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@CovidAnalysis

COVID-19 early treatment: real-time analysis of 4,504 studies

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Analysis of 81 COVID-19 early treatments, approvals in 118 countries, database of 7,847 treatments  
Recently added (more..)  Remdesivir  Nigella Sativa  HCQ  Zinc  Vitamin D
Sise
243 patient remdesivir late treatment RCT: no change in mortality (p=1), 18% lower combined mortality/intubation (p=0.61), and 16% improvement (p=0.5)
Sebghatollahi
150 patient nigella sativa late treatment RCT: 73% lower mortality (p=0.001), 77% lower ICU admission (p=0.0005), and 41% shorter hospitalization (p<0.0001)
Hitti
In Vitro study showing that HCQ reduces inflammation by inhibiting the double-stranded RNA-stimulated phosphorylation of tristetraprolin (TTP) and..
Ferreira
In Vitro and In Silico study showing synergistic antiviral effects of luteolin, vitamin C, magnesium, and zinc against SARS-CoV-2 3CLpro. Authors..
Wimalawansa
Review showing reduced efficacy of interventions with new variants and suggesting that regulators and health organizations should consider approval..
$0 $1,000 $2,000+ -25+% 0% 25% 50% Treatment cost (US$) Efficacy vs. cost for COVID-19 treatments Glenzocimab -60% ~$2,000+ PPIs -46% BMS mAbs -36% ~$2,000+ Acetaminophen -28% Lufotrelvir ~$2,000+ Losartan Cannabidiol Vitamin B9 Conv. Plasma $5,000 Acebilustat ~$2,000+ Ibuprofen Remdesivir $3,120 Ambavirumab/r.. Aspirin Molnupiravir mutagenic/teratogenic Favipiravir Famotidine Paxlovid Vitamin C NAC Sotrovimab $2,100 Nitric Oxide Colchicine Zinc HCQ Budesonide Probiotics Azvudine Sleep Antiandro.. Metformin Bebtelovimab Vitamin A Vitamin D Sunlight H. Peroxide Fluvox. H1RAs Exercise Curcumin Tixagevimab/c.. N. Sativa NaHCO₃ Melatonin Ensovibep ~$2,000+ Bamlanivimab/e.. Casirivimab/i.. $2,100 pH+ Quercetin Diet PVP-I Thermotherapy Ivermectin Regdanvimab $2,100 Lifestyle / free No prescription Prescription required High-cost Lower risk Higher risk c19early.org July 2024 COVID-19 involves the interplay of 50+ host/viral proteins andfactors, known to be modulated by many treatments. 0.6% of7,000+ proposed treatments show efficacy with ≥3 studies.Protocols combine treatments, none are 100% effective.c19early analyzes over 4,500 studies for 81 treatments.
$0 $1,000 $2,000+ -25+% 0% 25% 50% Treatment cost (US$) Efficacy vs. cost for COVID-19 treatments Glenzocimab -60% PPIs -46% BMS mAbs -36% Acetaminophen -28% Lufotrelvir Losartan Cannabidiol Vitamin B9 Conv. Plasma Acebilustat Ibuprofen Remdesivir Ambavirumab/r.. Aspirin Molnupiravir mutagenic/teratogenic Favipiravir Famotidine Paxlovid Vitamin C NAC Sotrovimab Nitric Oxide Colchicine Zinc HCQ Budesonide Probiotics Azvudine Sleep Antiandro.. Metformin Bebtelovimab Vitamin A Vitamin D Sunlight H. Peroxide Fluvox. H1RAs Exercise Curcumin Tixagevimab/c.. N. Sativa NaHCO₃ Melatonin Ensovibep Bamlan.. Casirivim.. pH+ Quercetin Diet PVP-I Thermotherapy Ivermectin Regdanvimab Lifestyle / free No prescription Prescription required High-cost Lower risk Higher risk c19early.org July 2024 COVID-19 involves the interplay of 50+ host/viral proteins/factors, modulated by many treatments. 0.6% of 7,000+treatments show efficacy in ≥3 studies. Protocols combinetreatments, none are 100% effective. c19early analyzes4,500+ studies for 81 treatments.
Azvudine Evusheld Sodium Bicarbonate Paxlovid Regdanvimab Vitamin B12 Sunlight Phthalocyanine Montelukast Alkalinization Fluvoxamine Famotidine Molnupiravir Quercetin Diet Bamlanivimab/e.. Hydrogen Peroxide Budesonide Probiotics Casirivimab/i.. Sleep Curcumin Povidone-Iodine Nigella Sativa Melatonin Antihistamine H1RAs Acetaminophen ↑risk Exercise Vitamin D Antiandrogens Vitamin C PPIs ↑risk Colchicine Ivermectin Metformin Zinc HCQ 2020 2021 2023 2024 Pooled outcomes Specific outcome RCT pooled RCT specific Statistically significant ≥10% improvement ≥3 studies c19early.org July 2024 Time when COVID-19 studies showed efficacy
Azvudine Evusheld Sodium Bicarb.. Paxlovid Regdanvimab Vitamin B12 Sunlight Phthalocyanine Montelukast Alkalinization Fluvoxamine Famotidine Molnupiravir Quercetin Diet Bamlanivimab/e.. Hydrogen Peroxide Budesonide Probiotics Casirivimab/i.. Sleep Curcumin Povidone-Iodine Nigella Sativa Melatonin H1RAs Acetaminophen ↑risk Exercise Vitamin D Antiandrogens Vitamin C PPIs ↑risk Colchicine Ivermectin Metformin Zinc HCQ 2020 2021 2023 2024 Pooled outcomes Specific outcome RCT pooled RCT specific Statistically significant ≥10% improvement ≥3 studies c19early.org July 2024 Time when COVID-19 studies showed efficacy
Timeline for when studies showed efficacy - details and limitations. 0.6% of treatments show efficacy.
