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@CovidAnalysis

COVID-19 early treatment: real-time analysis of 3,494 studies

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Analysis of 57 COVID-19 early treatments, approvals in 102 countries, database of 5,852 treatments  
Recently added (more..)  Vitamin D  HCQ  Paxlovid  Sotrovimab  Curcumin
Renieris
190 patients vitamin D sufficiency: 52% lower mortality (p=0.04)
Rabe
6,145 patients HCQ prophylaxis: 29% fewer cases (p=0.22)
Wei
725 patients paxlovid late treatment: no change in mortality (p=1), 38% higher ventilation (p=0.04), 122% higher ICU admission (p=0.05), and 28% higher progression (p=0.07)
Leducq
Prospective study of 264 high-risk COVID-19 patients treated with monoclonal antibodies. Tixagevimab/cilgavimab was associated with 5 times higher..
Hulscher
Review of evidence that the SARS-CoV-2 spike protein can damage cardiovascular, hematological, neurological, respiratory, gastrointestinal, and..
Evolution of COVID-19 clinical evidence Vitamin D p<0.0000000001 early treatment Acetaminophen p=0.00000045 2020 2021 2022 2023 Effective Harmful c19early.org November 2023 meta analysis results (pooled effects) 100% 50% 0% -50%
November 2023
c19early.org
Cost per life saved from NNT in
studies to date
Melatonin
9
48%
  $8
Vitamin D
67
36%
  $10
Vitamin C
39
19%
  $14
Zinc
20
29%
  $16
Ivermectin
51
49%
  $24
HCQ
247
25%
  $27
Alkalinization
5
42%
  $28
Vitamin A
6
42%
  $30
Colchicine
39
33%
  $31
Aspirin
59
11%
  $41
Curcumin
8
63%
  $59
Famotidine
20
19%
  $94
Probiotics
8
61%
  $99
Quercetin
5
61%
  $127
Metformin
55
32%
  $163
Antiandrogens
33
38%
  $175
Nigella Sativa
4
73%
  $279
Nitazoxanide
6
42%
  $680
Budesonide
11
26%
  $887
Favipiravir
36
14%
  $1,258
Fluvoxamine
9
43%
  $1,283
Molnupiravir
16
24%
  $137,653
Casirivimab/i..
8
40%
  $181,694
Paxlovid
23
34%
  $181,887
Bamlaniv../e..
11
59%
  $269,237
Sotrovimab
10
49%
  $352,800
Bebtelovimab
4
60%
  $737,601
Remdesivir
53
9%
  $997,792
Tixagev../c..
6
36%
  $14,894,456
Conv. Plasma
41
-0%
N/A
Acetaminophen
14
-24%
N/A
Treatment cost times median NNT - details and limitations. 0.6% of treatments show efficacy.
Evusheld Paxlovid 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 November 2023 Time when COVID-19 studies showed efficacy
Evusheld Paxlovid 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 November 2023 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 Proxalutamide 78% [70-83%] 4 $500 1,953 limited data Indomethacin 74% [-20-94%] 4 $5 605 limited data Ivermectin 62% [54-68%] 99 $1 137,255 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 Nigella Sativa 49% [27-64%] 12 $5 3,132 Ensovibep 46% [-173-89%] 2 $2,100 885 limited data Tixagev../c.. 44% [24-58%] 12 $855 27,448 variant dependent Adintrevimab 43% [-169-88%] 2 $5,000 2,483 intramuscular Melatonin 43% [30-54%] 18 $1 14,301 Bromhexine 43% [-5-69%] 7 $5 875 very limited data Alkalinization 43% [24-57%] 8 $1 1,148 Curcumin 42% [30-52%] 26 $5 14,736 Exercise 40% [34-45%] 64 $0 1,813,021 Fluvoxamine 38% [21-52%] 20 $4 37,785 Vitamin A 38% [4-60%] 13 $2 22,277 Phthalocyanine 38% [20-51%] 4 $5 5,245 Hydrogen Per.. 38% [4-59%] 7 $1 835 limited data Sunlight 37% [22-50%] 5 $0 19,665 Vitamin D 36% [30-41%] 118 $1 194,403 Spironolactone 35% [16-50%] 11 $5 28,019 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 Sleep 32% [22-40%] 14 $0 360,105 Colchicine 30% [20-39%] 49 $1 32,401 Antiandrogens 30% [20-38%] 49 $5 119,838 Vitamin B12 30% [5-48%] 4 $1 11,407 Budesonide 30% [16-41%] 13 $4 27,762 Metformin 28% [23-32%] 77 $10 263,902 Zinc 27% [17-36%] 43 $1 55,200 Probiotics 27% [17-36%] 25 $5 19,328 Hydroxychlor.. 