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Home   COVID-19 treatment studies  COVID-19 treatment studies  COVID-19 studies   Select treatmentSelect treatmentTreatmentsTreatments
Antiandrogens (meta) Melatonin (meta)
Aspirin (meta) Metformin (meta)
Bamlaniv../e.. (meta) Molnupiravir (meta)
Bromhexine (meta) N-acetylcys.. (meta)
Budesonide (meta) Nigella Sativa (meta)
Cannabidiol (meta) Nitazoxanide (meta)
Casirivimab/i.. (meta) Paxlovid (meta)
Colchicine (meta) Povidone-Iod.. (meta)
Conv. Plasma (meta) Probiotics (meta)
Curcumin (meta) Proxalutamide (meta)
Ensovibep (meta) Quercetin (meta)
Favipiravir (meta) Remdesivir (meta)
Fluvoxamine (meta) Sotrovimab (meta)
Hydroxychlor.. (meta) Vitamin A (meta)
Iota-carragee.. (meta) Vitamin C (meta)
Ivermectin (meta) Vitamin D (meta)
Lactoferrin (meta) Zinc (meta)
Other Treatments Global Adoption
COVID-19 early treatment: real-time analysis of 1,352 studies
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All studies   Early treatment   Mortality   Early mortality   Recently added   Recent studies   Adoption
Analysis of 34 COVID-19 early treatments, database of 429 potential treatments. 67 countries have approved early treatments. Recently added:
Melatonin:
Kumar Yadalam
Vitamin D:
Saponaro
Zinc:
PVSN
Ekemen Keleş
Lactoferrin:
Mirabelli
Ostrov
Vitamin C:
Goc
(more..)
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 mortality, morbidity, collateral damage, and risk of endemic status.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Paxlovid 83% [1-97%] 2 $700 2,939 very few trials/events Cost Studies Patients Improvement Relative Risk Iota-carragee.. 80% [11-96%] 1 $1 394 very few trials/events Proxalutamide 78% [70-84%] 3 n/a 1,223 few trials/events Quercetin 74% [36-90%] 8 $5 1,229 few trials/events Nigella Sativa 67% [48-79%] 4 $5 1,291 few trials/events Casirivimab/i.. 66% [45-80%] 15 $2,100 39,275 intravenous/subcutaneous Ivermectin 65% [57-72%] 76 $1 57,647 Melatonin 63% [42-77%] 12 $1 13,597 Bamlaniv../e.. 62% [37-77%] 11 $1,250 23,338 high variant dependence Vitamin A 59% [8-81%] 6 $2 15,923 Nitazoxanide 58% [-11-84%] 7 $4 1,508 Povidone-Iod.. 52% [36-64%] 12 $1 2,549 Curcumin 49% [24-66%] 10 $5 918 few trials/events Lactoferrin 48% [30-62%] 4 $5 786 Sotrovimab 46% [-285-92%] 2 $2,100 1,417 intravenous Antiandrogens 46% [4-70%] 8 $5 5,900 Ensovibep 45% [-276-92%] 2 $2,100 400 intravenous Bromhexine 45% [23-60%] 6 $5 663 few trials/events Vitamin D 44% [36-51%] 59 $1 123,354 Budesonide 36% [-5-61%] 4 $4 8,786 Zinc 35% [19-48%] 24 $1 52,031 Fluvoxamine 34% [7-53%] 6 $4 2,599 Molnupiravir 34% [-13-62%] 8 $700 3,015 mutagenic/teratogenic Colchicine 31% [13-45%] 13 $1 17,797 Favipiravir 28% [11-42%] 26 $20 6,386 Hydroxychlor.. 26% [22-30%] 306 $1 423,654 N-acetylcys.. 25% [9-39%] 8 $1 817 Vitamin C 24% [10-36%] 31 $1 32,573 Aspirin 21% [8-33%] 23 $1 66,304 Probiotics 21% [10-31%] 15 $5 17,480 Remdesivir 20% [11-27%] 27 $3,120 98,777 Metformin 17% [12-23%] 26 $10 104,580 Conv. Plasma -1% [-15-12%] 14 $5,000 15,607 intravenous Cannabidiol -19% [-1178-89%] 2 $25 1,153 few trials/events All studies combined (pooled effects, all stages) c19early.com Jan 26, 2022 Favors treatment Favors control
