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Hydroxychlor..
Iota-carragee..
Ivermectin
Lactoferrin
Lifestyle..
Melatonin
Metformin
Molnupiravir
Monoclonals..
Nigella Sativa
Nitazoxanide
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COVID-19 early treatment: real-time analysis of 2,665 studies
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All studies   Early treatment   Mortality   Early mortality   Prophylaxis   Prophylaxis mortality   Physicians   Recent
Analysis of 50 COVID early treatments, approvals in 101 countries, database of 2,727 treatments  
Recently added (more..)  Vitamin B9  Vitamin D  Sotrovimab  Paxlovid  Colchicine
Farag
363 patient vitamin B9 prophylaxis RCT: 88% fewer cases [p<0.0001]
Schmidt
Vitamin D sufficiency: 86% lower mortality [p=0.003]
Shapiro
RCT 982 high risk outpatients in the USA reporting that intramuscular sotrovimab was non-inferior to intravenous administration. Death and..
Igho-Osagie
Analysis of 15,685 adults in the USA estimating that 29.3% of the population risk a major or contraindicated drug interaction with paxlovid, which..
Villamañán
222 patients colchicine late treatment: 42% lower mortality [p=0.03]
Cost per life saved from NNT in
studies to date c19early.org Mar 2023
Melatonin
9
48%
  $8
Vitamin D
60
36%
  $10
Vitamin C
34
27%
  $12
Alkalinization
4
42%
  $18
Ivermectin
48
51%
  $22
Zinc
19
29%
  $23
Colchicine
37
35%
  $26
HCQ
231
22%
  $28
Vitamin A
6
42%
  $30
Aspirin
56
12%
  $33
Curcumin
7
63%
  $40
Fluvoxamine
6
47%
  $69
Probiotics
8
61%
  $99
Famotidine
18
17%
  $105
Metformin
46
32%
  $172
Antiandrogens
32
38%
  $179
Quercetin
4
59%
  $188
Nigella Sativa
4
73%
  $279
Nitazoxanide
6
42%
  $680
Budesonide
9
28%
  $887
Favipiravir
32
15%
  $1,015
Paxlovid
13
59%
  $46,111
Molnupiravir
15
23%
  $137,653
Casirivimab/i..
8
40%
  $181,694
Remdesivir
44
14%
  $208,615
Bamlaniv../e..
10
56%
  $301,549
Sotrovimab
9
57%
  $442,638
Tixagev../c..
5
38%
  $740,002
Conv. Plasma
39
-6%
N/A
Acetaminophen
13
-27%
N/A
Treatment cost times median NNT - details and limitations. 1.3% of treatments show efficacy.
Evusheld Paxlovid Alkalinization Fluvoxamine Famotidine Molnupiravir Quercetin Bamlanivimab/e.. Budesonide Probiotics Curcumin REGEN-COV Aspirin Povidone-Iodine Nigella Sativa Melatonin Acetaminophen ↑risk Favipiravir Vitamin D Vitamin C Colchicine Remdesivir Antiandrogens Ivermectin Metformin Zinc HCQ 2020 2021 2022 Pooled outcomes Specific outcome RCT pooled RCT specific Statistically significant ≥10% improvement ≥3 studies c19early.org Mar 2023 Time when COVID-19 studies showed efficacy
Evusheld Paxlovid Alkalinization Fluvoxamine Famotidine Molnupiravir Quercetin Bamlanivimab/e.. Budesonide Probiotics Curcumin REGEN-COV Aspirin Povidone-Iodine Nigella Sativa Melatonin Acetaminophen ↑risk Favipiravir Vitamin D Vitamin C Colchicine Remdesivir Antiandrogens Ivermectin Metformin Zinc HCQ 2020 2021 2022 Pooled outcomes Specific outcome RCT pooled RCT specific Statistically significant ≥10% improvement ≥3 studies c19early.org Mar 2023 Time when COVID-19 studies showed efficacy
Timeline for when studies showed efficacy - details and limitations. 1.3% of treatments show efficacy.