July 2024
c19early.org
Cost per life saved from NNT in
studies to date
Melatonin
9
48%
  $8
Vitamin D
69
36%
  $11
Alkalinization
8
46%
  $11
Zinc
21
30%
  $15
Sodium Bicarb..
4
41%
  $17
Vitamin C
43
19%
  $18
Colchicine
43
28%
  $26
HCQ
247
26%
  $26
Ivermectin
53
47%
  $26
Aspirin
64
11%
  $33
Vitamin A
5
30%
  $45
Curcumin
8
63%
  $59
Famotidine
21
18%
  $94
Probiotics
8
61%
  $99
Quercetin
5
61%
  $127
Metformin
66
35%
  $133
Antiandrogens
32
37%
  $179
Nigella Sativa
5
57%
  $187
Fluvoxamine
10
44%
  $411
Budesonide
12
26%
  $574
Azvudine
15
32%
  $1,248
Favipiravir
39
11%
  $1,934
Tixagev../c..
10
42%
  $74,506
Regdanvimab
7
63%
  $139,860
Casirivimab/..
9
31%
  $203,958
Paxlovid
32
27%
  $206,705
Bamlaniv../e..
13
54%
  $301,549
Sotrovimab
11
49%
  $355,740
Bebtelovimab
4
60%
  $737,601
Remdesivir
63
3%
  $1,558,440
Molnupiravir
21
17%
  $2,400,867
Conv. Plasma
47
-1%
N/A
Acetaminophen
14
-24%
N/A
PPIs
20
-40%
N/A
Treatment cost times median NNT - details and limitations. 0.6% of treatments show efficacy.
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All clinical results for selected treatments. 0.6% of treatments show efficacy.
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0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Iota-carragee.. 80% [22-95%] 1 $1 394 very limited data Cost Studies Patients Improvement Relative Risk Chlorhexidine 79% [66-87%] 3 $1 509 limited data Proxalutamide 78% [70-83%] 4 $500 1,953 limited data Indomethacin 74% [-20-94%] 4 $5 605 limited data Cetylpyridin.. 68% [-620-99%] 1 $1 23 very limited data Regdanvimab 63% [51-71%] 11 $2,100 7,430 Ivermectin 60% [52-67%] 105 $1 220,423 Chlorpheniram.. 56% [46-64%] 3 $5 806 very limited data Thermotherapy 56% [9-78%] 4 $0 217 very limited data Povidone-Iod.. 51% [38-61%] 21 $1 3,249 Diet 50% [41-58%] 28 $0 693,236 Quercetin 49% [21-68%] 11 $5 1,436 Alkalinization 49% [36-59%] 14 $1 6,383 HH-120 49% [-60-84%] 2 $500 345 very limited data Bemnifosbuvir 47% [-57-82%] 3 $500 359 very limited data Casirivimab/i.. 47% [28-61%] 29 $2,100 59,056 variant dependent Bamlaniv../e.. 47% [25-62%] 21 $1,250 35,320 variant dependent Ensovibep 46% [-173-89%] 2 $2,100 885 limited data Adintrevimab 43% [-169-88%] 2 $2,100 2,483 intramuscular Melatonin 43% [30-54%] 18 $1 14,301 Bromhexine 43% [-5-69%] 7 $5 875 very limited data Sodium Bicarb.. 43% [24-57%] 7 $1 1,092 Nigella Sativa 43% [24-57%] 14 $5 3,333 Tixagev../c.. 43% [26-56%] 17 $855 29,530 variant dependent Propolis 41% [-13-69%] 3 $1 410 very limited data Curcumin 41% [30-51%] 27 $5 14,886 Montelukast 40% [15-58%] 8 $2 2,868 limited data Exercise 39% [34-44%] 66 $0 1,936,481 H1RAs 39% [23-52%] 15 $5 71,705 Fluvoxamine 39% [21-52%] 21 $4 38,283 Hydrogen Per.. 38% [5-59%] 7 $1 835 very limited data Phthalocyanine 38% [20-51%] 4 $5 5,245 Xiannuoxin 38% [-46-73%] 2 $106 1,027 very limited data Sunlight 37% [22-50%] 5 $0 19,665 Vitamin D 37% [31-42%] 122 $1 195,710 Vitamin A 36% [6-56%] 14 $2 22,297 Nitazoxanide 35% [-8-61%] 14 $4 3,632 Selenium 34% [-40-69%] 4 $1 21,452 Bebtelovimab 34% [-24-65%] 6 $1,200 13,329 intravenous Spironolactone 31% [15-44%] 12 $5 28,019 Metformin 30% [26-34%] 93 $10 282,079 Antiandrogens 30% [21-38%] 49 $5 120,172 Sleep 30% [22-38%] 15 $0 429,001 Vitamin B12 30% [5-48%] 4 $1 11,407 Azvudine 29% [15-40%] 20 $25 12,324 Probiotics 28% [18-37%] 26 $5 19,398 Budesonide 28% [18-36%] 15 $4 28,194 Hydroxychlor.. 28% [24-31%] 417 $1 536,655 Zinc 28% [18-36%] 45 $1 55,380 Colchicine 27% [18-36%] 56 $1 33,066 Andrographol.. 27% [-8-50%] 7 $5 1,245 Nitric Oxide 27% [-8-50%] 11 $11 2,201 Ensitrelvir 26% [-14-52%] 3 $500 1,450 very limited data Sotrovimab 26% [10-39%] 24 $2,100 54,452 variant dependent N-acetylcys.. 