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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 3,887 studies

Analysis of 66 COVID-19 early treatments, approvals in 104 countries, database of 6,687 treatments  
Sartini
Systematic review and meta analysis of 7 RCTs and 12 observational studies including over 1.2 million participants showing vitamin D prophylaxis..
Low
In vitro study showing that andrographolide exhibits broad anti-inflammatory and cytokine inhibiting activity against lipopolysaccharide (LPS) and..
de Gabory
173 patient alkalinization early treatment RCT: 75% lower progression (p<0.0001), 24% faster recovery (p=0.02), and 37% improved viral clearance (p=0.54)
Standing
592 patient molnupiravir early treatment RCT: 103% worse viral clearance (p=0.33)
Wang
Systematic review and meta-analysis of 17 studies showing significantly lower mortality with azvudine compared to no antiviral treatment in COVID-19..
Evolution of COVID-19 clinical evidence Vitamin D p<0.0000000001 early treatment Acetaminophen p=0.00000029 2020 2021 2022 2023 2024 Effective Harmful c19early.org February 2024 meta analysis results (pooled effects) 100% 50% 0% -50%
February 2024
c19early.org
Cost per life saved from NNT in
studies to date
Melatonin
9
48%
  $8
Vitamin D
67
36%
  $11
Vitamin C
39
19%
  $14
Zinc
20
29%
  $16
Ivermectin
51
49%
  $24
HCQ
249
24%
  $27
Alkalinization
5
42%
  $28
Vitamin A
6
42%
  $30
Colchicine
40
29%
  $31
Aspirin
61
10%
  $41
Curcumin
8
63%
  $59
Famotidine
21
18%
  $94
Probiotics
8
61%
  $99
Quercetin
5
61%
  $127
Metformin
60
34%
  $155
Antiandrogens
33
38%
  $175
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
Casirivimab/i..
8
40%
  $181,694
Paxlovid
28
32%
  $181,887
Bamlaniv../e..
11
59%
  $269,237
Sotrovimab
10
49%
  $352,800
Bebtelovimab
4
60%
  $737,601
Remdesivir
56
7%
  $1,502,505
Conv. Plasma
42
-0%
N/A
Acetaminophen
14
-24%
N/A
Treatment cost times median NNT - details and limitations. 0.6% of treatments show efficacy.
Azvudine Evusheld Paxlovid Regdanvimab Vitamin B12 Sunlight Alkalinization Phthalocyanine Fluvoxamine Famotidine Molnupiravir Quercetin Bamlanivimab/e.. Diet 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 February 2024 Time when COVID-19 studies showed efficacy
Azvudine Evusheld Paxlovid Regdanvimab Vitamin B12 Sunlight Alkalinization Phthalocyanine Fluvoxamine Famotidine Molnupiravir Quercetin Bamlanivimab/e.. Diet 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 February 2024 Time when COVID-19 studies showed efficacy
Timeline for when studies showed efficacy - 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% [53-68%] 100 $1 138,284 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 Bamlaniv../e.. 50% [27-66%] 17 $1,250 31,839 variant dependent 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 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 38% [21-52%] 20 $4 37,785 Vitamin A 38% [4-60%] 13 $2 22,277 Hydrogen Per.. 38% [5-59%] 7 $1 921 very limited data Phthalocyanine 38% [20-51%] 4 $5 5,245 Xiannuoxin 37% [-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 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 Azvudine 33% [19-44%] 15 $25 8,821 Spironolactone 31% [15-44%] 12 $5 28,019 Antiandrogens 30% [21-39%] 50 $5 120,212 Sleep 30% [22-38%] 15 $0 429,001 Vitamin B12 30% [5-48%] 4 $1 11,407 Metformin 29% [25-33%] 84 $10 264,872 Budesonide 29% [17-39%] 14 $4 27,882 Sotrovimab 29% [12-42%] 22 $2,100 43,988 variant dependent Probiotics 28% [18-37%] 26 $5 19,398 Colchicine 28% [18-36%] 50 $1 32,401 Zinc 27% [17-36%] 43 $1 55,200 Andrographis 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%] 67 $1 84,789 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 Paxlovid 14% [11-18%] 56 $1,390 118,172 independent trials refused Deuremidevir 11% [8-14%] 2 $112 1,432 very limited data Aspirin 11% [6-16%] 71 $1 185,894 Peg.. Lambda 7% [-138-63%] 4 $500 2,143 subcutaneous Remdesivir 6% [-1-12%] 66 $3,120 184,108 worse w/longer followup Ibuprofen 0% [-9-9%] 13 $1 54,707 Conv. Plasma -1% [-5-4%] 43 $5,000 24,299 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 February 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% 100 Thermotherapy 56% 4 very limited data Casirivimab/.. 