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All clinical results for selected treatments. 1.3% of treatments show efficacy.
0 0.25 0.5 0.75 1 1.25 1.5 1.75 2+ Iota-carragee.. 80% [11-96%] 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% [54-69%] 95 $1 134,554 Bamlaniv../e.. 55% [30-71%] 14 $1,250 24,423 variant dependent Nigella Sativa 53% [27-70%] 11 $5 2,959 Casirivimab/i.. 53% [33-66%] 26 $2,100 54,453 variant dependent Quercetin 50% [20-69%] 10 $5 1,387 Povidone-Iod.. 50% [37-61%] 20 $1 3,226 Tixagev../c.. 48% [27-64%] 9 $855 26,568 variant dependent Ensovibep 46% [-173-89%] 2 $2,100 885 limited data Diet 46% [36-54%] 22 $0 687,588 Sunlight 45% [19-62%] 4 $0 19,635 Bebtelovimab 44% [-827-97%] 2 $1,200 1,134 intravenous Melatonin 43% [30-54%] 18 $1 14,301 Alkalinization 43% [23-58%] 7 $1 1,092 Vitamin A 40% [-10-67%] 11 $2 18,305 Exercise 40% [33-46%] 53 $0 1,791,863 Fluvoxamine 39% [19-54%] 14 $4 35,144 Curcumin 38% [26-47%] 23 $5 5,029 Vitamin D 37% [31-42%] 107 $1 182,747 Paxlovid 35% [26-43%] 25 $529 65,803 independent trials refused Spironolactone 34% [15-49%] 11 $5 28,145 Nitazoxanide 33% [-22-63%] 13 $4 3,606 Colchicine 32% [22-41%] 46 $1 31,711 Bromhexine 32% [-0-54%] 8 $5 1,025 very limited data Budesonide 31% [16-43%] 11 $4 26,206 Antiandrogens 29% [20-38%] 47 $5 119,885 Zinc 29% [18-39%] 40 $1 45,723 Sleep 29% [20-37%] 13 $0 356,150 Metformin 27% [22-32%] 61 $10 605,395 Ensitrelvir 27% [-19-55%] 2 $500 255 very limited data Nitric Oxide 27% [-11-52%] 9 $11 1,484 Sotrovimab 25% [-17-52%] 16 $2,100 33,142 variant dependent Hydroxychlor.. 25% [21-29%] 384 $1 512,826 Probiotics 24% [15-33%] 22 $5 18,114 Lactoferrin 24% [-30-56%] 6 $5 1,213 Vitamin C 23% [15-31%] 58 $1 58,655 Favipiravir 20% [9-30%] 59 $20 28,804 N-acetylcys.. 19% [8-29%] 19 $1 25,043 Molnupiravir 16% [-5-33%] 30 $707 104,953 mutagenic/teratogenic Famotidine 15% [5-25%] 25 $5 92,443 Remdesivir 12% [4-20%] 48 $3,120 134,963 intravenous Aspirin 12% [6-17%] 64 $1 172,879 Peg.. Lambda 7% [-138-63%] 4 $500 2,143 subcutaneous Ibuprofen -1% [-10-8%] 12 $1 54,527 Conv. Plasma -5% [-16-5%] 40 $5,000 27,132 intravenous Vitamin B9 -11% [-60-23%] 8 $1 19,180 Cannabidiol -19% [-128-38%] 7 $25 16,883 Acetaminoph.. -28% [-43--14%] 21 $1 497,235 All studies (pooled effects, all stages) c19early.org Mar 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% 95 Bamlaniv../e.. 55% 14 variant dependent Nigella Sativa 53% 11 Casirivimab/.. 53% 26 variant dependent Quercetin 50% 10 Povidone-Iod.. 50% 20 Tixagev../c.. 48% 9 variant dependent Ensovibep 46% 2 limited data Diet 46% 22 Sunlight 45% 4 Bebtelovimab 44% 2 intravenous Melatonin 43% 18 Alkalinization 43% 7 Vitamin A 40% 11 Exercise 40% 53 Fluvoxamine 39% 14 Curcumin 38% 23 Vitamin D 37% 107 Paxlovid 35% 25 independent trials refused Spironolactone 34% 11 Nitazoxanide 33% 13 Colchicine 32% 46 Bromhexine 32% 8 very limited data Budesonide 31% 11 Antiandrogens 29% 47 Zinc 29% 40 Sleep 29% 13 Metformin 27% 61 Ensitrelvir 27% 2 very limited data Nitric Oxide 27% 9 Sotrovimab 25% 16 variant dependent Hydroxychlor.. 25% 384 Probiotics 24% 22 Lactoferrin 24% 6 Vitamin C 23% 58 Favipiravir 20% 59 N-acetylcys.. 19% 19 Molnupiravir 16% 30 mutagenic/teratogenic Famotidine 15% 25 Remdesivir 12% 48 intravenous Aspirin 12% 64 Peg.. Lambda 7% 4 subcutaneous Ibuprofen -1% 12 Conv. Plasma -5% 40 intravenous Vitamin B9 -11% 8 Cannabidiol -19% 7 Acetaminoph.. -28% 21 All studies (pooled effects, all stages) c19early.org Mar 23 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. 