26% [23-30%] 414 $1 535,832 Ensitrelvir 26% [-14-52%] 3 $500 1,450 very limited data Sotrovimab 26% [9-40%] 21 $2,100 42,808 variant dependent Nitric Oxide 26% [-12-50%] 10 $11 2,008 Lactoferrin 22% [-33-54%] 7 $5 1,369 N-acetylcys.. 21% [12-30%] 23 $1 25,993 Vitamin C 20% [13-26%] 66 $1 84,189 Favipiravir 17% [7-26%] 67 $20 30,542 worse w/longer followup Famotidine 17% [6-26%] 29 $5 114,119 Paxlovid 16% [12-19%] 49 $1,390 110,273 independent trials refused Molnupiravir 15% [4-24%] 37 $707 126,024 mutagenic/teratogenic Aspirin 11% [6-17%] 69 $1 185,894 Remdesivir 7% [1-14%] 62 $3,120 183,315 worse w/longer followup Peg.. Lambda 7% [-138-63%] 4 $500 2,143 subcutaneous Ibuprofen 0% [-9-9%] 13 $1 54,707 Conv. Plasma -1% [-5-4%] 42 $5,000 24,249 intravenous Vitamin B9 -11% [-47-15%] 11 $1 54,354 Cannabidiol -19% [-128-38%] 7 $25 16,883 Acetaminoph.. -29% [-42--17%] 26 $1 542,859 All studies (pooled effects, all stages) c19early.org November 2023 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 Proxalutamide 78% 4 limited data Indomethacin 74% 4 limited data Ivermectin 62% 99 Casirivimab/.. 52% 27 variant dependent Diet 50% 28 Bamlaniv../e.. 50% 17 variant dependent Povidone-Iod.. 50% 20 Quercetin 49% 11 Nigella Sativa 49% 12 Ensovibep 46% 2 limited data Tixagev../c.. 44% 12 variant dependent Adintrevimab 43% 2 intramuscular Melatonin 43% 18 Bromhexine 43% 7 very limited data Alkalinization 43% 8 Curcumin 42% 26 Exercise 40% 64 Fluvoxamine 38% 20 Vitamin A 38% 13 Phthalocyanine 38% 4 Hydrogen Per.. 38% 7 limited data Sunlight 37% 5 Vitamin D 36% 118 Spironolactone 35% 11 Selenium 34% 4 Bebtelovimab 34% 6 intravenous Nitazoxanide 33% 13 Sleep 32% 14 Colchicine 30% 49 Antiandrogens 30% 49 Vitamin B12 30% 4 Budesonide 30% 13 Metformin 28% 77 Zinc 27% 43 Probiotics 27% 25 Hydroxychlor.. 26% 414 Ensitrelvir 26% 3 very limited data Sotrovimab 26% 21 variant dependent Nitric Oxide 26% 10 Lactoferrin 22% 7 N-acetylcys.. 21% 23 Vitamin C 20% 66 Favipiravir 17% 67 worse w/longer followup Famotidine 17% 29 Paxlovid 16% 49 independent trials refused Molnupiravir 15% 37 mutagenic/teratogenic Aspirin 11% 69 Remdesivir 7% 62 worse w/longer followup Peg.. Lambda 7% 4 subcutaneous Ibuprofen 0% 13 Conv. Plasma -1% 42 intravenous Vitamin B9 -11% 11 Cannabidiol -19% 7 Acetaminoph.. -29% 26 All studies (pooled effects, all stages) c19early.org November 2023 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.
Vitamin D
Renieris
190 patients sufficiency: 52% lower mortality (p=0.04)
HCQ
Rabe
6,145 patients prophylaxis: 29% fewer cases (p=0.22)
Paxlovid
Wei
725 patients late treatment: no change in mortality (p=1), 38% higher ventilation (p=0.04), 122% higher ICU admission (p=0.05), and 28% higher progression (p=0.07)
Sotrovimab
Leducq
Prospective study of 264 high-risk COVID-19 patients treated with monoclonal antibodies. Tixagevimab/cilgavimab was associated with 5 times higher..
