PMID- 33564788 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240403 DP - 2021 Feb 8 TI - DrugWAS: Leveraging drug-wide association studies to facilitate drug repurposing for COVID-19. LID - 2021.02.04.21251169 [pii] LID - 10.1101/2021.02.04.21251169 [doi] AB - Importance: There is an unprecedented need to rapidly identify safe and effective treatments for the novel coronavirus disease 2019 (COVID-19). Objective: To systematically investigate if any of the available drugs in Electronic Health Record (EHR), including prescription drugs and dietary supplements, can be repurposed as potential treatment for COVID-19. Design, Setting, and Participants: Based on a retrospective cohort analysis of EHR data, drug-wide association studies (DrugWAS) were performed on COVID-19 patients 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. Exposures: Patient exposure to a drug during 1-year prior to the pandemic and COVID-19 diagnosis was chosen as exposure of interest. Natural language processing was employed to extract drug information from clinical notes, in addition to the prescription drug data available in structured format. Main Outcomes and Measures: All-cause of death was selected as primary outcome. Hospitalization, admission to the intensive care unit (ICU), and need for mechanical ventilation were identified as secondary outcomes. Results: The study included 7,768 COVID-19 patients, of which 509 (6.55%) were hospitalized, 82 (1.06%) were admitted to ICU, 64 (0.82%) received mechanical ventilation, and 90 (1.16%) died. Overall, 15 drugs were significantly associated with decreased COVID-19 severity. Previous exposure to either Streptococcus pneumoniae vaccines (adjusted odds ratio [OR], 0.38; 95% CI, 0.14-0.98), diphtheria toxoid vaccine (OR, 0.39; 95% CI, 0.15-0.98), and tetanus toxoid vaccine (OR, 0.39; 95% CI, 0.15-0.98) 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: 2 vaccines (acellular pertussis, Streptococcus pneumoniae), 3 dietary supplements (turmeric extract, flaxseed extract, omega-3 fatty acids), methylprednisolone acetate, pseudoephedrine, ethinyl estradiol, estradiol, ibuprofen, and fluticasone. Conclusions and Relevance: 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. FAU - Bejan, Cosmin A AU - Bejan CA AD - Department of Biomedical Informatics; Vanderbilt University Medical Center; Nashville, 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, 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, USA. FAU - Choi, Leena AU - Choi L AD - Department of Biostatistics; Vanderbilt University Medical Center; Nashville, USA. FAU - Peterson, Josh F AU - Peterson JF AD - Department of Biomedical Informatics; Vanderbilt University Medical Center; Nashville, USA. AD - Department of Medicine; Vanderbilt University Medical Center; Nashville, USA. FAU - Phillips, Elizabeth J AU - Phillips EJ AD - Department of Pathology, Microbiology and Immunology; Vanderbilt University Medical Center; Nashville, USA. AD - Department of Medicine; Division of Infectious Diseases; Vanderbilt University Medical Center; Nashville, USA. AD - Department of Pharmacology; Vanderbilt University Medical Center; Nashville, USA. LA - eng GR - UL1 TR000445/TR/NCATS NIH HHS/United States GR - R01 HG010863/HG/NHGRI NIH HHS/United States GR - P50 GM115305/GM/NIGMS NIH HHS/United States GR - R01 AI150295/AI/NIAID NIH HHS/United States GR - K23 AI118804/AI/NIAID NIH HHS/United States PT - Preprint DEP - 20210208 PL - United States TA - medRxiv JT - medRxiv : the preprint server for health sciences JID - 101767986 UIN - Clin Pharmacol Ther. 2021 Dec;110(6):1537-1546. PMID: 34314511 PMC - PMC7872383 COIS- Conflict of Interest Disclosures: Dr Cahill 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, and personal fees from Regeneron, outside the submitted work. Dr Peterson reported personal fees from Color Genomics outside the submitted work. Dr Phillips 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. No other disclosures were reported. EDAT- 2021/02/11 06:00 MHDA- 2021/02/11 06:01 PMCR- 2021/02/09 CRDT- 2021/02/10 05:57 PHST- 2021/02/10 05:57 [entrez] PHST- 2021/02/11 06:00 [pubmed] PHST- 2021/02/11 06:01 [medline] PHST- 2021/02/09 00:00 [pmc-release] AID - 2021.02.04.21251169 [pii] AID - 10.1101/2021.02.04.21251169 [doi] PST - epublish SO - medRxiv [Preprint]. 2021 Feb 8:2021.02.04.21251169. doi: 10.1101/2021.02.04.21251169.