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@CovidAnalysis

COVID-19 early treatment: real-time analysis of 4,145 studies

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Analysis of 69 COVID-19 early treatments, approvals in 105 countries, database of 7,568 treatments  
Recently added (more..)  Vitamin D  Zinc  Molnupiravir  Curcumin
Sobczak
Vitamin D meta analysis: 44% lower mortality (p=0.02), 27% lower ICU admission (p=0.02), and 21% lower need for oxygen therapy (p=0.07)
Jin
Review of zinc for the immune system and COVID-19. Zinc is an essential trace element that plays a critical role in the immune system, immune cell..
Gruber
Analysis of 38 COVID-19 outpatients treated with molnupiravir showing significantly increased SARS-CoV-2 genetic diversity and complexity compared..
Kali
Review of curcumin for COVID-19. Authors discuss the molecular mechanisms of COVID-19 pathogenesis and the properties and mechanisms of action of..
Sagar
Retrospective 73 COVID-19 outpatients and 219 matched controls showing a significantly higher rate of cerebral microbleeds on MRI in COVID-19..
$0 $1,000 $2,000+ -25% 0% 25% 50% Treatment cost (US$) Efficacy vs. cost for COVID-19 treatments Acetaminophen Lufotrelvir $2,000+ Cannabidiol Vitamin B9 Conv. Plasma $5,000 Ibuprofen Remdesivir $3,120 Aspirin Molnupiravir mutagenic/teratogenic Favipiravir Famotidine Paxlovid Vitamin C NAC HCQ Zinc Probiotics Colchicine Sotrovimab $2,100 Budesonide Metformin Sleep Antiandro.. Azvudine Bebtelovimab Vitamin A Vitamin D Sunlight H. Peroxide Fluvox. Exercise Curcumin N. Sativa Melatonin Tixagevimab/c.. Ensovibep $2,000+ Bamlanivimab/e.. pH+ Quercetin Casirivimab/i.. $2,100 Diet PVP-I Thermotherapy Ivermectin Regdanvimab $2,100 Lifestyle / free No prescription Prescription required High-cost Lower risk Higher risk c19early.org May 2024 COVID-19 involves the interplay of 50+ host and viral proteinsand other factors, many treatments are known to modulate these.0.6% of 7,000+ proposed treatments show efficacy with ≥3 studies.Protocols combine treatments, none are 100% effective.c19early analyzes over 4,100 studies for 69 treatments.
$0 $1,000 $2,000+ -25% 0% 25% 50% Treatment cost (US$) Efficacy vs. cost for COVID-19 treatments Acetaminophen Lufotrelvir Cannabidiol Vitamin B9 Conv. Plasma Ibuprofen Remdesivir Aspirin Molnupiravir mutagenic/teratogenic Favipiravir Famotidine Paxlovid Vitamin C NAC HCQ Zinc Probiotics Colchicine Sotrovimab Budesonide Metformin Sleep Antiandro.. Azvudine Bebtelovimab Vitamin A Vitamin D Sunlight H. Peroxide Fluvox. Exercise Curcumin N. Sativa Melatonin Tixagevimab/c.. Ensovibep Bamlaniv.. pH+ Quercetin Casirivim.. Diet PVP-I Thermotherapy Ivermectin Regdanvimab Lifestyle / free No prescription Prescription required High-cost Lower risk Higher risk c19early.org May 2024 COVID-19 involves the interplay of 50+ host and viralproteins and other factors, many treatments are knownto modulate these. 0.6% of 7,000+ proposed treatmentsshow efficacy with ≥3 studies. Protocols combinetreatments, none are 100% effective. c19early analyzesover 4,100 studies for 69 treatments.
