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COVID-19 early treatment: real-time analysis of 779 studies
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Analysis of the efficacy of early treatments for COVID-19. Treatments do not replace vaccines and other measures. All practical, effective, and safe means should be used. Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage.
Treatment
Improvement
  (early)
Studies
  (early)
BUBudesonide 82% 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IVMIvermectin 74% 26
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CICasirivimab/im.. 72% 4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SSotrovimab 67% 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RDRemdesivir 66% 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(H)CQHydroxychloro.. 65% 30
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FPVFavipiravir 38% 3
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medications approved for early treatment by >2 countries. 56 countries have officially approved early treatment. For details see global early treatment adoption.
00.250.50.7511.251.51.752+Fluvoxamine89%0.11 [0.01-0.85]2277StudiesPatientsImprovement, RR [CI]Proxalutamide86%0.14 [0.10-0.20]41,327Iota-carragee..80%0.20 [0.04-0.91]1394Molnupiravir77%0.23 [0.01-5.69]1202Quercetin76%0.24 [0.07-0.79]4754Povidone-Iodine72%0.28 [0.14-0.56]62,082Curcumin71%0.29 [0.13-0.63]4281Ivermectin70%0.30 [0.24-0.39]6021,838Casirivimab/i..69%0.31 [0.13-0.76]722,925Sotrovimab67%0.33 [0.01-8.16]1583Bamlanivimab59%0.41 [0.23-0.74]79,136Nitazoxanide58%0.42 [0.14-1.30]61,464Budesonide54%0.46 [0.11-1.96]21,806Zinc47%0.53 [0.39-0.72]1428,539Bromhexine44%0.56 [0.40-0.78]5291Colchicine43%0.57 [0.38-0.85]917,059Vitamin D42%0.58 [0.50-0.67]3346,860Aspirin37%0.63 [0.40-0.99]729,024Favipiravir28%0.72 [0.57-0.92]92,169Hydroxychloro..27%0.73 [0.69-0.78]266389,065Remdesivir22%0.78 [0.67-0.90]1932,608Vitamin C20%0.80 [0.70-0.92]152,201All studies combined (pooled effects, all stages)c19early.com 8/2/21Lower RiskIncreased Risk
Random effects meta-analysis of all studies combined (pooled effects, all stages). Treatments with 3 or fewer studies 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.
00.250.50.7511.251.51.752+Proxalutamide91%0.09 [0.04-0.19]3682StudiesPatientsImprovement, RR [CI]Fluvoxamine89%0.11 [0.01-0.85]2277Curcumin86%0.14 [0.04-0.47]3241Povidone-Iodine82%0.18 [0.09-0.36]5728Budesonide82%0.18 [0.04-0.79]1146Vitamin D80%0.20 [0.10-0.37]5898Bromhexine79%0.21 [0.06-0.72]296Quercetin79%0.21 [0.02-1.82]2194Molnupiravir77%0.23 [0.01-5.69]1202Bamlanivimab76%0.24 [0.12-0.50]47,389Zinc76%0.24 [0.04-1.63]3982Ivermectin74%0.26 [0.16-0.43]263,883Casirivimab/i..72%0.28 [0.11-0.71]411,226Sotrovimab67%0.33 [0.01-8.16]1583Remdesivir66%0.34 [0.12-0.96]1372Hydroxychloro..65%0.35 [0.24-0.49]3054,537Vitamin C55%0.45 [0.16-1.29]2208Nitazoxanide49%0.51 [0.12-2.27]51,414Favipiravir38%0.62 [0.38-1.02]3410Early treatment studies (pooled effects)c19early.com 8/2/21Lower RiskIncreased Risk
Random effects meta-analysis of early treatment studies (pooled effects). Treatments with 3 or fewer studies 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.
