The role of IL-6 and IL-6 blockade in COVID-19

ABSTRACT

Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a dysregulated hyperinflammatory response.

Areas covered

Authors review evidence on IL-6 and IL-6 blockade in coronavirus disease 2019 (COVID-19) and discuss the pathophysiological and prognostic roles of this cytokine and the clinical impact of pharmacological blockade of IL-6 . The material includes original articles and reviews published from March 2020 to March 2021 and searched on PubMed, medRxiv, and bioRxiv.

Expert opinion

IL-6 is one of the most prominent pro-inflammatory cytokines. Increased levels are recorded in COVID-19 patients, especially those with severe-to-critical disease. Evidence is accumulating on the relevance of IL-6 as a prognostic marker in COVID-19. Since IL-6 is a druggable target for several inflammatory diseases, pharmacological blockers of the IL-6 signaling pathway were repurposed to blunt the abnormal SARS-CoV-2-induced cytokine release. Data are limited to few randomized controlled trials that reported encouraging, though not conclusive, results, indicating the usefulness of IL-6 blockade early in the course of the disease in patients with hyperinflammation and no or limited organ damage. Further research is warranted to explore the role of IL-6 in different COVID-19 phenotypes and identify subgroups of patients who may mostly benefit from IL-6 pathway inhibition.

KEYWORDS:

• IL-6
• COVID-19
• SARS-CoV-2
• hyperinflammation
• cytokine storm
• lymphocytes
• tocilizumab
• sarilumab
• siltuximab
• pathophysiology
• prognosis

Declaration of interest

A Vecchié received a travel grant from Kiniksa Pharmaceuticals Ltd. to attend the 2019 AHA Scientific Sessions and currently receives honoraria from Effetti s.r.l. (Milan, Italy) to collaborate on the medical website www.inflammology.org. A Abbate has served as a consultant for Astra Zeneca, Cromos Pharma, Eli Lilly, Effetti, Janssen, Kiniksa Pharmaceuticals Ltd., Merck, Novartis, Olatec, and Serpin Pharma. A Bonaventura received a travel grant from Kiniksa Pharmaceuticals Ltd. to attend the 2019 AHA Scientific Sessions and currently receives honoraria from Effetti s.r.l. (Milan, Italy) to collaborate on the medical website www.inflammology.org. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• IL-6 is a pro-inflammatory cytokine involved in the pathophysiology of several inflammatory diseases.

• Patients with COVID-19 often present with increased levels of IL-6.

• Increased levels of IL-6 in COVID-19 are strongly correlated with adverse clinical outcomes.

• IL-6 blockade was evaluated in several randomized controlled trials with overall encouraging results, despite some inconsistency in individual studies.

• Based on currently available evidence, IL-6 blockade should be considered for patients with severe-to-critical COVID-19, and it may be mostly beneficial in those with an early hyperinflammatory phenotype and without substantial organ damage.

Additional information

Funding

This paper was not funded.