1.3% 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. 1.3% 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. 1.3% 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. 1.3% 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. 1.3% 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. 1.3% 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 - 38 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. Vladimir Zelenko USA 2,200 0.5% (12) 98.6% 0.1% (2) 96.3%
Mean improvement with early treatment protocols 236,564 HospitalizationHosp. 94.0% MortalityDeath 94.8%
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.
Treatment
Improvement
  (early)
Studies
  (early)
BUBudesonide 82% 1
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PXProxalutamide 71% 3
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
BLBamlaniv../e.. 69% 8
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(H)CQHydroxychlor.. 62% 36
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IVMIvermectin 62% 37
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
RDRemdesivir 61% 4
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
V.DVitamin D 60% 11
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FVFluvoxamine 56% 6
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CICasirivimab/i.. 47% 20
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
PLPaxlovid 41% 23
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ZnZinc 41% 6
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SSotrovimab 34% 14
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
FPVFavipiravir 26% 17
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
V.CVitamin C 24% 5
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MPMolnupiravir 18% 26
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ACEAcetaminophen -17% 3
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
TCTixagev../c.. -29% 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IBIbuprofen -52% 2
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Early treatments approved by >2 countries. 101 countries have officially approved treatments. Details.
Vitamin B9
Farag
363 patient prophylaxis RCT: 88% fewer cases [p<0.0001]
Tseimakh
Prospective study of 117 patients in Serbia, 78 treated with folic acid, pyridoxine hydrochloride, and cyanocobalamin, showing improved resolution..
Monserrat Villatoro
Prophylaxis PSM: 132% higher mortality [p=0.003]
Doğan
66 patients sufficiency: 56% lower mortality [p=0.46] and 11% higher ICU admission [p=1]
Zhang
In Vitro and mouse study showing that folic acid decreased ACE2 expression and inhibited SARS-CoV-2.
Yas
Retrospective 75 COVID-19 patients and 45 healthy controls in Iraq, showing lower folic acid levels in COVID-19 patients, and lower levels for..
Itelman
Retrospective 162 COVID-19 patients in Israel, showing lower vitamin B9 levels associated with increased COVID-19 severity.
Meisel
334 patients prophylaxis: 27% lower mortality [p=0.54] and 6% lower combined mortality/intubation [p=0.88]
Ersöz
Retrospective 310 hospitalized COVID-19 patients in Turkey, showing patients that were admitted to the ICU, intubated, or died had lower vitamin B9..
Galmés
Ecological study in Spain, showing lower intake of vitamin D, A, B9, and zinc in regions with the highest COVID-19 incidence and mortality. Vitamin..