52% 27 variant dependent Diet 50% 28 Bamlaniv../e.. 50% 17 variant dependent Povidone-Iod.. 50% 20 Quercetin 49% 11 HH-120 49% 2 very limited data 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 38% 20 Vitamin A 38% 13 Hydrogen Per.. 38% 7 very limited data Phthalocyanine 38% 4 Xiannuoxin 37% 2 very limited data Sunlight 37% 5 Vitamin D 37% 119 Selenium 34% 4 Bebtelovimab 34% 6 intravenous Nitazoxanide 33% 13 Azvudine 33% 15 Spironolactone 31% 12 Antiandrogens 30% 50 Sleep 30% 15 Vitamin B12 30% 4 Metformin 29% 84 Budesonide 29% 14 Sotrovimab 29% 22 variant dependent Probiotics 28% 26 Colchicine 28% 50 Zinc 27% 43 Andrographis 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% 67 Famotidine 17% 30 UDCA 15% 12 Favipiravir 15% 68 worse w/longer followup Molnupiravir 14% 39 mutagenic/teratogenic Paxlovid 14% 56 independent trials refused Deuremidevir 11% 2 very limited data Aspirin 11% 71 Peg.. Lambda 7% 4 subcutaneous Remdesivir 6% 66 worse w/longer followup Ibuprofen 0% 13 Conv. Plasma -1% 43 intravenous Vitamin B9 -11% 11 Cannabidiol -19% 7 Acetaminoph.. -28% 27 All studies (pooled effects, all stages) c19early.org February 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.
Sartini
Systematic review and meta analysis of 7 RCTs and 12 observational studies including over 1.2 million participants showing vitamin D prophylaxis..
Comunale
282 patients prophylaxis: 91% fewer symptomatic cases (p=0.0006) and 88% fewer cases (p=0.001)
Low
In vitro study showing that andrographolide exhibits broad anti-inflammatory and cytokine inhibiting activity against lipopolysaccharide (LPS) and..
Wan
In Vitro and mouse study showing that andrographolide and baicalin have synergistic antiviral effects against SARS-CoV-2. Andrographolide and..
de Gabory
173 patient early treatment RCT: 75% lower progression (p<0.0001), 24% faster recovery (p=0.02), and 37% improved viral clearance (p=0.54)
Standing
592 patient early treatment RCT: 103% worse viral clearance (p=0.33)
Wang
Systematic review and meta-analysis of 17 studies showing significantly lower mortality with azvudine compared to no antiviral treatment in COVID-19..
Hao
Systematic review and dose-response meta-analysis of 5 studies with 197,929 participants showing higher SARS-CoV-2 infection risk and COVID-19..
Kumar
In vitro study showing interindividual variability in iPSC-derived alveolar epithelial type 2 cells' susceptibility to SARS-CoV-2 infection and..
Bell
546,317 patients early treatment: 24% lower combined mortality/hospitalization (p=0.0001) and 21% lower hospitalization (p=0.001)
Zhu
311 patients early treatment: 79% worse viral clearance (p<0.0001)
Bonnet
Review of clinical studies on the potential benefits of antidepressants for prevention and treatment of COVID-19 and its sequelae. Authors summarize..
Chanyandura
Analysis of commonly purchased vitamin C supplements in South Africa during the COVID-19 pandemic finding that vitamin C tablets failed quality..
Mohta
Retrospective case-control study of 540 COVID-19 patients hospitalized in India, showing higher COVID-19 severity and mortality among those with..
Huang
Review of the relationship between bile acids and COVID-19. Authors discuss emerging basic and clinical evidence linking bile acids to COVID-19..
Pasinato
50 patient prophylaxis RCT: 50% fewer cases (p=1)
Hites
226 patient late treatment RCT: 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)
Halma
Review of autophagy pathways for treating SARS-CoV-2 spike protein-related pathology. Authors note that the spike protein is implicated in long..
Halma
Review of autophagy pathways for treating SARS-CoV-2 spike protein-related pathology. Authors note that the spike protein is implicated in long..
Moshawih
Review of NSAIDs and their complex immunomodulatory roles in SARS-CoV-2 infection. Authors discuss the mechanisms by which NSAIDs impact viral..
Moshawih
Review of NSAIDs and their complex immunomodulatory roles in SARS-CoV-2 infection. Authors discuss the mechanisms by which NSAIDs impact viral..
Recent studies (see the individual treatment pages for all studies):

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 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..
