COVID-19 treatment: real-time analysis of 6,452 studies
Summary of clinical evidence for COVID-19 treatment:
c19early.org
COVID-19 involves the interplay of 400+ viral and host proteins and factors, providing many therapeutic targets.
c19early analyzes 6,400+ studies for 215 treatments—over 17 million hours of research.
Only three high-profit early treatments are approved in the US.
In reality, many treatments reduce risk,
with 25 low-cost treatments approved across 163 countries.
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Naso/
oropharyngeal treatment Effective Treatment directly to the primary source of initial infection. -
Healthy lifestyles Protective Exercise, sunlight, a healthy diet, and good sleep all reduce risk.
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Immune support Effective Vitamins A, C, D, and zinc show reduced risk, as with other viruses.
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Thermotherapy Effective Methods for increasing internal body temperature, enhancing immune system function.
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Systemic agents Effective Many systemic agents reduce risk, and may be required when infection progresses.
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High-profit systemic agents Conditional Effective, but with greater access and cost barriers.
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Monoclonal antibodies Limited Utility Effective but rarely used—high cost, variant dependence, IV/SC admin.
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Acetaminophen Harmful Increased risk of severe outcomes and mortality.
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Remdesivir Harmful Increased mortality with longer followup. Increased kidney and liver injury, cardiac disorders.
Treatment protocols varied widely around the world:
Clinical evidence timeline:
Timeline for when studies showed efficacy - details and limitations.
0.5% of treatments show efficacy.
Treatment cost per life saved:
Treatment cost times median NNT - details and limitations.
0.5% of treatments show efficacy.
All clinical results for selected treatments. 0.5% of treatments show efficacy.
Top journals with less bias against low-cost treatments:
Top journals that accept positive studies for low cost treatments:
Nutrients,
Scientific Reports,
PLOS ONE,
International Journal of Infectious Diseases,
Frontiers in Medicine,
Cureus,
more...
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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. | |||||
| 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) | 2.5% (54) |
| Dr. Jake Scott (**) | USA | 1,000 | 10.0% (100) | |
| Average | 38.6% | 6.2% | ||
| EARLY TREATMENT PROTOCOLS - 40 physicians/teams | ||||
| Physician / Team | Location | Patients | HospitalizationHosp. | MortalityDeath |
| Dr. Roberto Alfonso Accinelli 0/360 deaths for treatment within 3 days |
Peru | 1,265 | 0.6% (7) | |
| Dr. Mohammed Tarek Alam patients up to 84 years old |
Bangladesh | 100 | 0.0% (0) | |
| Dr. Oluwagbenga Alonge | Nigeria | 310 | 0.0% (0) | |
| Dr. Raja Bhattacharya up to 88yo, 81% comorbidities |
India | 148 | 1.4% (2) | |
| Dr. Flavio Cadegiani | Brazil | 3,450 | 0.1% (4) | 0.0% (0) |
| Dr. Alessandro Capucci | Italy | 350 | 4.6% (16) | |
| Dr. Shankara Chetty | South Africa | 8,000 | 0.0% (0) | |
| Dr. Deborah Chisholm | USA | 100 | 0.0% (0) | |
| Dr. Ryan Cole | USA | 400 | 0.0% (0) | 0.0% (0) |
| Dr. Marco Cosentino earlier treatment results were better |
Italy | 392 | 6.4% (25) | 0.3% (1) |
| Dr. Jeff Davis | USA | 6,000 | 0.0% (0) | |
| Dr. Dhanajay | India | 500 | 0.0% (0) | |
| Dr. Bryan Tyson & Dr. George Fareed | USA | 20,000 | 0.0% (6) | 0.0% (4) |
| Dr. Raphael Furtado | Brazil | 170 | 0.6% (1) | 0.0% (0) |
| Rabbi Yehoshua Gerzi | Israel | 860 | 0.1% (1) | 0.0% (0) |
| Dr. Heather Gessling | USA | 1,500 | 0.1% (1) | |
| Dr. Ellen Guimarães | Brazil | 500 | 1.6% (8) | 0.4% (2) |
| Dr. Syed Haider | USA | 4,000 | 0.1% (5) | 0.0% (0) |
| Dr. Mark Hancock | USA | 24 | 0.0% (0) | |
| Dr. Sabine Hazan | USA | 1,000 | 0.0% (0) | |
| Dr. Mollie James | USA | 3,500 | 1.1% (40) | 0.0% (1) |
| Dr. Roberta Lacerda | Brazil | 550 | 1.5% (8) | 0.4% (2) |
| Dr. Katarina Lindley | USA | 100 | 5.0% (5) | 0.0% (0) |
| Dr. Ben Marble | USA | 150,000 | 0.0% (4) | |
| Dr. Edimilson Migowski | Brazil | 2,000 | 0.3% (7) | 0.1% (2) |