Voelkle
57 patients sufficiency: 12% lower combined mortality/ICU admission [p=0.02]
Darand
Retrospective 9,189 adults showing no significant relationship between vitamin B9 intake and COVID-19 cases.
Bliek-Bueno
8,570 patients prophylaxis: 87% higher mortality [p<0.0001]
Topless
376,254 patients prophylaxis: 164% higher mortality [p<0.0001] and 51% more cases [p<0.0001]
Vitamin D
Schmidt
Sufficiency: 86% lower mortality [p=0.003]
Sposato
Retrospective 8,221 COVID+ patients in Italy, showing significantly lower ICU admission and CPAP/NIV use in the spring/summer compared to the winter..
Pugach
Analysis of COVID-19 in European countries, finding a correlation between the prevalence of severe vitamin D deficiency and the mortality rate.
Sotrovimab
Shapiro
RCT 982 high risk outpatients in the USA reporting that intramuscular sotrovimab was non-inferior to intravenous administration. Death and..
Paxlovid
Igho-Osagie
Analysis of 15,685 adults in the USA estimating that 29.3% of the population risk a major or contraindicated drug interaction with paxlovid, which..
Colchicine
Villamañán
222 patients late treatment: 42% lower mortality [p=0.03]
Quercetin
Ibeh
In Silico study identifying quercetin and naringenin as potent multitarget-directed ligands for 3CLpro, PLpro, and ACE2 with favorable ADME..
Antiandrogen
Davidsson
655 patients prophylaxis: 2% lower IgG positivity [p=0.95]
Zinc
Young
Retrospective 5 patients in the USA, showing 100% recovery of post-COVID-19 taste and smell disorders with a treatment protocol including zinc,..
HCQ
Million
Retrospective 424 consecutive patients in France showing that HCQ+AZ treatment was safe for early stage COVID-19 treatment with the protocol used,..
Exercise
Zhang
Mendelian randomization study showing lower risk of COVID-19 severity, hospitalization, and cases with light physical activity, but no significant..
Recent studies (see the individual treatment pages for all studies):
Mar 27
 Sposato et al., Epidemiol Prev., doi:10.19191/EP23.1.A503.016 COVID-19 severity appears to be reduced in spring/summer
Retrospective 8,221 COVID+ patients in Italy, showing significantly lower ICU admission and CPAP/NIV use in the spring/summer compared to the winter. There was no significant difference in viral load. Vitamin D levels were higher and CRP ..
Mar 24
 Huang et al., Frontiers in Medicine, doi:10.3389/fmed.2023.1121256 Effect of vitamin D status on adult COVID-19 pneumonia induced by Delta variant: A longitudinal, real-world cohort study
25% faster recovery [p=0.02]. Retrospective COVID-19 pneumonia patients in China, showing slower recovery with vitamin D deficiency.
Mar 24
 Shapiro et al., medRxiv, doi:10.1101/2023.03.21.23287410 (Preprint) Intramuscular Versus Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Non-inferiority Clinical Trial
RCT 982 high risk outpatients in the USA reporting that intramuscular sotrovimab was non-inferior to intravenous administration. Death and hospitalization was more frequent with intramuscular administration, without statistical significan..
Mar 23
 Igho-Osagie et al., Clinical Therapeutics, doi:10.1016/j.clinthera.2023.03.012 Prevalence of Potential Drug-Drug Interactions with Ritonavir-Containing COVID-19 therapy in the United States: An Analysis of the National Health and Nutrition Examination Survey
Analysis of 15,685 adults in the USA estimating that 29.3% of the population risk a major or contraindicated drug interaction with paxlovid, which may increase significantly for patients over 60 or with several comorbidities that also inc..
Mar 23
 Villamañán et al., Section 4: Clinical pharmacy services, doi:10.1136/ejhpharm-2023-eahp.56 Targeting patients with pneumonia by COVID-19 that could be beneficiated by colchicine
42% lower mortality [p=0.03]. Retrospective 111 hospitalized COVID-19 pneumonia patients treated with colchicine and 111 matched controls, showing lower mortality with colchicine treatment.
