Covid 19 early treatment: real time analysis of 977 studies
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COVID-19 early treatment analysis. Treatments do not replace vaccines and other measures. All practical, effective, and safe means should be used. Elimination is a race against viral evolution. No treatment, vaccine, or intervention is 100% available and effective for all variants. Denying efficacy increases the risk of COVID-19 becoming endemic; and increases mortality, morbidity, and collateral damage.
This is a very interesting document comparing all tested early treatments against Covid 19 infection.
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| Random effects meta-analysis of all studies combined (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. | |||||
| 00.250.50.7511.251.51.752+Proxalutamide91%0.09 [0.04-0.19]3n/a682few trials/eventsCostStudiesPatientsImprovement, RR [CI]Fluvoxamine89%0.11 [0.01-0.85]2$4277very few trials/eventsNigella Sativa84%0.16 [0.05-0.48]3$5915few trials/eventsBudesonide82%0.18 [0.04-0.79]1$4146very few trials/eventsPovidone-Iod..81%0.19 [0.10-0.37]6$1807few trials/eventsVitamin D80%0.20 [0.10-0.37]5$1898few trials/eventsBromhexine79%0.21 [0.06-0.72]2$596very few trials/eventsVitamin A79%0.21 [0.07-0.61]2$2240very few trials/eventsQuercetin79%0.21 [0.02-1.82]2$5194very few trials/eventsMelatonin78%0.22 [0.06-0.75]2$191very few trials/eventsMolnupiravir77%0.23 [0.01-5.69]1$256202very few trials/eventsBamlanivimab76%0.24 [0.12-0.50]4$1,2507,389Zinc75%0.25 [0.04-1.71]3$1982very few trials/eventsCurcumin72%0.28 [0.09-0.91]4$5441very few trials/eventsCasirivimab/i..69%0.31 [0.13-0.74]4$2,10011,226few trials/eventsIvermectin68%0.32 [0.22-0.48]28$15,326Sotrovimab67%0.33 [0.01-8.16]1$2,100583very few trials/eventsHydroxychloro..64%0.36 [0.29-0.46]32$154,621Nitazoxanide49%0.51 [0.13-1.95]5$41,414few trials/eventsFavipiravir48%0.52 [0.36-0.76]4$20410very few trials/eventsVitamin C46%0.54 [0.19-1.51]2$1208very few trials/eventsProbiotics34%0.66 [0.55-0.80]2$5323few trials/eventsConv. Plasma-93%1.93 [0.47-7.87]3$5,000716very few trials/eventsEarly treatment studies (pooled effects)c19early.com Sep 27, 2021Favors treatmentFavors control | |||||
| 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. | |||||
| 00.250.50.7511.251.51.752+Povidone-Iod..88%0.12 [0.03-0.50]1$1606very few trials/eventsCostStudiesPatientsImprovement, RR [CI]Nigella Sativa87%0.13 [0.04-0.49]2$5732few trials/eventsBromhexine87%0.13 [0.01-1.23]2$5178very few trials/eventsProxalutamide84%0.16 [0.12-0.22]3n/a1,090few trials/eventsMolnupiravir77%0.23 [0.01-5.69]1$256202very few trials/eventsCasirivimab/i..76%0.24 [0.03-2.14]3$2,10018,132few trials/eventsMelatonin74%0.26 [0.09-0.74]3$11,492few trials/eventsSotrovimab67%0.33 [0.01-8.16]1$2,100583very few trials/eventsProbiotics66%0.34 [0.18-0.64]2$5270few trials/eventsCurcumin65%0.35 [0.13-0.90]2$5180few trials/eventsNitazoxanide60%0.40 [0.10-1.58]3$4923very few trials/eventsIvermectin58%0.42 [0.30-0.59]25$113,911Vitamin D57%0.43 [0.30-0.62]22$19,958Bamlanivimab57%0.43 [0.11-1.68]4$1,2507,566Quercetin46%0.54 [0.12-2.40]3$5623very few trials/eventsVitamin A42%0.58 [0.07-4.59]2$2207few trials/eventsZinc41%0.59 [0.47-0.75]9$110,393Colchicine40%0.60 [0.42-0.86]10$117,373Budesonide39%0.61 [0.22-1.67]1$41,586very few trials/eventsFluvoxamine29%0.71 [0.38-1.30]1$41,472very few trials/eventsAspirin26%0.74 [0.62-0.89]13$151,716Hydroxychloro..22%0.78 [0.73-0.84]179$1290,603Remdesivir21%0.79 [0.69-0.90]22$3,12039,653Vitamin C18%0.82 [0.67-1.01]14$113,924Favipiravir8%0.92 [0.60-1.41]5$202,119Conv. Plasma-1%1.01 [0.90-1.13]13$5,00014,426All mortality results (all stages)c19early.com Sep 27, 2021Favors treatmentFavors control | |||||
| 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. | |||||
| 00.250.50.7511.251.51.752+Casirivimab/i..92%0.08 [0.00-1.53]2$2,1008,347few trials/eventsCostStudiesPatientsImprovement, RR [CI]Bromhexine91%0.09 [0.01-1.59]1$578very few trials/eventsPovidone-Iod..88%0.12 [0.03-0.50]1$1606very few trials/eventsNigella Sativa87%0.13 [0.04-0.49]2$5732few trials/eventsVitamin A86%0.14 [0.03-0.61]1$2140very few trials/eventsBamlanivimab85%0.15 [0.03-0.77]2$1,2506,784few trials/eventsCurcumin82%0.18 [0.04-0.79]1$5140very few trials/eventsZinc79%0.21 [0.03-1.47]1$1518very few trials/eventsQuercetin79%0.21 [0.02-1.82]2$5194very few trials/eventsVitamin D78%0.22 [0.12-0.43]3$1500few trials/eventsMolnupiravir77%0.23 [0.01-5.69]1$256202very few trials/eventsHydroxychloro..75%0.25 [0.16-0.40]13$150,628Proxalutamide73%0.27 [0.03-2.39]2n/a445very few trials/eventsSotrovimab67%0.33 [0.01-8.16]1$2,100583very few trials/eventsFavipiravir45%0.55 [0.05-5.81]1$2092very few trials/eventsNitazoxanide41%0.59 [0.02-13.8]2$4873very few trials/eventsIvermectin37%0.63 [0.38-1.04]8$13,050Conv. Plasma-93%1.93 [0.47-7.87]3$5,000716very few trials/eventsEarly treatment mortality resultsc19early.com Sep 27, 2021Favors treatmentFavors control | |||||
