COVID-19 early treatment: real-time analysis of 975 studies

All studies Early treatment Mortality Early treatment mortality Recent studies Adoption

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.


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.


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.


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.


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.

Treatment

Improvement
(early)

Studies
(early)

82%

69%

68%

67%

64%

48%

Early treatments approved by >2 countries. 63 countries have officially approved treatments. Details.

Recent studies (see the individual treatment pages for all studies):


Sep 25	Meta	Borsche 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..
Sep 25	Details Source PDF Meta Meta
	Borsche et al., medRxiv, doi:10.1101/2021.09.22.21263977 (Preprint) (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
	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 maintain levels above 50 ng/ml. Borsche et al., 9/25/2021, preprint, 3 authors.
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Sep 23	Late	Dorward 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.
Sep 23	Details Source PDF Late treatment study Late treatment study
	Dorward et al., medRxiv, doi:2021.09.20.21263828 (Preprint)
	Colchicine for COVID-19 in adults in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial
	Late treatment RCT with 156 colchicine patients in the UK, showing no significant differences. ISRCTN86534580. risk of combined hospitalization/death, 29.8% higher, RR 1.30, p = 0.65, treatment 6 of 156 (3.8%), control 4 of 133 (3.0%), OR converted to RR, concurrent randomisation. risk of combined hospitalization/death, 22.1% lower, RR 0.78, p = 0.55, treatment 6 of 156 (3.8%), control 119 of 1145 (10.4%), OR converted to RR, including control patients before the colchicine arm started. risk of disease progression, 6.0% lower, RR 0.94, p = 0.45, treatment 102 of 156 (65.4%), control 83 of 120 (69.2%). risk of no recovery, 6.0% lower, RR 0.94, p = 0.67, treatment 156, control 133, time to alleviation of symptoms. Dorward et al., 9/23/2021, Randomized Controlled Trial, United Kingdom, Europe, preprint, 21 authors.
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Sep 22	Levels	Laing 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.
Sep 22	Details Source PDF Levels Analysis of outcomes based on serum levels
	Laing et al., Nutrients, doi:10.3390/nu13103304 (Peer Reviewed)
	Course and Survival of COVID-19 Patients with Comorbidities in Relation to the Trace Element Status at Hospital Admission
	Retrospective 79 hospitalized patients in Belgium, showing mortality associated with zinc and selenium deficiency. risk of death, 79.0% lower, RR 0.21, p = 0.01, high zinc levels 3 of 49 (6.1%), low zinc levels 7 of 24 (29.2%). Laing et al., 9/22/2021, retrospective, Belgium, Europe, peer-reviewed, 11 authors.
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Sep 22	Levels	Marino-Ramirez 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 ..
Sep 22	Details Source PDF Levels Analysis of outcomes based on serum levels
	Marino-Ramirez et al., medRxiv, doi:10.1101/2021.09.20.21263865 (Preprint)
	Vitamin D and socioeconomic deprivation mediate COVID-19 ethnic health disparities
	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 results support the use of vitamin D as both a prophylactic and a supplemental therapeutic for COVID-19 in those individuals. Marino-Ramirez et al., 9/22/2021, preprint, 7 authors.
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Sep 15	Late	Çivriz Bozdağ 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..
Sep 15	Details Source PDF Late treatment study Late treatment study
	Çivriz Bozdağ et al., Turk. J. Haematol., doi:10.4274/tjh.galenos.2021.2021.0287 (Peer Reviewed)
	Clinical Characteristics and Outcome of COVID-19 in Turkish Hematological Malignancy Patients
	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 significantly worse. risk of death, 399.2% higher, RR 4.99, p = 0.003, treatment 35, control 140. Çivriz Bozdağ et al., 9/15/2021, retrospective, Turkey, Europe, peer-reviewed, 62 authors.
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Sep 14	Late	Alotaibi 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..
Sep 14	Details Source PDF Late treatment study Late treatment study
	Alotaibi et al., International Journal of General Medicine, 2021:14 (Peer Reviewed)
	Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study