Azvudine Evusheld Paxlovid Regdanvimab Vitamin B12 Sunlight Phthalocyanine Alkalinization Fluvoxamine Famotidine Aspirin Molnupiravir Quercetin Diet Bamlanivimab/e.. Hydrogen Peroxide Budesonide Probiotics Casirivimab/i.. Sleep Curcumin Povidone-Iodine Nigella Sativa Melatonin Acetaminophen ↑risk Exercise Vitamin D Antiandrogens Vitamin C Colchicine Ivermectin Metformin Zinc HCQ 2020 2021 2022 2023 Pooled outcomes Specific outcome RCT pooled RCT specific Statistically significant ≥10% improvement ≥3 studies c19early.org May 2024 Time when COVID-19 studies showed efficacy
Azvudine Evusheld Paxlovid Regdanvimab Vitamin B12 Sunlight Phthalocyanine Alkalinization Fluvoxamine Famotidine Aspirin Molnupiravir Quercetin Diet Bamlanivimab/e.. Hydrogen Peroxide Budesonide Probiotics Casirivimab/i.. Sleep Curcumin Povidone-Iodine Nigella Sativa Melatonin Acetaminophen ↑risk Exercise Vitamin D Antiandrogens Vitamin C Colchicine Ivermectin Metformin Zinc HCQ 2020 2021 2022 2023 Pooled outcomes Specific outcome RCT pooled RCT specific Statistically significant ≥10% improvement ≥3 studies c19early.org May 2024 Time when COVID-19 studies showed efficacy
Timeline for when studies showed efficacy - details and limitations. 0.6% of treatments show efficacy.
May 2024
c19early.org
Cost per life saved from NNT in
studies to date
Melatonin
9
48%
  $8
Vitamin D
67
36%
  $11
Alkalinization
8
46%
  $11
Zinc
20
29%
  $16
Vitamin C
42
19%
  $17
Ivermectin
51
49%
  $25
Colchicine
42
29%
  $26
HCQ
250
25%
  $27
Aspirin
63
11%
  $33
Vitamin A
5
30%
  $45
Curcumin
8
63%
  $59
Famotidine
21
18%
  $94
Probiotics
8
61%
  $99
Quercetin
5
61%
  $127
Metformin
63
34%
  $144
Antiandrogens
32
37%
  $179
Nigella Sativa
5
57%
  $187
Budesonide
12
26%
  $574
Nitazoxanide
6
42%
  $680
Azvudine
13
34%
  $1,237
Fluvoxamine
9
43%
  $1,283
Favipiravir
38
12%
  $1,717
Tixagev../c..
10
42%
  $74,506
Molnupiravir
18
22%
  $148,470
Paxlovid
28
31%
  $157,070
Casirivimab/i..
9
31%
  $203,958
Bamlaniv../e..
12
56%
  $269,237
Sotrovimab
10
49%
  $352,800
Regdanvimab
6
74%
  $389,130
Bebtelovimab
4
60%
  $737,601
Remdesivir
59
4%
  $1,558,440
Conv. Plasma
45
-1%
N/A
Acetaminophen
14
-24%
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 64% [50-74%] 10 $2,100 7,200 Ivermectin 61% [53-68%] 103 $1 142,417 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 Casirivimab/i.. 49% [31-63%] 28 $2,100 58,965 variant dependent 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 Bamlaniv../e.. 48% [26-63%] 20 $1,250 34,837 variant dependent Bemnifosbuvir 47% [-57-82%] 3 $500 359 very limited data Ensovibep 46% [-173-89%] 2 $2,100 885 limited data Tixagev../c.. 44% [28-57%] 16 $855 29,439 variant dependent 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 Nigella Sativa 43% [24-57%] 14 $5 3,333 Curcumin 42% [30-52%] 26 $5 14,736 Exercise 39% [34-44%] 66 $0 1,936,481 Fluvoxamine 39% [22-53%] 21 $4 38,283 Hydrogen Per.. 38% [5-59%] 7 $1 921 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 Propolis 37% [-23-68%] 2 $1 270 very limited data Vitamin D 37% [31-42%] 120 $1 195,508 Vitamin A 36% [4-57%] 13 $2 22,237 Selenium 34% [-40-69%] 4 $1 21,452 Bebtelovimab 34% [-24-65%] 6 $1,200 13,329 intravenous Nitazoxanide 33% [-22-63%] 13 $4 3,606 Spironolactone 31% [15-44%] 12 $5 28,019 Azvudine 31% [16-42%] 18 $25 11,834 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 Metformin 29% [25-33%] 88 $10 273,498 Budesonide 29% [17-39%] 14 $4 27,882 Sotrovimab 29% [12-42%] 22 $2,100 43,988 variant dependent Colchicine 28% [19-37%] 53 $1 32,670 Probiotics 28% [18-37%] 26 $5 19,398 Zinc 27% [17-36%] 44 $1 55,200 Andrographol.. 