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c19early.org COVID-19 treatment researchSelect treatment..Select..
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

COVID-19 early treatment: real-time analysis of 3,957 studies

Analysis of 66 COVID-19 early treatments, approvals in 104 countries, database of 7,092 treatments  
Korves
Retrospective 12,538 COVID-19 patients, showing associations between specific SARS-CoV-2 lineages and amino acid mutations and increased..
Wannigama
498 patient fluvoxamine early treatment RCT: 98% lower ventilation (p<0.0001), 89% lower need for oxygen therapy (p<0.0001), 94% lower hospitalization (p<0.0001), and 40% lower PASC (p<0.0001)
Yang
RCT showing high rates of viral and symptom rebound with both paxlovid and deuremidevir (VV116). There are multiple potential reasons, with one..
Guðnadóttir
273 patients vitamin D sufficiency: 54% lower mortality (p=0.15), 8% lower ventilation (p=0.87), and 28% lower ICU admission (p=0.43)
Fujita
Zinc sufficiency: 86% lower need for oxygen therapy (p=0.007)
$0 $1,000 $2,000+ -25% 0% 25% 50% Treatment cost (US$) Efficacy vs. cost for COVID-19 treatments Acetaminophen 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 D Sunlight H. Peroxide Vitamin A Fluvox. Exercise Curcumin N. Sativa Melatonin Tixagevimab/c.. pH+ Bamlanivimab/e.. Quercetin PVP-I Diet Casirivimab/i.. $2,100 Thermotherapy Ivermectin Regdanvimab $2,100 Lifestyle / free No prescription Prescription required High-cost Lower risk Higher risk c19early.org March 2024 COVID-19 involves the interplay of 50+ host and viral proteinsand other factors, many treatments are known to modulate these.0.6% of 7,066 proposed treatments show efficacy with ≥3 studies.Protocols combine treatments, none are 100% effective.c19early analyzes 3,937 studies for 66 treatments.
$0 $1,000 $2,000+ -25% 0% 25% 50% Treatment cost (US$) Efficacy vs. cost for COVID-19 treatments Acetaminophen 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 D Sunlight H. Peroxide Vitamin A Fluvox. Exercise Curcumin N. Sativa Melatonin Tixagevimab/c.. pH+ Bamlaniv.. Quercetin PVP-I Diet Casirivim.. Thermotherapy Ivermectin Regdanvimab Lifestyle / free No prescription Prescription required High-cost Lower risk Higher risk c19early.org March 2024 COVID-19 involves the interplay of 50+ host and viral proteinsand other factors, many treatments are known to modulate these.0.6% of 7,066 proposed treatments show efficacy with ≥3 studies.Protocols combine treatments, none are 100% effective.c19early analyzes 3,937 studies for 66 treatments.
Azvudine Evusheld Paxlovid Regdanvimab Vitamin B12 Sunlight Alkalinization Phthalocyanine Fluvoxamine Famotidine Molnupiravir Quercetin Diet Bamlanivimab/e.. Hydrogen Peroxide Budesonide Aspirin Probiotics Casirivimab/i.. Sleep Curcumin Povidone-Iodine Nigella Sativa Melatonin Acetaminophen ↑risk Exercise Vitamin D Vitamin C Colchicine Antiandrogens Ivermectin Metformin Zinc HCQ 2020 2021 2022 2023 Pooled outcomes Specific outcome RCT pooled RCT specific Statistically significant ≥10% improvement ≥3 studies c19early.org March 2024 Time when COVID-19 studies showed efficacy
Azvudine Evusheld Paxlovid Regdanvimab Vitamin B12 Sunlight Alkalinization Phthalocyanine Fluvoxamine Famotidine Molnupiravir Quercetin Diet Bamlanivimab/e.. Hydrogen Peroxide Budesonide Aspirin Probiotics Casirivimab/i.. Sleep Curcumin Povidone-Iodine Nigella Sativa Melatonin Acetaminophen ↑risk Exercise Vitamin D Vitamin C Colchicine Antiandrogens Ivermectin Metformin Zinc HCQ 2020 2021 2022 2023 Pooled outcomes Specific outcome RCT pooled RCT specific Statistically significant ≥10% improvement ≥3 studies c19early.org March 2024 Time when COVID-19 studies showed efficacy
Timeline for when studies showed efficacy - details and limitations. 0.6% of treatments show efficacy.
