DrugWAS: Drug-wide association studies for COVID-19 drug repurposing.

This study aimed to systematically investigate if any of the available drugs in Electronic Health Record (EHR) can be repurposed as potential treatment for COVID-19. Based on a retrospective cohort analysis of EHR data, drug-wide association studies (DrugWAS) were performed on 9,748 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. Patient exposure to a drug between 3-months prior to the pandemic and COVID-19 diagnosis was chosen as exposure of interest. 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. Overall, 17 drugs were significantly associated with decreased COVID-19 severity. Previous exposure to two types of 13-valent pneumococcal conjugate vaccines, PCV13, (OR, 0.31; 95% 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.