27% [-8-50%] 7 $5 1,245 Nitric Oxide 27% [-8-50%] 11 $11 2,201 Hydroxychlor.. 26% [23-30%] 422 $1 539,736 Ensitrelvir 26% [-14-52%] 3 $500 1,450 very limited data N-acetylcys.. 25% [14-34%] 24 $1 26,243 Lactoferrin 24% [-24-53%] 8 $5 1,419 Vitamin C 21% [14-27%] 70 $1 86,267 UDCA 17% [5-29%] 13 $15 37,170 Paxlovid 17% [13-21%] 60 $1,390 120,221 independent trials refused Famotidine 17% [8-24%] 30 $5 114,119 Favipiravir 15% [5-24%] 68 $20 30,674 worse w/longer followup Molnupiravir 14% [5-23%] 40 $707 136,276 mutagenic/teratogenic Vitamin K 14% [1-26%] 1 $1 7,766 very limited data Aspirin 12% [6-17%] 73 $1 186,324 Deuremidevir 11% [-1-21%] 2 $112 1,432 very limited data Peg.. Lambda 7% [-138-63%] 4 $500 2,143 subcutaneous Remdesivir 2% [-6-9%] 70 $3,120 187,297 worse w/longer followup Ibuprofen 0% [-9-9%] 13 $1 54,707 Conv. Plasma -1% [-5-3%] 46 $5,000 29,830 intravenous Vitamin B9 -11% [-47-15%] 11 $1 54,354 Cannabidiol -19% [-128-38%] 7 $25 16,883 Lufotrelvir -22% [-198-50%] 1 $2,000 58 intravenous Acetaminoph.. -28% [-41--17%] 27 $1 543,459 All studies (pooled effects, all stages) c19early.org May 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 64% 10 Ivermectin 61% 103 Thermotherapy 56% 4 very limited data Povidone-Iod.. 51% 21 Diet 50% 28 Casirivimab/.. 49% 28 variant dependent Quercetin 49% 11 Alkalinization 49% 14 HH-120 49% 2 very limited data Bamlaniv../e.. 48% 20 variant dependent Bemnifosbuvir 47% 3 very limited data Ensovibep 46% 2 limited data Tixagev../c.. 44% 16 variant dependent Adintrevimab 43% 2 intramuscular Melatonin 43% 18 Bromhexine 43% 7 very limited data Nigella Sativa 43% 14 Curcumin 42% 26 Exercise 39% 66 Fluvoxamine 39% 21 Hydrogen Per.. 38% 7 very limited data Phthalocyanine 38% 4 Xiannuoxin 38% 2 very limited data Sunlight 37% 5 Propolis 37% 2 very limited data Vitamin D 37% 120 Vitamin A 36% 13 Selenium 34% 4 Bebtelovimab 34% 6 intravenous Nitazoxanide 33% 13 Spironolactone 31% 12 Azvudine 31% 18 Antiandrogens 30% 49 Sleep 30% 15 Vitamin B12 30% 4 Metformin 29% 88 Budesonide 29% 14 Sotrovimab 29% 22 variant dependent Colchicine 28% 53 Probiotics 28% 26 Zinc 27% 44 Andrographol.. 27% 7 Nitric Oxide 27% 11 Hydroxychlor.. 26% 422 Ensitrelvir 26% 3 very limited data N-acetylcys.. 25% 24 Lactoferrin 24% 8 Vitamin C 21% 70 UDCA 17% 13 Paxlovid 17% 60 independent trials refused Famotidine 17% 30 Favipiravir 15% 68 worse w/longer followup Molnupiravir 14% 40 mutagenic/teratogenic Vitamin K 14% 1 very limited data Aspirin 12% 73 Deuremidevir 11% 2 very limited data Peg.. Lambda 7% 4 subcutaneous Remdesivir 2% 70 worse w/longer followup Ibuprofen 0% 13 Conv. Plasma -1% 46 intravenous Vitamin B9 -11% 11 Cannabidiol -19% 7 Lufotrelvir -22% 1 intravenous Acetaminoph.. -28% 27 All studies (pooled effects, all stages) c19early.org May 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.