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.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Ensovibep 89% [-127-99%] 1 $2,100 400 intravenous Cost Studies Patients Improvement Relative Risk Sotrovimab 89% [-106-99%] 1 $2,100 1,057 intravenous Nigella Sativa 84% [52-95%] 3 $5 915 few trials/events Paxlovid 83% [1-97%] 2 $700 2,939 very few trials/events Budesonide 82% [21-96%] 1 $4 146 very few trials/events Vitamin D 81% [53-92%] 6 $1 16,864 Bromhexine 79% [28-94%] 2 $5 96 very few trials/events Vitamin A 79% [39-93%] 2 $2 240 very few trials/events Quercetin 79% [-82-98%] 2 $5 194 very few trials/events Bamlaniv../e.. 79% [59-89%] 6 $1,250 17,653 high variant dependence Melatonin 78% [25-94%] 2 $1 91 very few trials/events Lactoferrin 76% [-485-99%] 1 $5 121 very few trials/events Remdesivir 76% [39-90%] 2 $3,120 934 few trials/events Proxalutamide 73% [-139-97%] 2 n/a 445 very few trials/events Curcumin 71% [26-89%] 6 $5 707 few trials/events Povidone-Iod.. 71% [46-84%] 7 $1 878 few trials/events Antiandrogens 68% [41-83%] 2 $5 357 very few trials/events Ivermectin 66% [53-75%] 30 $1 27,832 Hydroxychlor.. 64% [54-71%] 35 $1 55,526 Fluvoxamine 64% [-93-93%] 3 $4 824 very few trials/events Casirivimab/i.. 63% [43-76%] 9 $2,100 23,276 intravenous/subcutaneous Zinc 61% [-16-87%] 4 $1 3,010 few trials/events Molnupiravir 55% [15-76%] 5 $700 2,724 mutagenic/teratogenic Nitazoxanide 49% [-95-87%] 5 $4 1,414 few trials/events Favipiravir 45% [11-66%] 6 $20 1,472 very few trials/events Vitamin C 43% [-23-73%] 3 $1 445 few trials/events Probiotics 34% [21-45%] 3 $5 673 few trials/events N-acetylcys.. 21% [1-37%] 2 $1 416 very few trials/events Metformin 6% [-61-45%] 1 $10 418 very few trials/events Conv. Plasma -93% [-687-53%] 3 $5,000 716 intravenous Early treatment studies (pooled effects) c19early.com Jan 26, 2022 Favors treatment Favors control
Random effects meta-analysis of early treatment studies (pooled effects). Treatments with ≤3 studies with distinct authors or with <50 control events are shown in grey. Pooled results across all outcomes are affected by the distribution of outcomes tested, please see detail pages for specific outcome analysis. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Paxlovid 96% [32-100%] 1 $700 2,085 very few trials/events Cost Studies Patients Improvement Relative Risk Ensovibep 89% [-127-99%] 1 $2,100 400 intravenous Nigella Sativa 87% [51-96%] 2 $5 732 few trials/events Lactoferrin 79% [-48-97%] 1 $5 547 very few trials/events Proxalutamide 78% [70-84%] 3 n/a 1,223 few trials/events Bromhexine 77% [-39-96%] 3 $5 550 very few trials/events Melatonin 75% [43-89%] 5 $1 1,730 Povidone-Iod.. 72% [8-92%] 2 $1 872 few trials/events Bamlaniv../e.. 71% [16-90%] 7 $1,250 21,451 high variant dependence N-acetylcys.. 67% [-36-92%] 4 $1 355 Nitazoxanide 63% [-7-87%] 4 $4 967 few trials/events Curcumin 59% [25-78%] 5 $5 485 Quercetin 59% [-55-89%] 4 $5 683 few trials/events Probiotics 59% [29-77%] 5 $5 889 Ivermectin 57% [43-68%] 37 $1 44,932 Vitamin A 57% [-174-93%] 3 $2 267 few trials/events Molnupiravir 50% [-445-95%] 3 $700 1,901 mutagenic/teratogenic Vitamin D 48% [34-60%] 34 $1 29,840 Casirivimab/i.. 48% [6-71%] 7 $2,100 32,895 intravenous/subcutaneous Sotrovimab 46% [-285-92%] 2 $2,100 1,417 intravenous Colchicine 39% [15-56%] 11 $1 17,408 Fluvoxamine 36% [14-53%] 3 $4 1,775 few trials/events Zinc 35% [21-47%] 13 $1 12,308 Vitamin C 30% [6-48%] 21 $1 15,716 Hydroxychlor.. 23% [17-28%] 190 $1 300,409 Metformin 22% [15-28%] 21 $10 60,095 Aspirin 19% [5-32%] 21 $1 55,872 Remdesivir 19% [11-26%] 25 $3,120 98,073 Budesonide 17% [-64-58%] 2 $4 1,621 few trials/events Antiandrogens 4% [-48-37%] 4 $5 5,543 few trials/events Conv. Plasma -1% [-15-12%] 14 $5,000 15,607 intravenous Favipiravir -3% [-33-20%] 13 $20 4,629 All mortality results (all stages) c19early.com Jan 26, 2022 Favors treatment Favors control