| Dr. Abdulrahman Mohana | Saudi Arabia | 2,733 | 0.0% (0) | |
| Dr. Carlos Nigro | Brazil | 5,000 | 0.9% (45) | 0.5% (23) |
| Dr. Benoit Ochs | Luxembourg | 800 | 0.0% (0) | |
| Dr. Ortore | Italy | 240 | 1.2% (3) | 0.0% (0) |
| Dr. Valerio Pascua one patient already on oxygen died |
Honduras | 415 | 6.3% (26) | 0.2% (1) |
| Dr. Sebastian Pop | Romania | 300 | 0.0% (0) | |
| Dr. Brian Proctor | USA | 869 | 2.3% (20) | 0.2% (2) |
| Dr. Anastacio Queiroz | Brazil | 700 | 0.0% (0) | |
| Dr. Didier Raoult | France | 8,315 | 2.6% (214) | 0.1% (5) |
| Dr. Karin Ried up to 99yo, 73% comorbidities |
Turkey | 237 | 0.4% (1) | |
| Dr. Roman Rozencwaig patients up to 86 years old |
Canada | 80 | 0.0% (0) | |
| Dr. Vipul Shah | India | 8,000 | 0.1% (5) | |
| Dr. Silvestre Sobrinho | Brazil | 116 | 8.6% (10) | 0.0% (0) |
| Dr. Unknown | Brazil | 957 | 1.7% (16) | 0.2% (2) |
| Dr. Vladimir Zelenko | USA | 2,200 | 0.5% (12) | 0.1% (2) |
| Average | 2.2% | 0.1% | ||
Physicians using early combined treatment protocols had much lower
hospitalization and mortality rates compared with those following guidelines focusing on
late treatment.
Results are subject to selection and ascertainment bias and accurate analysis requires
details of the patient populations and followup, however the results are consistent across
many teams, and consistent with the extensive controlled clinical evidence showing a
significant reduction in risk with many early treatments, and complementary/synergistic
benefits with combined treatments.
(*) Dr. Uip reportedly prescribed early treatment for himself, but not for
patients1.
(**) Dr. Scott reports treating hundreds of patients and losing over a hundred,
but has not provided specific numbers2.
Dr. Scott reports following (and helping create) US guidelines.
| McLindon | RCT 275 outpatients showing very low hospitalization with combination therapy including ivermectin, doxycycline, vitamin C, vitamin D3, and zinc,.. |
| Tokarczyk | In vitro study showing that zinc supplementation bioaccessibility varies significantly based on diet type and zinc chemical form using simulated.. |
| Li | Meta-analysis and multi-omics study showing reduced mortality with zinc supplementation in hospitalized COVID-19 patients. Authors found that zinc.. |
| McLindon | RCT 275 outpatients showing very low hospitalization with combination therapy including ivermectin, doxycycline, vitamin C, vitamin D3, and zinc,.. |
| McLindon | RCT 275 outpatients showing very low hospitalization with combination therapy including ivermectin, doxycycline, vitamin C, vitamin D3, and zinc,.. |
| Awla | Prospective case-control study of 95 COVID-19 patients and 75 healthy controls in Iraq showing strong associations between vitamin D deficiency, VDR.. |
| McLindon | RCT 275 outpatients showing very low hospitalization with combination therapy including ivermectin, doxycycline, vitamin C, vitamin D3, and zinc,.. |
| McLindon | RCT 275 outpatients showing very low hospitalization with combination therapy including ivermectin, doxycycline, vitamin C, vitamin D3, and zinc,.. |
| Lokugamage | In vitro and mouse study showing that PARP12/PARP13 proteins synergize with the nonsense-mediated RNA decay (NMD) pathway to degrade SARS-CoV-2 RNA.. |
| Kettunen | In vitro study showing that cathepsin B inhibitor CA-074-ME blocks SARS-CoV-2 infection in human induced pluripotent stem cell (hiPSC)-derived.. |
| Pivniouk | In vitro study showing that IL-13 protects epithelial cells from SARS-CoV-2 infection by inhibiting ACE2-mediated virus binding and cell entry. |
| Wang | Animal study showing that CD147 receptor blockade with meplazumab reduces SARS-CoV-2 infection and pathological lesions in rhesus macaques and.. |
| Yehia | Mouse study showing potential harm from SARS-CoV-2 spike protein through ferroptosis induction in K18-hACE2 transgenic mice. The findings suggest.. |
| Muntean | Review of molecular mechanisms underlying SARS-CoV-2 pathogenesis in emerging variants, particularly late Omicron sublineages including BA.2.86, JN.. |
| Jahantigh | Mouse study showing transcriptomic immune responses in wild-type C57BL/6J mice infected with SARS-CoV-2 Beta variant (B.1.351). |
| Pastey | In vitro study showing that SARS-CoV-Like virus-like particles (VLPs) preferentially bud from cholesterol-rich lipid raft microdomains in HEK-293T.. |
| Sun | In silico analysis identifying quercetin as a potent Mpro inhibitor through multi-stage virtual screening. |