	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 by indication and time are possible. risk of death, 57.2% lower, RR 0.43, p = 0.05, treatment 244, control 193, multivariate. Alotaibi et al., 9/14/2021, retrospective, Saudi Arabia, Middle East, peer-reviewed, 11 authors, this trial compares with another treatment - results may be better when compared to placebo.
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Sep 14	Late	Ader 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.
Sep 14	Details Source PDF Late treatment study Late treatment study
	Ader et al., Lancet Infectious Diseases, doi:10.1016/S1473-3099(21)00485-0 (Peer Reviewed)
	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
	RCT 857 hospitalized patients, showing no significant differences with remdesivir treatment. DISCOVERY trial. EudraCT2020-000936-23, NCT04315948. risk of death, 6.4% lower, RR 0.94, p = 0.77, treatment 34 of 414 (8.2%), control 37 of 418 (8.9%), adjusted, OR converted to RR, 28 days. risk of 7-point scale status, 9.9% lower, RR 0.90, p = 0.39, treatment 414, control 418, 28 days, RR approximated with OR. risk of 7-point scale status, 2.0% higher, RR 1.02, p = 0.85, treatment 414, control 418, 15 days, RR approximated with OR. Ader et al., 9/14/2021, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 17 authors.
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Sep 14	PrEP	Panda 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.
Sep 14	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Panda et al., medRxiv, doi:10.1101/2021.09.13.21262971 (Preprint)
	Low dose hydroxychloroquine prophylaxis for COVID-19 - a prospective study
	Small prophylaxis trial with 29 low dose HCQ and 455 control healthcare workers in India, showing no statistically significant differences. risk of hospitalization, 94.8% lower, RR 0.05, p = 0.61, treatment 0 of 29 (0.0%), control 17 of 455 (3.7%), continuity correction due to zero event. relative severity, 26.9% lower, RR 0.73, p = 0.21, treatment 29, control 455. risk of COVID-19 case, 4.6% higher, RR 1.05, p = 0.81, treatment 6 of 29 (20.7%), control 90 of 455 (19.8%). Panda et al., 9/14/2021, prospective, India, South Asia, preprint, 1 author.
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Sep 14	Early	Accinelli 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.
Sep 14	Details Source PDF Early treatment study Early treatment study
	Accinelli 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
	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. Accinelli et al., 9/14/2021, peer-reviewed, 6 authors.
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Sep 11	N/A	Walker 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..
Sep 11	Details Source PDF N/A N/A
	Walker 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
	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 target concentration on first dose and maintained throughout. NCT04746183. Walker et al., 9/11/2021, preprint, 32 authors.
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Sep 9	In Vitro	Pickard 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..
Sep 9	Details Source PDF In Vitro In Vitro
	Pickard et al., PLOS Pathogens, doi:10.1371/journal.ppat.1009840 (Peer Reviewed) (In Vitro)
	Discovery of re-purposed drugs that slow SARS-CoV-2 replication in human cells
	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, bedaquiline, ebastine, LY2835219, manidipine, and panobinosta. Authors use a nano-luciferase tagged version of the virus to quantify viral load. Pickard et al., 9/9/2021, peer-reviewed, 7 authors. In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
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Sep 9	Early	Sawanpanyalert 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..
Sep 9	Details Source PDF Early treatment study Early treatment study
	Sawanpanyalert et al., Southeast Asian Journal of Tropical Medicine and Public Health, 52:4 (Peer Reviewed)
	Assessment of outcomes following implementation of antiviral treatment guidelines for COVID-19 during the first wave in Thailand
	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 lower risk, but without statistical significance. Sample sizes for the number of patients treated within 4 days of symptom onset are not provided. risk of death, ICU, intubation, or high-flow oxygen, 68.0% lower, RR 0.32, p = 0.003, within 4 days of symptom onset, RR approximated with OR. Sawanpanyalert et al., 9/9/2021, retrospective, Thailand, South Asia, peer-reviewed, 11 authors.
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Sep 9	PrEP	Lee 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.