Random effects meta-analysis of all mortality results (all stages). Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Pooled results across all stages depend on the distribution of stages tested - for example late stage treatment may be less effective and if the majority of studies are late stage this may obscure the efficacy of early treatment. Please see the specific stage analyses. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Paxlovid 96% [32-100%] 1 $700 2,085 very few trials/events Cost Studies Patients Improvement Relative Risk Bromhexine 91% [-59-99%] 1 $5 78 very few trials/events Ensovibep 89% [-127-99%] 1 $2,100 400 intravenous Sotrovimab 89% [-106-99%] 1 $2,100 1,057 intravenous Povidone-Iod.. 88% [50-97%] 1 $1 606 very few trials/events Nigella Sativa 87% [51-96%] 2 $5 732 few trials/events Molnupiravir 86% [22-98%] 2 $700 1,610 mutagenic/teratogenic Bamlaniv../e.. 86% [50-96%] 4 $1,250 17,048 high variant dependence Vitamin A 86% [39-97%] 1 $2 140 very few trials/events Curcumin 84% [39-96%] 2 $5 314 few trials/events Quercetin 79% [-82-98%] 2 $5 194 very few trials/events Vitamin D 76% [37-91%] 4 $1 16,466 few trials/events Hydroxychlor.. 74% [61-83%] 14 $1 51,371 Proxalutamide 73% [-139-97%] 2 n/a 445 very few trials/events Casirivimab/i.. 73% [-48-95%] 4 $2,100 19,957 intravenous/subcutaneous Probiotics 67% [-716-99%] 1 $5 350 very few trials/events Remdesivir 66% [4-88%] 1 $3,120 372 very few trials/events Zinc 55% [36-67%] 2 $1 2,546 few trials/events Ivermectin 51% [30-65%] 11 $1 25,684 Nitazoxanide 41% [-1278-98%] 2 $4 873 very few trials/events Favipiravir 33% [-61-72%] 1 $20 774 very few trials/events Conv. Plasma -93% [-687-53%] 3 $5,000 716 intravenous Vitamin C -204% [-7189-87%] 1 $1 98 very few trials/events Early treatment mortality results c19early.com Jan 26, 2022 Favors treatment Favors control
Random effects meta-analysis of early treatment mortality results. Treatments with ≤3 studies with distinct authors or with <25 control events are shown in grey. Protocols typically combine multiple treatments which may be complementary and synergistic, and the SOC in studies often includes other treatments.
Treatment
Improvement
  (early)
Studies
  (early)
SSotrovimab 89% 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PLPaxlovid 83% 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BUBudesonide 82% 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RDRemdesivir 76% 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IVMIvermectin 66% 30
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(H)CQHydroxychlor.. 64% 35
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FVFluvoxamine 64% 3
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CICasirivimab/i.. 63% 9
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ZnZinc 61% 4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MPMolnupiravir 55% 5
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FPVFavipiravir 45% 6
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
V.CVitamin C 43% 3
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Early treatments approved by >2 countries. 67 countries have officially approved treatments. Details.
Recent studies (see the individual treatment pages for all studies):

Jan 25
 In Silico Kumar Yadalam et al., Saudi Journal of Biological Sciences, doi:10.1016/j.sjbs.2022.01.049 (Peer Reviewed)
In Silico
 Assessing the therapeutic potential of angomelatine, ramelteon, and melatonin against SARS-Cov-2
Details   In Silico study of melatonin, angomelatine, and ramelteon for SARS-CoV-2, predicting significant SARS-CoV-2 RBD and ACE2 binding with all three.
Jan 25
 PrEP, PEP Garcia-Albeniz et al., medRxiv, doi:10.1101/2020.09.29.20203869 (Preprint) (meta analysis)
cases, ↓28.0%, p=0.004
 Systematic review and meta-analysis of randomized trials of hydroxychloroquine for the prevention of COVID-19
Details   Systematic review and meta-analysis of HCQ prophylaxis RCTs showing a statistically significant reduction in cases for pre-exposure prophylaxis. For PEP trials there were very long treatment delays - in one trial about a third of partici..
