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

Abstract

Non‐steroidal 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 ratio (OR) with 95% confidence intervals (CI). Heterogeneity was assessed with I 2 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, I 2 = 24%, five 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, I 2 = 0%, 5 studies) nor all‐cause mortality among patients with COVID‐19 (OR 0.86, 95% CI 0.75–0.99, I 2 = 14%, four 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. Systematic review registration number : CRD42020216806 This article is protected by copyright. All rights reserved

Ibuprofen in the Management of Viral Infections: The Lesson of COVID‐19 for Its Use in a Clinical Setting

“…Similar results were obtained in recent reviews documenting that NSAID or ibuprofen exposure did not increase the severity of COVID‐19 disease 94–96 . In particular, Moore et al., 94 evaluating 92,853 papers on COVID‐19 and NSAIDs, failed to report an association between NDAID exposure and risk of hospital admission (OR, 0.90 [95% CI, 0.80–1.17]), death (OR, 0.88 [95% CI, 0.80–0.98]), or severe outcomes (OR, 1.14 [95% CI, 0.90–1.44]).…”

“…Prada et al., 95 reviewing 11 studies (683,715 patients with COVID‐19), documented that NSAID exposure did not increase the risk of severe/critical COVID‐19 disease (OR, 0.92 [95% CI, 0.80–1.05]; I 2 = 0%; 5 studies) nor all‐cause mortality among patients with COVID‐19 (OR, 0.86 [95% CI, 0.75–0.99]; I 2 = 14%; 4 studies).…”

“…Similar results were obtained in recent reviews documenting that NSAID or ibuprofen exposure did not increase the severity of COVID-19 disease. [94][95][96] In particular, Moore et al, 94 More recently, in a systematic review on 73 studies concerning generic viral respiratory infections and NSAID use, the World Health Organization 97 documented the analogy of acetaminophen and ibuprofen with respect to mortality, hospitalization, acute kidney injury, gastrointestinal bleeding, and quality of life, without the development of adverse drug reactions. 97 Ibuprofen appears to be a good therapeutic option not only due to its efficacy, but because at a daily dose of up to 1200 mg, it is the safest NSAID on both kidneys 98 and the gastrointestinal system.…”

COVID-19 as a polymorphic inflammatory spectrum of diseases: a review with focus on the brain

“…NSAIDs as a group do not increase the risk and/or severity of COVID-19 (Prada et al ., 2021; Zhao et al ., 2022). Similarly, the use of NSAIDs was not associated with 30-day mortality, hospitalisation, ICU admission, mechanical ventilation or renal replacement therapy (Lund et al ., 2020).…”

To clarify the safety profile of paracetamol for home-care patients with COVID-19: a real-world cohort study, with nested case–control analysis, in primary care

“…Second, the studies supporting a greater effectiveness for an early use of NSAIDs [ 11 ] were undersized and might suffer from methodological flaws [ 14 ]. Third, the relationship between paracetamol-induced GSH consumption and COVID-19 severity might be clinically observed because of protopathic bias [ 15 – 18 ].…”