AUTHOR=McKenna Ellen , Wubben Richard , Isaza-Correa Johana M. , Melo Ashanty M. , Mhaonaigh Aisling Ui , Conlon Niall , O’Donnell James S. , Ní Cheallaigh Clíona , Hurley Tim , Stevenson Nigel J. , Little Mark A. , Molloy Eleanor J. TITLE=Neutrophils in COVID-19: Not Innocent Bystanders JOURNAL=Frontiers in Immunology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.864387 DOI=10.3389/fimmu.2022.864387 ISSN=1664-3224 ABSTRACT=

Unusually for a viral infection, the immunological phenotype of severe COVID-19 is characterised by a depleted lymphocyte and elevated neutrophil count, with the neutrophil-to-lymphocyte ratio correlating with disease severity. Neutrophils are the most abundant immune cell in the bloodstream and comprise different subpopulations with pleiotropic actions that are vital for host immunity. Unique neutrophil subpopulations vary in their capacity to mount antimicrobial responses, including NETosis (the generation of neutrophil extracellular traps), degranulation and de novo production of cytokines and chemokines. These processes play a role in antiviral immunity, but may also contribute to the local and systemic tissue damage seen in acute SARS-CoV-2 infection. Neutrophils also contribute to complications of COVID-19 such as thrombosis, acute respiratory distress syndrome and multisystem inflammatory disease in children. In this Progress review, we discuss the anti-viral and pathological roles of neutrophils in SARS-CoV-2 infection, and potential therapeutic strategies for COVID-19 that target neutrophil-mediated inflammatory responses.