Jan 24
 Levels Saponaro et al., Frontiers in Immunology, doi:10.3389/fimmu.2021.745713 (Peer Reviewed)
ARDS, ↓36.5%, p=0.43
 Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19?
Details   Retrospective 93 COVID-19 pneumonia patients in Italy, showing low vitamin D levels associated with severe ARDS, and significantly lower vitamin D levels for non-survivors.
Jan 24
 Animal Tatham et al., bioRxiv, doi:10.1101/2022.01.23.477397 (Preprint)
animal study
 Lack of Ronapreve (REGN-CoV; casirivimab and imdevimab) virological efficacy against the SARS-CoV 2 Omicron variant (B.1.1.529) in K18-hACE2 mice
Details   K18-hACE2 mouse study showing that casirivimab/imdevimab was not effective for omicron at doses 2x higher than those effective for previous variants.
Jan 23
 In Vitro Liu et al., bioRxiv, doi:10.1101/2022.01.20.477147 (Preprint) (In Vitro)
In Vitro
 SARS-CoV-2 Viral Genes Compromise Survival and Functions of Human Pluripotent Stem Cell-derived Cardiomyocytes via Reducing Cellular ATP Level
Details   In Vitro study showing that ivermectin and meclizine may be protective for heart muscle damage due to SARS-CoV-2.
Jan 22
 Levels PVSN et al., Biological Trace Element Research, doi:10.1007/s12011-022-03124-7 (Peer Reviewed) Comparative Analysis of Serum Zinc, Copper and Magnesium Level and Their Relations in Association with Severity and Mortality in SARS-CoV-2 Patients
Details   Analysis of 150 COVID+ hospitalized patients in India, showing lower zinc levels associated with higher severity.
Jan 22
 Levels Ekemen Keleş et al., European Journal of Pediatrics, doi:10.1007/s00431-021-04348-w (Peer Reviewed)
hosp., ↓75.3%, p=0.01
 Serum zinc levels in pediatric patients with COVID-19
Details   Prospective study of 100 COVID+ pediatric patients in Turkey, showing significantly increased risk of hospitalization for patients with zinc deficiency.
Jan 22
 Levels Juraj et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2022.01.044 (Peer Reviewed)
death, ↓19.0%, p=0.05
 COVID-19 pneumonia patients with 25(OH)D levels lower than 12 ng/ml are at increased risk of death
Details   Retrospective 357 COVID-19 pneumonia patients in Slovakia, showing higher mortality with vitamin D deficiency (<12ng/mL). All patients received vitamin D supplementation in hospital. In multivariable linear regression, vitamin D levels we..
Jan 21
 In Vitro Goc et al., European Journal of Microbiology and Immunology, doi:10.1556/1886.2021.00022 (Peer Reviewed) (In Vitro)
In Vitro
 Inhibitory effects of specific combination of natural compounds against SARS-CoV-2 and its Alpha, Beta, Gamma, Delta, Kappa, and Mu variants
Details   In Vitro study testing combinations of plant extracts and micronutrients with several variants of SARS-CoV-2. A combination of vitamin C, N-acetylcysteine, curcumin, quercetin, resveratrol, theaflavin, naringenin, baicalin, and broccoli e..
Jan 20
 PrEP Nguyen et al., Science Advances, doi:10.1126/sciadv.abi6110 (preprint 3/10/2021) (Peer Reviewed)
cases, ↓49.6%, p=0.006
 Cannabidiol inhibits SARS-CoV-2 replication through induction of the host ER stress and innate immune responses
Details   Retrospective 1,212 patients in the USA with a history of seizure-related conditions, showing patients treated with CBD100 had significantly lower incidence of COVID-19 cases compared to a matched control group. In Vitro study showing CB..
Jan 18
 PrEP Usman et al., Journal of Thrombosis and Thrombolysis, doi:10.1007/s11239-022-02631-7 (Peer Reviewed)
death, ↓59.8%, p=0.21
 Metformin use in patients hospitalized with COVID-19: lower inflammation, oxidative stress, and thrombotic risk markers and better clinical outcomes
Details   Retrospective 75 diabetes patients, 34 on metformin, showing improved clinical outcomes with treatment, without statistical significance.