Sep 9	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Lee et al., Research Square, doi:10.21203/rs.3.rs-72221/v1 (Preprint)
	Association Between Inhaled Corticosteroid Use and the Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Nationwide Population-based Study in South Korea
	Retrospective 44,968 patients in South Korea, 7,019 on inhaled corticosteroids, showing no statistically significant differences in COVID-19 cases. risk of COVID-19 case, 32.6% lower, RR 0.67, p = 0.10, treatment 19 of 1674 (1.1%), control 95 of 5345 (1.8%), adjusted, OR converted to RR, multivariate. Lee et al., 9/9/2021, retrospective, South Korea, Asia, preprint, 5 authors.
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Sep 9	Late	Bégin 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.
Sep 9	Details Source PDF Late treatment study Late treatment study
	Bégin et al., Nature Medicine, doi:10.1038/s41591-021-01488-2 (Peer Reviewed)
	Convalescent plasma for hospitalized patients with COVID-19: an open-label, randomized controlled trial
	RCT 940 hospitalized patients, 614 assigned to convalescent plasma, showing no significant differences. NCT04348656. risk of death, 13.0% higher, RR 1.13, p = 0.33, treatment 156 of 625 (25.0%), control 69 of 313 (22.0%), day 90. risk of death, 12.0% higher, RR 1.12, p = 0.40, treatment 141 of 614 (23.0%), control 63 of 307 (20.5%), day 30. risk of combined intubation/death, 16.0% higher, RR 1.16, p = 0.18, treatment 199 of 614 (32.4%), control 86 of 307 (28.0%). Bégin et al., 9/9/2021, Randomized Controlled Trial, multiple countries, multiple regions, peer-reviewed, 32 authors.
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Sep 8	Late	Elamir 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..
Sep 8	Details Source PDF Late treatment study Late treatment study
	Elamir et al., Bone, doi:10.1016/j.bone.2021.116175 (Peer Reviewed)
	A Randomized Pilot Study Using Calcitriol in Hospitalized Patients
	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 statistical significance with the very small sample size. risk of death, 85.7% lower, RR 0.14, p = 0.23, treatment 0 of 25 (0.0%), control 3 of 25 (12.0%), continuity correction due to zero event. risk of mechanical ventilation, 80.0% lower, RR 0.20, p = 0.48, treatment 0 of 25 (0.0%), control 2 of 25 (8.0%), continuity correction due to zero event. risk of ICU admission, 37.5% lower, RR 0.62, p = 0.33, treatment 5 of 25 (20.0%), control 8 of 25 (32.0%). hospitalization time, 40.5% lower, relative time 0.60, p = 0.14, treatment 25, control 25. relative Δ SaO₂/FiO₂, RR 0.14, p = 0.03, treatment 25, control 25. Elamir et al., 9/8/2021, Randomized Controlled Trial, USA, North America, peer-reviewed, 9 authors, dosage calcitriol 0.5μg days 1-14.
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Sep 7	Late	Xia 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.
Sep 7	Details Source PDF Late treatment study Late treatment study
	Xia 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
	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. Xia et al., 9/7/2021, China, Asia, peer-reviewed, 5 authors.
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Sep 6	Early	Buonfrate 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..
Sep 6	Details Source PDF Early treatment study Early treatment study
	Buonfrate et al., SSRN, doi:10.2139/ssrn.3918289 (Preprint)
	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
	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 low viral load at day 7, there is little room for improvement with a treatment at day 7. Intermediate results may show significantly greater improvement, but are not provided. Authors note that ivermectin remained safe even at the very high dose used, although tolerability was reduced. 3 patients were hospitalized in the very high dose ivermectin arm (and 1 in the high dose arm) versus 0 in the control arm. While this result is not statistically significant, it may be in part due to randomization failure because 9 patients were randomized at the hospital for very high dose ivermectin versus 4 in the control arm, suggesting higher baseline severity. Supplementary data is not currently available. COVIER. NCT04438850. risk of hospitalization, 600.0% higher, RR 7.00, p = 0.30, treatment 4 of 58 (6.9%), control 0 of 29 (0.0%), continuity correction due to zero event. relative change in viral load, RR 0.69, p = 0.10, treatment 30, control 29, day 7, arm C. relative change in viral load, RR 0.86, p = 0.12, treatment 28, control 29, day 7, arm B. Buonfrate et al., 9/6/2021, Double Blind Randomized Controlled Trial, Italy, Europe, preprint, 18 authors, dosage 1200μg/kg days 1-5, arm B 600µg/kg, arm C 1200µg/kg.
