Abstract: PLOS ONE RESEARCH ARTICLE Chronic use of non-steroidal antiinflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Campbell HM, Murata AE, Conner TA, Fotieo G (2022) Chronic use of non-steroidal antiinflammatory drugs (NSAIDs) or acetaminophen and relationship with mortality among United States Veterans after testing positive for COVID-19. PLoS ONE 17(5): e0267462. https://doi.org/ 10.1371/journal.pone.0267462 Editor: Chiara Lazzeri, Azienda Ospedaliero Universitaria Careggi, ITALY Received: May 19, 2021 Accepted: April 8, 2022 Published: May 5, 2022 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: Data cannot be shared publicly because it involves sensitive human subject information. Data may be available for researchers who meet the criteria for access to confidential data after evaluation from affiliated IRB and VA Research and Development Committees. As a VA national legal policy (VHA Directive 1605.01), VA will only share patient data if there is a fully executed contractual agreement in place for the specific project. A common contractual mechanism utilized for this type of sharing is a Heather M. Campbell ID1☯*, Allison E. Murata1☯, Todd A. Conner1, Greg Fotieo2 1 Cooperative Studies Program, Clinical Research Pharmacy Coordinating Center, US Department of Veterans Affairs, Albuquerque, New Mexico, United States of America, 2 New Mexico VA Healthcare System, US Department of Veterans Affairs, Albuquerque, New Mexico, United States of America ☯ These authors contributed equally to this work. * heather.campbell@va.gov Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are among the mostfrequently used medications. Although these medications have different mechanisms of action, they have similar indications and treatment duration has been positively correlated with cardiovascular risk although the degree of risk varies by medication. Our objective was to study treatment effects of chronic use of individual NSAID medications and acetaminophen on all-cause mortality among patients who tested positive for COVID-19 while accounting for adherence. We used the VA national datasets in this retrospective cohort study to differentiate between sporadic and chronic medication use: sporadic users filled an NSAID within the last year, but not recently or regularly. Using established and possible risk factors for severe COVID-19, we used propensity scores analysis to adjust for differences in baseline characteristics between treatment groups. Then, we used multivariate logistic regression incorporating inverse propensity score weighting to assess mortality. The cohort consisted of 28,856 patients. Chronic use of aspirin, ibuprofen, naproxen, meloxicam, celecoxib, diclofenac or acetaminophen was not associated with significant differences in mortality at 30 days (OR = 0.98, 95% CI: 0.95–1.00; OR = 0.99, 95% CI: 0.98–1.00; OR = 1.00, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.98–1.00; OR = 1.00, 95% CI: 0.98–1.01; OR = 0.99, 95% CI: 0.97–1.01; and OR = 1.00, 95% CI: 0.99–1.02, respectively) nor at 60..