| 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. |
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| Budesonide | 82% | 1 |
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| Casirivimab/im.. | 69% | 4 |
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| Ivermectin | 68% | 28 |
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| Sotrovimab | 67% | 1 |
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| Hydroxychloro.. | 64% | 32 |
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| Favipiravir | 48% | 4 |
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| Remdesivir | - | 0 |
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Early treatments approved by >2 countries. 63 countries have officially approved treatments. Details.
Recent studies (see the individual treatment pages for all studies):
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Sep 25
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Meta | et al., medRxiv, doi:10.1101/2021.09.22.21263977 (Preprint) (meta analysis) | meta-analysis | COVID-19 mortality risk correlates inversely with vitamin D3 status, and a mortality rate close to zero could theoretically be achieved at 50 ng/ml 25(OH)D3: Results of a systematic review and meta-analysis |
| Details Meta analysis of 8 studies with vitamin D levels measured pre-infection or on the day of hospital admission, showing a correlation between the levels and mortality. Authors recommend combining vaccination with vitamin D supplementation to.. | ||||
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Sep 23
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Late | et al., medRxiv, doi:2021.09.20.21263828 (Preprint) | hosp./death, ↑29.8%, p=0.65 | Colchicine for COVID-19 in adults in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial |
| Details Late treatment RCT with 156 colchicine patients in the UK, showing no significant differences. ISRCTN86534580. | ||||
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Sep 22
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Levels | et al., Nutrients, doi:10.3390/nu13103304 (Peer Reviewed) | death, ↓79.0%, p=0.01 | Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission |
| Details Retrospective 79 hospitalized patients in Belgium, showing mortality associated with zinc and selenium deficiency. | ||||
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Sep 22
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Levels | et al., medRxiv, doi:10.1101/2021.09.20.21263865 (Preprint) | Vitamin D and socioeconomic deprivation mediate COVID-19 ethnic health disparities | |
| Details UK Biobank retrospective showing that vitamin supplements, including vitamin D, mediate the Asian disparity in COVID-19 susceptibility, and vitamin D levels mediate Asian and Black COVID-19 severity disparities. Authors conclude that the .. | ||||
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Sep 15
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Late | et al., Northern Clinics of Istanbul, doi:10.14744/nci.2021.65471 (Peer Reviewed) | viral- time, ↓12.2%, p=0.05 | Effect of Hydroxychloroquine Use on the Length Of Hospital Stay in Children Diagnosed With Covid 19 |
| Details Retrospective 40 pediatric hospitalized patients, 15 treated with HCQ, showing 7.2 vs. 8.2 days until PCR-, not quite reaching statistical significance. | ||||
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Sep 15
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Late | et al., Turk. J. Haematol., doi:10.4274/tjh.galenos.2021.2021.0287 (Peer Reviewed) | death, ↑399.2%, p=0.003 | Clinical Characteristics and Outcome of COVID-19 in Turkish Hematological Malignancy Patients |
| Details Retrospective 340 patients with hematological malignancy in Turkey, showing higher mortality with HCQ treatment. Confounding by time is likely because more HCQ patients were earlier in time when overall treatment protocols were significan.. | ||||
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Sep 14
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Late | et al., International Journal of General Medicine, 2021:14 (Peer Reviewed) | death, ↓57.2%, p=0.05 | Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study |
