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Home   COVID-19 treatment studies  COVID-19 treatment studies  COVID-19 studies   Select treatmentSelect treatmentTreatmentsTreatments
Antiandrogens (meta) Metformin (meta)
Aspirin (meta) Molnupiravir (meta)
Bamlanivimab (meta) N-acetylcys.. (meta)
Bromhexine (meta) Nigella Sativa (meta)
Budesonide (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)
Melatonin (meta) Zinc (meta)

Other Treatments Global Adoption
COVID-19 early treatment: real-time analysis of 1,316 studies
Analysis of 32 COVID-19 early treatments, database of 393 potential treatments. 67 countries have approved early treatments. Recently added: Metformin: Alamgir Ojeda-Fernández Hydroxychlor..: Juneja Tyson Quercetin: Fazio (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 Ivermectin 66% [58-72%] 75 $1 57,459 Casirivimab/i.. 66% [44-79%] 14 $2,100 39,071 intravenous/subcutaneous Melatonin 63% [42-77%] 12 $1 13,597 Bamlanivimab 62% [37-77%] 11 $1,250 23,338 high variant dependence Curcumin 59% [30-76%] 9 $5 867 few trials/events 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 Sotrovimab 46% [-285-92%] 2 $2,100 1,417 intravenous Antiandrogens 46% [4-70%] 8 $5 5,900 Budesonide 45% [2-69%] 3 $4 8,751 few trials/events 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 Fluvoxamine 34% [7-53%] 6 $4 2,599 Molnupiravir 34% [-13-62%] 8 $700 3,015 Zinc 33% [16-47%] 23 $1 50,003 Colchicine 31% [12-46%] 12 $1 17,762 Favipiravir 28% [11-42%] 26 $20 6,386 Hydroxychlor.. 25% [21-30%] 305 $1 418,319 N-acetylcys.. 25% [9-39%] 8 $1 817 Aspirin 21% [8-33%] 23 $1 66,304 Probiotics 21% [10-31%] 14 $5 17,130 Remdesivir 20% [11-27%] 27 $3,120 98,777 Metformin 17% [11-22%] 25 $10 104,505 Vitamin C 11% [-1-22%] 29 $1 31,940 Conv. Plasma -1% [-15-12%] 14 $5,000 15,607 intravenous All studies combined (pooled effects, all stages) c19early.com Jan 16, 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 Bamlanivimab 79% [59-89%] 6 $1,250 17,653 high variant dependence Melatonin 78% [25-94%] 2 $1 91 very few trials/events Remdesivir 76% [39-90%] 2 $3,120 934 few trials/events Zinc 74% [-133-97%] 3 $1 982 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% [54-72%] 34 $1 54,783 Fluvoxamine 64% [-93-93%] 3 $4 824 very few trials/events Casirivimab/i.. 62% [40-76%] 8 $2,100 23,072 intravenous/subcutaneous Molnupiravir 55% [15-76%] 5 $700 2,724 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% [20-45%] 2 $5 323 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 16, 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 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 Bamlanivimab 71% [16-90%] 7 $1,250 21,451 high variant dependence Curcumin 70% [36-86%] 4 $5 434 N-acetylcys.. 67% [-36-92%] 4 $1 355 Nitazoxanide 63% [-7-87%] 4 $4 967 few trials/events Quercetin 59% [-55-89%] 4 $5 683 few trials/events Probiotics 59% [28-77%] 4 $5 539 few trials/events Ivermectin 59% [44-69%] 36 $1 44,744 Vitamin A 57% [-174-93%] 3 $2 267 few trials/events Molnupiravir 50% [-445-95%] 3 $700 1,901 very few trials/events 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 40% [14-58%] 10 $1 17,373 Budesonide 39% [-67-78%] 1 $4 1,586 very few trials/events Fluvoxamine 36% [14-53%] 3 $4 1,775 few trials/events Zinc 32% [16-45%] 12 $1 10,280 Hydroxychlor.. 22% [16-27%] 187 $1 292,307 Metformin 21% [15-28%] 20 $10 60,020 Aspirin 19% [5-31%] 20 $1 55,760 Remdesivir 19% [11-26%] 25 $3,120 98,073 Vitamin C 15% [-4-31%] 19 $1 15,083 Antiandrogens 5% [-46-39%] 3 $5 5,495 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 16, 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 very few trials/events Bamlanivimab 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 Zinc 79% [-47-97%] 1 $1 518 very 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.. 75% [60-84%] 13 $1 50,628 Proxalutamide 73% [-139-97%] 2 n/a 445 very few trials/events Casirivimab/i.. 73% [-48-95%] 4 $2,100 19,957 intravenous/subcutaneous Remdesivir 66% [4-88%] 1 $3,120 372 very 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 16, 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
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BUBudesonide 82% 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RDRemdesivir 76% 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IVMIvermectin 66% 30
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(H)CQHydroxychlor.. 64% 34
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FVFluvoxamine 64% 3
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CICasirivimab/i.. 62% 8
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MPMolnupiravir 55% 5
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FPVFavipiravir 45% 6
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Early treatments approved by >2 countries. 67 countries have officially approved treatments. Details.