Feb 13
Mohta et al., Indian Dermatology Online Journal, doi:10.4103/idoj.idoj_222_23 The Association between COVID-19 Infection and Gabrin Sign: A Case-Control Study
Retrospective case-control study of 540 COVID-19 patients hospitalized in India, showing higher COVID-19 severity and mortality among those with androgenetic alopecia. Cases were further divided into those with more severe alopecia (Gabri..
Feb 13
Huang et al., Acta Pharmaceutica Sinica B, doi:10.1016/j.apsb.2024.02.011 Bile acids and coronavirus disease 2019
Review of the relationship between bile acids and COVID-19. Authors discuss emerging basic and clinical evidence linking bile acids to COVID-19 infection and potential mechanisms. Functionally, studies indicate that certain bile acids lik..
Feb 13
De Jesús-González et al., Microorganisms, doi:10.3390/microorganisms12020383 A Dual Pharmacological Strategy against COVID-19: The Therapeutic Potential of Metformin and Atorvastatin
Review of the therapeutic potential of metformin and atorvastatin against COVID-19. Authors discuss the immunomodulatory and antiviral capabilities of these commonly prescribed diabetes and cholesterol medications. They note metformin's a..
Feb 13
Muñoz-Vergara et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2023.55808 Prepandemic Physical Activity and Risk of COVID-19 Diagnosis and Hospitalization in Older Adults
27% lower hospitalization (p=0.002) and 9% fewer cases (p=0.004). Prospective study of 61,557 adults aged 45+ years showing reduced risk of COVID-19 diagnosis and hospitalization for those meeting physical activity guidelines of ≥7.5 MET-hours/week before the pandemic compared to inactive individuals.
Feb 11
Petakh et al., Viruses, doi:10.3390/v16020281 Metformin Alters mRNA Expression of FOXP3, RORC, and TBX21 and Modulates Gut Microbiota in COVID-19 Patients with Type 2 Diabetes
Retrospective 30 COVID-19 patients with type 2 diabetes showing improved T lymphocyte gene expression, gut microbiota diversity, and lower inflammatory markers with metformin treatment. Metformin-treated patients had a 1.96-fold increase ..
Feb 9
Chen et al., Scientific Reports, doi:10.1038/s41598-024-53862-y Comparison of azvudine, molnupiravir, and nirmatrelvir/ritonavir in adult patients with mild-to-moderate COVID-19: a retrospective cohort study
Retrospective 157 hospitalized mild-to-moderate COVID-19 patients showing no significant differences between azvudine, molnupiravir, and paxlovid for time to viral clearance and length of hospitalization.
Feb 9
Wang et al., eClinicalMedicine, doi:10.1016/j.eclinm.2024.102468 Antiviral effectiveness and survival correlation of azvudine and nirmatrelvir/ritonavir in elderly severe patients with COVID-19: a retrospective real-world study
20% lower mortality (p=0.44) and 3% lower progression (p=0.91). Retrospective 249 elderly patients with severe COVID-19, 128 treated with azvudine, 66 treated with paxlovid, and 55 receiving neither treatment, showing no significant differences for Ct value changes, progression, or survival for either..
Feb 9
Cheng et al., Kidney International Reports, doi:10.1016/j.ekir.2024.02.009 Effectiveness of molnupiravir and nirmatrelvir–ritonavir in CKD patients with COVID-19
15% lower mortality (p=0.003), no change in oxygen therapy (p=1), and 12% lower ICU admission (p=0.52). Retrospective emulated target trial of hospitalized COVID-19 patients with chronic kidney disease in Hong Kong showing lower mortality with molnupiravir and paxlovid treatment. No significant reduction was found in ICU admission or ventil..
Feb 6
Alkafaas et al., BMC Public Health, doi:10.1186/s12889-024-17747-z Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity
In Silico molecular docking analysis evaluating 71 functional inhibitors of acid sphingomyelinase (FIASMAs), showing that FIASMAs may prevent SARS-CoV-2 cell entry and infection via inhibiting ceramide platform formation that facilitates ..
Feb 6
Yoshida et al., Research Square, doi:10.21203/rs.3.rs-3899998/v1 Real-world Efficacy of Ensitrelvir in Hospitalized Patients with COVID-19 in Japan: A Retrospective Observational Study
Retrospective 154 hospitalized COVID-19 patients in Japan showing faster viral clearance and shorter hospitalization with ensitrelvir treatment compared to remdesivir or molnupiravir. There was no significant difference for fever resoluti..