Casirivimab/imdevimab
Leducq
Prospective study of 264 high-risk COVID-19 patients treated with monoclonal antibodies. Tixagevimab/cilgavimab was associated with 5 times higher..
Tixagevimab/cilgavimab
Leducq
Prospective study of 264 high-risk COVID-19 patients treated with monoclonal antibodies. Tixagevimab/cilgavimab was associated with 5 times higher..
Curcumin
Hulscher
Review of evidence that the SARS-CoV-2 spike protein can damage cardiovascular, hematological, neurological, respiratory, gastrointestinal, and..
Quercetin
DiGuilio
In Vitro analysis of quercetin on airway epithelial barrier function using the Calu-3 cell culture model. Results show that quercetin increases..
Wu
In Vitro and mouse study showing that quercetin may ameliorate COVID-19 associated acute kidney injury through modulation of macrophage polarization..
Budesonide
Yong
PSM retrospective 64,587 asthmatic patients using inhaled corticosteroids (ICS) and 64,587 matched controls without ICS use. ICS medications..
Exercise
Pavlidou
5,197 patients: 42% fewer cases (p=0.001)
Sleep
Pavlidou
5,197 patients: 40% fewer cases (p=0.01)
Diet
Pavlidou
5,197 patients: 55% fewer cases (p=0.0009)
Recent studies (see the individual treatment pages for all studies):
Nov 23
 Leducq et al., The Journal of Infectious Diseases, doi:10.1093/infdis/jiad523 Spike protein genetic evolution in patients at high-risk of severe COVID-19 treated by monoclonal antibodies
Prospective study of 264 high-risk COVID-19 patients treated with monoclonal antibodies. Tixagevimab/cilgavimab was associated with 5 times higher risk of emergence of mutations. Treatment with sotrovimab was linked to mutations associate..
Nov 23
 Strizki et al., Infectious Diseases and Therapy, doi:10.1007/s40121-023-00891-1 Virologic Outcomes with Molnupiravir in Non-hospitalized Adult Patients with COVID-19 from the Randomized, Placebo-Controlled MOVe-OUT Trial
Virological outcomes for the MOVe-OUT trial. Results are shown with the main paper [Jayk Bernal].
Nov 23
 DiGuilio et al., Frontiers in Cell and Developmental Biology, doi:10.3389/fcell.2023.1271201 Quercetin improves and protects Calu-3 airway epithelial barrier function
In Vitro analysis of quercetin on airway epithelial barrier function using the Calu-3 cell culture model. Results show that quercetin increases transepithelial electrical resistance and decreases transepithelial leaks, indicating improved..
Nov 21
 Hulscher et al., Cureus, doi:10.7759/cureus.49204 Clinical Approach to Post-acute Sequelae After COVID-19 Infection and Vaccination
Review of evidence that the SARS-CoV-2 spike protein can damage cardiovascular, hematological, neurological, respiratory, gastrointestinal, and immunological systems, and may be a primary cause of long COVID symptoms. Authors introduce a ..
Nov 20
 Tare et al., BJGP Open, doi:10.3399/bjgpo.2023.0109 The DAWN antivirals trial: process evaluation of a COVID-19 trial in general practice
83% worse recovery (p=0.36). Very small early terminated RCT with 8 molnupiravir and 17 placebo patients showing worse recovery with molnupiravir, without statistical significance.
Nov 20
 Atefi et al., Immunity, Inflammation and Disease, doi:10.1002/iid3.1083 Evaluation of the efficacy and safety of oral N‐acetylcysteine in patients with COVID‐19 receiving the routine antiviral and hydroxychloroquine protocol: A randomized controlled clinical trial
67% lower mortality (p=0.61). RCT 60 hospitalized COVID-19 patients evaluating the efficacy and safety of adding oral N-acetylcysteine (NAC) at 600mg three times daily to standard antiviral treatment regimens. The NAC group showed significantly greater reduction in C-..
Nov 17
 Tallaksen, E., Do Your Own Research, Nov 17, 2023 Waiting for PRINCIPLE
Discussion of issues in the ivermectin arm of the PRINCIPLE trial [PRINCIPLE], including the unsupported supply claim and continuation, design issues favoring finding no effect, changes to include lower risk patients, and the extended del..
