Abstract: PLOS ONE RESEARCH ARTICLE Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients Kin Wah Fung ID*, Seo H. Baik, Fitsum Baye, Zhaonian Zheng, Vojtech Huser, Clement J. McDonald Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, Maryland, United States of America a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 * kfung@mail.nih.gov Abstract Background OPEN ACCESS Citation: Fung KW, Baik SH, Baye F, Zheng Z, Huser V, McDonald CJ (2022) Effect of common maintenance drugs on the risk and severity of COVID-19 in elderly patients. PLoS ONE 17(4): e0266922. https://doi.org/10.1371/journal. pone.0266922 Editor: Masaki Mogi, Ehime University Graduate School of Medicine, JAPAN Received: October 1, 2021 Accepted: March 29, 2022 Published: April 18, 2022 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0266922 Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Data Availability Statement: The minimal data set relevant to this study is included in the Supporting information. All data in Supporting information can be used without restriction. As for raw data, CMS Maintenance drugs are used to treat chronic conditions. Several classes of maintenance drugs have attracted attention because of their potential to affect susceptibility to and severity of COVID-19. Methods Using claims data on 20% random sample of Part D Medicare enrollees from April to December 2020, we identified patients diagnosed with COVID-19. Using a nested case-control design, non-COVID-19 controls were identified by 1:5 matching on age, race, sex, dualeligibility status, and geographical region. We identified usage of angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), statins, warfarin, direct factor Xa inhibitors, P2Y12 inhibitors, famotidine and hydroxychloroquine based on Medicare prescription claims data. Using extended Cox regression models with time-varying propensity score adjustment we examined the independent effect of each study drug on contracting COVID-19. For severity of COVID-19, we performed extended Cox regressions on all COVID-19 patients, using COVID-19-related hospitalization and all-cause mortality as outcomes. Covariates included gender, age, race, geographic region, low-income indicator, and co-morbidities. To compensate for indication bias related to the use of hydroxychloroquine for the prophylaxis or treatment of COVID-19, we censored patients who only started on hydroxychloroquine in 2020. Results Up to December 2020, our sample contained 374,229 Medicare patients over 65 who were diagnosed with COVID-19. Among the COVID-19 patients, 278,912 (74.6%) were on at least one study drug. The three most common study drugs among COVID-19 patients were statins 187,374 (50.1%), ACEI 97,843 (26.2%) and ARB 83,290 (22.3%). For all three outcomes (diagnosis, hospitalization and death), current users of ACEI,..