| Details Retrospective hospitalized patients in Saudi Arabia, showing lower mortality with favipiravir compared to HCQ, not quite reaching statistical significance. Authors do not indicate the factors behind which therapy was chosen. Confounding b.. | ||||
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Sep 14
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Late | et al., Lancet Infectious Diseases, doi:10.1016/S1473-3099(21)00485-0 (Peer Reviewed) | death, ↓6.4%, p=0.77 | Remdesivir plus standard of care versus standard of care alone for the treatment of patients admitted to hospital with COVID-19 (DisCoVeRy): a phase 3, randomised, controlled, open-label trial |
| Details RCT 857 hospitalized patients, showing no significant differences with remdesivir treatment. DISCOVERY trial. EudraCT2020-000936-23, NCT04315948. | ||||
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Sep 14
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PrEP | et al., medRxiv, doi:10.1101/2021.09.13.21262971 (Preprint) | hosp., ↓94.8%, p=0.61 | Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective study |
| Details Small prophylaxis trial with 29 low dose HCQ and 455 control healthcare workers in India, showing no statistically significant differences. | ||||
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Sep 14
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Early | et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2021.102163 (Peer Reviewed) | Hydroxychloroquine / azithromycin in COVID-19: The association between time to treatment and case fatality rate | |
| Details Retrospective 1,265 outpatients in Peru treated with HCQ+AZ showing mortality associated with treatment delay. Mortality was six times lower than the national average. | ||||
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Sep 11
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N/A | et al., medRxiv, doi:10.1101/2021.09.10.21263376 (Preprint) | An open label, adaptive, phase 1 trial of high-dose oral nitazoxanide in healthy volunteers: an antiviral candidate for SARS-CoV-2 | |
| Details Phase I trial of high dose nitazoxanide, 1500mg twice daily, with 14 participants. Trreatment was safe and well tolerated. PBPK predictions were confirmed on day 1 but with underprediction at day 5. Median Cmin was above the in vitro targ.. | ||||
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Sep 9
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In Vitro | et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009840 (Peer Reviewed) (In Vitro) | in vitro | Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells |
| Details In Vitro studying identifying 35 compounds that inhibit SARS-CoV-2 in Vero cells and hepatocytes when treated prior to infection, and several compounds that slow replication when treated after infection: vitamin D, amodiaquine, atovaquone.. | ||||
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Sep 9
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Early | et al., Southeast Asian Journal of Tropical Medicine and Public Health, 52:4 (Peer Reviewed) | progression, ↓68.0%, p=0.003 | Assessment of outcomes following implementation of antiviral treatment guidelines for COVID-19 during the first wave in Thailand |
| Details Retrospective 744 hospitalized patients in Thailand, showing lower risk of a poor outcome for favipiravir treatment within 4 days of symptom onset. Early treatment with CQ/HCQ and lopinavir/ritonavir or darunavir/ritonavir also showed low.. | ||||
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Sep 9
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PrEP | et al., Research Square, doi:10.21203/rs.3.rs-72221/v1 (Preprint) | cases, ↓32.6%, p=0.10 | Association Between Inhaled Corticosteroid Use and the Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Nationwide Population-based Study in South Korea |
| Details Retrospective 44,968 patients in South Korea, 7,019 on inhaled corticosteroids, showing no statistically significant differences in COVID-19 cases. | ||||
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Sep 9
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Late | et al., Nature Medicine, doi:10.1038/s41591-021-01488-2 (Peer Reviewed) | death, ↑13.0%, p=0.33 | Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial |
| Details RCT 940 hospitalized patients, 614 assigned to convalescent plasma, showing no significant differences. NCT04348656. | ||||
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Sep 8
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Late | et al., Bone, doi:10.1016/j.bone.2021.116175 (Peer Reviewed) | death, ↓85.7%, p=0.23 | A Randomized Pilot Study Using Calcitriol in Hospitalized Patients |