25% [14-35%] 24 $1 26,243 Lactoferrin 24% [-24-53%] 8 $5 1,419 Vitamin C 21% [14-27%] 72 $1 88,913 Leritrelvir 21% [3-35%] 2 $1,000 1,399 very limited data Paxlovid 17% [13-20%] 64 $1,390 125,388 independent trials refused Famotidine 17% [8-24%] 30 $5 114,119 UDCA 16% [4-26%] 15 $15 37,452 Favipiravir 14% [4-23%] 69 $20 30,778 worse w/longer followup Vitamin K 14% [0-25%] 2 $1 7,806 very limited data Molnupiravir 12% [3-20%] 43 $707 137,606 mutagenic/teratogenic Aspirin 11% [5-16%] 73 $1 186,700 Deuremidevir 11% [-1-21%] 2 $112 1,432 very limited data Ambavir../r.. 11% [-154-69%] 3 $1,380 1,531 intravenous Peg.. Lambda 7% [-138-63%] 4 $500 2,143 subcutaneous Remdesivir 1% [-7-9%] 74 $3,120 201,789 worse w/longer followup Ibuprofen 0% [-9-9%] 13 $1 54,707 Acebilustat 0% [-1462-94%] 1 $2,000 120 very limited data Conv. Plasma -1% [-5-3%] 48 $5,000 30,004 intravenous Vitamin B9 -11% [-47-15%] 11 $1 54,354 Cannabidiol -12% [-86-33%] 8 $25 16,883 Losartan -15% [-127-42%] 5 $5 665 very limited data Lufotrelvir -22% [-198-50%] 1 $2,000 58 intravenous Acetaminoph.. -28% [-41--17%] 27 $1 543,459 BMS mAbs -36% [-492-69%] 1 $2,100 210 subcutaneous PPIs -46% [-68--27%] 37 $5 221,083 Glenzocimab -60% [-236-24%] 1 $2,000 62 intravenous All studies (pooled effects, all stages) c19early.org July 2024 Favors treatment Favors control
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Iota-carragee.. 80% 1 very limited data Studies, Improvement Relative Risk Chlorhexidine 79% 3 limited data Proxalutamide 78% 4 limited data Indomethacin 74% 4 limited data Cetylpyridin.. 68% 1 very limited data Regdanvimab 63% 11 Ivermectin 60% 105 Chlorphenira.. 56% 3 very limited data Thermotherapy 56% 4 very limited data Povidone-Iod.. 51% 21 Diet 50% 28 Quercetin 49% 11 Alkalinization 49% 14 HH-120 49% 2 very limited data Bemnifosbuvir 47% 3 very limited data Casirivimab/.. 47% 29 variant dependent Bamlaniv../e.. 47% 21 variant dependent Ensovibep 46% 2 limited data Adintrevimab 43% 2 intramuscular Melatonin 43% 18 Bromhexine 43% 7 very limited data Sodium Bicar.. 43% 7 Nigella Sativa 43% 14 Tixagev../c.. 43% 17 variant dependent Propolis 41% 3 very limited data Curcumin 41% 27 Montelukast 40% 8 limited data Exercise 39% 66 H1RAs 39% 15 Fluvoxamine 39% 21 Hydrogen Per.. 38% 7 very limited data Phthalocyanine 38% 4 Xiannuoxin 38% 2 very limited data Sunlight 37% 5 Vitamin D 37% 122 Vitamin A 36% 14 Nitazoxanide 35% 14 Selenium 34% 4 Bebtelovimab 34% 6 intravenous Spironolactone 31% 12 Metformin 30% 93 Antiandrogens 30% 49 Sleep 30% 15 Vitamin B12 30% 4 Azvudine 29% 20 Probiotics 28% 26 Budesonide 28% 15 Hydroxychlor.. 28% 417 Zinc 28% 45 Colchicine 27% 56 Andrographol.. 27% 7 Nitric Oxide 27% 11 Ensitrelvir 26% 3 very limited data Sotrovimab 26% 24 variant dependent N-acetylcys.. 25% 24 Lactoferrin 24% 8 Vitamin C 21% 72 Leritrelvir 21% 2 very limited data Paxlovid 17% 64 independent trials refused Famotidine 17% 30 UDCA 16% 15 Favipiravir 14% 69 worse w/longer followup Vitamin K 14% 2 very limited data Molnupiravir 12% 43 mutagenic/teratogenic Aspirin 11% 73 Deuremidevir 11% 2 very limited data Ambavir../r.. 11% 3 intravenous Peg.. Lambda 7% 4 subcutaneous Remdesivir 1% 74 worse w/longer followup Ibuprofen 0% 13 Acebilustat 0% 1 very limited data Conv. Plasma -1% 48 intravenous Vitamin B9 -11% 11 Cannabidiol -12% 8 Losartan -15% 5 very limited data Lufotrelvir -22% 1 intravenous Acetaminoph.. -28% 27 BMS mAbs -36% 1 subcutaneous PPIs -46% 37 Glenzocimab -60% 1 intravenous All studies (pooled effects, all stages) c19early.org July 2024 Rotate device for details Favors treatment Favors control
Random effects meta-analysis of all studies (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. 0.6% of proposed treatments show efficacy in clinical studies.
