Anakinra for severe forms of COVID-19.

Abstract

There is an urgent need to seek new therapeutic approaches to combat the infective and post-infective stages of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The Article by Thomas Huet and colleagues1Huet T Beaussier H Voisin O et al.Anakinra for severe forms of COVID-19: a cohort study.Lancet Rheumatol. 2020; 2: e393-e400Summary Full Text Full Text PDF PubMed Scopus (408) Google Scholar on the clinical use of the interleukin-1 (IL-1) receptor antagonist, anakinra, to treat patients with COVID-19 is very interesting. The main hypothesis of the study was based on hyperinflammation caused by an increase in proinflammatory cytokines, such as IL-1β, IL-6, and tumour necrosis factor (TNF), triggered by SARS-CoV-2 infection. The recruited participants in this study did not have any other infection, but what if the patients did have another proinflammatory condition, such as obesity, rheumatoid arthritis, or other autoimmune disease? The strategy to block peripheral inflammation as a treatment is not new. Humanised antibodies raised against TNF have been very promising for the treatment of inflammation-associated pathologies, such as rheumatoid arthritis.2Wook SH Kim YG Ye BD An updated review of infliximab biosimilar, CT-P13, in the treatment of immune-mediated inflammatory diseases.Immunotherapy. 2020; 12: 609-623Crossref PubMed Scopus (2) Google Scholar Tocilizumab, another humanised antibody which blocks the action of circulating IL-6, has been shown to increase survival in patients with COVID-19.3Sciascia S Aprà F Baffa A et al.Pilot prospective open, single-arm multicentre study on off-label use of tocilizumab in patients with severe COVID-19.Clin Exp Rheumatol. 2020; 38: 529-532PubMed Google Scholar At the start of the COVID-19 pandemic, there was controversy regarding the use of classic anti-inflammatory drugs, such as glucocorticoids, because these drugs might exacerbate the pathogenesis. However, corticosteroid therapy along with tocilizumab is associated with improved clinical outcome of patients with COVID-19.4Campins L Boixeda R Perez-Cordon L Aranega R Lopera C Force L Early tocilizumab treatment could improve survival among COVID-19 patients.Clin Exp Rheumatol. 2020; 38: 578PubMed Google Scholar Can anakinra and tocilizumab be used as a combination therapy with corticosteroids in the treatment of severe SARS-CoV-2 infection, in the presence of inflammation-associated pathologies? A subgroup of patients with COVID-19 have a cytokine storm, characterised by a large increase in proinflammatory cytokines.5Mehta P McAuley DF Brown M Sanchez E Tattersall RS Manson JJ COVID-19: consider cytokine storm syndromes and immunosuppression.Lancet. 2020; 395: 1033-1034Summary Full Text Full Text PDF PubMed Scopus (5723) Google Scholar Therefore, the use of combination therapy might be justified for improved protection and treatment of patients with severe COVID-19 associated with systemic hyperinflammation. However, one should be careful; corticosteroids exert not only an anti-inflammatory effect but also immunosuppression, and the aforementioned cytokine storm is also followed by an immunosuppression. SARS-CoV-2 infection in patients with obesity is associated with an increased rate of pneumonia, artificial ventilation, and respiratory tract illness. The pathology of obesity is also marked with a cytokine storm, with high concentrations of IL-6 and TNF, largely from inflamed adipocytes. Inflamed adipocytes provide a favourable habitat for infiltrated macrophages and can cause some of the adipocytes to be transformed into macrophage-like cells, which can result in immunosuppression. Obesity with known increased viral shedding and hyperinflammation might lead to life-threatening outcomes in case of SARS-CoV-2 infection. The question regarding the use of anti-inflammatory drugs in patients with COVID-19 patients remains open. I declare no conflict of interest. Anakinra for severe forms of COVID-19We read with interest the Article by Thomas Huet and colleagues1 that shows an association between anakinra use and reduced need for invasive mechanical ventilation in an intensive care unit and mortality in patients with severe forms of COVID-19, without serious side-effects. Full-Text PDF Anakinra for severe forms of COVID-19We read the Article by Thomas Huet and colleagues1 describing the effects of the interleukin-1 receptor antagonist anakinra in patients with severe COVID-19 with great interest. The authors compared a composite endpoint of death or admission to an intensive care unit for invasive ventilation between a group of patients with severe COVID-19 treated with anakinra plus standard of care (anakinra group) with a historical control group that received standard care alone. Full-Text PDF Anakinra for severe forms of COVID-19: a cohort studyAnakinra reduced both need for invasive mechanical ventilation in the ICU and mortality among patients with severe forms of COVID-19, without serious side-effects. Confirmation of efficacy will require controlled trials. Full-Text PDF Anakinra for severe forms of COVID-19 – Authors' replyWe thank Marc Laine and Laurent Bonello, Adil Rashid Khan and colleagues, and Naim Khan for their interest in our Article on treatment of patients with severe forms of COVID-19 with the interleukin (IL)-1 receptor antagonist anakinra.1 Full-Text PDF