March 2024
c19early.org
Cost per life saved from NNT in
studies to date
Melatonin
9
48%
  $8
Vitamin D
67
36%
  $11
Vitamin C
40
19%
  $14
Zinc
20
29%
  $16
Ivermectin
51
49%
  $25
Colchicine
41
29%
  $26
HCQ
249
24%
  $27
Alkalinization
5
42%
  $28
Aspirin
62
9%
  $41
Vitamin A
5
30%
  $45
Curcumin
8
63%
  $59
Famotidine
21
18%
  $94
Probiotics
8
61%
  $99
Quercetin
5
61%
  $127
Metformin
61
34%
  $144
Antiandrogens
32
37%
  $179
Nigella Sativa
5
57%
  $187
Budesonide
12
26%
  $574
Nitazoxanide
6
42%
  $680
Azvudine
12
35%
  $1,237
Fluvoxamine
9
43%
  $1,283
Favipiravir
38
12%
  $1,717
Tixagev../c..
10
42%
  $74,506
Molnupiravir
17
23%
  $137,653
Regdanvimab
3
70%
  $139,860
Paxlovid
27
31%
  $157,070
Casirivimab/i..
8
40%
  $181,694
Bamlaniv../e..
12
56%
  $269,237
Sotrovimab
10
49%
  $352,800
Bebtelovimab
4
60%
  $737,601
Remdesivir
58
6%
  $1,502,505
Conv. Plasma
43
-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% [46-76%] 7 $2,100 5,322 Ivermectin 61% [53-67%] 101 $1 142,247 Thermotherapy 56% [9-78%] 4 $0 217 very limited data Casirivimab/i.. 52% [34-65%] 27 $2,100 58,886 variant dependent Diet 50% [41-58%] 28 $0 693,236 Povidone-Iod.. 50% [37-61%] 20 $1 3,226 Quercetin 49% [21-68%] 11 $5 1,436 HH-120 49% [-60-84%] 2 $500 345 very limited data Bamlaniv../e.. 49% [26-64%] 19 $1,250 34,558 variant dependent Alkalinization 49% [32-61%] 11 $1 1,461 Bemnifosbuvir 47% [-57-82%] 3 $500 359 very limited data Ensovibep 46% [-173-89%] 2 $2,100 885 limited data Tixagev../c.. 46% [28-59%] 15 $855 27,464 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 Vitamin D 37% [31-42%] 119 $1 194,685 Vitamin A 36% [1-59%] 12 $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 30% [15-43%] 17 $25 8,971 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%] 85 $10 265,302 Budesonide 29% [17-39%] 14 $4 27,882 Sotrovimab 29% [12-42%] 22 $2,100 43,988 variant dependent Colchicine 28% [19-37%] 51 $1 32,580 Probiotics 28% [18-37%] 26 $5 19,398 Zinc 27% [17-36%] 44 $1 55,200 Andrographol.. 27% [-8-50%] 7 $5 1,245 Hydroxychlor.. 26% [23-30%] 421 $1 539,310 Ensitrelvir 26% [-14-52%] 3 $500 1,450 very limited data Nitric Oxide 25% [-8-48%] 11 $11 2,201 N-acetylcys.. 25% [14-34%] 24 $1 26,243 Lactoferrin 24% [-24-53%] 8 $5 1,419 Vitamin C 21% [14-27%] 68 $1 85,819 Paxlovid 17% [13-21%] 57 $1,390 118,172 independent trials refused Famotidine 17% [8-24%] 30 $5 114,119 UDCA 15% [2-26%] 12 $15 36,975 Favipiravir 15% [5-24%] 68 $20 30,674 worse w/longer followup Molnupiravir 14% [5-23%] 39 $707 136,198 mutagenic/teratogenic Deuremidevir 11% [-1-21%] 2 $112 1,432 very limited data Aspirin 10% [5-15%] 72 $1 186,324 Peg.. Lambda 7% [-138-63%] 4 $500 2,143 subcutaneous Remdesivir 6% [-1-12%] 