Association between NSAIDs use and adverse clinical outcomes among adults hospitalised with COVID-19 in South Korea: A nationwide study

Jeong, H. E.; Lee, H.; Shin, H. J.; Choe, Y. J.; Filion, K. B.; Shin, J.-Y.

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) may exacerbate COVID-19 and worsen associated outcomes by upregulating the enzyme that SARS-CoV-2 binds to enter cells. However, to our knowledge, no study has examined the association between NSAID use and the risk of COVID-19-related outcomes among hospitalised patients. METHODS: We conducted a population-based cohort study using South Korea nationwide healthcare database, which contains data of all subjects who received a test for COVID-19 (n=69,793) as of April 8, 2020. We identified a cohort of adults hospitalised with COVID-19, where cohort entry was the date of hospitalisation. NSAIDs users were those prescribed NSAIDs while hospitalised and non-users were those not prescribed NSAIDs. Our primary outcome was a composite of death, intensive care unit admission, mechanical ventilation use, and sepsis; secondary outcome was cardiovascular or renal complications. We conducted logistic regression analysis to estimate adjusted odds ratio (aOR) with 95% confidence intervals (CI) for the risk of these outcomes associated with NSAIDs users versus non-users, using propensity score-inverse probability of treatment weighting to minimize potential confounding. In sensitivity analyses, we compared NSAIDs to paracetamol (acetaminophen) to minimize confounding by indication. FINDINGS: Of 1,824 adults hospitalised with COVID-19 (mean age 44.7 years; female 59%), 285 were NSAIDs users and 1,539 were non-users. Compared with non-users, NSAIDs users were associated with increased risks of the primary composite outcome (aOR 1.54, 95% CI 1.11-2.15) and cardiovascular or renal complications (aOR 2.64, 95% CI 1.67-4.16). The association with primary outcome remained consistent when comparing NSAIDs to paracetamol (aOR 1.31, 95% CI 0.89-1.95). INTERPRETATION: Use of NSAIDs, compared with non-use, is associated with worse outcomes among hospitalised COVID-19 patients. While awaiting the results of confirmatory studies, we suggest NSAIDs be used with caution as the harms associated with their use may outweigh their benefits in this population.