DrugWAS: Leveraging drug-wide association studies to facilitate drug repurposing for COVID-19

Abstract

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.

DrugWAS: Drug‐wide Association Studies for COVID‐19 Drug Repurposing

“…An important finding by our study is that recent exposure to various types of Streptococcus pneumoniae vaccines and diphtheria toxoid and tetanus toxoid vaccine, with or without acellular pertussis vaccine, is associated with a decreased risk of death and other severe COVID‐19 outcomes. This finding replicates the results of our preliminary analysis on 7,768 patients infected with SARS‐CoV‐2 41 . Recently, Streptococcus pneumoniae vaccines were also found to have a protective effect against COVID‐19 outcomes suggesting that pneumococci may interact with SARS‐CoV‐2 in the respiratory tract 42 .…”

“…This finding replicates the results of our preliminary analysis on 7,768 patients infected with SARS‐CoV‐2. 41 Recently, Streptococcus pneumoniae vaccines were also found to have a protective effect against COVID‐19 outcomes suggesting that pneumococci may interact with SARS‐CoV‐2 in the respiratory tract. 42 A double‐blind placebo‐randomized trial showed that the pneumococcal conjugate vaccine protects children against pneumococcal coinfections with seasonal coronaviruses.…”