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Sep 4	PrEP	Kim 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..
Sep 4	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Kim et al., Medicina, doi:10.3390/medicina57090931 (Peer Reviewed)
	Aspirin Is Related to Worse Clinical Outcomes of COVID-19
	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 use after COVID-19 was related to a higher risk of oxygen therapy. risk of death, 700.0% higher, RR 8.00, p = 0.03, treatment 6 of 15 (40.0%), control 1 of 20 (5.0%), PSM, prior aspirin use. risk of mechanical ventilation, 433.3% higher, RR 5.33, p = 0.14, treatment 4 of 15 (26.7%), control 1 of 20 (5.0%), PSM, prior aspirin use. risk of ICU admission, 433.3% higher, RR 5.33, p = 0.14, treatment 4 of 15 (26.7%), control 1 of 20 (5.0%), PSM, prior aspirin use. risk of COVID-19 case, 33.4% lower, RR 0.67, p = 0.23, treatment 15 of 136 (11.0%), control 20 of 136 (14.7%), adjusted, OR converted to RR, PSM, logistic regression, prior aspirin use. risk of death, 33.7% lower, RR 0.66, p = 0.22, treatment 14 of 124 (11.3%), control 23 of 135 (17.0%), PSM, aspirin treatment after diagnosis. risk of mechanical ventilation, 102.2% higher, RR 2.02, p = 0.16, treatment 13 of 124 (10.5%), control 7 of 135 (5.2%), PSM, aspirin treatment after diagnosis. risk of ICU admission, 90.5% higher, RR 1.91, p = 0.36, treatment 7 of 124 (5.6%), control 4 of 135 (3.0%), PSM, aspirin treatment after diagnosis. Kim et al., 9/4/2021, retrospective, propensity score matching, South Korea, Asia, peer-reviewed, 7 authors.
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Sep 3	Levels	Jahromi 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.
Sep 3	Details Source PDF Levels Analysis of outcomes based on serum levels
	Jahromi 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
	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. Jahromi et al., 9/3/2021, peer-reviewed, 14 authors.
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Sep 3	Early	Okogbenin 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.
Sep 3	Details Source PDF Early treatment study Early treatment study
	Okogbenin 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
	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. Okogbenin et al., 9/3/2021, peer-reviewed, 13 authors.
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Sep 3	Late	Al Harthi 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. ..
Sep 3	Details Source PDF Late treatment study Late treatment study
	Al Harthi et al., Research Square, doi:10.21203/rs.3.rs-872891/v1 (Preprint)
	Evaluation of low-dose aspirin use among COVID-19 critically ill patients: A Multicenter Propensity Score Matched Study
	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. Authors note that the use of aspirin during an ICU stay should be tailored to each patient. risk of death, 27.0% lower, RR 0.73, p = 0.03, treatment 98 of 176 (55.7%), control 107 of 173 (61.8%), adjusted, in-hospital mortality, multivariable Cox proportional hazards. risk of death, 14.0% lower, RR 0.86, p = 0.30, treatment 95 of 176 (54.0%), control 97 of 175 (55.4%), adjusted, day 30, multivariable Cox proportional hazards. Al Harthi et al., 9/3/2021, retrospective, propensity score matching, Saudi Arabia, Middle East, preprint, 20 authors.
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Sep 2	Meta	Marik 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.
Sep 2	Details Source PDF Meta Meta
	Marik et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001443 (Peer Reviewed) (meta analysis)
	Ivermectin, A Reanalysis of the Data
	Updated meta analysis showing no significant change if Elgazzar et al. is excluded. Marik et al., 9/2/2021, peer-reviewed, 2 authors.
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Sep 2	Meta	Neil 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..
Sep 2	Details Source PDF Meta Meta
	Neil et al., American Journal of Therapeutics, doi:10.1097/MJT.0000000000001450 (Peer Reviewed) (meta analysis)
	Bayesian Hypothesis Testing and Hierarchical Modeling of Ivermectin Effectiveness
	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, including exclusion of Elgazzar et al. Neil et al., 9/2/2021, peer-reviewed, 2 authors.
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Sep 1	PrEP	Bagheri 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.