| Details RCT 50 hospitalized patients in the USA, 25 treated with calcitriol, showing significantly improved oxygenation with treatment. Mortality, intubation, ICU admission, and hospitalization time also favored treatment, while not reaching stat.. | ||||
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Sep 7
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Late | et al., Aging, doi:10.18632/aging.203503 (Peer Reviewed) | High-dose vitamin C ameliorates cardiac injury in COVID-19 pandemic: a retrospective cohort study | |
| Details Retrospective 113 severe and critical patients in China with cardiac injury, 51 treated with high dose vitamin C, showing treatment associated with improvement of myocardial injury. | ||||
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Sep 6
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Early | et al., SSRN, doi:10.2139/ssrn.3918289 (Preprint) | hosp., ↑600.0%, p=0.30 | High Dose Ivermectin for the Early Treatment of COVID-19 (COVIER Study): A Randomised, Double-Blind, Multicentre, Phase II, Dose-Finding, Proof of Concept Clinical Trial |
| Details Early terminated 89 patient RCT with 29 high dose and 32 very high dose ivermectin patients, showing dose dependent viral load reduction, although not reaching statistical significance due to early termination. Since most patients have lo.. | ||||
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Sep 4
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PrEP | et al., Medicina, doi:10.3390/medicina57090931 (Peer Reviewed) | death, ↑700.0%, p=0.03 | Aspirin Is Related to Worse Clinical Outcomes of COVID-19 |
| Details Retrospective database analysis of 22,660 patients tested for COVID-19 in South Korea. There was no significant difference in cases according to aspirin use. Aspirin use before COVID-19 was related to an increased death rate and aspirin u.. | ||||
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Sep 3
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Levels | et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06617-3 (Peer Reviewed) | The correlation between serum selenium, zinc, and COVID-19 severity: an observational study | |
| Details Prospective analysis of 84 patients in Iran, showing higher selenium and zinc levels associated with a decrease in serum CRP level. There was no statistically significant association between selenium/zinc levels and disease severity. | ||||
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Sep 3
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Early | et al., Nigerian Postgraduate Medical Journal, doi:10.4103/npmj.npmj_532_21 (Peer Reviewed) | Clinical characteristics, treatment modalities and outcome of coronavirus disease 2019 patients treated at thisday dome isolation and treatment centre, federal capital territory Abuja, Nigeria | |
| Details Retrospective 300 COVID-19 patients in Nigeria treated with ivermectin, zinc, vitamin C, and azithromycin, reporting no deaths. Authors conclude that early treatment is critical. | ||||
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Sep 3
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Late | et al., Research Square, doi:10.21203/rs.3.rs-872891/v1 (Preprint) | death, ↓27.0%, p=0.03 | Evaluation of low-dose aspirin use among COVID-19 critically ill patients: A Multicenter Propensity Score Matched Study |
| Details Retrospective 1,033 critical condition patients, showing lower in-hospital mortality with aspirin in PSM analysis. Patients receiving aspirin also had a higher risk of significant bleeding, although not reaching statistical significance. .. | ||||
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Sep 2
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Meta | et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001443 (Peer Reviewed) (meta analysis) | meta-analysis | Ivermectin, A Reanalysis of the Data |
| Details Updated meta analysis showing no significant change if Elgazzar et al. is excluded. | ||||
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Sep 2
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Meta | et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001450 (Peer Reviewed) (meta analysis) | meta-analysis | Bayesian Hypothesis Testing and Hierarchical Modeling of Ivermectin Effectiveness |
| Details Updated Bayesian analysis of a subset of ivermectin trials showing that there is strong evidence to support a causal link between ivermectin and COVID-19 severity and mortality, and that the result is robust in sensitivity analysis, inclu.. | ||||