Vitamin D
Sobczak
Meta analysis: 44% lower mortality (p=0.02), 27% lower ICU admission (p=0.02), and 21% lower need for oxygen therapy (p=0.07)
Ochoa-Ramírez
Retrospective 292 COVID-19 patients finding that haplotype TC of the FokI and TaqI vitamin D receptor (VDR) gene polymorphisms was associated with..
Zinc
Jin
Review of zinc for the immune system and COVID-19. Zinc is an essential trace element that plays a critical role in the immune system, immune cell..
Molnupiravir
Gruber
Analysis of 38 COVID-19 outpatients treated with molnupiravir showing significantly increased SARS-CoV-2 genetic diversity and complexity compared..
Curcumin
Kali
Review of curcumin for COVID-19. Authors discuss the molecular mechanisms of COVID-19 pathogenesis and the properties and mechanisms of action of..
Agamah
In Silico study identifying potential drugs beneficial for COVID-19 by integrating transcriptomics, proteomics, metabolomics, lipidomics, and drug..
Miscellaneous
Sagar
Retrospective 73 COVID-19 outpatients and 219 matched controls showing a significantly higher rate of cerebral microbleeds on MRI in COVID-19..
Zhang
In Vitro study showing that the SARS-CoV-2 BA.2.87.1 lineage efficiently enters human cells but is more sensitive to neutralization by antibodies..
Cokljat
Comparison of COVID-19 treatment guidelines from 109 countries with WHO guidelines, showing very high variation between national guidelines and..
Ivermectin
Varnaseri
110 patient late treatment RCT: 82% lower ventilation (p=0.02), 83% lower ICU admission (p=0.0004), 33% shorter hospitalization (p=0.001), and 28% faster recovery (p<0.0001)
de Oliveira Só
In Silico study showing that ivermectin and nirmatrelvir interact with the SARS-CoV-2 main protease (Mpro). Authors used molecular docking and 100ns..
Scheim
Review of the biochemical underpinnings of the severe morbidities of COVID-19, focusing on the binding of the SARS-CoV-2 spike protein (SP) to..
Ensovibep
Kingsley
400 patient early treatment RCT: 89% lower mortality (p=0.06), 78% fewer combined hospitalization/ER visits (p=0.02), 87% lower hospitalization (p=0.01), and 87% improvement (p=0.01)
Nitazoxanide
Brechot
Review of nitazoxanide as a potential treatment for COVID-19. Authors highlight nitazoxanide's unique mechanism of action, which involves inhibiting..
Tixagevimab/cilgavimab
Solera
1,975 patients prophylaxis: 26% lower severe cases (p=0.48)
Quercetin
Ho
Review of quercetin and its derivatives for prevention and treatment of COVID-19. Authors discuss molecular docking evidence showing quercetin and..
Melatonin
Chacin-Bonilla
Review of the potential therapeutic effects of melatonin on viral infections, with a focus on SARS-CoV-2 and COVID-19. Authors highlight melatonin's..
Andrographolide
Thomas
In Silico study showing that andrographolide derivatives (PubChem CID 2734589 and 138968421) are potential dual inhibitors of SARS-CoV-2..
Paxlovid
de Oliveira Só
In Silico study showing that ivermectin and nirmatrelvir interact with the SARS-CoV-2 main protease (Mpro). Authors used molecular docking and 100ns..
Fluvoxamine
Scheim
Review of the biochemical underpinnings of the severe morbidities of COVID-19, focusing on the binding of the SARS-CoV-2 spike protein (SP) to..
HCQ
Scheim
Review of the biochemical underpinnings of the severe morbidities of COVID-19, focusing on the binding of the SARS-CoV-2 spike protein (SP) to..
Metformin
Song
Meta analysis: 34% lower mortality (p<0.0001), 35% lower severe cases (p=0.002), and 23% lower hospitalization (p=0.02)
Agamah
In Silico study identifying potential drugs beneficial for COVID-19 by integrating transcriptomics, proteomics, metabolomics, lipidomics, and drug..
N-acetylcysteine
Agamah
In Silico study identifying potential drugs beneficial for COVID-19 by integrating transcriptomics, proteomics, metabolomics, lipidomics, and drug..