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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. 0.6% of proposed treatments show efficacy in clinical studies.
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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. 0.6% of proposed treatments show efficacy in clinical studies.
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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. 0.6% of proposed treatments show efficacy in clinical studies.
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Random effects meta-analysis of prophylaxis 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. 0.6% of proposed treatments show efficacy in clinical studies.
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Random effects meta-analysis of prophylaxis 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. 0.6% of proposed treatments show efficacy in clinical studies.
LATE TREATMENT
Physician / TeamLocationPatients HospitalizationHosp. MortalityDeath
Dr. David Uip (*) Brazil 2,200 38.6% (850) Ref. 2.5% (54) Ref.
EARLY TREATMENT - 40 physicians/teams
Physician / TeamLocationPatients HospitalizationHosp. ImprovementImp. MortalityDeath ImprovementImp.
Dr. Roberto Alfonso Accinelli
0/360 deaths for treatment within 3 days		 Peru 1,265 0.6% (7) 77.5%
Dr. Mohammed Tarek Alam
patients up to 84 years old		 Bangladesh 100 0.0% (0) 100.0%
Dr. Oluwagbenga Alonge Nigeria 310 0.0% (0) 100.0%
Dr. Raja Bhattacharya
up to 88yo, 81% comorbidities		 India 148 1.4% (2) 44.9%
Dr. Flavio Cadegiani Brazil 3,450 0.1% (4) 99.7% 0.0% (0) 100.0%
Dr. Alessandro Capucci Italy 350 4.6% (16) 88.2%
Dr. Shankara Chetty South Africa 8,000 0.0% (0) 100.0%
Dr. Deborah Chisholm USA 100 0.0% (0) 100.0%
Dr. Ryan Cole USA 400 0.0% (0) 100.0% 0.0% (0) 100.0%
Dr. Marco Cosentino
vs. 3-3.8% mortality during period; earlier treatment better		 Italy 392 6.4% (25) 83.5% 0.3% (1) 89.6%
Dr. Jeff Davis USA 6,000 0.0% (0) 100.0%
Dr. Dhanajay India 500 0.0% (0) 100.0%
Dr. Bryan Tyson & Dr. George Fareed USA 20,000 0.0% (6) 99.9% 0.0% (4) 99.2%
Dr. Raphael Furtado Brazil 170 0.6% (1) 98.5% 0.0% (0) 100.0%
Rabbi Yehoshua Gerzi Israel 860 0.1% (1) 99.7% 0.0% (0) 100.0%
Dr. Heather Gessling USA 1,500 0.1% (1) 97.3%
Dr. Ellen Guimarães Brazil 500 1.6% (8) 95.9% 0.4% (2) 83.7%
Dr. Syed Haider USA 4,000 0.1% (5) 99.7% 0.0% (0) 100.0%
Dr. Mark Hancock USA 24 0.0% (0) 100.0%
Dr. Sabine Hazan USA 1,000 0.0% (0) 100.0%
Dr. Mollie James USA 3,500 1.1% (40) 97.0% 0.0% (1) 98.8%
Dr. Roberta Lacerda Brazil 550 1.5% (8) 96.2% 0.4% (2) 85.2%
Dr. Katarina Lindley USA 100 5.0% (5) 87.1% 0.0% (0) 100.0%
Dr. Ben Marble USA 150,000 0.0% (4) 99.9%
Dr. Edimilson Migowski Brazil 2,000 0.3% (7) 99.1% 0.1% (2) 95.9%
Dr. Abdulrahman Mohana Saudi Arabia 2,733 0.0% (0) 100.0%
Dr. Carlos Nigro Brazil 5,000 0.9% (45) 97.7% 0.5% (23) 81.3%
Dr. Benoit Ochs Luxembourg 800 0.0% (0) 100.0%
Dr. Ortore Italy 240 1.2% (3) 96.8% 0.0% (0) 100.0%
Dr. Valerio Pascua
one death for a patient presenting on the 5th day in need of supplemental oxygen		 Honduras 415 6.3% (26) 83.8% 0.2% (1) 90.2%
Dr. Sebastian Pop Romania 300 0.0% (0) 100.0%
Dr. Brian Proctor USA 869 2.3% (20) 94.0% 0.2% (2) 90.6%
Dr. Anastacio Queiroz Brazil 700 0.0% (0) 100.0%
Dr. Didier Raoult France 8,315 2.6% (214) 93.3% 0.1% (5) 97.6%
Dr. Karin Ried
up to 99yo, 73% comorbidities, av. age 63		 Turkey 237 0.4% (1) 82.8%
Dr. Roman Rozencwaig
patients up to 86 years old		 Canada 80 0.0% (0) 100.0%
Dr. Vipul Shah India 8,000 0.1% (5) 97.5%