Nov 16
 García-Aguilar et al., International Journal of Molecular Sciences, doi:10.3390/ijms242216392 In Vitro Analysis of SARS-CoV-2 Spike Protein and Ivermectin Interaction
In Vitro analysis showing a definitive interaction between ivermectin and the spike (S) protein of SARS-CoV-2, suggesting therapeutic potential for COVID-19. Using equilibrium dialysis and UV–Vis techniques, the study determined the affin..
Nov 15
 Cyril et al., Inflammopharmacology, doi:10.1007/s10787-023-01385-9 Nigella sativa and its chemical constituents: pre-clinical and clinical evidence for their potential anti-SARS-CoV-2 effects
Review of pre-clinical and clinical evidence for the the use of nigella sativa for the prevention and treatment of SARS-CoV-2 infection.
Nov 15
 Moatasim et al., Microorganisms, doi:10.3390/microorganisms11112777 Potent Antiviral Activity of Vitamin B12 against Severe Acute Respiratory Syndrome Coronavirus 2, Middle East Respiratory Syndrome Coronavirus, and Human Coronavirus 229E
In Vitro and In Silico analysis finding that methylcobalamin, hydroxocobalamin, and cyanocobalamin forms of vitamin B12 showed broad-spectrum inhibition against SARS-CoV-2, MERS-CoV, and HCoV-229E. Methylcobalamin had the highest activity..
Nov 14
 Flynn et al., Biology Methods and Protocols, doi:10.1093/biomethods/bpad033 Crowdsourcing Temporal Transcriptomic Coronavirus Host Infection Data: resources, guide, and novel insights
Ensemble transcriptomic analyses showing that HCQ exhibited strong inverse correlations to SARS-CoV-1 infected lung early temporal meta-signatures at 1, 2, and 4 days post-infection. This suggests HCQ may help counteract pathogenic proces..
Nov 11
 Xu et al., Nucleic Acids Research, doi:10.1093/nar/gkad1002 Uridine–cytidine kinase 2 potentiates the mutagenic influence of the antiviral β-d-N4-hydroxycytidine
In Vitro study showing that molnupiravir increased mutation rates in mouse blood cancer cell lines. The mutagenic effects were enhanced by overexpression of the enzyme uridine-cytidine kinase 2 (Uck2), and lessened in Uck2 knockout cells...
Nov 11
 Qin et al., Medical Data Mining, doi:10.53388/MDM202407003 Exploring the bioactive compounds of Feiduqing formula for the prevention and management of COVID-19 through network pharmacology and molecular docking
In Silico study of components of Feiduqing finding that quercetin, among other compounds, has significant binding affinity to PTGS2, HSP90AA1, SARS-CoV-2 Mpro, and ACE2, suggesting that quercetin may have therapeutic potential for COVID-1..
Nov 11
 Hafizi et al., Trials, doi:10.1186/s13063-023-07624-2 Beneficial effects of the combination of BCc1 and Hep-S nanochelating-based medicines on IL-6 in hospitalized moderate COVID-19 adult patients: a randomized, double-blind, placebo-controlled clinical trial
35% lower mortality (p=0.68), 81% lower need for oxygen therapy, and 22% improved recovery. Randomized, double-blind, placebo-controlled trial of 122 moderate hospitalized COVID-19 patients in Iran, evaluating the addition of BCc1 iron chelator and Hep-S selenium nanomedicines to standard treatment. The nanomedicine group showed..
Nov 10
 Zhang et al., Journal of Medical Virology, doi:10.1002/jmv.29208 Discovery of the covalent SARS‐CoV‐2 Mpro inhibitors from antiviral herbs via integrating target‐based high‐throughput screening and chemoproteomic approaches
In Vitro study showing that quercetin can potently inhibit SARS-CoV-2 Mpro activity. Screening of 60 antiviral herbs showed Lonicera japonica extract inhibited Mpro in a time-dependent manner, indicating the presence of covalent cysteine-..
Nov 9
 Pavlidou et al., Diseases, doi:10.3390/diseases11040165 Association of COVID-19 Infection with Sociodemographic, Anthropometric and Lifestyle Factors: A Cross-Sectional Study in an Older Adults’ Population Aged over 65 Years Old
42% fewer cases (p=0.001). Retrospective 5,197 Greek adults over 65. After adjustment for confounders, COVID-19 infection was independently associated with poor sleep, low physical activity, low Mediterranean diet adherence, living in urban areas, smoking, obesity,..