Vitamin C
Agamah
In Silico study identifying potential drugs beneficial for COVID-19 by integrating transcriptomics, proteomics, metabolomics, lipidomics, and drug..
Recent studies (see the individual treatment pages for all studies):
May 7
 Sobczak et al., Nutrients, doi:10.3390/nu16101402 Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials
44% lower mortality (p=0.02), 27% lower ICU admission (p=0.02), and 21% lower need for oxygen therapy (p=0.07). Meta analysis of 13 RCTs for severe COVID-19 showing lower ICU admission and lower COVID-19 mortality with vitamin D treatment. Other outcomes show lower risk with treatment but without statistical significance. Authors conclude that it i..
May 6
 Gruber et al., Journal of Medical Virology, doi:10.1002/jmv.29642 Molnupiravir increases SARS‐CoV‐2 genome diversity and complexity: A case‐control cohort study
Analysis of 38 COVID-19 outpatients treated with molnupiravir showing significantly increased SARS-CoV-2 genetic diversity and complexity compared to 17 patients treated with tixagevimab/cilgavimab. Molnupiravir increased the mutation rat..
May 4
 Kali et al., Global Journal of Medical, Pharmaceutical, and Biomedical Update, doi:10.25259/GJMPBU_78_2023 Curcumin as a Promising Therapy for COVID-19: A Review
Review of curcumin for COVID-19. Authors discuss the molecular mechanisms of COVID-19 pathogenesis and the properties and mechanisms of action of curcumin. Curcumin exhibits antiviral activity against SARS-CoV-2 by interfering with viral ..
May 3
 Kingsley et al., Open Forum Infectious Diseases, doi:10.1093/ofid/ofae233 The DARPin antiviral ensovibep for non-hospitalized patients with COVID-19: Results from EMPATHY, a randomized, placebo-controlled Phase 2 study
89% lower mortality (p=0.06), 78% fewer combined hospitalization/ER visits (p=0.02), 87% lower hospitalization (p=0.01), and 87% improvement (p=0.01). RCT 407 mild to moderate COVID-19 outpatients showing faster viral clearance, lower risk of hospitalization/ER visits, and shorter time to sustained recovery with ensovibep treatment (75/225/600mg single infusion). There were 2 COVID-19 r..
May 3
 Mohammadifard et al., Scientific Reports, doi:10.1038/s41598-024-57424-0 Comparing vitamin D receptor gene polymorphisms in rs11568820, rs7970314, rs4334089 between COVID-19 patients with mild and severe symptoms: a case control study
Case control study of 176 COVID-19 patients showing the TT genotype of the rs11568820 vitamin D receptor (VDR) polymorphism was associated with a lower risk of severe COVID-19 requiring hospitalization. No significant differences were fou..
Apr 30
 Brechot et al., Medical Research Archives, doi:10.18103/mra.v12i4.5252 Nitazoxanide in the Treatment of COVID-19: A paradigm for Antiviral Drugs Targeting Host-Infected Cells
Review of nitazoxanide as a potential treatment for COVID-19. Authors highlight nitazoxanide's unique mechanism of action, which involves inhibiting mitochondrial oxidative phosphorylation in host cells, thereby lowering cellular ATP cont..
Apr 30
 Ho et al., Heliyon, doi:10.1016/j.heliyon.2024.e30080 Therapeutic Implications of Quercetin and its Derived-products in COVID-19 Protection and Prophylactic
Review of quercetin and its derivatives for prevention and treatment of COVID-19. Authors discuss molecular docking evidence showing quercetin and its derivatives can bind to multiple SARS-CoV-2 proteins including the main protease, spike..
Apr 30
 Varnaseri et al., Jundishapur Journal of Health Sciences, doi:10.5812/jjhs-146703 Ivermectin as a Potential Addition to the Limited Anti-COVID-19 Arsenal: A Double-Blinded Clinical Trial
82% lower ventilation (p=0.02), 83% lower ICU admission (p=0.0004), 33% shorter hospitalization (p=0.001), and 28% faster recovery (p<0.0001). Double-blind RCT 110 hospitalized moderate to severe COVID-19 patients showing significantly reduced ICU admission, shorter hospitalization, faster resolution of symptoms, and improved CRP and LDH levels with ivermectin treatment compared..