68 $3,120 185,086 worse w/longer followup Ibuprofen 0% [-9-9%] 13 $1 54,707 Conv. Plasma -1% [-5-3%] 44 $5,000 24,729 intravenous Vitamin B9 -11% [-47-15%] 11 $1 54,354 Cannabidiol -19% [-128-38%] 7 $25 16,883 Acetaminoph.. -28% [-41--17%] 27 $1 543,459 All studies (pooled effects, all stages) c19early.org March 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% 7 Ivermectin 61% 101 Thermotherapy 56% 4 very limited data Casirivimab/.. 52% 27 variant dependent Diet 50% 28 Povidone-Iod.. 50% 20 Quercetin 49% 11 HH-120 49% 2 very limited data Bamlaniv../e.. 49% 19 variant dependent Alkalinization 49% 11 Bemnifosbuvir 47% 3 very limited data Ensovibep 46% 2 limited data Tixagev../c.. 46% 15 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 Vitamin D 37% 119 Vitamin A 36% 12 Selenium 34% 4 Bebtelovimab 34% 6 intravenous Nitazoxanide 33% 13 Spironolactone 31% 12 Azvudine 30% 17 Antiandrogens 30% 49 Sleep 30% 15 Vitamin B12 30% 4 Metformin 29% 85 Budesonide 29% 14 Sotrovimab 29% 22 variant dependent Colchicine 28% 51 Probiotics 28% 26 Zinc 27% 44 Andrographol.. 27% 7 Hydroxychlor.. 26% 421 Ensitrelvir 26% 3 very limited data Nitric Oxide 25% 11 N-acetylcys.. 25% 24 Lactoferrin 24% 8 Vitamin C 21% 68 Paxlovid 17% 57 independent trials refused Famotidine 17% 30 UDCA 15% 12 Favipiravir 15% 68 worse w/longer followup Molnupiravir 14% 39 mutagenic/teratogenic Deuremidevir 11% 2 very limited data Aspirin 10% 72 Peg.. Lambda 7% 4 subcutaneous Remdesivir 6% 68 worse w/longer followup Ibuprofen 0% 13 Conv. Plasma -1% 44 intravenous Vitamin B9 -11% 11 Cannabidiol -19% 7 Acetaminoph.. -28% 27 All studies (pooled effects, all stages) c19early.org March 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 - 39 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%
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 237,521 HospitalizationHosp. 94.1% MortalityDeath 94.7%
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.
Korves
Retrospective 12,538 COVID-19 patients, showing associations between specific SARS-CoV-2 lineages and amino acid mutations and increased..
Duloquin
Review of the extrapulmonary manifestations of SARS-CoV-2 infection, which can affect multiple organs beyond the lungs including the cardiovascular,..
Chen
80 patients prophylaxis: 91% fewer moderate/severe cases (p=0.05), 83% fewer symptomatic cases (p<0.0001), and 60% fewer cases (p=0.0001)
Moustgaard
Meta-analysis of 142 meta-analyses (1,153 trials) finding no evidence that lack of blinding of patients, healthcare providers, or outcome assessors..
Hampshire
Observational study of 112,964 adults in England completing an online cognitive assessment, showing significant cognitive deficits persisting over a..