Nov 9
 Erbaş et al., Journal of Biochemical and Molecular Toxicology, doi:10.1002/jbt.23536 Assessment of toxicological effects of favipiravir (T‐705) on the lung tissue of rats: An experimental study
Analysis of the toxicological effects of favipiravir on healthy lung tissue in rats. Authors found that favipiravir treatment increased oxidative stress, apoptosis, and inflammation in the lung tissue as evidenced by changes in antioxidan..
Nov 8
 Bondareva et al., Cell Host & Microbe, doi:10.1016/j.chom.2023.10.007 Cross-regulation of antibody responses against the SARS-CoV-2 Spike protein and commensal microbiota via molecular mimicry
Analysis of the role of oral microbiota, particularly Streptococcus salivarius, in enhancing immune response against SARS-CoV-2. Authors show that several commensal bacteria express proteins that mimic the receptor binding domain of the s..
Nov 7
 Avula et al., Journal of Clinical and Translational Science, doi:10.1017/cts.2023.668 Strategies used for the COVID-OUT decentralized trial of outpatient treatment of SARS-CoV-2
Report on the operation of the COVID-OUT trial noting several issues affecting the reliability of the results: - Use of home pulse oximeters for measuring oxygen saturation: authors note that the FDA warned about inaccuracies with home pu..
Nov 7
 Akbar et al., MDPI AG, doi:10.20944/preprints202311.0330.v1 Association between lifestyle factors and COVID-19: findings from Qatar Biobank
18% more cases (p=0.29). Retrospective 10,000 adults in Qatar, showing higher risk of COVID-19 cases with vitamin B9 supplementation, without statistical significance. Authors do not analyze COVID-19 severity.
Nov 7
 Vargas-Castro et al., MDPI AG, doi:10.20944/preprints202311.0402.v1 Calcitriol Downregulates ACE1/ACE2, Renin and TMPRSS2 Gene Expression in the Human Placenta
In Vitro study showing calcitriol downregulated ACE2 and TMPRSS2 (involved in SARS-CoV-2 entry), renin (involved in blood pressure regulation), and ACE1/ACE2 ratio in cultured human placental cells. Authors suggest calcitriol could potent..
Nov 6
 Vanhelst et al., Scientific Reports, doi:10.1038/s41598-023-46162-4 Association of SARS-CoV-2 infection with physical activity domains and types
Retrospective 22,165 adults in the French NutriNet-Santé cohort showing higher levels of total physical activity, vigorous activity, leisure-time activity, household activity, outdoor activity, and indoor activity during the COVID-19 lock..
Nov 6
 Tallaksen, E., Do Your Own Research TOGETHER Files 2: Lawsuit reveals FTX bought effective control of TOGETHER trial, part of SBF's dream of a pharma empire
Analysis of legal documents showing that a non-profit controlled by FTX's SBF and a former colleague invested >$50 million in the Together Trial and had the right to potentially control the company. Author notes that incorrect and mislead..
Nov 5
 Daramola et al., DIGITAL HEALTH, doi:10.1177/20552076231207593 Detecting the most critical clinical variables of COVID-19 breakthrough infection in vaccinated persons using machine learning
Retrospective 257 individuals, finding higher physical activity as one of the most predictive variables for lower risk of COVID-19 breakthrough infection.
Nov 3
 Wu et al., Frontiers in Immunology, doi:10.3389/fimmu.2023.1264447 SARS-CoV-2 N protein induced acute kidney injury in diabetic db/db mice is associated with a Mincle-dependent M1 macrophage activation
In Vitro and mouse study showing that quercetin may ameliorate COVID-19 associated acute kidney injury through modulation of macrophage polarization by blocking the Mincle/Syk/NF-kB pathway. Authors suggest that the SARS-CoV-2 N protein c..
Nov 2
 Sarlin et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2023.40608 Streptococcus salivarius Probiotics to Prevent Acute Otitis Media in Children
33% fewer cases (p=1). RCT 827 children aged 1-6 years in daycare in Finland analyzing the effectiveness of daily Streptococcus salivarius K12 oral probiotic use for 6 months in preventing acute otitis media (AOM). The probiotic group did not have a significant..
