COVID-19 early treatment: real-time analysis of 702 studies

All studies Early treatment Mortality Early treatment mortality Recent studies

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)

92%

89%

86%

82%

82%

79%

78%

77%

76%

75%

68%

66%

49%

42%

38%

18%

Global early treatment adoption. Details.


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.


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.


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.


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):


6/18	Early	Fischer et al., medRxiv, doi:10.1101/2021.06.17.21258639 (Preprint)	death, ↓76.5%, p=0.31	Molnupiravir, an Oral Antiviral Treatment for COVID-19
	Details RCT 202 outpatients in the USA showing significantly faster viral clearance, but no significant differences in symptom duration or severity. NCT04405570.
6/18	Details Source PDF Early treatment study Early treatment study
	Fischer et al., medRxiv, doi:10.1101/2021.06.17.21258639 (Preprint)
	Molnupiravir, an Oral Antiviral Treatment for COVID-19
	RCT 202 outpatients in the USA showing significantly faster viral clearance, but no significant differences in symptom duration or severity. NCT04405570. risk of death, 76.5% lower, RR 0.23, p = 0.31, treatment 0 of 140 (0.0%), control 1 of 62 (1.6%), continuity correction due to zero event, all. risk of death, 65.4% lower, RR 0.35, p = 1.00, treatment 0 of 55 (0.0%), control 1 of 62 (1.6%), continuity correction due to zero event, 800mg. risk of death, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 62 (0.0%), control 1 of 62 (1.6%), continuity correction due to zero event, 400mg. risk of death, 57.8% lower, RR 0.42, p = 1.00, treatment 0 of 23 (0.0%), control 1 of 62 (1.6%), continuity correction due to zero event, 200mg. risk of hospitalization, 32.9% higher, RR 1.33, p = 1.00, treatment 3 of 140 (2.1%), control 1 of 62 (1.6%), all. risk of hospitalization, 12.7% higher, RR 1.13, p = 1.00, treatment 1 of 55 (1.8%), control 1 of 62 (1.6%), 800mg. risk of hospitalization, 100% higher, RR 2.00, p = 1.00, treatment 2 of 62 (3.2%), control 1 of 62 (1.6%), 400mg. risk of hospitalization, 57.8% lower, RR 0.42, p = 1.00, treatment 0 of 23 (0.0%), control 1 of 62 (1.6%), continuity correction due to zero event, 200mg. risk of no virological cure, 49.2% lower, RR 0.51, p = 0.12, treatment 10 of 118 (8.5%), control 9 of 54 (16.7%), infectious, day 3, all. risk of no virological cure, 88.7% lower, RR 0.11, p = 0.02, treatment 1 of 53 (1.9%), control 9 of 54 (16.7%), infectious, day 3, 800mg. risk of no virological cure, 30.2% lower, RR 0.70, p = 0.57, treatment 5 of 43 (11.6%), control 9 of 54 (16.7%), infectious, day 3, 400mg. risk of no virological cure, 9.1% higher, RR 1.09, p = 1.00, treatment 4 of 22 (18.2%), control 9 of 54 (16.7%), infectious, day 3, 200mg. risk of no virological cure, 92.3% lower, RR 0.08, p = 0.004, treatment 1 of 117 (0.9%), control 6 of 54 (11.1%), infectious, day 5, all. risk of no virological cure, 92.2% lower, RR 0.08, p = 0.03, treatment 0 of 53 (0.0%), control 6 of 54 (11.1%), continuity correction due to zero event, infectious, day 5, 800mg. risk of no virological cure, 91.4% lower, RR 0.09, p = 0.03, treatment 0 of 42 (0.0%), control 6 of 54 (11.1%), continuity correction due to zero event, infectious, day 5, 400mg. risk of no virological cure, 59.1% lower, RR 0.41, p = 0.67, treatment 1 of 22 (4.5%), control 6 of 54 (11.1%), infectious, day 5, 200mg. risk of no virological cure, 29.5% lower, RR 0.70, p = 0.30, treatment 19 of 137 (13.9%), control 12 of 61 (19.7%), all. risk of no virological cure, 61.6% lower, RR 0.38, p = 0.10, treatment 4 of 53 (7.5%), control 12 of 61 (19.7%), 800mg. risk of no virological cure, 8.3% higher, RR 1.08, p = 1.00, treatment 13 of 61 (21.3%), control 12 of 61 (19.7%), 400mg. risk of no virological cure, 55.8% lower, RR 0.44, p = 0.33, treatment 2 of 23 (8.7%), control 12 of 61 (19.7%), 200mg. Fischer et al., 6/18/2021, USA, North America, preprint, 18 authors.
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6/18	Early	Krolewiecki et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100959 (Peer Reviewed)	ventilation, ↑151.9%, p=1.00	Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial
	Details Proof of concept RCT with 30 ivermectin patients and 15 control patients, showing a concentration dependent antiviral activity, but no significant difference in clinical outcomes. There was no significant difference in viral load reductio..
6/18	Details Source PDF Early treatment study Early treatment study
	Krolewiecki et al., EClinicalMedicine, doi:10.1016/j.eclinm.2021.100959 (Peer Reviewed)
	Antiviral effect of high-dose ivermectin in adults with COVID-19: A proof-of-concept randomized trial