Feb 6
Hidayah et al., International Conference on Organic and Applied Chemistry, doi:10.1063/5.0197724 Bioinformatics study of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin compounds in Curcuma longa as an antiviral agent via nucleocapsid on SARS-CoV-2 inhibition
In Silico study showing binding of curcumin, demethoxycurcumin, bisdemethoxycurcumin and cyclocurcumin to the SARS-CoV-2 nucleocapsid protein. Authors find curcumin has the strongest predicted binding affinity. All compounds showed suitab..
Feb 6
Maen et al., Frontiers in Pharmacology, doi:10.3389/fphar.2024.1291212 Individual ingredients of NP-101 (Thymoquinone formula) inhibit SARS-CoV-2 pseudovirus infection
In Vitro study showing that components of thymoquinone formulation NP-101, including thymoquinone, oleic acid, linoleic acid, and palmitic acid, showed dose-dependent inhibition of SARS-CoV-2 variants in a pseudovirus model. Combinations ..
Feb 6
Butzin-Dozier et al., medRxiv, doi:10.1101/2024.02.05.24302352 SSRI Use During Acute COVID-19 Infection Associated with Lower Risk of Long COVID Among Patients with Depression
N3C retrospective 506,903 outpatients with depression showing lower risk of long COVID with SSRI use. There was insufficient sample size to analyze the subgroup of fluvoxamine users.
Feb 5
Liu et al., Lupus, doi:10.1177/09612033241230736 Factors affecting different COVID-19 outcomes in patients with systemic lupus erythematosus during the second pandemic wave of COVID-19 in China
39% lower severe cases (p=0.26). Retrospective 301 consecutive SLE patients with COVID-19, showing lower risk of severe outcomes with HCQ use, with statistical significance in multivariable adjusted model 1 but not model 2.
Feb 2
Moshawih et al., Heliyon, doi:10.1016/j.heliyon.2024.e25734 Evaluating NSAIDs in SARS-CoV-2: Immunomodulatory mechanisms and future therapeutic strategies
Review of NSAIDs and their complex immunomodulatory roles in SARS-CoV-2 infection. Authors discuss the mechanisms by which NSAIDs impact viral replication, immune responses, and inflammation. They note NSAIDs can reduce neutrophil recruit..
Feb 2
Prasoppokakorn et al., OBM Integrative and Complementary Medicine, doi:10.21926/obm.icm.2401013 Efficacy and Safety of Andrographolide and Favipiravir Versus Favipiravir Monotherapy in Patients with Mild COVID-19 Infection: A Multicenter Randomized Controlled Trial
37% improved recovery (p=0.005). Randomized controlled trial of 82 mild COVID-19 outpatients showing significantly greater reduction in cough and lower inflammatory markers at day 7. Symptomatic improvement was significant at day 7 when combining all symptoms reported, b..
Feb 1
Frasson et al., Journal of Molecular Cell Biology. doi:10.1093/jmcb/mjae004 Identification of druggable host dependency factors shared by multiple SARS-CoV-2 variants of concern
In vitro study showing that inhibition of host cell factors rather than viral elements may prevent emergence of SARS-CoV-2 variants resistant to current drugs. Authors identified host genes/proteins commonly required for infection by majo..
Jan 31
Zhu et al., The Journal of Infection in Developing Countries, doi:10.3855/jidc.18138 Clinical characteristics and risk factors of non-mild outcomes in patients with Omicron variant COVID-19 in Shanghai, China
79% worse viral clearance (p<0.0001). Retrospective 311 COVID-19 patients in China showing significantly slower viral clearance with paxlovid in multivariable analysis.
Jan 31
Wang et al., medRxiv, doi:10.1101/2024.01.30.24302040 Healthy lifestyle for the prevention of post-COVID-19 multisystem sequelae, hospitalization, and death: a prospective cohort study
30% lower mortality (p<0.0001), 12% lower hospitalization (p<0.0001), and 14% lower PASC (p<0.0001). Prospective study of 68,896 UK Biobank participants with COVID-19 showing adherence to a healthy lifestyle prior to infection, characterized by 10 factors including adequate physical activity and sleep, not smoking, and a healthy BMI, was..
Jan 31
Soto et al., MDPI AG, doi:10.20944/preprints202401.2069.v1 The Redox Homeostasis Alteration Is Restored by Melatonin Treatment in COVID-19 Patients
Prospective study of 17 hospitalized COVID-19 patients showing restored redox homeostasis, decreased oxidative stress, improved antioxidant enzyme activity, modulated glucose homeostasis, and inhibited Warburg effect with melatonin treatm..