Dr. Silvestre Sobrinho Brazil 116 8.6% (10) 77.7% 0.0% (0) 100.0%
Dr. Unknown Brazil 957 1.7% (16) 95.7% 0.2% (2) 91.5%
Dr. Vladimir Zelenko USA 2,200 0.5% (12) 98.6% 0.1% (2) 96.3%
Mean improvement with early treatment protocols 238,381 HospitalizationHosp. 94.4% MortalityDeath 94.9%
Physician results with early treatment protocols compared to no early treatment. These results are subject to selection and ascertainment bias and more accurate analysis requires details of the patient populations and followup, however results are consistently better across many teams, and consistent with the extensive controlled trial evidence that shows a significant reduction in risk with many early treatments, and improved results with the use of multiple treatments in combination.
Remdesivir
Sise
243 patient late treatment RCT: no change in mortality (p=1), 18% lower combined mortality/intubation (p=0.61), and 16% improvement (p=0.5)
Nigella Sativa
Sebghatollahi
150 patient late treatment RCT: 73% lower mortality (p=0.001), 77% lower ICU admission (p=0.0005), and 41% shorter hospitalization (p<0.0001)
HCQ
Hitti
In Vitro study showing that HCQ reduces inflammation by inhibiting the double-stranded RNA-stimulated phosphorylation of tristetraprolin (TTP) and..
Zinc
Ferreira
In Vitro and In Silico study showing synergistic antiviral effects of luteolin, vitamin C, magnesium, and zinc against SARS-CoV-2 3CLpro. Authors..
Vitamin C
Ferreira
In Vitro and In Silico study showing synergistic antiviral effects of luteolin, vitamin C, magnesium, and zinc against SARS-CoV-2 3CLpro. Authors..
Vitamin D
Wimalawansa
Review showing reduced efficacy of interventions with new variants and suggesting that regulators and health organizations should consider approval..
Abdelhai
250 patient late treatment RCT: 83% lower mortality (p<0.0001), 45% shorter hospitalization (p<0.0001), and 74% improved viral clearance (p<0.0001)
Ivermectin
Wimalawansa
Review showing reduced efficacy of interventions with new variants and suggesting that regulators and health organizations should consider approval..
Wijewickrema
249 patient early treatment RCT: 51% improved viral clearance (p=0.03)
Metformin
Sugimoto
168,550 patients late treatment: 40% lower mortality (p<0.0001)
Vitamin B9
Wu
In Silico study identifying key genes and potential therapeutic agents related to brain fog in COVID-19 patients. Authors analyzed frontal cortex..
Quercetin
Wu
In Silico study identifying key genes and potential therapeutic agents related to brain fog in COVID-19 patients. Authors analyzed frontal cortex..
Recent studies (see the individual treatment pages for all studies):
Jul 24
 Ferreira et al., Bioscience Reports, doi:10.1042/BSR20240617 Boosting Immunity: Synergistic Antiviral Effects of Luteolin, Vitamin C, Magnesium, and Zinc Against SARS-CoV-2 3CLpro
In Vitro and In Silico study showing synergistic antiviral effects of luteolin, vitamin C, magnesium, and zinc against SARS-CoV-2 3CLpro. Authors found that luteolin inhibited SARS-CoV-2 3CLpro with an IC50 of 78 μM, which decreased 10-fo..
Jul 24
 Hitti et al., Immunology, doi:10.1111/imm.13835 Hydroxychloroquine attenuates double-stranded RNA-stimulated hyper-phosphorylation of tristetraprolin/ZFP36 and AU-rich mRNA stabilization
In Vitro study showing that HCQ reduces inflammation by inhibiting the double-stranded RNA-stimulated phosphorylation of tristetraprolin (TTP) and decreasing the stability of AU-rich mRNAs. This suggests that HCQ could mitigate excessive ..
