Cyclooxygenase inhibitor use is associated with increased COVID-19 severity

BACKGROUND Cyclooxygenase (COX) inhibitors including non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to reduce pain, fever, and inflammation but have been associated with complications in community acquired pneumonia and other respiratory tract infections (RTIs). Conclusive data are not available about potential beneficial or adverse effects of COX inhibitors on COVID-19 patients. METHODS We conducted a retrospective, multi-center observational study by leveraging the harmonized, high-granularity electronic health record data of the National COVID Cohort Collaborative (N3C). Potential associations of eight COX inhibitors with COVID-19 severity were assessed using ordinal logistic regression (OLR) on treatment with the medication in question after matching by treatment propensity as predicted by age, race, ethnicity, gender, smoking status, comorbidities, and BMI. Cox proportional hazards analysis was used to estimate the correlation of medication use with morbidity for eight subcohorts defined by common indications for COX inhibitors. RESULTS OLR revealed statistically significant associations between use of any of five COX inhibitors and increased severity of COVID-19. For instance, the odds ratio of aspirin use in the osteoarthritis cohort (n=2266 patients) was 3.25 (95% CI 2.76 - 3.83). Aspirin and acetaminophen were associated with increased mortality. CONCLUSIONS The association between use of COX inhibitors and COVID-19 severity was consistent across five COX inhibitors and multiple indication subcohorts. Our results align with earlier reports associating NSAID use with complications in RTI patients. Further research is needed to characterize the precise risk of individual COX inhibitors in COVID-19 patients. Competing Interest Statement Katie Rebecca Bradwell: employee of Palantir Technologies; Melissa A. Haendel: co-founder Pryzm Health; Julie A. McMurry: Cofounder, Pryzm Health; Jasvinder Singh: JAS has received consultant fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications: and the National Institutes of Health and the American College of Rheumatology. JAS owns stock options in TPT Global Tech, Vaxart pharmaceuticals and Charlotte's Web Holdings, Inc. JAS previously owned stock options in Amarin, Viking and Moderna pharmaceuticals. JAS is on the speaker's bureau of Simply Speaking. JAS is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organization that develops outcome measures in rheumatology and receives arms-length funding from 12 companies. Funding Statement Justin T. Reese supported by Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy Contract No. DE-AC02-05CH11231; Nomi L. Harris supported by Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy Contract No. DE-AC02-05CH11231; Rachel Deer supported by UTMB CTSA, 2P30AG024832-16 (PI: Volpi); Christopher G. Chute supported by U24 TR002306; Heidi Spratt supported by NIH UL1TR001439 ; Christopher J. Mungall supported by Director, Office of Science, Office of Basic Energy Sciences of the U.S. Department of Energy Contract No. DE-AC02-05CH11231; Peter N. Robinson supported by Donald A. Roux Family Fund at the Jackson Laboratory.