| Leal | RCT 162 hospitalized COVID-19 pneumonia patients showing harm with siltuximab compared to corticosteroids. |
| Ngiam | Retrospective 19,689 hospitalized COVID-19 patients in Singapore showing no significant reduction in overall post-acute sequelae of COVID-19 (PASC).. |
| Ngiam | Retrospective 19,689 hospitalized COVID-19 patients in Singapore showing no significant reduction in overall post-acute sequelae of COVID-19 (PASC).. |
| Ngiam | Retrospective 19,689 hospitalized COVID-19 patients in Singapore showing no significant reduction in overall post-acute sequelae of COVID-19 (PASC).. |
| Aggunna | In silico study showing potential harm from molnupiravir-induced mutations in human CYP3A4 enzyme during COVID-19 treatment. Authors identified six.. |
| Lee | Animal study showing that the SARS-CoV-2 spike protein causes cognitive impairment in rats, with metformin providing protective effects. |
| Ling | Systematic review and meta-analysis of 26 studies showing lower mortality, hospitalization, and long COVID wiht metformin treatment. |
| Madamombe | 672 patients early treatment: 130% higher mortality (p<0.0001) |
Recent studies (see the individual treatment pages for all studies):
Feb 16 |
et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000002118 | Safety and Tolerability of Multimodal Therapy (Ivermectin, Doxycycline, Vitamin C, Vitamin D, and Zinc) With or Without Famotidine in Australian Patients With COVID-19 Infection: A Pilot Cohort Trial |
| RCT 275 outpatients showing very low hospitalization with combination therapy including ivermectin, doxycycline, vitamin C, vitamin D3, and zinc, with or without famotidine. There was no control group. Only 4 patients were hospitalized wi.. | ||
Feb 5 |
et al., Clinical and Translational Science, doi:10.1111/cts.70491 | Effects of Siltuximab Versus Corticosteroids in Preventing COVID−19 Pneumonia Disease Progression: Multicentre, Open‐Label, Randomized Clinical Trial |
| RCT 162 hospitalized COVID-19 pneumonia patients showing harm with siltuximab compared to corticosteroids. | ||
Feb 5 |
et al., MDPI AG, doi:10.20944/preprints202602.0361.v1 | Vitamin D3 Supplementation Enhances Symptom Relief and Modulates Microbiome and Immune Responses in Pediatric Post-Acute Sequelae of COVID-19: A Randomized Controlled Trial |
| RCT 33 pediatric outpatients with post-acute sequelae of COVID-19 (PASC) showing significant symptom improvement with vitamin D3 treatment. | ||
Feb 4 |
et al., Targetome, doi:10.48130/targetome-0026-0006 | Multi-Omics Integration Identifies MT2A as a Biomarker and a Candidate Host Target Linking Zinc Dysregulation to COVID-19 Mortality |
| Meta-analysis and multi-omics study showing reduced mortality with zinc supplementation in hospitalized COVID-19 patients. Authors found that zinc treatment was associated with a significant reduction in mortality (OR 0.48) across seven s.. | ||
Feb 4 |
et al., International Journal of Molecular Sciences, doi:10.3390/ijms27031526 | SARS-CoV-2 Spike Protein Induces Time-Dependent and Brain-Region-Specific Alterations in Ferroptosis Markers: A Preliminary Study in K18-hACE2 Mice |
| Mouse study showing potential harm from SARS-CoV-2 spike protein through ferroptosis induction in K18-hACE2 transgenic mice. The findings suggest spike protein exposure may contribute to persistent neurological manifestations seen in post.. | ||
Feb 4 |
, D., Innovative Medicines & Omics, doi:10.36922/IMO025440058 | Mast cells and histamine receptor-targeted adjunctive treatments for COVID-19: A literature review |
| Review of clinical studies on antihistamines, mast cell stabilizers, and leukotriene receptor antagonists for COVID-19 treatment. Author finds that several mast cell-targeting agents show clinical benefits, with quercetin emerging as one .. | ||
Feb 3 |
et al., Signal Transduction and Targeted Therapy, doi:10.1038/s41392-025-02551-x | Inducible CD147 up-regulation boosts extended SARS-CoV-2 infection triggering severe COVID-19 independent of ACE2 |
| Animal study showing that CD147 receptor blockade with meplazumab reduces SARS-CoV-2 infection and pathological lesions in rhesus macaques and humanized CD147 mice. Authors demonstrate that SARS-CoV-2 infection induces CD147 up-regulation.. | ||
Jan 31 |
et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2026.108435 | Early administration of neutralising monoclonal antibodies and post-acute sequelae of COVID-19 |