Wannigama
498 patient early treatment RCT: 98% lower ventilation (p<0.0001), 89% lower need for oxygen therapy (p<0.0001), 94% lower hospitalization (p<0.0001), and 40% lower PASC (p<0.0001)
Wannigama
686 patient early treatment RCT: 98% lower ventilation (p<0.0001), 100% lower need for oxygen therapy (p<0.0001), 98% lower hospitalization (p<0.0001), and 55% lower PASC (p<0.0001)
Yang
RCT showing high rates of viral and symptom rebound with both paxlovid and deuremidevir (VV116). There are multiple potential reasons, with one..
Schreiber
In Vitro study showing that molnupiravir and paxlovid induced resistant variants in SARS-CoV-2 during serial passaging, while the host-directed..
Yang
RCT showing high rates of viral and symptom rebound with both paxlovid and deuremidevir (VV116). There are multiple potential reasons, with one..
Guðnadóttir
273 patients sufficiency: 54% lower mortality (p=0.15), 8% lower ventilation (p=0.87), and 28% lower ICU admission (p=0.43)
Talebzadeh
Retrospective study of 707 COVID-19 patients showing higher platelet count and mean platelet volume (MPV) in patients with vitamin D deficiency..
Grant
Review of vitamin D and solar ultraviolet radiation-B (UVB) for reducing the risk of diseases related to viruses including certain respiratory tract..
Fujita
Sufficiency: 86% lower need for oxygen therapy (p=0.007)
Seifi
Prophylaxis: 31% lower hospitalization (p=0.02)
Li
84 patients late treatment: 11% shorter hospitalization (p=0.26) and 50% improved viral clearance (p=0.03)
Vaziri
179 patient late treatment RCT: 81% lower mortality (p=0.03), 87% lower ICU admission (p=0.002), and 35% shorter hospitalization (p<0.0001)
Kow
Meta-analysis of 10 randomized controlled trials with 17,976 COVID-19 patients showing significantly shorter hospitalization with colchicine..
Vaziri
179 patient late treatment RCT: 81% lower mortality (p=0.03), 87% lower ICU admission (p=0.002), and 35% shorter hospitalization (p<0.0001)
Turrubiates-Hernández
Analysis of 39 COVID-19 outpatients showing a positive correlation between vitamin A nutritional status and secretory immunoglobulin A (SIgA) levels..
Schreiber
In Vitro study showing that molnupiravir and paxlovid induced resistant variants in SARS-CoV-2 during serial passaging, while the host-directed..
Kow
Meta analysis: 50% lower mortality (p=0.008)
Hayward
Significantly improved recovery and significantly lower risk of long COVID with ivermectin (PRINCIPLE trial).
Yong
Review of nanoformulations for inhaled therapeutics for respiratory diseases including potential for COVID-19. Inhaled formulations deliver..
Yong
Review of nanoformulations for inhaled therapeutics for respiratory diseases including potential for COVID-19. Inhaled formulations deliver..
Recent studies (see the individual treatment pages for all studies):

Mar 14
Bostancıklıoğlu et al., Gene, doi:10.1016/j.gene.2024.148366 Nigella sativa, Anthemis hyaline and Citrus sinensis extracts reduce SARS-CoV-2 replication by fluctuating Rho GTPase, PI3K-AKT, and MAPK/ERK pathways in HeLa-CEACAM1a cells
In Vitro study showing that nigella sativa, anthemis hyaline, and citrus sinensis extracts reduce SARS-CoV-2 replication in HeLa-CEACAM1a cells. Nigella sativa extract notably increased IL-8 levels, indicating its potential role in modula..
Mar 14
Wannigama et al., NCT05087381 Early treatment with fluvoxamine, bromhexine, cyproheptadine, and niclosamide to prevent clinical deterioration in patients with symptomatic COVID-19: a randomized clinical trial
98% lower ventilation (p<0.0001), 100% lower need for oxygen therapy (p<0.0001), 98% lower hospitalization (p<0.0001), and 55% lower PASC (p<0.0001). RCT 995 outpatients showing significantly lower progression with early treatment within 48 hours using fluvoxamine, fluvoxamine+bromhexine, fluvoxamine+cyproheptadine, and niclosamide+bromhexine. 70% of patients received treatment within ..