Jan 18
 Late Zubair et al., Monaldi Archives for Chest Disease, doi:10.4081/monaldi.2022.2062 (Peer Reviewed)
death, ↑8.9%, p=1.00
 The effect of ivermectin on non-severe and severe COVID-19 disease and gender-based difference of its effectiveness
Details   Retrospective 188 hospitalized patients in Pakistan, 90 treated with ivermectin, showing no significant differences with treatment. The ivermectin group had more severe disease (66% vs 58%, with 6x higher risk for severe disease patients)..
Jan 17
 Late Asadirad et al., Phytotherapy Research, doi:10.1002/ptr.7375 (Peer Reviewed)
death, ↓25.9%, p=0.74
 Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial
Details   RCT 60 hospitalized patients in Iran, 30 treated with nano-curcumin, showing significant improvements in inflammatory cytokines, and improvements in clinical outcomes without statistical significance. 240 mg/day nano-curcumin for 7 days.
Jan 14
 Early O'Brien et al., JAMA, doi:10.1001/jama.2021.24939768 (Peer Reviewed)
hosp., ↓85.5%, p=0.25
 Effect of Subcutaneous Casirivimab and Imdevimab Antibody Combination vs Placebo on Development of Symptomatic COVID-19 in Early Asymptomatic SARS-CoV-2 Infection: A Randomized Clinical Trial
Details   RCT 204 asymptomatic COVID+ patients, 100 treated with subcutaneous casirivimab/imdevimab, showing lower development of symptoms, lower hospitalization, and faster viral clearance with treatment. Study conducted prior to widespread circul..
Jan 14
 Meta Lan et al., Journal of Medical Virology, doi:10.1002/jmv.27595 (Peer Reviewed)
meta-analysis
 Efficacy of Melatonin in the Treatment of Patients With COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Details   Systematic review and meta analysis including 3 of the 5 melatonin RCTs at the time, showing significantly higher recovery with treatment, and lower ICU admission and mortality without statistical signficance. The analysis only includes t..
Jan 13
 Early Tyson et al., Preprint (Preprint)
death, ↓99.8%, p<0.0001
 Low Rates of Hospitalization and Death in 4,376 COVID-19 Patients Given Early Ambulatory Medical and Supportive Care. A Case Series and Observational Study.
Details   Retrospective 4,376 patients with mild/moderate COVID-19 in the USA treated with multiple medications including HCQ/ivermectin, favipiravir, vitamin C, D, quercetin, zinc, mAbs, budesonide, dexamethasone, prednisone, and colchicine (exact..
Jan 12
 Late Honarkar Shafie et al., Phytotherapy Research, doi:10.1002/ptr.7374 (Peer Reviewed)
hosp. time, ↓28.9%, p=0.22
 Effect of nanocurcumin supplementation on the severity of symptoms and length of hospital stay in patients with COVID-19: A randomized double-blind placebo-controlled trial
Details   RCT 48 hospitalized patients in Iran, 24 treated with nanocurcumin, showing lower hospitalization time with treatment. The number of patients shown in Table 3 (31 and 27 for each arm) is inconsistent with the number reported as randomized..
Jan 12
 In Vitro Unal et al., bioRxiv, doi:10.1101/2022.01.11.475889 (Preprint) (In Vitro)
In Vitro
 Favipiravir, umifenovir and camostat mesylate: a comparative study against SARS-CoV-2
Details   In Vitro and In Silico study showing that the combination of favipiravir and umifenovir or camostat mesylate has greater antiviral efficacy than single drug treatment.
Jan 12
 Meta Zein et al., Diabetes & Metabolic Syndrome: Clinical Research & Reviews, doi:10.1016/j.dsx.2022.102395 (Peer Reviewed) (meta analysis)
meta-analysis
 Effect of colchicine on mortality in patients with COVID-19 – A systematic review and meta-analysis
Details   Systematic review and meta analysis showing that colchicine was associated with lower mortality in COVID-19 patients: All studies: RR 0.66 [95%CI 0.53, 0.83], p < 0.001; I2: 42% RCTs: RR 0.81 [95%CI 0.54, 1.20], p = 0.29; I2: 10% The RC..
Jan 11
 Late AbdelGhaffar et al., PLOS ONE, doi:10.1371/journal.pone.0262348 (Peer Reviewed)
death, ↓99.9%, p<0.0001
 Prediction of mortality in hospitalized Egyptian patients with Coronavirus disease-2019: A multicenter retrospective study
Details   Retrospective 3,712 hospitalized patients in Egypt, showing lower mortality with HCQ treatment in unadjusted results. According to the official treatment protocol, HCQ was recommended with higher risk and/or more serious cases.
