Prior Routine Use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) and Important Outcomes in Hospitalised Patients with COVID-19.

Eilidh Bruce,Jonathan Hewitt,Arturo Vilches-Moraga,Philip Braude,Michael J Stechman,Angeline Price,Fenella Barlow-Pay,Susan Moug,Phyo Kyaw Myint,Aine Mcgovern,Roxanna Short,Ben Carter,Kathryn Mccarthy

doi:10.3390/jcm9082586

Abstract

Coronavirus disease 2019 (COVID-19) infection causes acute lung injury, resulting from aggressive inflammation initiated by viral replication. There has been much speculation about the potential role of non-steroidal inflammatory drugs (NSAIDs), which increase the expression of angiotensin-converting enzyme 2 (ACE2), a binding target for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cell, which could lead to poorer outcomes in COVID-19 disease. The aim of this study was to examine the association between routine use of NSAIDs and outcomes in hospitalised patients with COVID-19. This was a multicentre, observational study, with data collected from adult patients with COVID-19 admitted to eight UK hospitals. Of 1222 patients eligible to be included, 54 (4.4%) were routinely prescribed NSAIDs prior to admission. Univariate results suggested a modest protective effect from the use of NSAIDs, but in the multivariable analysis, there was no association between prior NSAID use and time to mortality (adjusted HR (aHR) = 0.89, 95% CI 0.52–1.53, p = 0.67) or length of stay (aHR 0.89, 95% CI 0.59–1.35, p = 0.58). This study found no evidence that routine NSAID use was associated with higher COVID-19 mortality in hospitalised patients; therefore, patients should be advised to continue taking these medications until further evidence emerges. Our findings suggest that NSAID use might confer a modest benefit with regard to survival. However, as this finding was underpowered, further research is required.

Highlights

The pattern of acute lung injury seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—commonly referred to as coronavirus disease 2019 (COVID-19)—is thought to be a result of aggressive inflammation initiated by viral replication; the exact pathophysiology behind this phenomenon remains largely unknown [1]
To the best of our knowledge, this study is the first to report on routine non-steroidal inflammatory drugs (NSAIDs) use and outcomes in hospitalized patients with COVID-19
We found that the routine use of NSAIDs might confer a modest survival benefit and is not associated with poorer outcomes

Summary

Introduction

The pattern of acute lung injury seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection—commonly referred to as coronavirus disease 2019 (COVID-19)—is thought to be a result of aggressive inflammation initiated by viral replication; the exact pathophysiology behind this phenomenon remains largely unknown [1]. Following recognition that the angiotensin-converting enzyme 2 receptor (ACE2) serves as a binding site for SARS CoV-2 to enter the host cell, a number of European authorities, including those in France and Belgium, issued federal reports suggesting that the use of non-steroidal inflammatory drugs (NSAIDs) in the presence of COVID-19 might adversely affect patients’ clinical course and recovery [2]. It has been speculated that ibuprofen may upregulate the cellular expression of ACE2 [5], and in the context of COVID-19, it is postulated that NSAID use could result in a higher viral infective load in the respiratory tract. It has been proposed that the inhibition of COX enzymes reduces the recruitment of polymorphonuclear cells and inhibits the synthesis of lipoxins and resolvins, delaying the resolution of inflammation

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