Jan 30
Chanyandura et al., J. Basic Appl. Pharm. Sci., doi:10.33790/jbaps1100105 Evaluation of The Pharmaceutical Quality of the Most Commonly Purchased Vitamin C (Ascorbic Acid) Formulations in COVID-19 Infection in South Africa
Analysis of commonly purchased vitamin C supplements in South Africa during the COVID-19 pandemic finding that vitamin C tablets failed quality tests like friability and had only 18% of the labelled vitamin C content, however vitamin C ca..
Jan 30
Halma et al., Endocrine and Metabolic Science, doi:10.1016/j.endmts.2024.100163 Exploring autophagy in treating SARS-CoV-2 spike protein-related pathology
Review of autophagy pathways for treating SARS-CoV-2 spike protein-related pathology. Authors note that the spike protein is implicated in long COVID and post-vaccination syndrome through mechanisms like inflammation, vascular damage, and..
Jan 30
Oranu et al., GSC Biological and Pharmaceutical Sciences, doi:10.30574/gscbps.2024.26.1.0030 Validation of the binding affinities and stabilities of ivermectin and moxidectin against SARS-CoV-2 receptors using molecular docking and molecular dynamics simulation
In Silico study showing that ivermectin and moxidectin bind strongly to SARS-CoV-2 viral targets including the main protease, helicase, and RNA polymerase. Binding was further validated through molecular dynamics simulations indicating st..
Jan 30
Koyama et al., medRxiv, doi:10.1101/2024.01.29.24301882 Possible roles of phytochemicals with bioactive properties in the prevention of and recovery from COVID-19
Survey of 1,583 participants globally showing higher daily intake of vegetables, herbs/spices, and fermented foods/beverages among those who did not contract COVID-19 compared to those who tested positive or suspected they had it. Shorter..
Jan 30
Mohammed et al., European Journal of Pharmaceutical Sciences, doi:10.1016/j.ejps.2024.106714 A remodeled ivermectin polycaprolactone-based nanoparticles for inhalation as a promising treatment of pulmonary inflammatory diseases
In Vitro and rat study showing that an optimized polycaprolactone-based nanoparticle formulation of ivermectin for inhalation had improved lung deposition, bioavailability, and anti-inflammatory effects compared to oral ivermectin. Author..
Jan 29
Taufer et al., Microorganisms, doi:10.3390/microorganisms12020284 Lactobacilli in COVID-19: A Systematic Review Based on Next-Generation Sequencing Studies
Review of nine studies using next generation sequencing to analyze the association between lactobacilli and COVID-19, focusing on the gut and upper respiratory tract microbiota. Studies showed that lactobacilli have reduced abundance in C..
Jan 29
Singh et al., Research Square, doi:10.21203/rs.3.rs-3888947/v1 Unlocking the potential of phytochemicals in inhibiting SARS-CoV-2 M Pro protein - An in-silico and cell-based approach
In Silico and In Vitro study including quercetin and curcumin derivatives as potential SARS-CoV-2 main protease (Mpro) inhibitors. Molecular dynamics simulations and virtual screening identified quercetin and curcumin derivatives demethox..
Jan 29
Jang et al., Endocrinology and Metabolism, doi:10.3803/EnM.2024.1857 Impact of Antidiabetic Drugs on Clinical Outcomes of COVID-19: A Nationwide Population-Based Study
60% lower mortality (p=0.02), 72% lower ventilation (p=0.008), 39% lower ICU admission (p=0.12), and 30% lower need for oxygen therapy (p=0.23). Retrospective 556 diabetic patients in South Korea with COVID-19 showing lower risk of mechanical ventilation and death with metformin, lower risks of oxygen treatment and death with DPP-4 inhibitors, and increased risk of mechanical vent..
Jan 29
Rozemeijer et al., Nutrients, doi:10.3390/nu16030385 Micronutrient Status of Critically Ill Patients with COVID-19 Pneumonia
Prospective pilot study of 20 critically ill COVID-19 ICU patients showing high deficiency rates of 50-100% for vitamins A, B6, and D; zinc; and selenium at admission. Deficiencies of vitamins B6 and D, and low iron status, persisted afte..
Jan 28
Saito et al., Infection Prevention in Practice, doi:10.1016/j.infpip.2024.100341 Predictors of in-hospital mortality in elderly unvaccinated patients during SARS-CoV-2 Alpha variants epidemic
168% higher mortality (p=0.06). Retrospective 132 hospitalized COVID-19 patients over age 65 in Japan during the Alpha variant surge, showing higher mortality with favipiravir in unadjusted results, without statistical significance.
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 3,887 studies, 2,099 present results comparing with a control group, 1,907 are treatment studies, and 192 analyze outcomes based on serum levels. There are 58 animal studies, 120 in silico studies, 215 in vitro studies, 240 reviews, and 165 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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