Jan 11
 Early Bosaeed et al., Clinical Microbiology and Infection, doi:10.1016/j.cmi.2021.12.026 (Peer Reviewed)
ICU, ↑618.8%, p=0.11
 Efficacy of favipiravir in adults with mild COVID-19: a randomized, double-blind, multicenter, placebo-controlled trial clinical trial
Details   RCT with 112 favipiravir and 119 control patients showing no significant differences in outcomes. Viral clearance and clinical recovery for patients treated within 48 hours was better than those treated later. NCT04464408.
Jan 10
 In Vitro van Breemen et al., Journal of Natural Products, doi:10.1021/acs.jnatprod.1c00946 (Peer Reviewed) (In Vitro)
In Vitro
 Cannabinoids Block Cellular Entry of SARS-CoV-2 and the Emerging Variants
Details   In Vitro study showing that cannabigerolic acid and cannabidiolic acid inhibited SARS-CoV-2 entry into cells.
Jan 10
 PrEP Ojeda-Fernández et al., Diabetes, Obesity and Metabolism, doi:10.1111/dom.14648 (Peer Reviewed)
death, ↓16.2%, p<0.0001
 Metformin use is associated with a decrease in risk of hospitalization and mortality in COVID-19 diabetic patients: a population-based study in Lombardy
Details   Retrospective 31,966 COVID+ patients using anti-hyperglycemic drugs in Italy, showing lower mortality and ICU admission with metformin use.
Jan 10
 Early Novartis Press Release (News)
death, ↓89.0%, p=0.06
 Novartis and Molecular Partners report positive topline data from Phase 2 study for ensovibep (MP0420), a DARPin antiviral therapeutic for COVID-19
Details   EMPATHY Part A RCT with 407 patients, 301 treated with ensovibep, showing statistically significant viral load reduction (details not provided), and lower mortality and hospitalization. For discussion see [1].
Jan 7
 Review Hashimoto et al., Molecular Psychiatry, doi:10.1038/s41380-021-01432-3 (Review) (Peer Reviewed)
review
 Mechanisms of action of fluvoxamine for COVID-19: a historical review
Details   Review of the potential mechanisms of action of fluvoxamine for COVID-19.
Jan 7
 Late Vahedian-Azimi et al., Nutrients, doi:10.3390/nu14020256 (Peer Reviewed) Effectiveness of Curcumin on Outcomes of Hospitalized COVID-19 Patients: A Systematic Review of Clinical Trials
Details   Review of 6 COVID-19 curcumin studies showing that treatment resulted in significant improvement in symptoms, duration of hospitalization, and mortality, and a significant decrease in proinflammatory cytokines and increase in anti-inflamm..
Jan 7
 PrEP Juneja et al., Journal of Basic and Clinical Physiology and Pharmacology, doi:10.1515/jbcpp-2021-0221 (Peer Reviewed)
severe case, ↑141.8%, p=0.59
 Hydroxychloroquine pre-exposure prophylaxis provides no protection against COVID-19 among health care workers: a cross-sectional study in a tertiary care hospital in North India
Details   Retrospective 2,200 healthcare workers in India, 996 taking HCQ prophylaxis, showing no significant differences. There were large differences in the occupation of participants and therefore exposure, and the authors make no adjustments.
Jan 5
 PEP Wischmeyer et al., medRxiv, doi:10.1101/2022.01.04.21268275 (Preprint)
m/s case, ↓33.3%, p=0.15
 Daily Lactobacillus Probiotic versus Placebo in COVID-19-Exposed Household Contacts (PROTECT-EHC): A Randomized Clinical Trial
Details   RCT 182 COVID-19 exposed patients, 91 treated with daily probiotic Lactobacillus rhamnosus GG starting a median of 3 days from exposure, showing lower symptomatic COVID-19 with treatment. There were no hospitalizations or deaths. PROTECT-..
Jan 4
 PrEP Rondanelli et al., Life, doi:10.3390/life12010066 (Peer Reviewed)
symp. case, ↓92.9%, p=0.04
 Promising Effects of 3-Month Period of Quercetin Phytosome® Supplementation in the Prevention of Symptomatic COVID-19 Disease in Healthcare Workers: A Pilot Study
Details   RCT 120 healthcare workers, 60 treated with quercetin phytosome, showing lower risk of cases with treatment. Quercetin phytosome 250mg twice a day. NCT05037240.