Mar 22
 Schmidt et al., Journal of Clinical Medicine, doi:10.3390/jcm12062429 Identification of Clinical Response Predictors of Tocilizumab Treatment in Patients with Severe COVID-19 Based on Single-Center Experience
86% lower mortality [p=0.003]. Prospective study of 120 severe COVID-19 patients in Poland treated with tocilizumab, showing significantly higher mortality with low vitamin D levels.
Mar 22
 Ibeh et al., Informatics in Medicine Unlocked, doi:10.1016/j.imu.2023.101230 Computational studies of potential antiviral compounds from some selected Nigerian medicinal plants against SARS-CoV-2 proteins
In Silico study identifying quercetin and naringenin as potent multitarget-directed ligands for 3CLpro, PLpro, and ACE2 with favorable ADME properties.
Mar 21
 Lahaye et al., Nutrients, doi:10.3390/nu15061516 Minerals and Antioxidant Micronutrients Levels and Clinical Outcome in Older Patients Hospitalized for COVID-19 during the First Wave of the Pandemic
28% lower mortality [p=0.26] and 53% lower severe cases [p=0.02]. Retrospective 235 hospitalized COVID-19 patients in France, showing lower zinc levels associated with severe cases. Results are provided for zinc levels as a continuous value.
Mar 21
 Asoudeh et al., Clinical Nutrition ESPEN, doi:10.1016/j.clnesp.2023.03.013 The association between dietary intakes of zinc, vitamin C and COVID-19 severity and related symptoms: A cross-sectional study
57% lower severe cases [p=0.03]. Retrospective 250 recovered COVID-19 patients, showing lower risk of severe cases with higher zinc intake.
Mar 21
 Young et al., Research Square, doi:10.21203/rs.3.rs-2702282/v1 (Preprint) Novel Protocol Using a Comprehensive Training ‘N’ Treatment (TNT) Approach Rapidly Reverses Olfactory and Gustatory Dysfunction in Patients with Acute Loss of Taste and Smell Induced by SARS-CoV-2 Infection
Retrospective 5 patients in the USA, showing 100% recovery of post-COVID-19 taste and smell disorders with a treatment protocol including zinc, vitamin A, B-complex, vitamin D, and alpha lipoic acid in addition to saline nasal irrigation,..
Mar 17
 Million et al., MDPI AG, doi:10.20944/preprints202303.0325.v1 (Preprint) Cardiovascular Safety of Hydroxychloroquine-Azithromycin in 424 COVID-19 Patients
Retrospective 424 consecutive patients in France showing that HCQ+AZ treatment was safe for early stage COVID-19 treatment with the protocol used, which excluded 11 patients for contraindications. Treatment contraindications were the pres..
Mar 16
 Kelleni, M., Center for Open Science, doi:10.31219/osf.io/5xd6q (Review) (Preprint) Peg-interferon Lambda Single Dose Treatment for COVID-19: A Call to Avoid another Hydroxychloroquine Fiasco
Review of critical issues with [Reis]. Author notes that NEJM declined to publish these issues without comment.
Mar 15
 Davran et al., Konuralp Tıp Dergisi, doi:10.18521/ktd.1134319 Relationship between vitamin D level and clinical status in COVID-19 patients
75% lower mortality [p=0.02]. Retrospective 47 outpatient and 47 hospitalized COVID-19 patients in Turkey, showing higher mortality with vitamin D deficiency in unadjusted results.
Mar 15
 Wang et al., Frontiers in Public Health, doi:10.3389/fpubh.2023.1145669 Efficacy of nasal irrigation and oral rinse with sodium bicarbonate solution on virus clearance for COVID-19 patients
39% shorter hospitalization [p=0.0009]. RCT 55 mild/moderate patients in China, showing shorter hospitalization with sodium bicarbonate nasal irrigation and oral rinsing. Oral rinse with 5% sodium bicarbonate solution three times daily. Nasal irrigation two times with the solut..