Apr 29
 Song et al., Therapeutic Innovation & Regulatory Science, doi:10.1007/s43441-024-00633-6 The Effect of Antihyperglycemic Medications on COVID-19: A Meta-analysis and Systematic Review from Observational Studies
34% lower mortality (p<0.0001), 35% lower severe cases (p=0.002), and 23% lower hospitalization (p=0.02). Meta analysis of 56 studies showing lower mortality and hospitalization with metformin, GLP-1 receptor agonists, and SGLT-2 inhibitors in COVID-19 patients with type 2 diabetes, while insulin was associated with increased risks.
Apr 29
 Thomas et al., Scientific Reports, doi:10.1038/s41598-024-58532-7 Cheminformatics approach to identify andrographolide derivatives as dual inhibitors of methyltransferases (nsp14 and nsp16) of SARS-CoV-2
In Silico study showing that andrographolide derivatives (PubChem CID 2734589 and 138968421) are potential dual inhibitors of SARS-CoV-2 methyltransferases nsp14 and nsp16, which are crucial for viral replication and evading host immune r..
Apr 28
 de Oliveira Só et al., MDPI AG, doi:10.20944/preprints202404.1825.v1 In Silico Comparative Analysis of Ivermectin and Nirmatrelvir Inhibitors Interacting with the SARS-CoV-2 Main Protease
In Silico study showing that ivermectin and nirmatrelvir interact with the SARS-CoV-2 main protease (Mpro). Authors used molecular docking and 100ns molecular dynamics simulations to investigate the binding interactions. Nirmatrelvir form..
Apr 28
 Ochoa-Ramírez et al., International Journal of Immunogenetics, doi:10.1111/iji.12674 Vitamin D receptor gene polymorphisms role in COVID‐19 severity: Results of a Mexican patients’ cohort
Retrospective 292 COVID-19 patients finding that haplotype TC of the FokI and TaqI vitamin D receptor (VDR) gene polymorphisms was associated with an increased risk of critical COVID-19.
Apr 27
 Autier et al., medRxiv, doi:10.1101/2024.04.26.24306354 Vitamin D, acute respiratory infections, and Covid-19: the curse of small-size randomised trials. A critical review with meta-analysis of randomised trials
Unregistered meta analysis cherry-picking the ICU outcome and including 9 late treatment RCTs with ICU outcomes for vitamin D. It's unclear why ICU risk would be used when there are more studies reporting mortality which is also less subj..
Apr 26
 Wang et al., BMC Pulmonary Medicine, doi:10.1186/s12890-024-03013-w Retinol and retinol binding protein 4 levels and COVID-19: a Mendelian randomization study
Mendelian randomization study suggesting a causal association between retinol and related proteins (RBP4, RDH16, CRABP1) and COVID-19. The study found that genetically-predicted higher retinol levels were associated with lower COVID-19..
Apr 26
 Nalban et al., Journal of Proteins and Proteomics, doi:10.1007/s42485-024-00136-w Targeting COVID-19 (SARS-CoV-2) main protease through phytochemicals of Albizia lebbeck: molecular docking, molecular dynamics simulation, MM–PBSA free energy calculations, and DFT analysis
In Silico study showing potential benefits of quercetin and other phytochemicals from Albizia lebbeck as SARS-CoV-2 main protease (Mpro) inhibitors. Using molecular docking, the authors identified four promising compounds: vicenin 2, myri..
Apr 25
 Onozuka et al., BMC Oral Health, doi:10.1186/s12903-024-04246-1 Oral mouthwashes for asymptomatic to mildly symptomatic adults with COVID-19 and salivary viral load: a randomized, placebo-controlled, open-label clinical trial
RCT 90 low-risk asymptomatic to mildly symptomatic COVID-19 patients showing no significant difference in salivary viral load with cetylpyridinium chloride or on-demand aqueous chlorine dioxide mouthwash. Both treatments increased Ct valu..