Jan 3
 In Vitro Peacock et al., bioRxiv, doi:10.1101/2021.12.31.474653 (Preprint) (In Vitro)
In Vitro
 The SARS-CoV-2 variant, Omicron, shows rapid replication in human primary nasal epithelial cultures and efficiently uses the endosomal route of entry
Details   In Vitro study showing that omicron can efficiently enter cells via the endosomal route, independent of TMPRSS2.
Jan 3
 In Vitro Willett et al., medRxiv, doi:10.1101/2022.01.03.21268111 (Preprint) (In Vitro)
In Vitro
 The hyper-transmissible SARS-CoV-2 Omicron variant exhibits significant antigenic change, vaccine escape and a switch in cell entry mechanism
Details   In Vitro study showing that the entry process for omicron has moved towards TMPRSS2-independent fusion, indicating that TMPRSS2 inhibitors may be less effective for omicron.
Jan 3
 Animal Cecon et al., bioRxiv, doi:10.1101/2021.12.30.474561 (Preprint)
animal study
 Melatonin drugs inhibit SARS-CoV-2 entry into the brain and virus-induced damage of cerebral small vessels
Details   K18-hACE2 mouse study showing treatment with melatonin and derived drugs agomelatine and ramelteon inhibited SARS-CoV-2 infection in the brain.
Jan 1
 Levels Seal et al., Journal of General Internal Medicine, doi:10.1007/s11606-021-07170-0 (Peer Reviewed)
death, ↓45.1%, p=0.001
 Association of Vitamin D Status and COVID-19-Related Hospitalization and Mortality
Details   Retrospective 4,599 COVID+ veterans in the USA with vitamin D levels measured 15 to 90 days prior to testing positive, showing a significant independent inverse dose-response relationship between vitamin D levels (from 15 to 60ng/mL) and ..
Jan 1
 In Vitro Esharkawy et al., Bioorganic Chemistry, doi:10.1016/j.bioorg.2021.105587 (Peer Reviewed) (In Vitro)
In Vitro
 In vitro Potential Antiviral SARS-CoV-19- Activity of Natural Product Thymohydroquinone and Dithymoquinone from Nigela sativia
Details   In Vitro and In Silico study of nigella sativa components, showing anti-SARS-CoV-2 activity at non-cytotoxic nanomolar concentrations for thymohydroquinone with selectivity index 1.4.
Jan 1
 Late Bilir et al., Journal of Contemporary Medicine, doi:10.16899/jcm.990057 (Peer Reviewed)
death, ↓23.1%, p=0.26
 Does Vitamin D Supplementation Reduce Cytokine Storm and Mortality in Geriatric Intensive Care Patients Diagnosed with COVID-19
Details   Retrospective 80 elderly ICU patients in Turkey, 40 with vitamin D levels <30ng/ml received vitamin D treatment, showing no significant differences in outcomes. Although not statistically significant, results favored treatment which sugge..
Dec 31
 Late Wang et al., Annals of Palliative Medicine, doi:10.21037/apm-21-3373 (Peer Reviewed) The efficacy of probiotics in patients with severe COVID-19
Details   Retrospective 156 COVID-19 patients in China, showing that diarrhea was significantly more common in severe/critical cases, and for severe/critical patients experiencing diarrhea, the duration of diarrhea was shorter with probiotic treatm..
Dec 31
 Late Alsultan et al., Interdisciplinary Perspectives on Infectious Diseases, doi:10.1155/2021/2129006 (Peer Reviewed)
death, ↓35.7%, p=0.70
 Efficacy of Colchicine and Budesonide in Improvement Outcomes of Patients with Coronavirus Infection 2019 in Damascus, Syria: A Randomized Control Trial
Details   Small RCT 49 severe condition hospitalized patients in Syria, showing lower mortality with colchicine and shorter hospitalization time with both colchicine and budesonide (all of these were not statistically significant).
Dec 31
 Early Abbas et al., Indian Journal of Pharmaceutical Sciences, doi:10.36468/pharmaceutical-sciences.spl.416 (Peer Reviewed)
death, ↑4.0%, p=1.00
 The Effect of Ivermectin on Reducing Viral Symptoms in Patients with Mild COVID-19
Details   RCT 99 ivermectin and 103 control low risk patients in China, up to 7 days from symptom onset, showing statistically significant improvement in recovery with treatment, and non-statistically significant improvements in recovery time and d..
