Risk of SARS‐CoV‐2 Infection and COVID‐19 Severity Associated With Exposure to Nonsteroidal Anti‐Inflammatory Drugs: Systematic Review and Meta‐Analysis

Nonsteroidal anti‐inflammatory drugs (NSAIDs) were thought to increase the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) virus entrance into cells. Hence, it was suggested in the media that NSAIDs could lead to a higher risk of infection and/or disease severity. To determine the existence or absence of this association, we aimed to systematically evaluate the risk of SARS‐CoV‐2 infection and mortality and the risk of severe coronavirus disease 2019 (COVID‐19) associated with previous exposure to NSAIDs. MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE were searched in February 2021 for controlled studies. The results were calculated through random‐effect meta‐analyses and reported in terms of odds ratios (ORs) with 95% confidence intervals (CIs). Heterogeneity was assessed with I2 test. Eleven studies were included, comprising a total of 683 715 patients. NSAID exposure did not increase the risk of having a positive test for SARS‐CoV‐2 infection (OR, 0.97; 95%CI, 0.85‐1.11, I2 = 24%; 5 studies). The exposure to NSAIDs did not increase the risk of severe/critical COVID‐19 disease (OR, 0.92; 95%CI, 0.80‐1.05; I2 = 0%; 5 studies) nor all‐cause mortality among patients with COVID‐19 (OR, 0.86; 95%CI, 0.75‐0.99; I2 = 14%, 4 studies). Our data did not suggest that exposure to NSAIDs increases the risk of having SARS‐CoV‐2 infection or increases the severity of COVID‐19 disease. Also, the fragility of the studies included precludes definite conclusions and highlights the need for further robust data.