Mar 13
Yang et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2024.1765 COVID-19 Rebound After VV116 vs Nirmatrelvir-Ritonavir Treatment
RCT showing high rates of viral and symptom rebound with both paxlovid and deuremidevir (VV116). There are multiple potential reasons, with one being the highly specific targets within viral replication (Mpro and RdRp respectively). Paxlo..
Mar 8
Talebzadeh et al., Frontiers in Cellular and Infection Microbiology, doi:10.3389/fcimb.2024.1360075 The effect of vitamin D deficiency on platelet parameters in patients with COVID-19
Retrospective study of 707 COVID-19 patients showing higher platelet count and mean platelet volume (MPV) in patients with vitamin D deficiency compared to those without deficiency and healthy controls. There was a significant negative co..
Mar 8
Fujita et al., Journal of Infection and Chemotherapy, doi:10.1016/j.jiac.2024.03.007 Zinc deficiency is a potential risk factor for COVID-19 progression to pneumonia requiring oxygen therapy
86% lower need for oxygen therapy (p=0.007). Retrospective 60 hospitalized COVID-19 patients in Japan showing higher risk of progression to pneumonia requiring oxygen therapy with zinc deficiency at the time of diagnosis.
Mar 7
Lewandowski et al., Biomedicines, doi:10.3390/biomedicines12030605 Insulin and Metformin Administration: Unravelling the Multifaceted Association with Mortality across Various Clinical Settings Considering Type 2 Diabetes Mellitus and COVID-19
23% lower mortality (p=0.15). Retrospective 430 hospitalized COVID-19 patients with type 2 diabetes in Poland showing lower mortality with metformin and higher mortality with remdesivir, convalescent plasma, and aspirin in univariable analysis. These results were not..
Mar 7
Turrubiates-Hernández et al., Journa of Clinical Medicine, doi:10.3390/jcm13061538 Vitamin A Positively Correlates with Secretory Immunoglobulin A: A Cross-Sectional Study in Omicron COVID-19 Outpatients
Analysis of 39 COVID-19 outpatients showing a positive correlation between vitamin A nutritional status and secretory immunoglobulin A (SIgA) levels. Patients with higher dietary vitamin A intake showed higher SIgA/IgG1 and SIgA/IgG3 rati..
Mar 6
Vaziri et al., Heliyon, doi:10.1016/j.heliyon.2024.e27373 Investigating efficacy of colchicine plus phenolic monoterpenes fraction as a potential treatment for patients diagnosed with COVID-19: A randomized controlled parallel clinical trial
81% lower mortality (p=0.03), 87% lower ICU admission (p=0.002), and 35% shorter hospitalization (p<0.0001). RCT 179 hospitalized COVID-19 patients showing lower mortality, ICU admission, and hospitalization duration with colchicine plus phenolic monoterpenes compared to standard care alone. The intervention group received 0.8 mg/day colchicine ..
Mar 4
Guðnadóttir et al., Clinical Nutrition ESPEN, doi:10.1016/j.clnesp.2024.02.023 High risk of malnutrition among hospitalised coronavirus disease 2019 (COVID-19) patients is associated with mortality and other clinical outcomes
54% lower mortality (p=0.15), 8% lower ventilation (p=0.87), and 28% lower ICU admission (p=0.43). Retrospective 273 hospitalized COVID-19 patients in Iceland showing high risk of malnutrition associated with ICU admission, mechanical ventilation, and mortality. Mortality was higher with vitamin D insufficiency, but this result was not..
Mar 4
Li et al., Journal of Cancer, doi:10.7150/jca.91530 A Retrospective Analysis of Azvudine in Patients with COVID-19 and Pre-existing Cancer
11% shorter hospitalization (p=0.26) and 50% improved viral clearance (p=0.03). PSM retrospective 84 hospitalized COVID-19 patients with pre-existing cancer in China, showing faster viral clearance with azvudine. There was no significant difference in length of hospital stay or ICU admission.