	Proof of concept RCT with 30 ivermectin patients and 15 control patients, showing a concentration dependent antiviral activity, but no significant difference in clinical outcomes. There was no significant difference in viral load reduction between groups overall, but a significant difference was found in patients with higher median plasma ivermectin levels (72% vs. 42%, p=0.004). Mean ivermectin plasma concentration levels correlated with viral decay rate (r=0.47, p=0.02). NCT004381884. risk of mechanical ventilation, 151.9% higher, RR 2.52, p = 1.00, treatment 1 of 27 (3.7%), control 0 of 14 (0.0%), continuity correction due to zero event. risk of disease progression, 3.7% higher, RR 1.04, p = 1.00, treatment 2 of 27 (7.4%), control 1 of 14 (7.1%). Krolewiecki et al., 6/18/2021, Randomized Controlled Trial, Argentina, South America, peer-reviewed, 23 authors.
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6/17	Levels	Jude et al., Journal of Clinical Endocrinology & Metabolism, doi:10.1210/clinem/dgab439 (Peer Reviewed)	hosp., ↓71.6%, p<0.0001	Vitamin D deficiency is associated with higher hospitalisation risk from COVID-19: a retrospective case-control study
	Details Retrospective 80,670 people in the UK with vitamin D levels measured within the last 12 months, showing higher risk of hospitalization with low vitamin D levels.
6/17	Details Source PDF Levels Analysis of outcomes based on serum levels
	Jude et al., Journal of Clinical Endocrinology & Metabolism, doi:10.1210/clinem/dgab439 (Peer Reviewed)
	Vitamin D deficiency is associated with higher hospitalisation risk from COVID-19: a retrospective case-control study
	Retrospective 80,670 people in the UK with vitamin D levels measured within the last 12 months, showing higher risk of hospitalization with low vitamin D levels. risk of hospitalization, 71.6% lower, RR 0.28, p < 0.001, adjusted, OR converted to RR, >25 nmol/L, control prevalence approximated with overall prevalence. risk of hospitalization, 57.9% lower, RR 0.42, p < 0.001, adjusted, OR converted to RR, >50 nmol/L, control prevalence approximated with overall prevalence. Jude et al., 6/17/2021, retrospective, United Kingdom, Europe, peer-reviewed, 5 authors.
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6/16	Late	Horby et al., medRxiv, doi:10.1101/2021.06.15.21258542 (Peer Reviewed)	death, ↓6.0%, p=0.17	Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
	Details RCT 9,785 hospitalized patients in the UK showing lower mortality with casirivimab/imdevimab, with statistical significance reached for baseline seronegative patients.
6/16	Details Source PDF Late treatment study Late treatment study
	Horby et al., medRxiv, doi:10.1101/2021.06.15.21258542 (Peer Reviewed)
	Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial
	RCT 9,785 hospitalized patients in the UK showing lower mortality with casirivimab/imdevimab, with statistical significance reached for baseline seronegative patients. risk of death, 6.0% lower, RR 0.94, p = 0.17, treatment 944 of 4839 (19.5%), control 1026 of 4946 (20.7%), all patients. risk of mechanical ventilation, no change, RR 1.00, p = 1.00, treatment 479 of 4556 (10.5%), control 487 of 4642 (10.5%), all patients. risk of death, 20.0% lower, RR 0.80, p = 0.001, treatment 396 of 1633 (24.2%), control 451 of 1520 (29.7%), seronegative patients. risk of mechanical ventilation, 12.0% lower, RR 0.88, p = 0.18, treatment 189 of 1599 (11.8%), control 200 of 1484 (13.5%), seronegative patients. Horby et al., 6/16/2021, Randomized Controlled Trial, United Kingdom, Europe, peer-reviewed, 34 authors.
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6/15	Review	Zaidi et al., The Journal of Antibiotics, doi:10.1038/s41429-021-00430-5 (Review) (Peer Reviewed)	review	The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article
	Details Extensive review of 20 mechanisms of action of ivermectin for SARS-CoV-2.
6/15	Details Source PDF Review Review
	Zaidi et al., The Journal of Antibiotics, doi:10.1038/s41429-021-00430-5 (Review) (Peer Reviewed)
	The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article
	Extensive review of 20 mechanisms of action of ivermectin for SARS-CoV-2. Zaidi et al., 6/15/2021, peer-reviewed, 2 authors.
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6/15	In Vitro	Panchariya et al., bioRxiv, doi:10.1101/2021.06.15.448551 (Preprint) (In Vitro)	in vitro	Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro
	Details In Silico and In Vitro study showing that ionic zinc inhibits SARS-CoV-2 main protease (Mpro) and inhibits viral replication. Zinc acetate inhibited viral replication in Vero E6 cells, while zinc glycinate and zinc gluconate did not at n..
6/15	Details Source PDF In Vitro In Vitro
	Panchariya et al., bioRxiv, doi:10.1101/2021.06.15.448551 (Preprint) (In Vitro)
	Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro
	In Silico and In Vitro study showing that ionic zinc inhibits SARS-CoV-2 main protease (Mpro) and inhibits viral replication. Zinc acetate inhibited viral replication in Vero E6 cells, while zinc glycinate and zinc gluconate did not at non-toxic concentrations. The combination of zinc acetate with zinc ionophore quercetin signficantly improved inhibition at low concentrations. Panchariya et al., 6/15/2021, preprint, 14 authors.