00.250.50.7511.251.51.752+Bromhexine91%0.09 [0.01-1.57]2178StudiesPatientsImprovement, RR [CI]Povidone-Iodine88%0.12 [0.03-0.50]1606Proxalutamide84%0.16 [0.12-0.22]31,090Molnupiravir77%0.23 [0.01-5.69]1202Casirivimab/i..76%0.24 [0.03-2.14]318,132Ivermectin67%0.33 [0.21-0.51]2310,797Sotrovimab67%0.33 [0.01-8.16]1583Curcumin65%0.35 [0.13-0.90]2180Nitazoxanide60%0.40 [0.10-1.58]3923Quercetin58%0.42 [0.09-1.82]3641Bamlanivimab57%0.43 [0.11-1.68]47,566Vitamin D55%0.45 [0.32-0.64]199,760Colchicine43%0.57 [0.38-0.85]917,059Aspirin41%0.59 [0.36-0.96]628,957Zinc33%0.67 [0.59-0.76]85,002Hydroxychloro..24%0.76 [0.70-0.82]166271,661Remdesivir24%0.76 [0.65-0.90]1832,466Vitamin C20%0.80 [0.70-0.93]111,549Favipiravir-4%1.04 [0.66-1.66]31,456All mortality results (all stages)c19early.com 8/2/21Lower RiskIncreased Risk
Random effects meta-analysis of all mortality results (all stages). Treatments with 3 or fewer studies 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.
00.250.50.7511.251.51.752+Casirivimab/i..92%0.08 [0.00-1.53]28,347StudiesPatientsImprovement, RR [CI]Bromhexine91%0.09 [0.01-1.59]178Povidone-Iodine88%0.12 [0.03-0.50]1606Bamlanivimab85%0.15 [0.03-0.77]26,784Curcumin82%0.18 [0.04-0.79]1140Zinc79%0.21 [0.03-1.47]1518Quercetin79%0.21 [0.02-1.82]2194Vitamin D78%0.22 [0.12-0.43]3500Molnupiravir77%0.23 [0.01-5.69]1202Hydroxychloro..75%0.25 [0.16-0.40]1350,628Proxalutamide73%0.27 [0.03-2.39]2445Sotrovimab67%0.33 [0.01-8.16]1583Remdesivir66%0.34 [0.12-0.96]1372Ivermectin64%0.36 [0.15-0.85]71,694Favipiravir45%0.55 [0.05-5.81]192Nitazoxanide41%0.59 [0.02-13.8]2873Early treatment mortality resultsc19early.com 8/2/21Lower RiskIncreased Risk
Random effects meta-analysis of early treatment mortality results. Treatments with 3 or fewer studies are shown in grey.
Recent studies (see the individual treatment pages for all studies):

7/30
Levels Matin et al., Archives of Microbiology, doi:10.1007/s00203-021-02482-5 (Peer Reviewed) cases, ↓66.1%, p<0.0001 The sufficient vitamin D and albumin level have a protective effect on COVID-19 infection
Details   Case control study with 191 COVID-19 patients and 203 healthy controls in Iran, showing an association between vitamin D deficiency and COVID-19 infection and severity. 84.4% of COVID-19 patients had vitamin D deficiency.
7/30
Late Abdelwahab et al., Clinical Drug Investigation, doi:10.1007/s40261-021-01061-2 (Peer Reviewed) ventilation, ↑7.8%, p=0.93 Acetylsalicylic Acid Compared with Enoxaparin for the Prevention of Thrombosis and Mechanical Ventilation in COVID-19 Patients: A Retrospective Cohort Study
Details   Retrospective 225 hospitalized patients in Egypt, showing significantly lower thromboembolic events with aspirin treatment, but no significant difference in the need for mechanical ventilation.
7/29
Meta Ghasemian et al., The International Journal of Clinical Practice, doi:10.1111/ijcp.14675 (Peer Reviewed) (meta analysis) meta-analysis The Role of Vitamin D in the Age of COVID-19: A Systematic Review and Meta-Analysis
Details   Systematic review and meta analysis of 23 studies, finding significantly higher risk of COVID-19 cases and severity with vitamin D deficiency. Mortality risk was higher with deficiency, but not reaching statistical significance, OR 1.6 [0..