Jul 22
 Sebghatollahi et al., Avicenna J Phytomed, doi:10.22038/ajp.2024.24633 The adjuvant therapy of edible herbal product including colchicum bulb, olive leaf, black cumin seeds, lavender flower, and ginger rhizome on the outcome of patients with severe and critical COVID-19: A double-blind randomized controlled clinical trial
73% lower mortality (p=0.001), 77% lower ICU admission (p=0.0005), and 41% shorter hospitalization (p<0.0001). RCT 150 severe and critical COVID-19 patients showing lower mortality, lower ICU admission, and improved recovery with a treatment including nigella sativa, colchicum autumnal, olea europaea, lavandula angustifolia, and zingiber officinal..
Jul 22
 Wijewickrema et al., BMC Infectious Diseases, doi:10.1186/s12879-024-09563-y Efficacy and safety of oral ivermectin in the treatment of mild to moderate Covid-19 patients: a multi-centre double-blind randomized controlled clinical trial
51% improved viral clearance (p=0.03). RCT 249 hospitalized patients with mild to moderate COVID-19 in Sri Lanka, showing statistically significant lower viral load. There was no significant difference in clinical outcomes. Only one patient had a serious outcome. Mid-recovery ..
Jul 21
 Sugimoto et al., medRxiv, doi:10.1101/2024.07.20.24310736 Biguanides Associate with Decreased Early Mortality and Risk of Acute Kidney Injury In Hospitalized COVID-19 Patients: a nationwide retrospective cohort study in Japan
40% lower mortality (p<0.0001). Retrospective 168,370 hospitalized COVID-19 patients with diabetes in Japan showing lower mortality and reduced risk of acute kidney injury with biguanide (likely primarily or only metformin) use. Authors hypothesize that metformin's acti..
Jul 18
 Wu et al., Elsevier BV, doi:10.2139/ssrn.4897774 Biomarkers Prediction and Immune Landscape in Covid-19 and “Brain Fog”
In Silico study identifying key genes and potential therapeutic agents related to brain fog in COVID-19 patients. Authors analyzed frontal cortex transcriptome data and found upregulated genes involved in immune-related pathways and downr..
Jul 17
 Wimalawansa, S., Heliyon, doi:10.1016/j.heliyon.2024.e34691 Unlocking Insights: Navigating COVID-19 Challenges and Emulating Future Pandemic Resilience Strategies with Strengthening Natural Immunity
Review showing reduced efficacy of interventions with new variants and suggesting that regulators and health organizations should consider approval and strategic use of cost-effective adjunct therapies such as vitamin D and ivermectin tha..
Jul 16
 Imran et al., Clinical Nutrition Open Science, doi:10.1016/j.nutos.2024.07.004 Therapeutic Role of Vitamin D in COVID-19 Patients
Review of vitamin D for COVID-19. Low vitamin D levels have been associated with increased susceptibility to and severity of COVID-19. Vitamin D plays an essential role in modulating the immune response and reducing inflammation, with pro..
Jul 16
 Bell et al., PLOS ONE, doi:10.1371/journal.pone.0304822 Real-world effectiveness of sotrovimab in preventing hospitalization and mortality in high-risk patients with COVID-19 in the United States: A cohort study from the Mayo Clinic electronic health records
50% lower mortality (p=0.2), 12% lower combined mortality/hospitalization (p=0.7), 74% lower ICU admission (p=0.006), and 59% lower need for oxygen therapy (p<0.0001). Retrospective 35,485 high-risk COVID-19 outpatients showing lower ICU admission and respiratory support with sotrovimab. There was no significant difference for hospitalization.
Jul 16
 Zeng et al., eLife, doi:10.7554/elife.94973 Associations of proton pump inhibitors with susceptibility to influenza, pneumonia, and COVID-19: Evidence from a large population-based cohort study
46% higher mortality (p=0.02), 33% higher severe cases (p=0.004), and 8% more cases (p=0.1). UK Biobank retrospective with 160,923 patients showing increased risks of influenza, pneumonia, COVID-19 severity, and COVID-19 mortality with proton pump inhibitor (PPI) use.
Jul 15
 Abdelhai et al., The Egyptian Journal of Hospital Medicine, doi:10.21608/EJHM.2024.368093 Impact of Rapid Correction of Vitamin D Deficiency on Patients with COVID-19 Disease: A Randomized-Controlled Trial
83% lower mortality (p<0.0001), 45% shorter hospitalization (p<0.0001), and 74% improved viral clearance (p<0.0001). RCT 250 hospitalized COVID-19 patients showing significant clinical improvement with high-dose intramuscular vitamin D3 treatment. Patients receiving 200,000 IU cholecalciferol daily for 4 days had increased vitamin D levels, reduced infl..
Jul 15
 Choi et al., The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0 Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study
267% higher mortality (p=0.07), 600% higher ICU admission (p<0.0001), 686% higher need for oxygen therapy (p<0.0001), and 182% worse results (p<0.0001). Target trial emulation study of 18,196 hospitalized COVID-19 patients in Hong Kong showing significantly higher ICU admission and AKI with remdesivir + paxlovid compared with paxlovid alone, and lower mortality and ventilatory support wit..