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6/15	Early	Aref et al., International Journal of Nanomedicine, doi:10.2147/IJN.S313093 (Peer Reviewed)	recov. time, ↓63.2%, p=0.0001	Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19
	Details RCT 114 patients in Egypt, 57 treated with ivermectin mucoadhesive nanosuspension intranasal spray, showing faster recovery and viral clearance with treatment. NCT04716569.
6/15	Details Source PDF Early treatment study Early treatment study
	Aref et al., International Journal of Nanomedicine, doi:10.2147/IJN.S313093 (Peer Reviewed)
	Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19
	RCT 114 patients in Egypt, 57 treated with ivermectin mucoadhesive nanosuspension intranasal spray, showing faster recovery and viral clearance with treatment. NCT04716569. relative duration of fever, 63.2% lower, relative time 0.37, p < 0.001, treatment 57, control 57. risk of no virological cure, 78.6% lower, RR 0.21, p = 0.004, treatment 3 of 57 (5.3%), control 14 of 57 (24.6%). Aref et al., 6/15/2021, Randomized Controlled Trial, Egypt, Middle East, peer-reviewed, 7 authors.
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6/14	Levels	Campi et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06281-7 (Peer Reviewed)	death, ↓24.3%, p=0.53	Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy
	Details Prospective study of 103 hospitalized patients in Italy, showing very high prevalence of vitamin D deficiency, and increased severity for lower vitamin D levels.
6/14	Details Source PDF Levels Analysis of outcomes based on serum levels
	Campi et al., BMC Infectious Diseases, doi:10.1186/s12879-021-06281-7 (Peer Reviewed)
	Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy
	Prospective study of 103 hospitalized patients in Italy, showing very high prevalence of vitamin D deficiency, and increased severity for lower vitamin D levels. risk of death for severe patients, 24.3% lower, RR 0.76, p = 0.53, treatment 6 of 39 (15.4%), control 13 of 64 (20.3%), >20ng/mL. risk of ICU for severe patients, 53.1% lower, RR 0.47, p < 0.001, treatment 12 of 39 (30.8%), control 42 of 64 (65.6%), >20ng/mL. Campi et al., 6/14/2021, prospective, Italy, Europe, peer-reviewed, 21 authors.
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6/9	Late	Saib et al., PLOS ONE, doi:10.1371/journal.pone.0252388 (Peer Reviewed)	int./death, ↑125.0%, p=0.23	Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective study
	Details 203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding.
6/9	Details Source PDF Late treatment study Late treatment study
	Saib et al., PLOS ONE, doi:10.1371/journal.pone.0252388 (Peer Reviewed)
	Lack of efficacy of hydroxychloroquine and azithromycin in patients hospitalized for COVID-19 pneumonia: A retrospective study
	203 hospitalized patients in France, not showing significant differences with treatment. Confounding by indication is likely. Authors do not discuss confounding. risk of combined intubation/death, 125.0% higher, RR 2.25, p = 0.23, treatment 9 of 52 (17.3%), control 4 of 52 (7.7%), PSM. Saib et al., 6/9/2021, prospective, France, Europe, peer-reviewed, 9 authors.
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6/8	Late	Singh et al., medRxiv, doi:0.1101/2021.06.06.21258091 (Preprint)	death, ↓47.5%, p=0.45	Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial)
	Details Very small early terminated RCT in India, showing lower mortality but without statistical significance with the very small sample size. Time since symptom onset is not provided. The recovery percentage for non-severe group B (86.7%) does ..
6/8	Details Source PDF Late treatment study Late treatment study
	Singh et al., medRxiv, doi:0.1101/2021.06.06.21258091 (Preprint)
	Safety and efficacy of antiviral therapy alone or in combination in COVID-19 - a randomized controlled trial (SEV COVID Trial)
	Very small early terminated RCT in India, showing lower mortality but without statistical significance with the very small sample size. Time since symptom onset is not provided. The recovery percentage for non-severe group B (86.7%) does not match any number of recoveries, we have used the closest number (15/17). risk of death, 47.5% lower, RR 0.53, p = 0.45, treatment 3 of 20 (15.0%), control 6 of 21 (28.6%), severe. risk of death, 50.0% lower, RR 0.50, p = 0.48, treatment 3 of 37 (8.1%), control 6 of 37 (16.2%), all patients. risk of no recovery, 14.1% lower, RR 0.86, p = 0.76, treatment 9 of 20 (45.0%), control 11 of 21 (52.4%), severe. risk of no recovery, 8.3% lower, RR 0.92, p = 1.00, treatment 11 of 37 (29.7%), control 12 of 37 (32.4%), all patients. Singh et al., 6/8/2021, Randomized Controlled Trial, India, South Asia, preprint, 13 authors, this trial uses multiple treatments in the treatment arm (combined with ribavirin) - results of individual treatments may vary.
