Abstract: International Journal of Environmental Research and Public Health Article Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Population-Based Cohort Study Jin-Woo Kim 1,† , Siyeong Yoon 2,† , Jongheon Lee 1 1 2 * † Citation: Kim, J.-W.; Yoon, S.; Lee, J.; and Soonchul Lee 2, * Department of Orthopaedic Surgery, Nowon Eulji Medical Center, Eulji University, Seoul 01830, Republic of Korea Department of Orthopaedic Surgery, CHA Bundang Medical Center, School of Medicine, CHA University, Seongnam-si 13488, Republic of Korea Correspondence: lsceline78@gmail.com; Tel.: +82-31-780-5289; Fax: +82-31-881-7114 These authors contributed equally to this work. Abstract: Acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs) have been widely prescribed to infected patients; however, the safety of them has not been investigated in patients with serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Our objective was to evaluate the association between the previous use of acetaminophen or NSAIDs and the clinical outcomes of SARS-CoV-2 infection. A nationwide population-based cohort study was conducted using the Korean Health Insurance Review and Assessment Database through propensity score matching (PSM). A total of 25,739 patients aged 20 years and older who tested for SARS-CoV-2 were included from 1 January 2015 to 15 May 2020. The primary endpoint was a positive result for a SARS-CoV-2 test, and the secondary endpoint was serious clinical outcomes of SARS-CoV-2 infection, such as conventional oxygen therapy, admission to the intensive care unit, need for invasive ventilation care, or death. Of 1058 patients, after propensity score matching, 176 acetaminophen users and 162 NSAIDs users were diagnosed with coronavirus disease 2019. After PSM, 162 paired data sets were generated, and the clinical outcomes of the acetaminophen group were not significantly different from those of the NSAIDs group. This suggests that acetaminophen and NSAIDs can be used safely to control symptoms in patients suspected of having SARS-CoV-2. Lee, S. Serious Clinical Outcomes of COVID-19 Related to Acetaminophen or NSAIDs from a Nationwide Keywords: SARS-CoV-2; COVID-19; acetaminophen; NSAIDs Population-Based Cohort Study. Int. J. Environ. Res. Public Health 2023, 20, 3832. https://doi.org/10.3390/ ijerph20053832 Academic Editor: Paul B. Tchounwou Received: 31 December 2022 Revised: 19 February 2023 Accepted: 20 February 2023 Published: 21 February 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).