Jul 15
 Budelon Gonçalves et al., International Journal of Molecular Sciences, doi:10.3390/ijms25147749 Nutritional and Inflammatory Markers Associated with SARS-CoV-2 Infection in the Elderly
Retrospective 43 elderly hospitalized COVID-19 patients in Brazil showing no significant association between vitamin D levels and clinical outcomes. Patients with vitamin D deficiency showed increased inflammatory markers. Data in this st..
Jul 8
 Corrao et al., Journal of Clinical Medicine, doi:10.3390/jcm13133987 Safety of High-Dose Vitamin C in Non-Intensive Care Hospitalized Patients with COVID-19: An Open-Label Clinical Study
39% lower mortality (p=0.37), 19% lower combined mortality/ICU admission (p=0.24), 102% higher ICU admission (p=0.51), and 25% shorter hospitalization (p=0.16). Prospective study of 146 hospitalized COVID-19 patients showing shorter hospitalization with high-dose intravenous vitamin C. 104 patients received 10g of vitamin C intravenously daily for 3 days and 42 patients received only standard car..
Jul 8
 Yu et al., Expert Review of Anti-infective Therapy, doi:10.1080/14787210.2024.2376153 Ursodeoxycholic acid and COVID-19 outcomes: a cohort study and data synthesis of state-of-art evidence
3% lower mortality (p=0.5) and 32% lower severe cases (p=0.02). Meta analysis of 9 studies showing lower risk of severe/critical COVID-19 with UDCA. There was no significant difference for mortality. Authors also perform a retrospective study which is listed separately [Yu].
Jul 6
 Zhao et al., Quantitative Biology, doi:10.1002/qub2.60 Assessing the inhibition efficacy of clinical drugs against the main proteases of SARS‐CoV‐2 variants and other coronaviruses
In Vitro study showing that leritrelvir and GC376 remained effective against some nirmatrelvir- and ensitrelvir-resistant Mpro mutants. Leritrelvir showed better broad-spectrum activity against other pathogenic coronaviruses compared to e..
Jul 5
 Brewitz et al., Journal of Medicinal Chemistry, doi:10.1021/acs.jmedchem.4c01342 Fixing the Achilles Heel of Pfizer’s Paxlovid for COVID-19 Treatment
Perspective article discussing the development of ibuzatrelvir (PF-07817883) as a SARS-CoV-2 main protease (Mpro) inhibitor which addresses the metabolic instability of nirmatrelvir and does not require co-administration with ritonavir, t..
Jul 5
 AlKhuzaie et al., Problems of Virology, doi:10.36233/0507-4088-236 Electrolytes, Zinc and Vitamin D3 in COVID-19 Patients with Cardiovascular Complications
Retrospective 142 COVID-19 patients and 50 controls showing significantly lower levels of zinc, vitamin D, calcium, potassium, and sodium in COVID-19 patients compared to controls. Lower levels of zinc, vitamin D, calcium, and sodium were..
Jul 4
 Shouman et al., Cell Communication and Signaling, doi:10.1186/s12964-024-01718-3 SARS-CoV-2-associated lymphopenia: possible mechanisms and the role of CD147
Review of possible mechanisms for lymphopenia in SARS-CoV-2 patients. Authors describe several indirect and direct mechanisms that may contribute to the T-cell depletion observed in COVID-19, including inflammatory cytokine storms, hyperl..
Jul 4
 Razia et al., Frontiers in Transplantation, doi:10.3389/frtra.2024.1408289 Remdesivir and molnupiravir had comparable efficacy in lung transplant recipients with mild-to-moderate COVID-19: a single center experience
272% higher mortality (p=0.28) and 28% lower hospitalization (p=0.58). Retrospective 113 lung transplant recipients with mild-to-moderate COVID-19 showing higher mortality with remdesivir and molnupiravir in unadjusted analysis, with statistical significance for remdesivir. mAb PrEP and treatment and the dom..
Jul 2
 Yu et al., mBio, doi:10.1128/mbio.01088-24 The histamine receptor H1 acts as an alternative receptor for SARS-CoV-2
In Vitro and mouse study showing that antihistamine drugs targeting the histamine receptor H1 (HRH1) inhibit SARS-CoV-2 infection. Authors find that HRH1 acts as an alternative receptor for SARS-CoV-2 by directly binding to the N-terminal..
Jul 1
 Chaopreecha et al., Elsevier BV, doi:10.2139/ssrn.4876852 Proteomic Analysis Identifies the Glutathione Synthesizing Enzyme Gclc as an Andrographolide Target and a Protective Factor Against Sars-Cov-2 Infection
In Vitro study showing andrographolide attenuates infection of SARS-CoV-2 wildtype and omicron variants in human lung epithelial cells and monkey kidney cells. Proteomic analysis revealed andrographolide induces expression of the glutathi..
Jul 1
 Li et al., Animals and Zoonoses, doi:10.1016/j.azn.2024.06.001 Thermal shift assay (TSA)-based drug screening strategy for rapid discovery of inhibitors against the Nsp13 helicase of SARS-CoV-2
In Vitro study showing that 11 compounds inhibited the SARS-CoV-2 helicase Nsp13, with 7 compounds inhibiting ATPase activity and 4 inhibiting RNA unwinding activity at micromolar concentrations. Authors screened 1,970 FDA-approved drugs ..