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6/7	Late	Al Sulaiman et al., Research Square, doi:10.21203/rs.3.rs-572942/v1 (Preprint)	death, ↓35.0%, p=0.05	Evaluation of Zinc Sulfate as an Adjunctive Therapy in COVID-19 Critically Ill Patients: a Two Center Propensity-score Matched Study
	Details Retrospective 266 ICU patients showing lower mortality with zinc treatment (very close to statistical significance), and higher odds of acute kidney injury.
6/7	Details Source PDF Late treatment study Late treatment study
	Al Sulaiman et al., Research Square, doi:10.21203/rs.3.rs-572942/v1 (Preprint)
	Evaluation of Zinc Sulfate as an Adjunctive Therapy in COVID-19 Critically Ill Patients: a Two Center Propensity-score Matched Study
	Retrospective 266 ICU patients showing lower mortality with zinc treatment (very close to statistical significance), and higher odds of acute kidney injury. risk of death, 35.0% lower, RR 0.65, p = 0.05, treatment 35 of 130 (26.9%), control 45 of 129 (34.9%), adjusted, 30 day, PSM, multivariable Cox proportional hazards. risk of mechanical ventilation, 23.0% lower, RR 0.77, p = 0.52, treatment 20 of 57 (35.1%), control 23 of 54 (42.6%), adjusted, among non-mechanically ventilated patients within 24 hours of ICU admission. Al Sulaiman et al., 6/7/2021, retrospective, Saudi Arabia, Middle East, preprint, 10 authors.
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6/7	PrEP	Dinesh et al., Journal of the Association of Physicians of India (Peer Reviewed)	cases, ↓60.1%, p<0.0001	Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers – A Multicentric Cohort Study Assessing Effectiveness and Safety
	Details Prophylaxis study with 2,727 Indian healthcare workers, showing lower risk of COVID-19 cases with treatment, and increasingly lower risk for longer durations of HCQ prophylaxis. The appendices are not currently available.
6/7	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Dinesh et al., Journal of the Association of Physicians of India (Peer Reviewed)
	Hydroxychloroquine for SARS CoV2 Prophylaxis in Healthcare Workers – A Multicentric Cohort Study Assessing Effectiveness and Safety
	Prophylaxis study with 2,727 Indian healthcare workers, showing lower risk of COVID-19 cases with treatment, and increasingly lower risk for longer durations of HCQ prophylaxis. The appendices are not currently available. risk of COVID-19 case, 60.1% lower, RR 0.40, p < 0.001, treatment 247 of 617 (40.0%), control 611 of 1473 (41.5%), adjusted, OR converted to RR, >=6 weeks, logistic regression. risk of COVID-19 case, 35.1% lower, RR 0.65, p < 0.001, treatment 88 of 185 (47.6%), control 611 of 1473 (41.5%), adjusted, OR converted to RR, 4-5 weeks, logistic regression. risk of COVID-19 case, 23.2% lower, RR 0.77, p = 0.002, treatment 80 of 181 (44.2%), control 611 of 1473 (41.5%), adjusted, OR converted to RR, 2-3 weeks, logistic regression. Dinesh et al., 6/7/2021, prospective, India, South Asia, peer-reviewed, 18 authors.
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6/7	Levels	Dror et al., medRxiv, doi:10.1101/2021.06.04.21258358 (Preprint)	severe case, ↓85.1%, p<0.0001	Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness
	Details Retrospective 253 hospitalized patients in Israel showing higher mortality and higher risk of severe cases with vitamin D deficiency. Vitamin D levels were measured 14 to 730 days before the COVID-19 test. Adjusted results are only provid..
6/7	Details Source PDF Levels Analysis of outcomes based on serum levels
	Dror et al., medRxiv, doi:10.1101/2021.06.04.21258358 (Preprint)
	Pre-infection 25-hydroxyvitamin D3 levels and association with severity of COVID-19 illness
	Retrospective 253 hospitalized patients in Israel showing higher mortality and higher risk of severe cases with vitamin D deficiency. Vitamin D levels were measured 14 to 730 days before the COVID-19 test. Adjusted results are only provided for severity. risk of severe or critical case, 85.1% lower, RR 0.15, p < 0.001, treatment 109 of 120 (90.8%), control 76 of 133 (57.1%), OR converted to RR, >40ng/mL vs. <20ng/mL, multivariate logistic regression. Dror et al., 6/7/2021, retrospective, Israel, Middle East, preprint, 18 authors.
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6/6	Levels	Diaz-Curiel, Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2021.105928 (Peer Reviewed)	ICU, ↓73.2%, p=0.02	The relationship between 25(OH) vitamin D levels and COVID-19 onset and disease course in Spanish patients
	Details Retrospective 1,549 patients in Spain showing that the frequency of vitamin D deficiency was higher in admitted patients compared to the overall Spanish population, and that vitamin D deficiency was associated with increased risk of ICU a..
6/6	Details Source PDF Levels Analysis of outcomes based on serum levels
	Diaz-Curiel, Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2021.105928 (Peer Reviewed)
	The relationship between 25(OH) vitamin D levels and COVID-19 onset and disease course in Spanish patients