Apr 24
 Jamilian et al., Public Health Nutrition, doi:10.1017/S1368980024000934 The role of vitamin D in outcomes of critical care in COVID-19 patients: Evidence from an umbrella meta-analysis of interventional and observational studies
58% lower mortality (p=0.05). Umbrella meta analysis of 13 meta analyses showing significantly lower mortality with vitamin D supplementation, and significantly higher mortality, infection risk, and severity with vitamin D deficiency in COVID-19 patients. Lower vitami..
Apr 24
 Manca et al., Viruses, doi:10.3390/v16050665 Exploring the Antiviral Potential of Esters of Cinnamic Acids with Quercetin
In Vitro study showing that esters of cinnamic acids with quercetin, particularly ester 7, inhibit SARS-CoV-2 and hCoV-OC43 coronavirus infection in Vero-76 and Vero E6 cells. Mechanism of action studies suggest ester 7 may inhibit corona..
Apr 23
 Amani et al., Immunity, Inflammation and Disease, doi:10.1002/iid3.1262 Comparison of effectiveness and safety of molnupiravir versus sotrovimab for COVID‐19: A systematic review and meta‐analysis
Meta analysis of 13 studies involving 16,166 patients showing higher mortality and higher incidence of adverse events with molnupiravir compared with sotrovimab.
Apr 22
 Zhou et al., PLOS ONE, doi:10.1371/journal.pone.0300441 Bioinformatics and system biology approaches to determine the connection of SARS-CoV-2 infection and intrahepatic cholangiocarcinoma
In Silico study suggesting that quercetin and tetrandrine are potential treatments for COVID-19 and intrahepatic cholangiocarcinoma (ICC). Authors identify 70 shared differentially expressed genes between COVID-19 and ICC, indicating simi..
Apr 22
 Scheim et al., Viruses, doi:10.3390/v16040647 Back to the Basics of SARS-CoV-2 Biochemistry: Microvascular Occlusive Glycan Bindings Govern Its Morbidities and Inform Therapeutic Responses
Review of the biochemical underpinnings of the severe morbidities of COVID-19, focusing on the binding of the SARS-CoV-2 spike protein (SP) to sialylated glycans on host cell surfaces. Authors highlight how the SP attaches particularly ti..
Apr 20
 Elshiwy et al., BMC Pulmonary Medicine, doi:10.1186/s12890-024-03001-0 The role of colchicine in the management of COVID-19: a meta-analysis
65% lower mortality (p=0.01), 60% lower ventilation (p=0.09), 71% lower ICU admission (p=0.08), and 93% lower need for oxygen therapy (p<0.0001). Systematic review and meta-analysis of 8 studies (4 RCTs) involving 16,488 COVID-19 patients showed significantly lower mortality and need for oxygen therapy with colchicine.
Apr 19
 Yehia et al., Molecular Neurodegeneration, doi:10.1186/s13024-024-00728-6 Melatonin: a ferroptosis inhibitor with potential therapeutic efficacy for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration
Review of melatonin as a potential ferroptosis inhibitor for the post-COVID-19 trajectory of accelerated brain aging and neurodegeneration. Authors propose that ferroptosis, an iron-dependent cell death triggered by lipid peroxidation, ma..
Apr 19
 Chacin-Bonilla et al., Melatonin Research, doi:10.32794/mr112500168 Melatonin and viral infections: A review focusing on therapeutic effects and SARS-CoV-2
Review of the potential therapeutic effects of melatonin on viral infections, with a focus on SARS-CoV-2 and COVID-19. Authors highlight melatonin's potent anti-inflammatory, antioxidant, and immunomodulatory properties, which suggest its..
Apr 19
 Jin et al., Frontiers in Nutrition, doi:10.3389/fnut.2024.1385591 The nutritional roles of zinc for immune system and COVID-19 patients
Review of zinc for the immune system and COVID-19. Zinc is an essential trace element that plays a critical role in the immune system, immune cell function, and cell signaling. Authors discuss the importance of zinc in human health, zinc ..
Apr 18
 Shahin et al., Research Square, doi:10.21203/rs.3.rs-4180797/v1 The selective effect of Ivermectin on different human coronaviruses; in-vitro study
In Vitro study showing dose-dependent inhibition of wildtype and omicron SARS-CoV-2 with 0.5-5μM ivermectin. Authors found no significant effect for alphacoronavirus NL63 and a moderate effect for betacoronavirus OC43. In contrast, iverme..
