The COVID‐19 ibuprofen controversy: A systematic review of NSAIDs in adult acute lower respiratory tract infections

Abstract

In light of the recent safety concerns relating to NSAID use in COVID-19, we sought to evaluate cardiovascular and respiratory complications in patients taking NSAIDs during acute lower respiratory tract infections. Methods: We carried out a systematic review of randomised controlled trials and observational studies. Studies of adult patients with short-term NSAID use during acute lower respiratory tract infections, including bacterial and viral infections, were included. Primary outcome was all-cause mortality. Secondary outcomes were cardiovascular, renal and respiratory complications. Results: In total, eight studies including two randomised controlled trials, three retrospective and three prospective observational studies enrolling 44 140 patients were included. Five of the studies were in patients with pneumonia, two in patients with influenza, and one in a patient with acute bronchitis. Meta-analysis was not possible due to significant heterogeneity. There was a trend towards a reduction in mortality and an increase in pleuro-pulmonary complications. However, all studies exhibited high risks of bias, primarily due to lack of adjustment for confounding variables. Cardiovascular outcomes were not reported by any of the included studies. Conclusion: In this systematic review of NSAID use during acute lower respiratory tract infections in adults, we found that the existing evidence for mortality, pleuro-pulmonary complications and rates of mechanical ventilation or organ failure is of extremely poor quality, very low certainty and should be interpreted with caution. Mechanistic and clinical studies addressing the captioned subject are urgently needed, especially in relation to COVID-19.

Association Between Prescribed Ibuprofen and Severe COVID‐19 Infection: A Nationwide Register‐Based Cohort Study

“…Whether patients actually were using ibuprofen or they avoided it on the basis of physician advice and/or the public attention in March 2020 on the potential negative effect on COVID‐19 infection severity remain unknown. In support of our study findings, a limited number of recent studies, including reviews, have also not found any evidence suggesting worsening of COVID‐19 infection in relation to ibuprofen or NSAID use 10,16–19 . Follow‐up data on outcome was limited to May 16, 2020, which may limit the registration of severe COVID‐19 infection for patients diagnosed with COVID‐19 at the end of the study period.…”

“…In support of our study findings, a limited number of recent studies, including reviews, have also not found any evidence suggesting worsening of COVID-19 infection in relation to ibuprofen or NSAID use. 10,[16][17][18][19] Follow-up data on outcome was limited to May 16, 2020, which may limit the registration of severe COVID-19 infection for patients diagnosed with COVID-19 at the end of the study period. However, the majority of patients hospitalized for COVID-19 were in the hospital in the beginning of April ensuring that the greater majority of the included patients had sufficient follow-up to allow the study of the 30-day outcome measure.…”

Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts

“…Two systematic reviews highlighted a lack of studies investigating the effect of NSAIDs on COVID-19, demonstrating the urgent need of new studies. 18 19 One cohort study was recently conducted to investigate such association, but individual NSAIDs were not specifically investigated. 20 …”

Paracetamol-Induced Glutathione Consumption: Is There a Link With Severe COVID-19 Illness?

“…Moreover, as pointed by Martins-Filho et al. (2020) in a commentary published at the beginning of June 2020 “ there is no evidence supporting the association between Ibuprofen and increased risk of severity of COVID-19 ,” a position strengthened by a systematic review appeared 2 months later ( Vaja et al. ).…”