Mar 15
 Goodwin et al., PLOS ONE, doi:10.1371/journal.pone.0281915 Evaluation of outpatient treatment for non-hospitalised patients with COVID-19: The experience of a regional centre in the UK
110% higher mortality [p=0.47] and 58% lower hospitalization [p=0.7]. Retrospective 604 outpatients in the UK, showing lower risk of hospitalization with molnupiravir treatment, without statistical significance due to the small number of hospitalizations.
Mar 15
 Schloss et al., Inflammopharmacology, doi:10.1007/s10787-023-01183-3 (Review) Nutritional deficiencies that may predispose to long COVID
Review of 22 nutritional factors that have been linked to COVID-19 outcomes, the role of nutrients in COVID-19 infection, and the prevalence of multiple nutritional deficiencies in the population.
Mar 13
 Kim et al., Proceedings of the National Academy of Sciences, doi:10.1073/pnas.2221857120 Computational prediction of interactions between Paxlovid and prescription drugs
In Silico analysis of drug–drug interactions for paxlovid. From 2,248 prescription drugs, 1,628 were predicted to have 2,445 interactions with nirmatrelvir and/or ritonavir (673 for nirmatrelvir and 1,403 ritonavir). For 873 drugs, author..
Mar 9
 Siuka et al., F1000Research, doi:10.12688/f1000research.131730.1 The effect of Vitamin D levels on the course of COVID-19 in hospitalized patients – a 1-year prospective cohort study
56% lower mortality [p=0.24], 59% higher ICU admission [p=0.59], and 61% higher severe cases [p=0.009]. Prospective study of 301 hospitalized patients in Slovenia, showing higher mortality with vitamin D deficiency, without statistical significance. Fewer patients with severe cases were deficient, which authors hypothesize was due to their..
Mar 8
 Zhang et al., Frontiers in Physiology, doi:10.3389/fphys.2023.1089637 The causal effect of physical activity intensity on COVID-19 susceptibility, hospitalization, and severity: Evidence from a mendelian randomization study
Mendelian randomization study showing lower risk of COVID-19 severity, hospitalization, and cases with light physical activity, but no significant difference for moderate-to-vigorous physical activity. Authors note that they were unable t..
Mar 6
 Bucurica et al., Diagnostics, doi:10.3390/diagnostics13050998 Association of Vitamin D Deficiency and Insufficiency with Pathology in Hospitalized Patients
28% fewer cases [p<0.0001]. Retrospective 11,182 hospitalized patients in Romania, showing vitamin D deficiency associated with COVID-19 cases.
Mar 6
 Bhat et al., Journal of Infection, doi:10.1016/j.jinf.2023.03.004 Effect of calcifediol supplementation as add-on therapy on the immune repertoire in recipients of the ChAdOx1 nCoV-19 vaccine: A prospective open-label, placebo-controlled, clinical trial
34% fewer symptomatic cases [p=0.01]. Prospective study of 580 ChAdOx1 recipients, 262 treated with calcifediol (patient choice), showing lower cases with treatment. Supplementation did not significantly affect antibody levels following ChAdOx1 receipt. Calcifediol patients w..
Mar 5
 Langen, M., Rounding The Earth (Review) (Preprint) Melatonin - the Hormone of Both Sun and Darkness - Protects Your Health and Can Save Your Life
Extensive review of melatonin and the evidence of beneficial effects for many health issues including COVID-19.
Mar 5
 Durstenfeld et al., medRxiv, doi:10.1101/2023.03.02.23286730 Association of Nirmatrelvir/Ritonavir Treatment with Long COVID Symptoms in an Online Cohort of Non-Hospitalized Individuals Experiencing Breakthrough SARS-CoV-2 Infection in the Omicron Era
14% higher PASC [p=0.4]. Retrospective 4,684 COVID+ patients mostly in the USA, 988 treated with paxlovid, showing higher odds of long COVID with treatment, without statistical significance.