Mar 4
Kow et al., International Journal of Pharmacy Practice, doi:10.1093/ijpp/riae003 Impact of uricosurics on mortality outcomes in patients with COVID-19: a systematic review and meta-analysis of randomized controlled trials
50% lower mortality (p=0.008). Systematic review and meta analysis of 27 RCTs investigating the impact of uricosuric drugs on mortality in COVID-19 patients. The pooled analysis found no significant association between uricosuric use and mortality risk. However, a subg..
Mar 4
Seifi et al., BMC Nutrition, doi:10.1186/s40795-024-00821-5 Dietary mineral intakes predict Coronavirus-disease 2019 (COVID-19) incidence and hospitalization in older adults
31% lower hospitalization (p=0.02). Analysis of 1,957 older adults showing lower risk of COVID-19 hospitalization with higher dietary zinc intake. Each unit increase in zinc intake was associated with a 31% reduction in the risk of COVID-19 hospitalization after adjustments..
Mar 2
Schreiber et al., Antiviral Research, doi:10.1016/j.antiviral.2024.105840 The host-targeted antiviral drug Zapnometinib exhibits a high barrier to the development of SARS-CoV-2 resistance
In Vitro study showing that molnupiravir and paxlovid induced resistant variants in SARS-CoV-2 during serial passaging, while the host-directed antiviral zapnometinib did not. Authors found that molnupiravir did not lead to abrogated vira..
Mar 2
Tentolouris et al., Nutrients, doi:10.3390/nu16050727 The Association of Vitamin D Receptor Polymorphisms with COVID-19 Severity
Case-control study of 137 COVID-19 patients and 72 controls in Greece showing an association between the TaqI vitamin D receptor polymorphism and increased risk of severe COVID-19, independent of potential confounders such as age, sex, an..
Mar 2
Grant, W., Advances in Food and Nutrition Research, doi:10.1016/bs.afnr.2023.12.007 Vitamin D and viral infections: Infectious diseases, autoimmune diseases, and cancers
Review of vitamin D and solar ultraviolet radiation-B (UVB) for reducing the risk of diseases related to viruses including certain respiratory tract diseases, autoimmune diseases, and several types of cancer. Author notes that vitamin D p..
Mar 1
Vu et al., Emerging Infectious Diseases, doi:10.3201/eid3003.231194 Estimates of Incidence and Predictors of Fatiguing Illness after SARS-CoV-2 Infection
Retrospective 4,589 COVID-19 patients and 9,022 matched controls showing that COVID-19 patients had a significantly higher risk of developing fatigue and chronic fatigue. Among COVID-19 patients, nutritional deficiency (including vitamin ..
Feb 29
Hayward et al., Journal of Infection, doi:10.1016/j.jinf.2024.106130 Ivermectin for COVID-19 in adults in the community (PRINCIPLE): an open, randomised, controlled, adaptive platform trial of short- and longer-term outcomes
Significantly improved recovery and significantly lower risk of long COVID with ivermectin (PRINCIPLE trial).. Significantly improved recovery and significantly lower risk of long COVID with ivermectin, despite very late treatment, low-risk patients, and poor administration. 36% lower ongoing persistent COVID-19 specific symptoms, p 0.999), missin..
Feb 29
Yong et al., International Journal of Nanomedicine, doi:10.2147/ijn.s451206 Natural Products-Based Inhaled Formulations for Treating Pulmonary Diseases
Review of nanoformulations for inhaled therapeutics for respiratory diseases including potential for COVID-19. Inhaled formulations deliver treatment directly to both the upper and lower respiratory tract, enabling higher local concentrat..
Feb 29
Nobori et al., Antiviral Research, doi:10.1016/j.antiviral.2024.105852 Prophylactic effect of ensitrelvir in mice infected with SARS-CoV-2
Mouse study showing protective effects against SARS-CoV-2 infection in aged mice with the 3CL protease inhibitor ensitrelvir. A single subcutaneous dose of ensitrelvir at 64, 96, or 128 mg/kg given 24 hours before a lethal SARS-CoV-2 chal..