	Retrospective 1,549 patients in Spain showing that the frequency of vitamin D deficiency was higher in admitted patients compared to the overall Spanish population, and that vitamin D deficiency was associated with increased risk of ICU admission amongst admitted patients. Adjusted vitamin D levels were lower in deceased patients, but statistical significance was not reached (authors provide only average levels, they do not provide mortality analysis based on deficiency). risk of ICU admission, 73.2% lower, RR 0.27, p = 0.02, treatment 3 of 214 (1.4%), control 91 of 1017 (8.9%), OR converted to RR, >30ng/mL vs. <20ng/mL. Diaz-Curiel et al., 6/6/2021, retrospective, Spain, Europe, peer-reviewed, 8 authors.
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6/6	N/A	Hariyanto et al., Reviews In Medical Virology, doi:10.1002/rmv.2265 (Peer Reviewed)	death, ↓69.0%, p=0.001	Ivermectin and outcomes from Covid-19 pneumonia: A systematic review and meta-analysis of randomized clinical trial studies
	Details Systematic review and meta analysis of 19 RCTs showing mortality RR 0.31 [0.15-0.62].
6/6	Details Source PDF N/A N/A
	Hariyanto et al., Reviews In Medical Virology, doi:10.1002/rmv.2265 (Peer Reviewed)
	Ivermectin and outcomes from Covid-19 pneumonia: A systematic review and meta-analysis of randomized clinical trial studies
	Systematic review and meta analysis of 19 RCTs showing mortality RR 0.31 [0.15-0.62]. risk of death, 69.0% lower, RR 0.31, p = 0.001. Hariyanto et al., 6/6/2021, peer-reviewed, 5 authors.
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6/4	Levels	Kotur et al., Frontiers in Nutrition, doi:10.3389/fnut.2021.689419 (Peer Reviewed)		Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity
	Details Analysis of variants in genes significant for the status of vitamin D in 120 Serbian COVID-19 patients, showing that vitamin D related genetic variants DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 were associated with severe COVID-19 in ..
6/4	Details Source PDF Levels Analysis of outcomes based on serum levels
	Kotur et al., Frontiers in Nutrition, doi:10.3389/fnut.2021.689419 (Peer Reviewed)
	Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity
	Analysis of variants in genes significant for the status of vitamin D in 120 Serbian COVID-19 patients, showing that vitamin D related genetic variants DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 were associated with severe COVID-19 in adults. Kotur et al., 6/4/2021, peer-reviewed, 13 authors.
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6/4	Late	Lagier et al., Preprint (Preprint)	death, ↓32.0%, p=0.004	Outcomes of 2,111 COVID-19 hospitalised patients treated with 2 hydroxychloroquine/azithromycin and other regimens in Marseille, France: a 3 monocentric retrospective analysis
	Details Retrospective 2,011 hospitalized patients in France, median age 67, showing lower mortality with HCQ+AZ, and further benefit with the addition of zinc.
6/4	Details Source PDF Late treatment study Late treatment study
	Lagier et al., Preprint (Preprint)
	Outcomes of 2,111 COVID-19 hospitalised patients treated with 2 hydroxychloroquine/azithromycin and other regimens in Marseille, France: a 3 monocentric retrospective analysis
	Retrospective 2,011 hospitalized patients in France, median age 67, showing lower mortality with HCQ+AZ, and further benefit with the addition of zinc. risk of death, 32.0% lower, RR 0.68, p = 0.004, treatment 93 of 1270 (7.3%), control 146 of 841 (17.4%), adjusted, weighted multivariate Cox proportional hazards model. Lagier et al., 6/4/2021, retrospective, France, Europe, preprint, 32 authors.
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6/4	Late	Byakika-Kibwika et al., Research Square, doi:10.21203/rs.3.rs-506195/v1 (Preprint)	recov. time, 0.0%, p=0.91	Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial
	Details Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatm..
6/4	Details Source PDF Late treatment study Late treatment study
	Byakika-Kibwika et al., Research Square, doi:10.21203/rs.3.rs-506195/v1 (Preprint)
	Safety and Efficacy of Hydroxychloroquine for Treatment of Non-Severe COVID-19 in Adults in Uganda: A Randomized Open Label Phase II Clinical Trial
	Small 105 patient RCT in Uganda showing no significant differences. No mortality was reported. The patients were very young (median age 32), recovering in a median time of 3 days with standard of care, so there is little room for a treatment to make improvements. Time since symptom onset is not specified, but the distribution of symptoms at baseline suggests that the enrollment is relatively late within a cohort of low risk patients. recovery time, no change, relative time 1.00, p = 0.91, treatment 36, control 29. relative improvement in Ct value, 29.3% lower, RR 0.71, p = 0.47, treatment 15, control 15. risk of COVID-19 case, 2.6% higher, RR 1.03, p = 1.00, treatment 35 of 55 (63.6%), control 31 of 50 (62.0%), day 6. risk of COVID-19 case, 6.7% higher, RR 1.07, p = 0.85, treatment 27 of 55 (49.1%), control 23 of 50 (46.0%), day 10. Byakika-Kibwika et al., 6/4/2021, Randomized Controlled Trial, Uganda, Africa, preprint, 17 authors.