7/29
Early, PrEP Annweiler et al., The Journal of Steroid Biochemistry and Molecular Biology, doi:0.1016/j.jsbmb.2021.105958 (Peer Reviewed) death, ↓64.2%, p=0.002 Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study
Details   Report on extended results from the GERIA-COVID study, showing significantly lower mortality at 3 months with vitamin D treatment. Results combine prophylaxis and early treatment.
7/29
Early Sobngwi et al., medRxiv, doi:10.1101/2021.07.25.21260838 (Preprint) no recov., ↓51.6%, p=0.44 Doxycycline is a safe alternative to Hydroxychloroquine + Azithromycin to prevent clinical worsening and hospitalization in mild COVID-19 patients: An open label randomized clinical trial (DOXYCOV)
Details   RCT 194 mild/asymptomatic low-risk patients in Cameroon, 97 treated with HCQ+AZ and 97 treated with doxycycline, showing 2.1% symptomatic patients at day 10 with HCQ+AZ, versus 4.3% with doxycycline, but without statistical significance. ..
7/28
Meta Popp et al., Cochrane Database of Systematic Reviews, doi:10.1002/14651858.CD015017.pub2 (Preprint) meta-analysis Ivermectin for preventing and treating COVID‐19
Details   Outdated very biased cherry-picking retrospective meta analysis, with a majority of results based on only 1 or 2 studies, showing positive (non-statistically significant) results for 10 of 11 primary outcomes across a total of 13 studies...
7/27
Levels Cozier et al., PLoS ONE, doi:10.1371/journal.pone.0255132 (Peer Reviewed) cases, ↓38.6%, p=0.02 Lower serum 25(OH)D levels associated with higher risk of COVID-19 infection in U.S. Black women
Details   Prospective study of vitamin D levels and COVID-19 infection in the Black Women's Health Study, showing higher risk of infection for lower vitamin D levels. Vitamin D levels were from 3-7 years before infection. Levels at the time of infe..
7/27
PrEP Israel et al., Epidemiology and Global Health Microbiology and Infectious Disease, doi:10.7554/eLife.68165 (Peer Reviewed) hosp., ↓9.1%, p=0.003 Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population
Details   Case control study examining medication usage with a healthcare database in Israel, showing lower risk of hospitalization with vitamin D (defined as being picked up within 35 days prior to PCR+). Other patients may have acquired vitamin D..
7/25
Early Ontai et al., medRxiv, doi:10.1101/2021.07.21.21260223 (Preprint) Early multidrug treatment of SARS-CoV-2 (COVID-19) and decreased case fatality rates in Honduras
Details   Report on the nationwide implementation of multi-drug COVID-19 inpatient and outpatient treatment protocols in Honduras, showing a case fatality rate decrease from 9.33% to 2.97%. No decrease was seen in Mexico, a similar Latin American c..
7/25
Early Cadegiani et al., medRxiv, doi:10.1101/2021.07.24.21261047 (Preprint) Proxalutamide Improves Inflammatory, Immunologic, and Thrombogenic Markers in Mild-to-Moderate COVID-19 Males and Females: an Exploratory Analysis of a Randomized, Double-Blinded, Placebo-Controlled Trial Early Antiandrogen Therapy (EAT) with Proxalutamide (The EAT-Proxa Biochemical AndroCoV-Trial)
Details   Analysis of data from two proxalutamide early treatment RCTs with 445 patients showing substantial improvements in immunologic, inflammatory, thrombotic, and oxygen markers, which may support the observed reduction in hospitalization.
7/24
News World Ivermectin Day (News) news World Ivermectin Day
Details   Joint event by 22 worldwide organizations.
7/23
Late Güven et al, European Journal of Clinical Nutrition, doi:10.1038/s41430-021-00984-5 (Peer Reviewed) death, ↓24.8%, p=0.32 The effect of high-dose parenteral vitamin D3 on COVID-19-related inhospital mortality in critical COVID-19 patients during intensive care unit admission: an observational cohort study
Details   Retrospective 175 ICU patients, 113 treated with a single dose of 300,000IU intramuscular cholecalciferol, showing lower mortality with treatment, but not reaching statistical significance. Calcifediol or calcitriol, which avoids several ..
