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Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans

Hunt et al., Journal of General Internal Medicine, doi:10.1007/s11606-022-07701-3
Jun 2022  
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Mortality 47% Improvement Relative Risk Vitamin D for COVID-19  Hunt et al.  EARLY TREATMENT Is early treatment with vitamin D beneficial for COVID-19? Retrospective 26,508 patients in the USA (March - September 2020) Lower mortality with vitamin D (p=0.00072) c19early.org Hunt et al., J. General Internal Medic.., Jun 2022 Favorsvitamin D Favorscontrol 0 0.5 1 1.5 2+
Vitamin D for COVID-19
8th treatment shown to reduce risk in October 2020, now with p < 0.00000000001 from 122 studies, recognized in 9 countries.
No treatment is 100% effective. Protocols combine treatments.
5,000+ studies for 109 treatments. c19early.org
Retrospective 26,508 consecutive COVID+ veterans in the USA, showing lower mortality with multiple treatments including vitamin D. Treatment was defined as drugs administered ≥50% of the time within 2 weeks post-COVID+, and may be a continuation of prophylactic treatment in some cases, and may be early or late treatment in other cases. Further reduction in mortality was seen with combinations of treatments.
This is the 87th of 122 COVID-19 controlled studies for vitamin D, which collectively show efficacy with p<0.0000000001 (1 in 587 sextillion).
30 studies are RCTs, which show efficacy with p=0.0000032.
Study covers vitamin D, metformin, antihistamine H1RAs, and colchicine.
risk of death, 47.0% lower, RR 0.53, p < 0.001, treatment 43 of 1,019 (4.2%), control 1,569 of 25,489 (6.2%), adjusted per study, day 30.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Hunt et al., 29 Jun 2022, retrospective, USA, peer-reviewed, 8 authors, study period 1 March, 2020 - 10 September, 2020, dosage not specified.
This PaperVitamin DAll
Medications Associated with Lower Mortality in a SARS-CoV-2 Positive Cohort of 26,508 Veterans
MD, MPH Christine M Hunt, PhD, MSc Jimmy T Efird, Thomas S Redding, MS, BSPH Andrew D Thompson Jr, MPH Ashlyn M Press, PhD, MPH Christina D Williams, MD MPH Christopher J Hostler, MD Ayako Suzuki
Journal of General Internal Medicine, doi:10.1007/s11606-022-07701-3
BACKGROUND: Many severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) positive patients take commonly prescribed medications with properties which may affect mortality. OBJECTIVE: Assess if common medications postulated to affect clinical outcomes are associated with mortality in SARS-CoV-2 positive patients in the Veterans Health Administration (VHA). DESIGN: Observational national cohort analysis. PARTICIPANTS: Consecutive 26,508 SARS-CoV-2 positive Veterans (7% of 399,290 tested from March 1 to September 10, 2020) constitute the study cohort. MAIN MEASURES: The primary outcome was 30-day mortality from the first positive SARS-CoV-2 test date. In patients receiving medications or drug pairs within 2 weeks post-SARS-CoV-2 positive test, 30-day mortality was estimated as relative risk (RR) on the log-binomial scale or using multinomial models with and without adjusting for covariates. KEY RESULTS: The 26,508 SARS-CoV-2 positive patients were predominantly male (89%) and White (59%), and 82% were overweight/obese. Medications associated with decreased 30-day mortality risk included the following: metformin (aRR, 0.33; 95% CI, 0.25-0.43), colchicine, angiotensinconverting-enzyme inhibitors (ACEi), angiotensin II receptor blockers, statins, vitamin D, antihistamines, alpha-blockers, anti-androgens, and nonsteroidal anti-inflammatory drugs (aRR, 0.69; 95% CI, 0.61-0.78). The effect of co-prescribed medications on 30-day mortality risk revealed the lowest risk for combined statins and metformin (aRR, 0.21; 95% CI, 0.15-0.31), followed by ACEi and statins (aRR, 0.25; 95% CI, 0.18-0.35), ACEi and metformin (aRR, 0.26; 95% CI, 0.17-0.40), antihistamines and NSAIDs (aRR, 0.41; 95% CI, 0.32-0.52), and in men, combined alpha-blockers and antiandrogens (aRR, 0.51; 95% CI, 0.42-0.64). CONCLUSIONS: In this large national cohort, treatment of SARS-CoV-2 positive patients with individual or coprescribed metformin and statins, ACEi and statins (or metformin) and other medications was associated with a markedly decreased 30-day mortality and can likely be continued safely. Clinical trials may assess their therapeutic benefit.
Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s11606-022-07701-3. Conflict of Interest: Dr. Hunt is a consultant to Akebia Therapeutics, Inc. Dr. Hostler is co-owner of Infection Control Education for Major Sports, LLC, and consultant for OneBeacon Insurance and Prime Education, LLC. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Lancet Diabetes Endocrinol 2021;9(5):293-303.', 'journal-title': 'Lancet Diabetes Endocrinol'}, { 'key': '7701_CR23', 'doi-asserted-by': 'publisher', 'first-page': '108183', 'DOI': '10.1016/j.diabres.2020.108183', 'volume': '164', 'author': 'S Sharma', 'year': '2020', 'unstructured': 'Sharma S, Ray A, Sadasivam B. Metformin in COVID-19: a possible role ' 'beyond diabetes. Diabetes Res Clin Pract 2020;164:108183.', 'journal-title': 'Diabetes Res Clin Pract'}, { 'issue': '1', 'key': '7701_CR24', 'doi-asserted-by': 'publisher', 'first-page': '53', 'DOI': '10.1007/s40618-021-01614-4', 'volume': '45', 'author': 'R Pal', 'year': '2021', 'unstructured': 'Pal R, Banerjee M, Bhadada SK, Shetty AJ, Singh B, Vyas A. Vitamin D ' 'supplementation and clinical outcomes in COVID-19: a systematic review ' 'and meta-analysis. 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Hell J Cardiol 2020;61(1):42-5.', 'journal-title': 'Hell J Cardiol'}, { 'key': '7701_CR27', 'doi-asserted-by': 'publisher', 'first-page': '101989', 'DOI': '10.1016/j.pupt.2021.101989', 'volume': '67', 'author': 'JI Morán Blanco', 'year': '2021', 'unstructured': 'Morán Blanco JI, Alvarenga Bonilla JA, Homma S, Suzuki K, Fremont-Smith ' 'P, Villar Gómez de Las Heras K. Antihistamines and azithromycin as a ' 'treatment for COVID-19 on primary health care - a retrospective ' 'observational study in elderly patients. Pulm Pharmacol Ther ' '2021;67:101989.', 'journal-title': 'Pulm Pharmacol Ther'}, { 'issue': '16', 'key': '7701_CR28', 'doi-asserted-by': 'publisher', 'first-page': '8486', 'DOI': '10.3390/ijerph18168486', 'volume': '18', 'author': 'A Suzuki', 'year': '2021', 'unstructured': 'Suzuki A, Efird JT, Redding TSt, Thompson AD, Jr., Press AM, Williams ' 'CD, et al. COVID-19-associated mortality in US Veterans with and without ' 'SARS-CoV-2 infection. 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Diabetes Care ' '2018;41(Suppl 1):S86-s104.', 'journal-title': 'Diabetes Care'}, { 'issue': 'Suppl 1', 'key': '7701_CR42', 'doi-asserted-by': 'publisher', 'first-page': 'S73', 'DOI': '10.2337/dc18-S008', 'volume': '41', 'author': 'American Diabetes Association', 'year': '2018', 'unstructured': 'American Diabetes Association. Pharmacologic approaches to glycemic ' 'treatment: standards of medical care in diabetes-2018. Diabetes Care ' '2018;41(Suppl 1):S73-s85.', 'journal-title': 'Diabetes Care'}, { 'key': '7701_CR43', 'doi-asserted-by': 'publisher', 'first-page': '167', 'DOI': '10.1016/j.biopha.2016.04.043', 'volume': '82', 'author': 'F Kong', 'year': '2016', 'unstructured': 'Kong F, Ye B, Lin L, Cai X, Huang W, Huang Z. Atorvastatin suppresses ' 'NLRP3 inflammasome activation via TLR4/MyD88/NF-κB signaling in ' 'PMA-stimulated THP-1 monocytes. 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Am J Trop Med Hyg ' '2020;103(1):69-72.', 'journal-title': 'Am J Trop Med Hyg'}, { 'issue': '1081', 'key': '7701_CR48', 'doi-asserted-by': 'publisher', 'first-page': '600439', 'DOI': '10.3389/fendo.2020.600439', 'volume': '11', 'author': 'AB Crouse', 'year': '2021', 'unstructured': 'Crouse AB, Grimes T, Li P, Might M, Ovalle F, Shalev A. Metformin use is ' 'associated with reduced mortality in a diverse population with COVID-19 ' 'and diabetes. Front Endocrinol 2021;11(1081):600439.', 'journal-title': 'Front Endocrinol'}, { 'issue': '625', 'key': '7701_CR49', 'doi-asserted-by': 'publisher', 'first-page': '587801', 'DOI': '10.3389/fendo.2021.587801', 'volume': '12', 'author': 'S Ibrahim', 'year': '2021', 'unstructured': 'Ibrahim S, Lowe JR, Bramante CT, Shah S, Klatt NR, Sherwood N, et al. ' 'Metformin and Covid-19: focused review of mechanisms and current ' 'literature suggesting benefit. 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Extent ' 'and reasons for nonadherence to antihypertensive, cholesterol, and ' 'diabetes medications: the association with depressive symptom burden in ' 'a sample of American veterans. 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Dr. Hostler is co-owner ' 'of Infection Control Education for Major Sports, LLC, and consultant for ' 'OneBeacon Insurance and Prime Education, LLC.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflict of Interest'}}, { 'value': 'This content has been made available to all.', 'name': 'free', 'label': 'Free to read'}]}
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Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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