Nov 2
 Moschovou et al., International Journal of Molecular Sciences, doi:10.3390/ijms242115894 Exploring the Binding Effects of Natural Products and Antihypertensive Drugs on SARS-CoV-2: An In Silico Investigation of Main Protease and Spike Protein
In Silico molecular docking and molecular dynamics analysis identifying curcumin, quercetin, rosmarinic acid, and salvianolic acid B as having favorable binding to Mpro and three distinct sites on the S protein. Molecular dynamics simulat..
Nov 1
 Yong et al., Frontiers in Pharmacology, doi:10.3389/fphar.2023.1204297 Associations between COVID-19 outcomes and asthmatic patients with inhaled corticosteroid
PSM retrospective 64,587 asthmatic patients using inhaled corticosteroids (ICS) and 64,587 matched controls without ICS use. ICS medications included budesonide, mometasone, flunisolide, beclomethasone, fluticasone, and ciclesonide. ICS u..
Nov 1
 Amirizadeh et al., Health Science Reports, doi:10.1002/hsr2.1676 The effect of remdesivir on mortality and the outcome of patients with COVID‐19 in intensive care unit: A case–control study
3% higher mortality (p=1), 52% longer ventilation (p=0.17), 27% longer ICU admission (p=0.23), and 24% longer hospitalization (p=0.22). Retrospective 70 COVID-19 ICU patients, 35 receiving remdesivir plus standard treatment and 35 receiving standard treatment only. No significant differences were found for mortality, hospitalization time, ICU time, or ventilation time.
Nov 1
 Zhang et al., Medical Gas Research, doi:10.4103/2045-9912.385414 Saying No to SARS-CoV-2: the potential of nitric oxide in the treatment of COVID-19 pneumonia
Review of nitric oxide (NO) in the treatment of COVID-19. Authors summarizes evidence from in vitro studies suggesting NO has direct antiviral effects against SARS-CoV-2 as well as immune modulating and pulmonary protective effects. Small..
Oct 31
 Lindsell et al., Journal of Clinical and Translational Science, doi:10.1017/cts.2023.644 ACTIV-6: Operationalizing a decentralized, outpatient randomized platform trial to evaluate efficacy of repurposed medicines for COVID-19
Discussion of the operation of ACTIV-6 [Naggie] revealing participant fraud - authors identified participants that signed up repeatedly, and participants that withdrew when not randomized to their preferred arm. Authors indicate that they..
Oct 31
 Ioannou et al., Annals of Internal Medicine, doi:10.7326/M23-1394 Effectiveness of Nirmatrelvir–Ritonavir Against the Development of Post–COVID-19 Conditions Among U.S. Veterans
1% lower PASC (p=0.75). Retrospective 9,593 veterans in the USA treated with paxlovid, matched to 9,593 untreated controls, showing no significant difference in post-COVID conditions across 31 different conditions. There was lower risk for the combination of 2 s..
Oct 31
 Winyupakorn et al., Research Square, doi:10.21203/rs.3.rs-3484296/v1 Liver injury in non-severe COVID-19 with various pandemic phases: a real-world study
Prospective study of 300 patients with mild to moderate COVID-19 in Thailand, showing the highest risk of liver injury with molnupiravir treatment, OR 3.4 (p = 0.06).
Oct 31
 Ho et al., HCA Healthcare Journal of Medicine, doi:10.36518/2689-0216.1546 A Retrospective Cohort Study Assessing the Impact of Statin Therapy on Hospital Length of Stay and Inpatient Mortality in COVID-19 Patients
62% higher mortality (p<0.0001). Retrospective 26,445 hospitalized COVID-19 patients in the USA, showing higher mortality with remdesivir.
Oct 29
 Berkowitz et al., International Journal of Molecular Sciences, doi:10.3390/ijms242115718 Sigma Receptor Ligands Prevent COVID Mortality In Vivo: Implications for Future Therapeutics
Mouse study showing the combination of lactoferrin and diphenhydramine resulted in slower weight loss, improved survival, and faster weight recovery in SARS-CoV-2 infected animals compared to controls. The study authors propose the..
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 3,494 studies, 1,982 present results comparing with a control group, 1,795 are treatment studies, and 187 analyze outcomes based on serum levels. There are 46 animal studies, 94 in silico studies, 185 in vitro studies, 212 reviews, and 146 meta analyses.
Please send us corrections, updates, or comments. c19early involves the extraction of over 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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