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6/3	Late	Sivapalan et al., European Respiratory Journal, doi:10.1183/13993003.00752-2021 (Peer Reviewed)	death, ↓92.0%, p=0.32	Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19–a randomised double-blinded placebo-controlled trial
	Details Early terminated late stage (8 days from onset, 59% on oxygen) RCT not showing statistically significant differences. NCT04322396. NNF20SA0062834.
6/3	Details Source PDF Late treatment study Late treatment study
	Sivapalan et al., European Respiratory Journal, doi:10.1183/13993003.00752-2021 (Peer Reviewed)
	Azithromycin and hydroxychloroquine in hospitalised patients with confirmed COVID-19–a randomised double-blinded placebo-controlled trial
	Early terminated late stage (8 days from onset, 59% on oxygen) RCT not showing statistically significant differences. NCT04322396. NNF20SA0062834. risk of death, 92.0% lower, RR 0.08, p = 0.32, treatment 1 of 61 (1.6%), control 2 of 56 (3.6%), adjusted. risk of ICU admission, 22.4% higher, RR 1.22, p = 1.00, treatment 4 of 61 (6.6%), control 3 of 56 (5.4%). relative days alive and discharged from hospital within 14 days (inverse), 8.4% higher, RR 1.08, p = 0.36, treatment 61, control 56, adjusted. Sivapalan et al., 6/3/2021, Double Blind Randomized Controlled Trial, Denmark, Europe, peer-reviewed, 32 authors.
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6/2	PrEP	Fasano et al., Movement Disorders, doi:10.1002/mds.28176 (Peer Reviewed)	cases, ↓42.0%, p=0.05	COVID-19 in Parkinson’s Disease Patients Living in Lombardy, Italy
	Details Retrospective phone survey of 1,486 Parkinson's disease patients in Italy, showing lower risk of COVID-19 cases with vitamin D supplementation. This paper also presents a case control study of PD patients and family member control patients.
6/2	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Fasano et al., Movement Disorders, doi:10.1002/mds.28176 (Peer Reviewed)
	COVID-19 in Parkinson’s Disease Patients Living in Lombardy, Italy
	Retrospective phone survey of 1,486 Parkinson's disease patients in Italy, showing lower risk of COVID-19 cases with vitamin D supplementation. This paper also presents a case control study of PD patients and family member control patients. risk of COVID-19 case, 42.0% lower, RR 0.58, p = 0.05, treatment 13 of 329 (4.0%), control 92 of 1157 (8.0%), OR converted to RR. Fasano et al., 6/2/2021, retrospective, Italy, Europe, peer-reviewed, 7 authors.
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6/2	Late	Abd-Elsalam et al., Journal of Medical Virology, doi:10.1002/jmv.27122 (Peer Reviewed)	death, ↓25.0%, p=0.70	Clinical Study Evaluating the Efficacy of Ivermectin in COVID-19 Treatment: A Randomized Controlled Study
	Details RCT 164 hospitalized patients in Egypt showing lower mortality and shorter hospitalization, but without statistical significance. There were no serious adverse effects. Authors suggest the low dosage may have resulted in lower efficacy th..
6/2	Details Source PDF Late treatment study Late treatment study
	Abd-Elsalam et al., Journal of Medical Virology, doi:10.1002/jmv.27122 (Peer Reviewed)
	Clinical Study Evaluating the Efficacy of Ivermectin in COVID-19 Treatment: A Randomized Controlled Study
	RCT 164 hospitalized patients in Egypt showing lower mortality and shorter hospitalization, but without statistical significance. There were no serious adverse effects. Authors suggest the low dosage may have resulted in lower efficacy than other trials, and recommend increased dosage in future trials. Time from symptom onset is not specified. risk of death, 25.0% lower, RR 0.75, p = 0.70, treatment 3 of 82 (3.7%), control 4 of 82 (4.9%), OR converted to RR, logistic regression. risk of mechanical ventilation, no change, RR 1.00, p = 1.00, treatment 3 of 82 (3.7%), control 3 of 82 (3.7%). hospitalization time, 19.6% lower, relative time 0.80, p = 0.09, treatment 82, control 82. Abd-Elsalam et al., 6/2/2021, Randomized Controlled Trial, Egypt, Middle East, peer-reviewed, 16 authors.
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6/1	PrEP	Korkmaz et al., Authorea, doi:10.22541/au.162257516.68665404/v1 (Preprint)	death, ↓82.1%, p=0.19	The effect of Hydroxychloroquine use due to rheumatic disease on the risk of Covid-19 infection and its course
	Details Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases for HCQ users.
6/1	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Korkmaz et al., Authorea, doi:10.22541/au.162257516.68665404/v1 (Preprint)
	The effect of Hydroxychloroquine use due to rheumatic disease on the risk of Covid-19 infection and its course
	Retrospective 683 patients in a rheumatology department, 384 chronic HCQ users and 299 control patients, showing no mortality for HCQ users vs. 2 deaths in the control group, and significantly fewer cases for HCQ users. risk of death, 82.1% lower, RR 0.18, p = 0.19, treatment 0 of 385 (0.0%), control 2 of 299 (0.7%), continuity correction due to zero event. risk of COVID-19 case, 93.7% lower, RR 0.06, p < 0.001, treatment 2 of 395 (0.5%), control 24 of 299 (8.0%). Korkmaz et al., 6/1/2021, retrospective, Turkey, Middle East, preprint, 4 authors.