Apr 17
 Gao et al., International Immunopharmacology, doi:10.1016/j.intimp.2024.112073 Ivermectin ameliorates acute myocarditis via the inhibition of importin-mediated nuclear translocation of NF-κB/p65
Mouse study showing that ivermectin improves cardiac function and reduces inflammation in models of viral and autoimmune myocarditis. Authors found that ivermectin inhibited the nuclear translocation of NF-κB/p65 in macrophages by targeti..
Apr 16
 Mohebbi et al., PLOS ONE, doi:10.1371/journal.pone.0298201 In silico study of alkaloids with quercetin nucleus for inhibition of SARS-CoV-2 protease and receptor cell protease
In Silico study showing that the alkaloids with a quercetin nucleus may inhibit SARS-CoV-2 infection by binding to the main protease (Mpro) and the host cell protease TMPRSS2. Molecular docking analysis found three compounds, Phyllospadin..
Apr 16
 Agamah et al., ScienceOpen, doi:10.58647/DRUGARXIV.PR000010.v1 Network-based multi-omics-disease-drug associations reveal drug repurposing candidates for COVID-19 disease phases
In Silico study identifying potential drugs beneficial for COVID-19 by integrating transcriptomics, proteomics, metabolomics, lipidomics, and drug data. Authors explore interactions between drugs, molecular features, and disease severity...
Apr 13
 Vaiss et al., European Journal of Pharmaceutical Sciences, doi:10.1016/j.ejps.2024.106766 Curcumin and quercetin co-encapsulated in nanoemulsions for nasal administration: a promising therapeutic and prophylactic treatment for viral respiratory infections
In Vitro and Ex Vivo study showing that curcumin and quercetin co-encapsulated in nanoemulsions (NEs) for nasal administration inhibited murine β-coronavirus (MHV-3) infection. MHV-3 belongs to the same family as SARS-CoV-2. Authors found..
Apr 12
 Fang et al., Journal of Nanobiotechnology, doi:10.1186/s12951-024-02435-2 Development of nanoparticles incorporated with quercetin and ACE2-membrane as a novel therapy for COVID-19
In Vitro study showing that nanoparticles coated with both ACE2-containing cell membranes and quercetin (CM-NP-Q) inhibit SARS-CoV-2 infection in human lung cells. Authors developed nanoparticles incorporated with quercetin (NP-Q), ACE2-c..
Apr 12
 Corral et al., Global Journal of Aging & Geriatric Research, doi:10.33552/GJAGR.2024.03.000557 Early Treatment Outcomes of SARS-Cov-2 with Ivermectin, Nitazoxanide and Acetylsalicylic Acid in 2 Nursing Homes During The COVID-19 Pandemic in Cali, Colombia
Retrospective 475 nursing home residents showing low mortality with early treatment using ivermectin, nitazoxanide, and acetylsalicylic acid. All residents were treated when the first positive cases were identified. 87 residents tested po..
Apr 12
 Hwang et al., Infectious Diseases and Therapy, doi:10.1007/s40121-024-00971-w Effect of Regdanvimab on Mortality in Patients Infected with SARS-CoV-2 Delta Variants: A Propensity Score-Matched Cohort Study
83% lower mortality (p=0.12), 33% lower ICU admission (p=0.49), and 55% lower need for oxygen therapy (p=0.01). PSM retrospective 378 hospitalized COVID-19 patients in Korea showing lower progression with regdanvimab treatment.
Apr 12
 Ware et al., medRxiv, doi:10.1101/2024.04.10.24305647 Incidence and Risk of Post-COVID-19 Thromboembolic Disease and the Impact of Aspirin Prescription; Nationwide Observational Cohort at the US Department of Veteran Affairs.
46% lower mortality (p=0.001). PSM retrospective 334,374 COVID-19 patients showing decreased risk of venous thromboembolism, including pulmonary embolism and deep vein thrombosis, but increased risk of arterial thromboembolic disorders, including ischemic stroke and ac..
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 4,145 studies, 2,168 present results comparing with a control group, 1,972 are treatment studies, and 196 analyze outcomes based on serum levels. There are 67 animal studies, 143 in silico studies, 237 in vitro studies, 260 reviews, and 175 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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