Recent studies (see the individual treatment pages for all studies):

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
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
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
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)
cases, ↓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
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.
Dec 25
Late Cadegiani et al., Cureus, doi:10.7759/cureus.20691 (Peer Reviewed)
death, ↓78.0%, p<0.0001
Final Results of a Randomized, Placebo-Controlled, Two-Arm, Parallel Clinical Trial of Proxalutamide for Hospitalized COVID-19 Patients: A Multiregional, Joint Analysis of the Proxa-Rescue AndroCoV Trial
Details   RCT 778 hospitalized patients in Brazil, 423 treated with proxalutamide, showing significantly lower mortality and improved recovery with treatment. NCT04728802 and NCT05126628. Authors note that cases in this trial were predominantly the..
Dec 23
Late Self et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(21)00751-9 (Peer Reviewed)
death, ↑2.0%, p=0.96
Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial
Details   RCT with 182 sotrovimab patients and 178 control patients, median 8 days from symptom onset, showing no significant differences and terminated early due to futility. TICO. NCT04501978.
Dec 23
PrEP McKinnon et al., International Journal of Infectious Diseases, doi:10.1016/j.ijid.2021.12.343 (Peer Reviewed)
symp. case, ↓2.5%, p=1.00
Safety and Tolerability of Hydroxychloroquine in healthcare workers and first responders for the prevention of COVID-19: WHIP COVID-19 Study
Details   HCQ PrEP RCT with 201 weekly HCQ patients, 197 daily HCQ patients, and 200 control patients, concluding the prophylaxis is safe. There were no grade 3 or 4 AEs, SAEs, ER visits, or hospitalizations. There was only 4 confirmed cases, 2 in ..
Dec 22
In Silico Banerjee et al., Natural Product Research, doi:10.1080/14786419.2021.2018430 (Peer Reviewed)
In Silico
Nigellidine (Nigella sativa, black-cumin seed) docking to SARS CoV-2 nsp3 and host inflammatory proteins may inhibit viral replication/transcription
Details   In Silico study showing nigella sativa docking to SARS CoV-2 Nsp3 and host inflammatory proteins, which may inhibit viral replication.
Dec 22
Early Gottlieb et al., New England Journal of Medicine, doi:10.1056/NEJMoa2116846 (Peer Reviewed)
hosp./death, ↓87.0%, p=0.008
Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients
Details   RCT high-risk outpatients, 279 treated with remdesivir and 283 control patients, median 5 days from symptoms, showing significantly lower hospitalization with treatment. NCT04501952.
Dec 22
Late Ferrer et al., Scientific Reports, doi:10.1038/s41598-021-03461-y (Peer Reviewed)
viral load, ↓34.0%, p=0.82
Clinical evaluation of antiseptic mouth rinses to reduce salivary load of SARS-CoV-2
Details   Small very late (>50% 7+ days from symptom onset, 9 PVP-I patients) RCT testing mouthwashing with cetylpyridinium chloride, chlorhexidine, povidone-iodine, hydrogen peroxide, and distilled water, showing no significant differences. Over 3..
Dec 22
Meta Chiodini et al., Frontiers in Public Health, doi:10.3389/fpubh.2021.736665 (Peer Reviewed)
meta-analysis
Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes
Details   Meta analysis concluding that "patients with low vitamin D levels present an increased risk of ARDS requiring admission to intensive care unit (ICU) or mortality due to SARS-CoV-2 infection and a higher susceptibility to SARS-CoV-2 i..
