Interleukin-6 in COVID-19: A Systematic Review and Meta-Analysis

Eric Anthony Coomes; Hourmazd Haghbayan

with an overall 2.3% case fatality rate and up to 6.1% of patients experiencing severe complications. 15 As preventative vaccines and effective antivirals remain unavailable, hostdirected therapeutics employing existing immunomodulatory agents must be explored. 16, 17 Coronaviruses have been observed to activate excessive and dysregulated host immune The biologic agent tocilizumab is a humanized monoclonal antibody targeting IL-6 receptors, blocking downstream pro-inflammatory effects of IL-6. It is approved by the Food and Drug Association for CRS induced by chimeric antigen receptor-T cell therapies and immunemediated rheumatic diseases. 21, 22 Exploratory studies have suggested that IL-6 inhibition may be beneficial in patients with severe COVID-19 and, despite the absence of definitive evidence, very high drug cost, and unclear potential for harm, it has already been incorporated into COVID-19 management guidelines generated in China and Italy. 23, 24 This may thus incite clinical use without definitive evidence supporting its safety in COVID-19. We therefore designed a systematic review and meta-analysis to assess the evidence describing IL-6 response in patients with COVID-19 and the existing and planned studies investigating the efficacy of tocilizumab to guide patient management, clarify guideline development, and inform future trials in this field.