Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study
Han Eol Jeong, Hyesung Lee, Hyun Joon Shin, Young June Choe, Kristian B Filion, Ju-Young Shin
Clinical Infectious Diseases, doi:10.1093/cid/ciaa1056
Background. Nonsteroidal antiinflammatory drugs (NSAIDs) may exacerbate coronavirus disease 2019 (COVID-19) and worsen associated outcomes by upregulating the enzyme that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to in order to enter cells. Methods. We conducted a cohort study using South Korea's nationwide healthcare database, which contains data for all individuals who received a COVID-19 test (n = 69 793) as of 8 April 2020. We identified adults hospitalized with COVID-19, where cohort entry was the date of hospitalization. NSAID users were those prescribed NSAIDs in the 7 days before and including cohort entry, and nonusers were those not prescribed NSAIDs during this period. Our primary outcome was a composite of in-hospital death, intensive care unit admission, mechanical ventilation use, and sepsis; our secondary outcomes were cardiovascular complications and acute renal failure. We conducted logistic regression analysis to estimate odds ratio (OR) with 95% confidence intervals (CIs) using inverse probability of treatment weighting to minimize confounding. Results. Of 1824 adults hospitalized with COVID-19 (mean age, 49.0 years; female, 59%), 354 were NSAID users and 1470 were nonusers. Compared with nonuse, NSAID use was associated with increased risks of the primary composite outcome (OR, 1.54; 95% CI, 1.13-2.11) but insignificantly associated with cardiovascular complications (OR, 1.54; 95% CI, 0.96-2.48) or acute renal failure (OR, 1.45; 95% CI, 0.49-4.14). Conclusions. While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution for COVID-19 patients as the harms associated with their use may outweigh their benefits.
Supplementary Data Supplementary materials are available at Clinical Infectious Diseases online. Consisting of data provided by the authors to benefit the reader, the posted materials are not copyedited and are the sole responsibility of the authors, so questions or comments should be addressed to the corresponding author.
Notes Author contributions. All authors contributed to the study design and interpretation of the data. H. E. J. and H. L. designed the study and interpreted the data. H. E. J. wrote the manuscript. H. L. conducted the statistical analyses. H. J. S., Y. J. C., and K. B. F. interpreted the data and critically revised the manuscript. All authors reviewed and commented on drafts, approved the final manuscript, and made the decision to submit it for publication. J-Y. S. is the guarantor. Acknowledgments. The authors thank healthcare professionals dedicated to treating coronavirus 2019 patients in South Korea, the Ministry of Health and Welfare, the Health Insurance Review & Assessment Service, and Do-Yeon Cho of the Health Insurance Review & Assessment Service of South Korea for sharing invaluable national health insurance claims data in a prompt manner. Disclaimer. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. Financial..
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