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6/1	Levels	Butler-Laporte et al., PLOS Medicine, doi:10.1371/journal.pmed.1003605 (Peer Reviewed)		Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study
	Details Mendelian randomization study not finding significant differences in COVID-19 outcomes based on vitamin D level. This study does not compare patients with deficiency/insuffiency/sufficiency, only providing ORs for increase in D levels. Au..
6/1	Details Source PDF Levels Analysis of outcomes based on serum levels
	Butler-Laporte et al., PLOS Medicine, doi:10.1371/journal.pmed.1003605 (Peer Reviewed)
	Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study
	Mendelian randomization study not finding significant differences in COVID-19 outcomes based on vitamin D level. This study does not compare patients with deficiency/insuffiency/sufficiency, only providing ORs for increase in D levels. Authors note that their results do not apply to individuals with vitamin D deficiency. For some background on Mendelian randomization studies and their limitations see [1]. For reasons why Mendelian randomization may fail in this case, see [2]. Authors suggest that it may come down to the use of 25-OHD concentration in serum as a less than ideal proxy for vitamin D status of cells involved in the immune response. For most other purposes, it may not matter much that unbound (free) 25-OHD is the better predictor of vitamin D deficiency and the resulting unfavourable outcomes. But for the MR analysis, the genetic instrument is strongly dominated by variation in the GC gene which modulates the concentration of vitamin D-binding protein (VDBP) in blood and thereby indirectly the concentrations of 25-OHD and 1,25-dihydroxy vitamin D. Thus, the common GC alleles rs4588A and rs7041T are both associated with much lower than average vitamin D concentrations. In contrast, directly measured unbound (free) vitamin D concentrations are minimally affected by these alleles, if at all. Authors cite only 2 of the 25 vitamin D treatment studies (2 of 5 RCTs), including the only study reporting a negative effect. Authors indicate that they believe Murai et al. was a significant result, however that study used cholecalciferol with very late stage patients. In practice, calcifediol/calcitrol would be used due to the long delay in conversion of cholecalciferol, hence the study is not informative of either normal late stage treatment, or earlier treatment. That authors believe the study is important suggests a strong bias. [1] nature.com/articles/d41586-019-03754-3 [2] nutrition.bmj.com/content/bmjnph/early/2021/03/22/bmjnph-2021-000265.full.pdf Butler-Laporte et al., 6/1/2021, peer-reviewed.
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6/1	PrEP	Kamstrup et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.05.076 (Peer Reviewed)	hosp., ↑44.0%, p=0.25	Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort study
	Details Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for ex..
6/1	Details Source PDF Pre-Exposure Prophylaxis study Pre-Exposure Prophylaxis study
	Kamstrup et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.05.076 (Peer Reviewed)
	Hydroxychloroquine as a primary prophylactic agent against sars-cov-2 infection: a cohort study
	Retrospective HCQ users in Denmark, not showing a significant difference, however authors do not adjust for the very different baseline risk for systemic autoimmune disease patients. Authors appear unaware of research in the area, for example saying that "currently, no obvious connection exists between a known rheumatological disorder and the risk of contracting SARS-CoV-2". Many papers show that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, e.g., Ferri et al. show OR 4.42, p<0.001 [1]. Supplementary data is not currently available. [1] c19study.com/ferri.html risk of hospitalization, 44.0% higher, RR 1.44, p = 0.25, treatment 5488, control 54846. risk of COVID-19 case, 10.0% lower, RR 0.90, p = 0.23, treatment 188 of 5488 (3.4%), control 2040 of 54846 (3.7%), adjusted Cox proportional hazards regression. Kamstrup et al., 6/1/2021, retrospective, population-based cohort, Denmark, Europe, peer-reviewed, 21 authors.
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5/31	Late	Smith et al., medRxiv, doi:10.1101/2021.05.28.21258012 (Peer Reviewed)	death, ↓27.2%, p<0.0001	Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic
	Details Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level. Although authors mention immort..
5/31	Details Source PDF Late treatment study Late treatment study
	Smith et al., medRxiv, doi:10.1101/2021.05.28.21258012 (Peer Reviewed)
	Observational Study on 255 Mechanically Ventilated Covid Patients at the Beginning of the USA Pandemic