Sep 1	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Bagheri et al., Journal of Family & Reproductive Health, doi:10.18502/jfrh.v14i3.4668 (Peer Reviewed)
	Supplement Usage Pattern in a Group of COVID- 19 Patients in Tehran
	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. risk of disease progression, 60.4% lower, RR 0.40, p = 0.41, treatment 33, control 477, adjusted, multinomial logistic regression, RR approximated with OR. risk of being in the hospitalized vs. outpatient group, 41.0% lower, RR 0.59, p = 0.37, treatment 4 of 33 (12.1%), control 167 of 477 (35.0%), adjusted, OR converted to RR, binary logistic regression. Bagheri et al., 9/1/2021, retrospective, Iran, Middle East, peer-reviewed, 6 authors.
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Sep 1	Late	Soliman 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.
Sep 1	Details Source PDF Late treatment study Late treatment study
	Soliman et al., Proceedings of Singapore Healthcare, doi:10.1177/20101058211041405 (Peer Reviewed)
	Impact of Vitamin D Therapy on the Progress COVID-19: Six Weeks Follow-Up Study of Vitamin D Deficient Elderly Diabetes Patients
	Small RCT with 56 eldery diabetes patients hospitalized in Egypt, 40 treated with cholecalciferol, not showing significant differences. risk of death, 63.4% lower, RR 0.37, p = 0.21, treatment 7 of 40 (17.5%), control 3 of 16 (18.8%), adjusted, OR converted to RR, logistic regression. risk of mechanical ventilation, 20.0% lower, RR 0.80, p = 0.56, treatment 14 of 40 (35.0%), control 7 of 16 (43.8%), unadjusted. risk of no recovery, 20.0% lower, RR 0.80, p = 0.56, treatment 14 of 40 (35.0%), control 7 of 16 (43.8%), unadjusted. Soliman et al., 9/1/2021, Randomized Controlled Trial, Egypt, Africa, peer-reviewed, 3 authors, dosage 200,000IU single dose.
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Aug 31	Meta	Ben-Eltriki 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.
Aug 31	Details Source PDF Meta Meta
	Ben-Eltriki et al., Journal of the American College of Nutrition, doi:10.1080/07315724.2021.1951891 (Peer Reviewed) (meta analysis)
	Association between Vitamin D Status and Risk of Developing Severe COVID-19 Infection: A Meta-Analysis of Observational Studies
	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. Ben-Eltriki et al., 8/31/2021, peer-reviewed, 4 authors.
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Aug 30	Late	Mousavi 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.
Aug 30	Details Source PDF Late treatment study Late treatment study
	Mousavi et al., Journal of Medical Virology, doi:10.1002/jmv.27312 (Peer Reviewed)
	Melatonin effects on sleep quality and outcomes of COVID-19 patients: An open-label, randomized, controlled trial
	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. risk of death, 66.7% lower, RR 0.33, p = 0.62, treatment 1 of 48 (2.1%), control 3 of 48 (6.2%), day 10. risk of ICU admission, 40.0% lower, RR 0.60, p = 0.41, treatment 6 of 48 (12.5%), control 10 of 48 (20.8%), day 10. Mousavi et al., 8/30/2021, Randomized Controlled Trial, Iran, Middle East, peer-reviewed, 7 authors.
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Aug 29	PrEP	Chow 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.
Aug 29	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Chow et al., Journal of Thrombosis and Haemostasis, doi:10.1111/jth.15517 (Peer Reviewed)
	Association of Pre-Hospital Antiplatelet Therapy with Survival in Patients Hospitalized with COVID-19: A Propensity Score-Matched Analysis
	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. risk of death, 19.0% lower, RR 0.81, p < 0.005, treatment 1280 of 6781 (18.9%), control 2271 of 10566 (21.5%), adjusted, Kaplan Meier. risk of mechanical ventilation, 2.8% lower, RR 0.97, p = 0.21, treatment 2122 of 6781 (31.3%), control 3403 of 10566 (32.2%). Chow et al., 8/29/2021, retrospective, propensity score matching, USA, North America, peer-reviewed, 12 authors.
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Aug 29	Levels	Karonova 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.
Aug 29	Details Source PDF Levels Analysis of outcomes based on serum levels
	Karonova et al., Nutrients, doi:10.3390/nu13093021 (Peer Reviewed)
	Low 25(OH)D Level Is Associated with Severe Course and Poor Prognosis in COVID-19
