Abstract: Citation: Clin Transl Sci (2020) 13, 1103–1107; doi:10.1111/cts.12904 ARTICLE Association Between Prescribed Ibuprofen and Severe COVID-19 Infection: A Nationwide Register-Based Cohort Study Kristian Kragholm1,2,*, Thomas A. Gerds3, Emil Fosbøl4, Mikkel Porsborg Andersen5, Matthew Phelps6, Jawad H. Butt4, Lauge Østergaard4, Casper N. Bang5,6, Jannik Pallisgaard7, Gunnar Gislason6,7, Morten Schou7, Lars Køber4 and Christian Torp-Pedersen5 Recommendations regarding ibuprofen use in relation to coronavirus disease 2019 (COVID-19) have been conflicting. We examined the risk of severe COVID-19 between ibuprofen-prescribed and non-ibuprofen patients with COVID-19 in a nationwide register-based study of patients with COVID-19 in Denmark between the end of February 2020 and May 16, 2020. Patients with heart failure (n = 208), < 30 years (n = 575), and prescribed other nonsteroidal anti-inflammatory drugs (n = 57) were excluded. Patients with ibuprofen prescription claims between January 1, 2020, and before COVID-19 diagnosis or April 30, 2020 (last available prescription) were compared with patients without ibuprofen prescription claims. Outcome was a 30-day composite of severe COVID-19 diagnosis with acute respiratory syndrome, intensive care unit admission, or death. Absolute risks and average risk ratios comparing outcome for ibuprofen vs. non-ibuprofen patients standardized to the age, sex, and comorbidity distribution of all patients were derived from multivariable Cox regression. Among 4,002 patients, 264 (6.6%) had ibuprofen prescription claims before COVID-19. Age, sex, and comorbidities were comparable between the two study groups. Standardized absolute risks of the composite outcome for ibuprofen-prescribed vs. non-ibuprofen patients were 16.3% (95% confidence interval (CI) 12.1–20.6) vs. 17.0% (95% CI 16.0–18.1), P = 0.74. The standardized average risk ratio for ibuprofen-prescribed vs. non-ibuprofen patients was 0.96 (95% CI 0.72–1.23). Standardized absolute risks of the composite outcome for patients with ibuprofen prescription claims > 14 days before COVID-19 vs. ≤ 14 days of COVID-19 were 17.1% (95% CI 12.3–22.0) vs. 14.3% (95% CI 7.1–23.1). In conclusion, in this nationwide study, there was no significant association between ibuprofen prescription claims and severe COVID-19. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? ✔ Recommendations regarding ibuprofen use in relation to coronavirus disease 2019 (COVID-19) have been conflicting and to date, no studies have addressed the risk of severe COVID-19 between ibuprofen and non-ibuprofen users. WHAT QUESTION DID THIS STUDY ADDRESS? ✔ Is ibuprofen prescription redemption associated with severe outcome of COVID-19? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? ✔ In this nationwide study, there was no significant association between ibuprofen prescription claims and severe COVID-19. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? ✔ Ibuprofen prescription to patients with COVID-19 does not appear to be associated with severe COVID-19 trajectory. The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to substantial changes in healthcare utilization, morbidity, intensive care resources, and mortality.1–7 The entry point for this novel coronavirus for its further pathogenesis in humans is thought to be through an angiotensin-converting enzyme 2 receptor found in the lungs,..