	Retrospective 255 mechanical ventilation patients in USA, showing that weight-adjusted HCQ+AZ improved survival by over 100%. QTc prolongation did not correlate with cumulative HCQ dose or HCQ serum level. Although authors mention immortal time bias, full details on the timing of HCQ administration is not provided and this is not fully addressed. Survival curves indicate immortal time bias will significantly change results, although the observed benefit appears to exceed the potential bias. risk of death, 27.2% lower, RR 0.73, p < 0.001, treatment 19 of 37 (51.4%), control 182 of 218 (83.5%), OR converted to RR, >3g HCQ and >1g AZ, multivariable cox proportional hazard regression. risk of death, 92.9% lower, RR 0.07, p < 0.001, ≥80mg/kg HCQ and >1g AZ. Smith et al., 5/31/2021, retrospective, USA, North America, peer-reviewed, 4 authors.
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5/29	Levels	Sooriyaarachchi et al., Clinical Nutrition ESPEN, doi:10.1016/j.clnesp.2021.05.011 (Peer Reviewed)		Impact of vitamin D deficiency on COVID-19
	Details Analysis of vitamin D deficiency and COVID-19 cases and deaths in 47 countries, showing vitamin D deficiency significantly associated with mortality.
5/29	Details Source PDF Levels Analysis of outcomes based on serum levels
	Sooriyaarachchi et al., Clinical Nutrition ESPEN, doi:10.1016/j.clnesp.2021.05.011 (Peer Reviewed)
	Impact of vitamin D deficiency on COVID-19
	Analysis of vitamin D deficiency and COVID-19 cases and deaths in 47 countries, showing vitamin D deficiency significantly associated with mortality. Sooriyaarachchi et al., 5/29/2021, peer-reviewed, 4 authors.
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5/28	Early	Pawar et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.669362 (Peer Reviewed)	death, ↓81.8%, p=0.02	Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial
	Details RCT 140 patients, 70 treated with curcumin and piperine (for absorption), showing faster recovery, lower progression, and lower mortality with treatment. Control group partients also received probiotics. CTRI/2020/05/025482.
5/28	Details Source PDF Early treatment study Early treatment study
	Pawar et al., Frontiers in Pharmacology, doi:10.3389/fphar.2021.669362 (Peer Reviewed)
	Oral Curcumin With Piperine as Adjuvant Therapy for the Treatment of COVID-19: A Randomized Clinical Trial
	RCT 140 patients, 70 treated with curcumin and piperine (for absorption), showing faster recovery, lower progression, and lower mortality with treatment. Control group partients also received probiotics. CTRI/2020/05/025482. risk of death, 81.8% lower, RR 0.18, p = 0.02, treatment 2 of 70 (2.9%), control 11 of 70 (15.7%). risk of death, 60.0% lower, RR 0.40, p = 0.39, treatment 2 of 15 (13.3%), control 5 of 15 (33.3%), severe group. risk of death, 90.9% lower, RR 0.09, p = 0.05, treatment 0 of 25 (0.0%), control 5 of 25 (20.0%), continuity correction due to zero event, moderate group. risk of death, 66.7% lower, RR 0.33, p = 1.00, treatment 0 of 30 (0.0%), control 1 of 30 (3.3%), continuity correction due to zero event, mild group. Pawar et al., 5/28/2021, Double Blind Randomized Controlled Trial, India, South Asia, peer-reviewed, 8 authors.
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5/28	Early	Sánchez-Zuno, J. Clinical Medicine, doi:10.3390/jcm10112378 (Peer Reviewed)	severe case, ↓89.4%, p=0.04	Vitamin D Levels in COVID-19 Outpatients from Western Mexico: Clinical Correlation and Effect of Its Supplementation
	Details Very small 42 PCR+ outpatient RCT in Mexico, 22 treated with vitamin D. Most patients had insufficient vitamin D levels, there were more symptoms in those with insufficient levels, and there were less cases with fever or with >3 symptoms ..
5/28	Details Source PDF Early treatment study Early treatment study
	Sánchez-Zuno, J. Clinical Medicine, doi:10.3390/jcm10112378 (Peer Reviewed)
	Vitamin D Levels in COVID-19 Outpatients from Western Mexico: Clinical Correlation and Effect of Its Supplementation
	Very small 42 PCR+ outpatient RCT in Mexico, 22 treated with vitamin D. Most patients had insufficient vitamin D levels, there were more symptoms in those with insufficient levels, and there were less cases with fever or with >3 symptoms at day 14 for treatment with vitamin D. risk of COVID-19 severe case, 89.4% lower, RR 0.11, p = 0.04, treatment 0 of 22 (0.0%), control 4 of 20 (20.0%), continuity correction due to zero event, risk of >3 symptoms at day 14. risk of no recovery, 80.8% lower, RR 0.19, p = 0.22, treatment 0 of 22 (0.0%), control 2 of 20 (10.0%), continuity correction due to zero event, risk of fever at day 14, Table S1. Sánchez-Zuno et al., 5/28/2021, Randomized Controlled Trial, Mexico, North America, peer-reviewed, 12 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 702 studies, 496 present results comparing with a control group, 437 are treatment studies, 59 analyze outcomes based on serum levels, and 45 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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