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

J Clin Pharmacol. 2021 Dec;61(12):1521-1533. doi: 10.1002/jcph.1949. Epub 2021 Sep 17.

Abstract

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.

Keywords: ACE-2; COVID-19; NSAIDs; SARS-CoV-2; nonsteroidal anti-inflammatory drugs.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage*
  • COVID-19 / epidemiology*
  • COVID-19 / mortality
  • Humans
  • SARS-CoV-2
  • Severity of Illness Index

Substances

  • Anti-Inflammatory Agents, Non-Steroidal