A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID-1

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Inflammopharmacology

REVIEW

A narrative review of the potential pharmacological influence and safety of ibuprofen on coronavirus disease 19 (COVID‑19), ACE2, and the immune system: a dichotomy of expectation and reality Lucinda Smart1 · Neil Fawkes1   · Paul Goggin2 · Graham Pennick1 · K. D. Rainsford3 · Bruce Charlesworth1 · Neil Shah2 Received: 18 July 2020 / Accepted: 1 August 2020 © The Author(s) 2020

Abstract The coronavirus disease 19 (COVID-19) pandemic is currently the most acute healthcare challenge in the world. Despite growing knowledge of the nature of Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2), treatment options are still poorly defined. The safety of non-steroidal anti-inflammatory drugs (NSAIDs), specifically ibuprofen, has been openly questioned without any supporting evidence or clarity over dose, duration, or temporality of administration. This has been further conflicted by the initiation of studies to assess the efficacy of ibuprofen in improving outcomes in severe COVID-19 patients. To clarify the scientific reality, a literature search was conducted alongside considerations of the pharmacological properties of ibuprofen in order to construct this narrative review. The literature suggests that double-blind, placebo-controlled study results must be reported and carefully analysed for safety and efficacy in patients with COVID-19 before any recommendations can be made regarding the use of ibuprofen in such patients. Limited studies have suggested: (i) no direct interactions between ibuprofen and SARS-CoV-2 and (ii) there is no evidence to suggest ibuprofen affects the regulation of angiotensin-converting-enzyme 2 (ACE2), the receptor for COVID-19, in human studies. Furthermore, in vitro studies suggest ibuprofen may facilitate cleavage of ACE2 from the membrane, preventing membrane-dependent viral entry into the cell, the clinical significance of which is uncertain. Additionally, in vitro evidence suggests that inhibition of the transcription factor nuclear factor-κB (NF-kB) by ibuprofen may have a role in reducing excess inflammation or cytokine release in COVID-19 patients. Finally, there is no evidence that ibuprofen will aggravate or increase the chance of infection of COVID-19. Keywords  Ibuprofen · COVID-19 · SARS-CoV-2 · ACE2 · Immune system · Safety

Introduction The world is currently impacted by the pandemic spread of Coronavirus-disease-2019 (COVID-19) caused by the Severe Acute Respiratory Syndrome coronavirus-2 (SARSCoV-2). Efforts to overcome the morbidity and mortality * Neil Fawkes [email protected] 1



Reckitt Benckiser Health Ltd, Dansom Lane, Hull HU8 7DS, UK

2



Reckitt Benckiser Health Ltd, 103‑105 Bath Road, Slough SL1 3UH, UK

3

Biomedical Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK



caused by this novel virus have been hampered by a lack of knowledge of the SARS-CoV-2 virus, particularly with regard to virulence, individual risk factors to host responses and appropriate treatment (Rokni et al. 2020). It is becoming clea