Mar 5
 Liu et al., The Journal of Nutrition, doi:10.1016/j.tjnut.2023.03.001 Vitamin D and SARS-CoV-2 Infection: SERVE Study (SARS-CoV-2 Exposure and the Role of Vitamin D among Hospital Employees)
Prospective study of 250 healthcare workers in the USA. The results are unclear - Figure 3 shows ~40% lower incidence with vitamin D supplementation, while the text indicates OR 1.18. Authors collected symptom information, stating that &q..
Mar 4
 Matino et al., Nutrients, doi:10.3390/nu15051285 Effect of Lactoferrin on Clinical Outcomes of Hospitalized Patients with COVID-19: The LAC Randomized Clinical Trial
12% higher mortality [p=0.85], 45% higher ventilation [p=0.39], 6% higher combined mortality/ICU admission [p=0.87], and 34% worse recovery [p=0.12]. RCT 218 hospitalized patients in Italy, showing no significant differences with lactoferrin treatment. Authors note that in several previous studies showing clinical improvement, lactoferrin was given at an earlier stage of disease. Autho..
Mar 4
 Ibrahim Alhajjaji et al., Saudi Pharmaceutical Journal, doi:10.1016/j.jsps.2023.02.011 Effect of zinc supplementation on symptom reduction and length of hospital stay among pediatric patients with Coronavirus Disease 2019 (COVID-19)
88% lower mortality [p=0.13], 26% lower ventilation [p=0.75], 3% lower ICU admission [p=1], and 73% lower progression [p=0.004]. Retrospective 101 hospitalized pediatric patients in Saudi Arabia, showing zinc treatment associated with lower respiratory failure and shorter hospitalization in unadjusted results. Patients receiving zinc were older. Authors note elevat..
Mar 3
 Al-Gharrawi et al., Scientific Reports, doi:10.1038/s41598-023-30859-7 Association of ApaI rs7975232 and BsmI rs1544410 in clinical outcomes of COVID-19 patients according to different SARS-CoV-2 variants
Retrospective 3,184 patients in Iran, showing COVID-19 outcomes for specific variants were associated with genotypes of the ApaI rs7975232 and BsmI rs1544410 vitamin D receptor polymorphisms.
Mar 3
 Samajdar et al., Lung India, doi:10.4103/lungindia.lungindia_268_22 Effectiveness of budesonide formoterol fixed-dose combination MDI in reducing cough symptoms in COVID-19 patients: A real-world evidence study
69% lower hospitalization [p=0.07] and 29% improved recovery [p=0.008]. Prospective study of 102 patients in India, showing improved recovery of cough with budesonide+formoterol. Authors note better results with earlier treatment. Budesonide 800mcg + formoterol 12mcg bid for 7 days.
Mar 3
 Kirenga et al., Molecular Psychiatry, doi:10.1038/s41380-023-02004-3 Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study
68% lower mortality [p<0.0001] and 53% improved recovery [p=0.04]. Prospective study of 316 hospitalized patients in Uganda, 94 receiving fluvoxamine, showing significantly lower mortality and improved recovery with treatment.
Mar 2
 Cousins et al., medRxiv, doi:10.1101/2023.02.28.23286515 Association between spironolactone use and COVID-19 outcomes in population-scale claims data: a retrospective cohort study
18% lower mortality [p=0.004] and 17% lower ventilation [p<0.0001]. PSM retrospective 898,303 hospitalized COVID-19 patients in the USA, 16,324 on spironolactone, showing lower mortality and ventilation with spironolactone use.