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Sep 1
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PrEP | et al., Journal of Family & Reproductive Health, doi:10.18502/jfrh.v14i3.4668 (Peer Reviewed) | progression, ↓60.4%, p=0.41 | Supplement Usage Pattern in a Group of COVID- 19 Patients in Tehran |
| Details Retrospective 510 patients in Iran, showing lower risk of severity with vitamin D (statistically significant) and zinc (not statistically significant) supplementation. IR.TUMS.VCR.REC.1398.1063. | ||||
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Sep 1
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Late | et al., Proceedings of Singapore Healthcare, doi:10.1177/20101058211041405 (Peer Reviewed) | death, ↓63.4%, p=0.21 | Impact of Vitamin D Therapy on the Progress COVID-19: Six Weeks Follow-Up Study of Vitamin D Deficient Elderly Diabetes Patients |
| Details Small RCT with 56 eldery diabetes patients hospitalized in Egypt, 40 treated with cholecalciferol, not showing significant differences. | ||||
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Aug 31
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Meta | et al., Journal of the American College of Nutrition, doi:10.1080/07315724.2021.1951891 (Peer Reviewed) (meta analysis) | meta-analysis | Association between Vitamin D Status and Risk of Developing Severe COVID-19 Infection: A Meta-Analysis of Observational Studies |
| Details Meta analysis of 24 observational studies with 3,637 participants, showing low vitamin D status associated with a higher risk of death and a higher risk of developing severe COVID-19 pneumonia. | ||||
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Aug 30
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Late | et al., Journal of Medical Virology, doi:10.1002/jmv.27312 (Peer Reviewed) | death, ↓66.7%, p=0.62 | Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial |
| Details RCT 96 hospitalized patients in Iran, 48 treated with melatonin, showing improved sleep quality and SpO2 with treatment. 3mg oral melatonin daily. Authors recommend studies with a higher dose. IRCT20200411047030N1. | ||||
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Aug 29
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PrEP | et al., Journal of Thrombosis and Haemostasis, doi:10.1111/jth.15517 (Peer Reviewed) | death, ↓19.0%, p<0.005 | Association of Pre-Hospital Antiplatelet Therapy with Survival in Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis |
| Details PSM retrospective 6,781 hospitalized patients ≥50 years old in the USA who were on pre-hospital antiplatelet therapy (84% aspirin), and 10,566 matched controls, showing lower mortality with treatment. | ||||
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Aug 29
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Levels | et al., Nutrients, doi:10.3390/nu13093021 (Peer Reviewed) | death, ↓77.8%, p=0.006 | Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19 |
| Details Retrospective 161 hospitalized patients in Russia, showing COVID-19 severity and mortality associated with vitamin D deficiency. Patients in this study may overlap with those in an earlier smaller study from some of the same authors. | ||||
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Aug 27
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Late | et al., Infectious Diseases and Therapy, doi:10.1007/s40121-021-00517-4 (Peer Reviewed) | no recov., ↓37.1%, p=0.01 | Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial |
| Details RCT 156 patients in Japan, 107 treated with favipiravir, showing significant improvement in a composite outcome defined as the time to improvement in temperature, SpO2, CT findings, and recovery to PCR-. | ||||
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Aug 27
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Levels | et al., Journal of Primary Care & Community Health, doi:10.1177/21501327211041206 (Peer Reviewed) | death, ↓35.9%, p=0.73 | Vitamin D Status and Severe COVID-19 Disease Outcomes in Hospitalized Patients |
| Details Retrospective 92 hospitalized patients not showing significant differences in outcomes based on vitamin D status or supplementation. | ||||
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 977 studies, 666 present results comparing with a control group, 593 are treatment studies, and 73 analyze outcomes based on serum levels. There are 13 animal studies, 34 in silico studies, 49 in vitro studies, and 58 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.
https://c19early.com/?fbclid=IwAR0zJYUGXuXtqGxaX6z1ofeC8qAAOCAf2QDlHEb_fSIdjutdamtrgEkbFyk