PMID- 34314511 OWN - NLM STAT- MEDLINE DCOM- 20211123 LR - 20240214 IS - 1532-6535 (Electronic) IS - 0009-9236 (Print) IS - 0009-9236 (Linking) VI - 110 IP - 6 DP - 2021 Dec TI - DrugWAS: Drug-wide Association Studies for COVID-19 Drug Repurposing. PG - 1537-1546 LID - 10.1002/cpt.2376 [doi] AB - This study aimed to systematically investigate if any of the available drugs in the electronic health record (EHR) can be repurposed as potential treatment for coronavirus disease 2019 (COVID-19). Based on a retrospective cohort analysis of EHR data, drug-wide association studies (DrugWAS) were performed on 9,748 patients with COVID-19 at Vanderbilt University Medical Center (VUMC). For each drug study, multivariable logistic regression with overlap weighting using propensity score was applied to estimate the effect of drug exposure on COVID-19 disease outcomes. Patient exposure to a drug between 3-months prior to the pandemic and the COVID-19 diagnosis was chosen as the exposure of interest. All-cause of death was selected as the primary outcome. Hospitalization, admission to the intensive care unit, and need for mechanical ventilation were identified as secondary outcomes. Overall, 17 drugs were significantly associated with decreased COVID-19 severity. Previous exposure to two types of 13-valent pneumococcal conjugate vaccines, PCV13 (odds ratio (OR), 0.31, 95% confidence interval (CI), 0.12-0.81 and OR, 0.33, 95% CI, 0.15-0.73), diphtheria toxoid and tetanus toxoid vaccine (OR, 0.38, 95% CI, 0.15-0.93) were significantly associated with a decreased risk of death (primary outcome). Secondary analyses identified several other significant associations showing lower risk for COVID-19 outcomes: acellular pertussis vaccine, 23-valent pneumococcal polysaccharide vaccine (PPSV23), flaxseed extract, ethinyl estradiol, estradiol, turmeric extract, ubidecarenone, azelastine, pseudoephedrine, dextromethorphan, omega-3 fatty acids, fluticasone, and ibuprofen. In conclusion, this cohort study leveraged EHR data to identify a list of drugs that could be repurposed to improve COVID-19 outcomes. Further randomized clinical trials are needed to investigate the efficacy of the proposed drugs. CI - (c) 2021 The Authors. Clinical Pharmacology & Therapeutics (c) 2021 American Society for Clinical Pharmacology and Therapeutics. FAU - Bejan, Cosmin A AU - Bejan CA AD - Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Cahill, Katherine N AU - Cahill KN AD - Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Staso, Patrick J AU - Staso PJ AD - Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Choi, Leena AU - Choi L AD - Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Peterson, Josh F AU - Peterson JF AD - Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, Tennessee, USA. AD - Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA. FAU - Phillips, Elizabeth J AU - Phillips EJ AD - Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. AD - Department of Medicine, Division of Infectious Diseases, Vanderbilt University Medical Center, Nashville, Tennessee, USA. AD - Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. LA - eng GR - UL1 TR000445/TR/NCATS NIH HHS/United States GR - P50GM115305/GF/NIH HHS/United States GR - UL1TR000445/GF/NIH HHS/United States GR - R01GM124109/GF/NIH HHS/United States GR - K23AI118804/GF/NIH HHS/United States GR - R01AI150295/GF/NIH HHS/United States GR - R01 GM124109/GM/NIGMS NIH HHS/United States GR - R01HG010863/GF/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210810 PL - United States TA - Clin Pharmacol Ther JT - Clinical pharmacology and therapeutics JID - 0372741 RN - 0 (13-valent pneumococcal vaccine) RN - 0 (23-valent pneumococcal capsular polysaccharide vaccine) RN - 0 (Pneumococcal Vaccines) SB - IM UOF - medRxiv. 2021 Feb 08;:. PMID: 33564788 MH - COVID-19/diagnosis/prevention & control MH - Cohort Studies MH - Drug Repositioning/*methods MH - Humans MH - Pneumococcal Vaccines/*administration & dosage MH - Product Surveillance, Postmarketing/*methods MH - Retrospective Studies MH - *COVID-19 Drug Treatment PMC - PMC8426999 COIS- K.N.C. reported personal fees from Teva, personal fees from Optinose, personal fees from Novartis, personal fees from GlaxoSmithKline, personal fees from Blueprint Medicines, personal fees from Third Harmonic Bio, personal fees from Sanofi Pasteur, personal fees from Genentech, personal fees from Regeneron and personal fees from Ribon Therapeutics, outside the submitted work. J.F.P. reported personal fees from Color Genomics outside the submitted work. E.J.P. receives Royalties from UpToDate and consulting fees from Janssen, Vertex, Biocryst, and Regeneron outside of the submitted work. She is co-director of IIID Pty Ltd that holds a patent for HLA-B*57:01 testing for abacavir hypersensitivity, and has a patent pending for Detection of Human Leukocyte Antigen-A*32:01 in connection with Diagnosing Drug Reaction with Eosinophilia and Systemic Symptoms without any financial remuneration and not directly related to the submitted work. All other authors declared no competing interests for this work. EDAT- 2021/07/28 06:00 MHDA- 2021/11/24 06:00 PMCR- 2021/08/10 CRDT- 2021/07/27 17:22 PHST- 2021/04/22 00:00 [received] PHST- 2021/07/21 00:00 [accepted] PHST- 2021/07/28 06:00 [pubmed] PHST- 2021/11/24 06:00 [medline] PHST- 2021/07/27 17:22 [entrez] PHST- 2021/08/10 00:00 [pmc-release] AID - CPT2376 [pii] AID - 10.1002/cpt.2376 [doi] PST - ppublish SO - Clin Pharmacol Ther. 2021 Dec;110(6):1537-1546. doi: 10.1002/cpt.2376. Epub 2021 Aug 10.