7/20
In Vitro Heinen et al., Viruses, doi:10.3390/v13071411 (Peer Reviewed) (In Vitro) in vitro Antiviral Effect of Budesonide against SARS-CoV-2
Details   In Vitro study showing dose-dependent inhibition of SARS-CoV-2 with budesonide.
7/19
Late Madan et al., medRxiv, doi:10.1101/2021.07.15.21260600 (Preprint) death, ↓44.4%, p=0.03 Remdesivir for the treatment of COVID-19 disease: A retrospective comparative study of patients treated with and without Remdesivir
Details   Retrospective 1,262 hospitalized patients, 398 treated with remdesivir, showing unadjusted lower mortality with treatment, and a treatment delay-response relationship.
7/17
PrEP Oristrell et al., Journal of Endocrinological Investigation, doi:10.1007/s40618-021-01639-9 (Peer Reviewed) death, ↑1.0%, p=0.91 Vitamin D supplementation and COVID-19 risk: a population-based, cohort study
Details   Retrospective study of cholecalciferol and calcitriol supplementation in Catalonia showing a small but significant lower risk of cases with cholecalciferol, but no significant difference for mortality, or for calcitriol supplementation. S..
7/16
News FLCCC Alliance and British Ivermectin Recommendation Development Group (News) news Joint Statement of the FLCCC Alliance and British Ivermectin Recommendation Development Group on Retraction of Early Research on Ivermectin
Details   News release noting that ivermectin remains effective after excluding Elgazzar et al. Given the large magnitude effects and 61 studies, excluding one study with ~3% of patients does not significantly change the evidence base.
7/16
News Kintor Pharmaceutical News Release (News) news Kintor Pharmaceutical Receives Emergency Use Authorization for Proxalutamide for the Treatment of COVID-19 in Paraguay
Details   News release announcing that proxalutamide has been granted an emergency use authorization for COVID-19 in Paraguay.
7/15
Late Ohl et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.14741 (Peer Reviewed) death, ↑6.0%, p=0.66 Association of Remdesivir Treatment With Survival and Length of Hospital Stay Among US Veterans Hospitalized With COVID-19
Details   Retrospective 5,898 hospitalized patients in the USA, 2,374 receiving remdesivir treatment, showing no significant difference in mortality, and a longer time to hospital discharge with treatment.
7/13
Late Barrat-Due et al., Annals of Internal Medicine, doi:10.7326/M21-0653 (Peer Reviewed) death, 0.0%, p=1.00 Evaluation of the Effects of Remdesivir and Hydroxychloroquine on Viral Clearance in COVID-19
Details   Small RCT in Norway with 52 HCQ and 42 remdesivir patients, showing no significant differences with treatment. Add-on trial to WHO Solidarity. NCT04321616.
7/12
Meta Neil et al., ResearchGate, doi:0.13140/RG.2.2.31800.88323 (Preprint) meta-analysis Bayesian Meta Analysis of Ivermectin Effectiveness in Treating Covid-19 Disease
Details   Bayesian analysis of a subset of ivermectin trial data concluding that there is overwhelming evidence to support a causal link between ivermectin, COVID-19 severity, and mortality.
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 779 studies, 546 present results comparing with a control group, 482 are treatment studies, 64 analyze outcomes based on serum levels, and 47 are meta analyses.
Please send us corrections, updates, or comments. Vaccines and treatments are both extremely valuable and complementary. All practical, effective, and safe means should be used. Elimination of COVID-19 is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. Denying the efficacy of any method increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage. 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. Treatment protocols for physicians are available from the FLCCC.
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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.
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Aspirin
Bamlanivimab
Bromhexine
Budesonide
Casirivimab/i..
Colchicine
Curcumin
Favipiravir
Fluvoxamine
Hydroxychloro..
Iota-carragee..
Ivermectin
Molnupiravir
Nitazoxanide
Povidone-Iodine
Proxalutamide
Quercetin
Remdesivir
Sotrovimab
Vitamin C
Vitamin D
Zinc

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