	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. risk of death, 77.8% lower, RR 0.22, p = 0.006, high D levels 8 of 96 (8.3%), low D levels 10 of 37 (27.0%), adjusted, OR converted to RR, >10ng/mL, logistic regression model 2. risk of death, 84.8% lower, RR 0.15, p = 0.06, high D levels 1 of 43 (2.3%), low D levels 17 of 90 (18.9%), adjusted, OR converted to RR, >20ng/mL, logistic regression model 2. risk of COVID-19 severe case, 67.3% lower, RR 0.33, p = 0.005, high D levels 12 of 96 (12.5%), low D levels 13 of 37 (35.1%), adjusted, OR converted to RR, >10ng/mL, logistic regression model 2. risk of COVID-19 severe case, 53.2% lower, RR 0.47, p = 0.13, high D levels 4 of 43 (9.3%), low D levels 21 of 90 (23.3%), adjusted, OR converted to RR, >20ng/mL, logistic regression model 2. Karonova et al., 8/29/2021, retrospective, Russia, Europe, peer-reviewed, 8 authors.
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Aug 27	Late	Shinkai 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-.
Aug 27	Details Source PDF Late treatment study Late treatment study
	Shinkai et al., Infectious Diseases and Therapy, doi:10.1007/s40121-021-00517-4 (Peer Reviewed)
	Efficacy and Safety of Favipiravir in Moderate COVID-19 Pneumonia Patients without Oxygen Therapy: A Randomized, Phase III Clinical Trial
	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-. time to improvement, 37.1% lower, RR 0.63, p = 0.01, treatment 107, control 49, adjusted, Cox proportional hazards, composite time to improvement in temperature, SpO2, CT findings, and recovery to PCR-. time to improvement, 58.5% lower, RR 0.41, p = 0.01, treatment 47, control 13, adjusted, <5 days from onset of fever, Cox proportional hazards, composite time to improvement in temperature, SpO2, CT findings, and recovery to PCR-. Shinkai et al., 8/27/2021, Single Blind Randomized Controlled Trial, Japan, Asia, peer-reviewed, 39 authors.
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Aug 27	Levels	Pecina 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.
Aug 27	Details Source PDF Levels Analysis of outcomes based on serum levels
	Pecina et al., Journal of Primary Care & Community Health, doi:10.1177/21501327211041206 (Peer Reviewed)
	Vitamin D Status and Severe COVID-19 Disease Outcomes in Hospitalized Patients
	Retrospective 92 hospitalized patients not showing significant differences in outcomes based on vitamin D status or supplementation. risk of death, 35.9% lower, RR 0.64, p = 0.73, high D levels 6 of 77 (7.8%), low D levels 1 of 15 (6.7%), OR converted to RR, >20ng/mL, multivariable logistic regression. risk of mechanical ventilation, 56.9% lower, RR 0.43, p = 0.13, high D levels 8 of 15 (53.3%), low D levels 4 of 15 (26.7%), OR converted to RR, >20ng/mL, multivariable logistic regression. risk of ICU admission, 13.1% higher, RR 1.13, p = 0.10, high D levels 54 of 77 (70.1%), low D levels 9 of 15 (60.0%), OR converted to RR, >20ng/mL, multivariable logistic regression. Pecina et al., 8/27/2021, retrospective, USA, North America, peer-reviewed, 4 authors.
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Aug 26	Levels	Golabi et al., Zenodo, doi:10.5281/zenodo.5266352 (Preprint)		The Association between Vitamin D and Zinc Status with the Disease Onset and Progression of Clinical Symptoms among Outpatients Infected with COVID-19 and Non-Infected Participants: A Cross-Sectional Study
	Details Analysis of vitamin D and zinc levels in 53 PCR+ outpatients and 53 controls, showing lower zinc levels in COVID-19 patients, and increased risk of symptomatic cases with vitamin D deficiency. Currently only the abstract is available.
Aug 26	Details Source PDF Levels Analysis of outcomes based on serum levels
	Golabi et al., Zenodo, doi:10.5281/zenodo.5266352 (Preprint)
	The Association between Vitamin D and Zinc Status with the Disease Onset and Progression of Clinical Symptoms among Outpatients Infected with COVID-19 and Non-Infected Participants: A Cross-Sectional Study
	Analysis of vitamin D and zinc levels in 53 PCR+ outpatients and 53 controls, showing lower zinc levels in COVID-19 patients, and increased risk of symptomatic cases with vitamin D deficiency. Currently only the abstract is available. Golabi et al., 8/26/2021, preprint, 10 authors.
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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 975 studies, 664 present results comparing with a control group, 591 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.

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	Molnupiravir
Bamlanivimab	Nigella Sativa
Bromhexine	Nitazoxanide
Budesonide	Povidone-Iod..
Casirivimab/i..	Probiotics
Colchicine	Proxalutamide
Conv. Plasma	Quercetin
Curcumin	Remdesivir
Favipiravir	Sotrovimab
Fluvoxamine	Vitamin A
Hydroxychloro..	Vitamin C
Iota-carragee..	Vitamin D
Ivermectin	Zinc
Melatonin

Other	Adoption