Feb 28
Gerayeli et al., medRxiv, doi:10.1101/2024.02.26.24302674 Single cell sequencing reveals cellular landscape alterations in the airway mucosa of patients with pulmonary long COVID
Single-cell RNA sequencing study of airway cells from patients with persistent respiratory symptoms due to COVID-19 infection (pulmonary long COVID) over 1 year after initial infection. Authors found increased neutrophils and neutrophil a..
Feb 28
Sokolski et al., Scientific Reports, doi:10.1038/s41598-024-55407-9 Antiplatelet therapy prior to COVID-19 infection impacts on patients mortality: a propensity score-matched cohort study
no change in mortality (p=1). Retrospective 2,170 hospitalized COVID-19 patients showing no difference in mortality with remdesivir in unadjusted results.
Feb 28
Sartini et al., Nutrients, doi:10.3390/nu16050679 Preventive Vitamin D Supplementation and Risk for COVID-19 Infection: A Systematic Review and Meta-Analysis
Systematic review and meta analysis of 7 RCTs and 12 observational studies including over 1.2 million participants showing vitamin D prophylaxis associated with lower COVID-19 cases and lower ICU admission.
Feb 23
Standing et al., Nature Communications, doi:10.1038/s41467-024-45641-0 Randomized controlled trial of molnupiravir SARS-CoV-2 viral and antibody response in at-risk adult outpatients
103% worse viral clearance (p=0.33). PANORAMIC virology-sub-study showing increased viral persistence with molnupiravir treatment. Molnupiravir 800mg twice daily for 5 days led to faster initial viral decline but 86% still had detectable virus by day 5. By day 14, molnupirav..
Feb 23
Wang et al., Virology Journal, doi:10.1186/s12985-024-02316-y Effectiveness of azvudine in reducing mortality of COVID-19 patients: a systematic review and meta-analysis
Systematic review and meta-analysis of 17 studies showing significantly lower mortality with azvudine compared to no antiviral treatment in COVID-19 patients. The mortality benefit was seen in both mild/moderate and severe disease, as wel..
Feb 22
Low et al., bioRxiv, doi:10.1101/2024.02.21.581396 The wide spectrum anti-inflammatory activity of andrographolide in comparison to NSAIDs: a promising therapeutic compound against the cytokine storm
In vitro study showing that andrographolide exhibits broad anti-inflammatory and cytokine inhibiting activity against lipopolysaccharide (LPS) and interferon-γ induced inflammation in murine RAW264.7 and human THP-1 macrophage cell lines...
Feb 21
Wan et al., Scientific Reports, doi:10.1038/s41598-024-54722-5 Synergistic inhibition effects of andrographolide and baicalin on coronavirus mechanisms by downregulation of ACE2 protein level
In Vitro and mouse study showing that andrographolide and baicalin have synergistic antiviral effects against SARS-CoV-2. Andrographolide and baicalin inhibited binding between the SARS-CoV-2 spike protein and ACE2 receptor in human cells..
Feb 21
Kumar et al., Cells, doi:10.3390/cells13050369 Pre-Infection Innate Immunity Attenuates SARS-CoV-2 Infection and Viral Load in iPSC-Derived Alveolar Epithelial Type 2 Cells
In vitro study showing interindividual variability in iPSC-derived alveolar epithelial type 2 cells' susceptibility to SARS-CoV-2 infection and postinfection viral load. Results indicate AT2s mount an antiviral interferon response, though..
Feb 21
Henderson et al., Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkae042 COVID-19 hospitalization risk after outpatient nirmatrelvir/ritonavir use, January to August 2022, North Carolina
84% lower hospitalization (p=0.002). EHR retrospective 44, 671 patients with 4,948 receiving paxlovid, showing lower hospitalization with treatment.
