AUTHOR=Stoy Nicholas 

TITLE=Involvement of Interleukin-1 Receptor-Associated Kinase 4 and Interferon Regulatory Factor 5 in the Immunopathogenesis of SARS-CoV-2 Infection: Implications for the Treatment of COVID-19

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.638446

DOI=10.3389/fimmu.2021.638446

ISSN=1664-3224

ABSTRACT=<p>Interleukin-1 receptor-associated kinase 4 (IRAK4) and interferon regulatory factor 5 (IRF5) lie sequentially on a signaling pathway activated by ligands of the IL-1 receptor and/or multiple TLRs located either on plasma or endosomal membranes. Activated IRF5, in conjunction with other synergistic transcription factors, notably NF-κB, is crucially required for the production of proinflammatory cytokines in the innate immune response to microbial infection. The IRAK4-IRF5 axis could therefore have a major role in the induction of the signature cytokines and chemokines of the hyperinflammatory state associated with severe morbidity and mortality in COVID-19. Here a case is made for considering IRAK4 or IRF5 inhibitors as potential therapies for the “cytokine storm” of COVID-19.</p>