Dec 31
 PrEP Kerr et al., Research Gate, doi:10.13140/RG.2.2.26793.52327 (Preprint)
death, ↓45.0%, p=0.046
 COVID-19 In-Hospital Mortality Rate is Reduced by Prophylactic Use of Ivermectin: Findings From a City-Wide, Prospective Observational Study Using Propensity Score Matching (PSM)
Details   PSM retrospective 378 hospitalized patients in Brazil, showing lower mortality for patients that were on ivermectin prophylaxis before admission (not taking into account the lower risk of being hospitalized shown in the related larger stu..
Dec 31
 Early Efird et al., International Journal of Environmental Research and Public Health, doi:10.3390/ijerph19010447 (Peer Reviewed)
death, ↓48.9%, p=0.10
 The Interaction of Vitamin D and Corticosteroids: A Mortality Analysis of 26,508 Veterans Who Tested Positive for SARS-CoV-2
Details   Retrospective 26,508 COVID+ veterans in USA, showing lower mortality with vitamin D use after testing positive (defined as being administered ≥7 days or half of the survival time within 2 weeks after testing), with statistical significanc..
Dec 31
 Late Shimizu et al., Journal of Infection and Chemotherapy, doi:10.1016/j.jiac.2021.12.024 (Peer Reviewed)
death, ↓99.9%, p<0.001
 Ivermectin administration is associated with lower gastrointestinal complications and greater ventilator-free days in ventilated patients with COVID-19: A propensity score analysis
Details   Retrospective 88 ventilated COVID-19 patients in Japan, 39 treated with ivermectin within 3 days of admission, showing significantly reduced incidence of GI complications and mortality, and increased ventilator-free days with treatment.
Dec 30
 Animal Vermillion et al., Science Translational Medicine, doi:10.1126/scitranslmed.abl8282 (Peer Reviewed)
animal study
 Inhaled remdesivir reduces viral burden in a nonhuman primate model of SARS-CoV-2 infection
Details   African green monkey study of inhaled versus IV remdesivir, showing similar efficacy with inhalation. Comparable concentrations of the active triphosphate in the lower respiratory tract were found with ~20x lower dose using inhalation, an..
Dec 30
 Review Semiz, S., Biomolecular Concepts, doi:10.1515/bmc-2021-0017 (Review) (Peer Reviewed)
review
 SIT1 transporter as a potential novel target in treatment of COVID-19
Details   Review of the potential connections between SLC6A20/SIT1, ACE2, Type 2 Diabetes, and COVID-19 severity. This provides another potential mechanism of action for ivermectin as a partial agonist of glycine-gated chloride channels, interferin..
Dec 29
 Late Mustafa et al., Exploratory Research in Clinical and Social Pharmacy, doi:10.1016/j.rcsop.2021.100101 (Peer Reviewed)
death, ↓44.1%, p=0.28
 Pattern of medication utilization in hospitalized patients with COVID-19 in three District Headquarters Hospitals in the Punjab province of Pakistan
Details   Retrospective 444 hospitalized patients in Pakistan, showing lower mortality with aspirin treatment in unadjusted results, not reaching statistical significance.
Dec 28
 Late Baguma et al., Research Square, doi:10.21203/rs.3.rs-1193578/v1 (Preprint)
death, ↓96.8%, p=0.31
 Characteristics of the COVID-19 patients treated at Gulu Regional Referral Hospital, Northern Uganda: A cross-sectional study
Details   Retrospective COVID+ hospitalized patients in Uganda, showing no statistically significant difference in mortality with ivermectin, however there was only 7 patients receiving ivermectin.
Dec 28
 In Vitro Munafò et al., Research Square, doi:10.21203/rs.3.rs-1149846/v1 (Preprint) (In Vitro)
In Vitro
 Quercetin and Luteolin Are Single-digit Micromolar Inhibitors of the SARS-CoV-2 RNA-dependent RNA Polymerase
Details   In Vitro and In Silico study showing quercetin and luteolin inhibiting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp).
Dec 27
 Early Kintor, News Releease (News)
news
 Kintor Pharma Provides Update on One of its Three Multi-Regional Phase 3 Trials of Proxalutamide for COVID-19
Details   News release reporting on interim analysis of NCT04870606, showing that statistical criteria were not met, there was a very low event rate, and that Kintor plans to amend the protocol and continue to enroll higher risk patients.
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 1,352 studies, 884 present results comparing with a control group, 783 are treatment studies, and 101 analyze outcomes based on serum levels. There are 20 animal studies, 42 in silico studies, 86 in vitro studies, and 77 meta analyses.
Please send us corrections, updates, or comments. Vaccines and treatments are both 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 mortality, morbidity, collateral damage, and the risk of endemic status. 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. WCH and FLCCC provide treatment protocols.
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