Feb 20
de Gabory et al., European Archives of Oto-Rhino-Laryngology, doi:10.1007/s00405-024-08518-y Seawater nasal wash to reduce symptom duration and viral load in COVID-19 and upper respiratory tract infections: a randomized controlled multicenter trial
75% lower progression (p<0.0001), 24% faster recovery (p=0.02), and 37% improved viral clearance (p=0.54). RCT 355 adults with COVID-19 or other upper respiratory tract infections (URTIs). For COVID-19 patients there was lower progression and faster symptom resolution with alkaline seawater nasal wash (pH ~8) 4 times daily for 21 days. There w..
Feb 20
Hao et al., Nutrition Journal, doi:10.1186/s12937-024-00927-3 Association of dietary inflammatory index and the SARS-CoV-2 infection incidence, severity and mortality of COVID-19: a systematic review and dose-response meta-analysis
Systematic review and dose-response meta-analysis of 5 studies with 197,929 participants showing higher SARS-CoV-2 infection risk and COVID-19 severity with higher Dietary Inflammatory Index (DII) scores. The odds of COVID-19 increased 31..
Feb 20
Bell et al., Clinical Drug Investigation, doi:10.1007/s40261-024-01344-4 Real-World Effectiveness of Sotrovimab for the Early Treatment of COVID-19: Evidence from the US National COVID Cohort Collaborative (N3C)
24% lower combined mortality/hospitalization (p=0.0001) and 21% lower hospitalization (p=0.001). N3C retrospective 4,992 high-risk outpatients with mild-to-moderate COVID-19 showing reduced risk of hospitalization or death with sotrovimab treatment compared to 541,325 untreated controls during periods of Delta and Omicron BA.2 varian..
Feb 20
Bonnet et al., Frontiers in Medicine, doi:10.3389/fmed.2024.1305184 Antidepressants for prevention of severe COVID-19, Long COVID and outlook for other viral diseases
Review of clinical studies on the potential benefits of antidepressants for prevention and treatment of COVID-19 and its sequelae. Authors summarize evidence from retrospective studies, randomized controlled trials, prospective studies, a..
Feb 16
Rius-Salvador et al., PLOS ONE, doi:10.1371/journal.pone.0297291 Cetylpyridinium chloride and chlorhexidine show antiviral activity against Influenza A virus and Respiratory Syncytial virus in vitro
In Vitro study showing antiviral activity against influenza A virus and respiratory syncytial virus with cetylpyridinium chloride (CPC) and chlorhexidine (CHX). Authors found CPC and CHX decreased infectivity of both viruses by 90-99.9% d..
Feb 16
Hites et al., Journal of Infection, doi:10.1016/j.jinf.2024.106120 Tixagevimab-cilgavimab (AZD7442) for the treatment of patients hospitalized with COVID-19 (DisCoVeRy): a phase 3, randomized, double-blind, placebo-controlled trial
40% lower mortality (p=0.17), 18% worse 7-point scale results (p=0.52), 1% faster recovery (p=0.93), and 9% higher hospital discharge (p=0.49). RCT 173 hospitalized COVID-19 patients showing no significant difference in clinical status, time to recovery, viral clearance, or mortality with tixagevimab/cilgavimab. Mortality was lower, without statistical significance. The trial was..
Feb 15
Pasinato et al., Children, doi:10.3390/children11020249 Lactoferrin in the Prevention of Recurrent Respiratory Infections in Preschool Children: A Prospective Randomized Study
50% fewer cases (p=1). RCT 50 preschool children, 25 treated with bovine lactoferrin (bLf) prophylaxis, showing significantly lower frequency and duration of respiratory infections during the active phase with treatment. The only COVID-19 specific results repor..
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 3,957 studies, 2,119 present results comparing with a control group, 1,925 are treatment studies, and 194 analyze outcomes based on serum levels. There are 63 animal studies, 123 in silico studies, 220 in vitro studies, 245 reviews, and 172 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. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, 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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