Jul 1
 Papantoniou et al., Occupational Medicine, doi:10.1093/occmed/kqae023.0340 Night shift work, sleep disruption and risk of COVID-19 outcomes
Prospective study of 3,319 adults in Spain showing that sleep problems and night shift work were associated with a higher risk of long COVID.
Jun 30
 Al-Momani et al., Annals of Medicine, doi:10.1080/07853890.2024.2355581 Proton pump inhibitors and gastrointestinal symptoms among patients with COVID-19 infection
100% higher mortality (p=0.39), 48% higher ventilation (p=0.54), and 25% higher ICU admission (p=0.64). Retrospective 254 hospitalized COVID-19 patients in Jordan showing higher rates of gastrointestinal symptoms such as abdominal pain and diarrhea with proton pump inhibitor (PPI) use. There were no significant differences for mortality, ve..
Jun 30
 Hussein et al., The Review of Diabetic Studies, doi:10.1900/RDS.2024.20.12 The Proportion and Associated Factors for Mortality among COVID-19 Infection with Diabetes in Iraq
64% lower mortality (p=0.05). Retrospective 545 hospitalized COVID-19 patients with diabetes showing high mortality (33%). Metformin, SGLT inhibitors, and DPP4 inhibitors were associated with lower mortality compared with insulin.
Jun 30
 Cui et al., Journal of Thoracic Disease, doi:10.21037/jtd-23-1604 Efficacy and safety of casirivimab and imdevimab for preventing and treating COVID-19: a systematic review and meta-analysis
Meta analysis of 12 RCTs with 27,179 participants showing that casirivimab/imdevimab treatment significantly reduced viral load, all-cause mortality, and cases. Efficacy was better in patients who were seronegative at baseline.
Jun 30
 Dey et al., Journal of College of Medical Sciences-Nepal, doi:10.3126/jcmsn.v20i2.43302 Hydroxy Chloroquine Prophylaxis Experience in Doctor Community with COVID-19 in West Bengal
92% lower mortality (p=0.09), 27% fewer moderate/severe cases (p=0.39), and 16% lower hospitalization (p=0.55). Retrospective 117 COVID-19 positive doctors in India showing lower mortality and severity with HCQ prophylaxis, without statistical significance in unadjusted results without group details. Results do not include the risk of positive cases.
Jun 30
 Costanza et al., Sexually Transmitted Infections, doi:10.1136/sextrans-ICAR-2024.256 Lactoferrin assumption in vaccinated subjects infected by SARS-CoV-2 may influence time length of negativization
12% faster viral clearance. RCT 120 patients showing faster viral clearance with lactoferrin treatment. The currently available abstract has minimal details and does not report the confidence interval of the result.
Jun 27
 Hirsch et al., The Journal of Pediatrics, doi:10.1016/j.jpeds.2024.114179 Proton Pump Inhibitors and Risk of COVID-19 Infection in Children
15% lower hospitalization (p=0.27) and 15% fewer cases (p=0.002). Retrospective 116,209 pediatric patients showing lower risk of COVID-19 with PPI use. There was no significant difference for hospitalization.
Jun 27
 Kamo et al., In Vivo, doi:10.21873/invivo.13637 Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure
Retrospective 176,197 adverse event reports in Japan showing paxlovid and remdesivir associated with increased risk of acute kidney injury (AKI) in COVID-19 patients.
Jun 26
 Romark, NCT04359680 Trial to Evaluate the Efficacy and Safety of Nitazoxanide (NTZ) for Pre- and Post Exposure Prophylaxis of COVID-19 and Other Viral Respiratory Illnesses (VRI) in Healthcare Workers and Others at Increased Risk of SARS-CoV-2 Infection
43% lower progression (p=0.02), 50% faster recovery (p=0.1), and 3% fewer cases (p=1). RCT 1,407 healthcare workers and others at high risk of SARS-CoV-2 exposure, showing no difference in COVID-19 cases (13 in each group). There was lower symptom severity for nitazoxanide and a trend towards shorter illness duration. There..
Jun 25
 Rahman et al., Asian Journal of Advanced Research and Reports, doi:10.9734/ajarr/2024/v18i7697 In silico Screening of Potential Drug Candidate against Chain a of Coronavirus Binding Protein from Major Nigella Bioactive Compounds
In Silico study of components of nigella sativa, showing nigellamine C, nigeglanine, nigellamine D, nigellicine, nigellidine, and nigellone had higher binding affinity compared to ribavirin, favipiravir, remdesivir, and nirmatrelvir, to t..
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 4,504 studies, 2,310 present results comparing with a control group, 2,111 are treatment studies, and 199 analyze outcomes based on serum levels. There are 73 animal studies, 166 in silico studies, 271 in vitro studies, 298 reviews, and 211 meta analyses.
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. 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. FLCCC and WCH provide treatment protocols.
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