| Retrospective 19,689 hospitalized COVID-19 patients in Singapore showing no significant reduction in overall post-acute sequelae of COVID-19 (PASC) with early monoclonal antibody treatment, but increased risk of autoimmune complications. .. | ||
Jan 31 |
et al., The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2025.106879 | Vitamin D pathway as a multi-level predictor of COVID-19 severity and mortality: Integrating serum levels, FokI (rs2228570) VDR polymorphism, and lung tissue expression |
| Prospective case-control study of 95 COVID-19 patients and 75 healthy controls in Iraq showing strong associations between vitamin D deficiency, VDR gene polymorphism, and COVID-19 severity and mortality. | ||
Jan 30 |
et al., Acta Cardiol Sin, doi:10.6515/ACS.202601_42(1).20250726A | Cardiovascular Outcomes in COVID-19 Patients Treated with Paxlovid: A Multicenter Retrospective Study |
| 11% lower mortality (p=0.21). Retrospective 606 COVID-19 patients treated with paxlovid and 1,809 propensity score-matched controls in Taiwan, showing short-term mortality benefits at 3 months, but reduced benefit at 6 months, and no significant benefit at 12 months. .. | ||
Jan 29 |
et al., Molecules, doi:10.3390/molecules31030474 | Structural Basis and Inhibitor Development of SARS-CoV-2 Papain-like Protease |
| Review of structural insights and inhibitor development for SARS-CoV-2 papain-like protease (PLpro). | ||
Jan 28 |
et al., medRxiv, doi:10.64898/2026.01.23.26343617 | Balancing data quality and participant burden: A comparative analysis of abbreviated vs extended symptom diaries in the CanTreatCOVID trial |
| Secondary analysis of the CanTreatCOVID paxlovid RCT comparing adherence and symptom reporting between a 9-item abbreviated diary and 34-item FLU-PRO Plus diary in 712 COVID-19 outpatients, showing no significant difference in compliance,.. | ||
Jan 28 |
et al., Journal of Emergency and Disaster Medicine, doi:10.1007/s44467-025-00004-7 | Efficacy of Nigella sativa in COVID-19 patients: a systematic review and meta-analysis |
| Systematic review and meta-analysis of 6 RCTs showing significantly lower mortality and symptom severity with nigella sativa treatment in 1,595 COVID-19 patients. | ||
Jan 28 |
et al., Laboratory Animal Research, doi:10.1186/s42826-025-00264-4 | Transcriptomic insights into the immune dynamics of wild-type mice challenged with SARS-CoV-2 Beta variant |
| Mouse study showing transcriptomic immune responses in wild-type C57BL/6J mice infected with SARS-CoV-2 Beta variant (B.1.351). | ||
Jan 22 |
et al., BMC Complementary Medicine and Therapies, doi:10.1186/s12906-026-05253-1 | Dose-dependent antiviral effects of glycyrrhizin, curcumin, and harmaline against clinical SARS-CoV-2 isolates, including D614G, Omicron BA.5, and Omicron XBB.1 |
| In vitro study in A549-AT cells showing that curcumin and glycyrrhizin effectively inhibit SARS-CoV-2 D614G, Omicron BA.5, and Omicron XBB.1 variants, while harmaline effectively inhibits only the Omicron variants, all at subtoxic concent.. | ||
Jan 22 |
et al., Viruses, doi:10.3390/v18010145 | Virion-Independent Extracellular Vesicle (EV)-Dependent Transmission of SARS-CoV-2 as a Potential New Mechanism of Viral RNA Spread in Human Cells |
| In vitro study showing that extracellular vesicles (EVs) can transmit SARS-CoV-2 replicon RNA between cells independently of infectious virus particles. | ||
Jan 20 |
et al., Chemical Senses, doi:10.1093/chemse/bjag001 | The APOLLO Trial: A Proof-of-Concept Study for Vitamin A Nasal Drops in COVID-19 Related Post-Infectious Olfactory Dysfunction |
| 50% worse recovery (p=0.54). RCT 57 COVID-19 patients with post-infectious olfactory dysfunction showing no significant difference with intranasal vitamin A versus placebo drops. Authors hypothesize that COVID-19's mechanism of damaging sustentacular cells rather tha.. | ||
Jan 19 |
et al., BMC Cancer, doi:10.1186/s12885-026-15553-x | Efficacy and safety of 7-day aerosolized epigallocatechin-3-gallate in oncologic patients with COVID-19 pneumonia |
| 38% greater improvement (p=0.002). RCT 108 hospitalized oncologic patients with COVID-19 pneumonia showing significant benefit with aerosolized epigallocatechin-3-gallate (EGCG). The EGCG group showed significantly greater CT imaging improvement (64.8% vs 40.5%, P=0.004) a.. | ||
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.
References