Province: A multicenter retrospective study |
| 74% lower mortality (p<0.0001). Retrospective 53,030 COVID-19 patients from 138 hospitals in Hubei, China showing lower mortality with metformin. | ||
Nov 29 |
et al., Diabetes and Vascular Disease Research, doi:10.1177/14791641241288390 | Impact of blood glucose control on clinical outcomes in type 2 diabetes patients hospitalized with COVID-19 infection |
| 70% lower mortality (p=0.01). Retrospective 857 hospitalized type 2 diabetes patients showing lower mortality with pre-admission metformin use. Authors report no significant difference in mortality with in-hospital metformin use, but do not report the actual result. | ||
Nov 28 |
et al., Medicinal Chemistry, doi:10.2174/0115734064318640241112071225 | Identification of Potential FDA-Approved Inhibitors of SARS-CoV-2 Helicase Through a Multistep In Silico Approach: A Promising Prospect for COVID-19 Treatment |
| In Silico study showing potential SARS-CoV-2 helicase inhibition by aspirin and eight other compounds. Authors screened 3,009 clinical and FDA-approved drugs for structural similarity to VXG (a known helicase co-crystallized ligand) and i.. | ||
Nov 27 |
et al., Bioresources and Bioprocessing, doi:10.1186/s40643-024-00822-z | Assessing multi-target antiviral and antioxidant activities of natural compounds against SARS-CoV-2: an integrated in vitro and in silico study |
| In Vitro and In Silico study showing that propolis, curcumin, quercetin, and ginseng compounds inhibit SARS-CoV-2 infection and bind to key viral proteins. In Vero CCL-81 cells, propolis and curcumin significantly reduced SARS-CoV-2 viral.. | ||
Nov 27 |
et al., ACS Pharmacology & Translational Science, doi:10.1021/acsptsci.4c00535 | Effective, but Safe? Physiologically Based Pharmacokinetic (PBPK)-Modeling-Based Dosing Study of Molnupiravir for Risk Assessment in Pediatric Subpopulations |
| In Silico physiologically based pharmacokinetic (PBPK) modeling study suggesting that effective doses of molnupiravir for pediatric COVID-19 treatment pose a bone and cartilage toxicity risk. | ||
Nov 26 |
et al., Journal of Medical Virology, doi:10.1002/jmv.70085 | In Vitro Characterization of Inhibition Function of Calcifediol to the Protease Activity of SARS-COV-2 PLpro |
| In Vitro study showing that calcifediol inhibits SARS-CoV-2 papain-like protease (PLpro) activity through targeted binding. Authors conducted a FRET-based screening experiment, supported by in vitro interaction studies, demonstrating calc.. | ||
Nov 26 |
et al., BMC Infectious Diseases, doi:10.1186/s12879-024-10211-8 | Mitigating the risks of post-acute sequelae of SARS-CoV-2 infection (PASC) with intranasal chlorpheniramine: perspectives from the ACCROS studies |
| 90% lower PASC (p=0.001). Prospective study of 259 COVID-19 outpatients from the ACROSS-I and ACROSS-III RCTs showing significantly lower long COVID with intranasal chlorpheniramine (iCPM) compared to placebo. 72% of placebo patients experienced at least one PASC .. | ||
Nov 25 |
et al., Revista Cubana de Medicina Militar, 53:4 | Content and characteristics of ivermectin in master formulations |
| Analysis of ivermectin in Peru showing significant variability in quality and concentration, with several formulations falling below the required dosage standards (36.2%-95.8%). Dosage inconsistencies were identified in products from priv.. | ||
Nov 25 |
, K., Asian Pacific Journal of Tropical Biomedicine, doi:10.4103/apjtb.apjtb_751_23 | Antiviral efficacy of Andrographis paniculata and andrographolides: A narrative review |
| Review of the efficacy of Andrographis paniculata and andrographolides against viruses including SARS-CoV-2. Author discusses extracts and andrographolide derivatives that have shown immunomodulatory and antiviral effects in vitro and in .. | ||
Nov 25 |
et al., Frontiers in Medicine, doi:10.3389/fmed.2024.1494129 | Vitamin D deficiency and duration of COVID-19 symptoms in UK healthcare workers |
| 7% faster recovery (p=0.49) and 27% lower progression (p=0.01). Retrospective 392 healthcare workers in the UK showing vitamin D deficiency associated with a greater quantity of COVID-19 symptoms and longer durations of body aches and fatigue. Authors hypothesize that the anti-inflammatory properties .. | ||
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 5,189 studies,
2,501 present results comparing with a control group,
2,290 are treatment studies, and
211 analyze outcomes based on serum levels. There are
97 animal studies,
188 in silico studies,
345 in vitro studies,
397 reviews,
and 229 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.