Association Between Nonsteroidal Antiinflammatory Drug Use and Adverse Clinical Outcomes Among Adults Hospitalized With Coronavirus 2019 in South Korea: A Nationwide Study.

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.

Clinical outcomes of COVID-19 following the use of angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers among patients with hypertension in Korea: a nationwide study.

OBJECTIVES: Recent evidence has shown no harm associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-receptor blockers (ARBs) in patients with coronavirus disease 2019 (COVID-19). We sought to further clarify the possible association between ACEI/ARB use and the risk of poor clinical outcomes of COVID-19. METHODS: From the completely enumerated COVID-19 cohort in Korea, we identified 1,290 patients with hypertension, of whom 682 had and 603 did not have records of ACEI/ARB use during the 30-day period before their COVID-19 diagnosis. Our primary endpoint comprised clinical outcomes, including all-cause mortality, use of mechanical ventilation, intensive care unit admission, and sepsis. We used inverse probability of treatment weighting (IPTW) to mitigate selection bias, and a Poisson regression model to estimate the relative risks (RRs) and 95% confidence intervals (CIs) for comparing outcomes between ACEI/ARB users and non-users. RESULTS: Compared to non-use, ACEI/ARB use was associated with lower clinical outcomes (IPTW-adjusted RR, 0.60; 95% CI, 0.42 to 0.85; p=0.005). For individual outcomes, ACEI/ARB use was not associated with all-cause mortality (IPTW-adjusted RR, 0.62; 95% CI, 0.35 to 1.09; p=0.097) or respiratory events (IPTW-adjusted RR, 0.99; 95% CI, 0.84 to 1.17; p=0.904). Subgroup analysis showed a trend toward a protective role of ACEIs and ARBs against overall outcomes in men (IPTW-adjusted RR, 0.84; 95% CI, 0.69 to 1.03; pinteraction=0.008) and patients with pre-existing respiratory disease (IPTW-adjusted RR, 0.74; 95% CI, 0.60 to 0.92; pinteraction=0.002). CONCLUSIONS: We present clinical evidence to support continuing ACE/ARB use in COVID-19 patients with hypertension based on the completely enumerated Korean cohort.