Dec 21
Early Rockett et al., medRxiv, doi:10.1101/2021.12.18.21267628 (Preprint) Resistance conferring mutations in SARS-CoV-2 delta following sotrovimab infusion
Details   Retrospective 100 sotrovimab patients in Australia, 23 PCR+ more than 10 days post-infusion (68 with status unknown), showing rapid development of spike gene mutations that have been shown to confer high level resistance to sotrovimab in ..
Dec 21
Early Suzuki et al., medRxiv, doi:10.1101/2021.12.19.21268078 (Preprint)
death, ↑200.0%, p=1.00
Real-world clinical outcomes of treatment with casirivimab-imdevimab among patients with mild-to-moderate coronavirus disease 2019 during the Delta variant pandemic
Details   Retrospective 949 patients in Japan, 314 treated with casirivimab/imdevimab showing significantly lower risk of deterioration with treatment.
Dec 21
Late Sullivan et al., medRxiv, doi:10.1101/2021.12.10.21267485 (Preprint)
death, ↓85.7%, p=0.12
Randomized Controlled Trial of Early Outpatient COVID-19 Treatment with High-Titer Convalescent Plasma
Details   RCT 1,181 outpatients in the USA, mean 6 days from symptom onset, showing lower hospitalization with treatment. NCT04373460.
Dec 21
Late Chew et al., medRxiv, doi:10.1101/2021.12.17.21268009 (Preprint)
hosp., ↓25.5%, p=0.60
Bamlanivimab reduces nasopharyngeal SARS-CoV-2 RNA levels but not symptom duration in non-hospitalized adults with COVID-19
Details   RCT 317 outpatients in the USA showing faster viral load and inflammatory biomarker decline, but no significant differences in clinical outcomes. ACTIV-2/A5401. NCT04518410. Supplementary data is not currently available.
Dec 21
Meta Lee et al., medRxiv, doi:10.1101/2021.12.17.21268008 (Preprint) (meta analysis)
meta-analysis
Fluvoxamine for Outpatient COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-Analysis
Details   Systematic review and meta analysis of outpatient RCTs, showing hospitalization RR 0.75 [0.57-0.97]. For discussion see [1].
Dec 20
PEP Tolouian et al., SSRN, doi:10.2139/ssrn.3989 (Preprint)
death, ↓32.9%, p=0.76
Bromhexine, for Post Exposure COVID-19 Prophylaxis: A Randomized, Double-Blind, Placebo Control Trial
Details   PEP RCT with 372 close contacts of COVID+ patients, 187 treated with bromhexine, showing significantly lower cases with treatment. IRCT20120703010178N22.
Dec 20
In Vitro Sheward et al., bioRxiv, doi:10.1101/2021.12.19.473354 (Preprint) (In Vitro)
In Vitro
Variable loss of antibody potency against SARS-CoV-2 B.1.1.529 (Omicron)
Details   In Vitro study showing that omicron is substantially resistant to neutralization by monoclonal antibodies REGN10933, REGN10987, Ly-CoV016 and Ly-CoV555. S309 (the parent of Sotrovimab) had only 2-fold loss in potency.
Dec 19
Early Komagamine et al., Journal of General and Family Medicine, doi:10.1002/jgf2.516 (Peer Reviewed)
ventilation, ↓77.3%, p=0.51
The effect of casirivimab with imdevimab on disease progression in nonsevere COVID‐19 patients in a single hospital in Japan
Details   Combined retrospective/prospective study in Japan with 53 casirivimab/imdevimab patients and 75 control patients, showing significantly lower progression with treatment.
Dec 17
News Kintor, News Comments (News)
news
开拓药业普克鲁胺治疗新冠预计本月发布临床数据
Details   News report noting that real-world results for proxalutamide in Paraguay show signfiicantly lower mortality and are consistent with the results of previous studies in Brazil.
Dec 17
In Vitro VanBlargan et al., bioRxiv, doi:10.1101/2021.12.15.472828 (Preprint) (In Vitro)
In Vitro
An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies
Details   In vitro study (Vero-TMPRSS2 and Vero-hACE2-TMPRSS2) showing complete loss of inhibitory activity for B.1.1.529 omicron with LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59, ~12-fold decrease for COV2-2196/COV2-2130, and minimal ch..
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 1,316 studies, 865 present results comparing with a control group, 766 are treatment studies, and 99 analyze outcomes based on serum levels. There are 19 animal studies, 41 in silico studies, 78 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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