Mar 2
 Spivak et al., Microbiology Spectrum, doi:10.1128/spectrum.04674-22 A Randomized Clinical Trial Testing Hydroxychloroquine for Reduction of SARS-CoV-2 Viral Shedding and Hospitalization in Early Outpatient COVID-19 Infection
73% higher hospitalization [p=0.54], 20% improved recovery [p=0.19], and 17% improved viral clearance [p=0.19]. Delayed publication of an early terminated late treatment RCT with low-risk (no mortality) outpatients in the USA, showing no significant differences with HCQ. Authors do not provide symptom onset data, but the subgroup analysis suggests ..
Mar 1
 Irie, K., Yakugaku Zasshi, doi:10.1248/yakushi.22-00169-1 (Dosing) Pharmacokinetic Study of Antiviral Drugs in Patients with COVID-19
Pharmacokinetics study measuring the blood concentration of favipiravir in 7 critical patients in Japan, showing concentrations below the EC50 in 33 of 36 samples when using the standard dosing regimen. Authors note that patient character..
Feb 28
 Punzalan et al., Frontiers in Immunology, doi:10.3389/fimmu.2023.1123497 Utility of laboratory and immune biomarkers in predicting disease progression and mortality among patients with moderate to severe COVID-19 disease at a Philippine tertiary hospital
42% higher mortality [p=0.12] and 59% higher progression [p=0.001]. Prospective study of 400 hospitalized patients in the Philippines, showing higher progression with remdesivir in unadjusted results, without statistical significance.
Feb 28
 Topan et al., Nutrients, doi:10.3390/nu15051227 25 Hydroxyvitamin D Serum Concentration and COVID-19 Severity and Outcome—A Retrospective Survey in a Romanian Hospital
31% lower mortality [p=0.02] and 11% lower severe cases [p=0.02]. Retrospective 2,342 hospitalized COVID-19 patients in Romania with vitamin D levels measured on admission day, showing lower risk of mortality and severe/critical cases with vitamin D levels ≥ 20ng/mL.
Feb 28
 Domazet Bugarin et al., Nutrients, doi:10.3390/nu15051234 Vitamin D Supplementation and Clinical Outcomes in Severe COVID-19 Patients—Randomized Controlled Trial
21% lower mortality [p=0.2], no change in recovery [p=0.71], and 6% longer hospitalization [p=0.76]. Very late stage RCT 155 ICU patients in Croatia with low vitamin D levels, showing no significant differences with 10,000IU cholecalciferol daily. Calcifediol or calcitriol, which avoids several days delay in conversion, may be more succe..
Feb 28
 Mathew et al., Rheumatology Advances in Practice, doi:10.1093/rap/rkad025 Predictors of COVID-19 severity and outcomes in Indian patients with rheumatic diseases: a prospective cohort study
20% lower mortality [p=0.8], no change in hospitalization [p=0.94], and 40% lower severe cases [p=0.37]. Prospective study of 64 rheumatic disease patients with COVID-19, showing no significant difference in outcomes with HCQ use.
Feb 28
 Llanos-Cuentas et al., BMC Research Notes, doi:10.1186/s13104-023-06281-7 Hydroxychloroquine to prevent SARS-CoV-2 infection among healthcare workers: early termination of a phase 3, randomised, open-label, controlled clinical trial
69% more cases [p=0.46]. Early terminated healthcare worker PrEP RCT with only 68 patients and 8 cases, showing no significant difference with HCQ. No information on symptoms per group, case severity, or the timing of cases is provided.
Feb 28
 Chen et al., Infection and Drug Resistance, doi:10.2147/idr.s400561 Plasma 25(OH)D Level is Associated with the Nucleic Acid Negative Conversion Time of COVID-19 Patients: An Exploratory Study
40% improved viral clearance [p=0.01]. Retrospective 158 COVID+ patients in China, showing low vitamin D levels associated with slower viral clearance.
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 2,665 studies, 1,719 present results comparing with a control group, 1,562 are treatment studies, and 157 analyze outcomes based on serum levels. There are 32 animal studies, 66 in silico studies, 134 in vitro studies, and 132 meta analyses.
Please send us corrections, updates, or comments. 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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