Neutrophils in Coronavirus Disease 2019: Guardians or Triggers of Immunopathology?

COVID-19 (coronavirus disease 2019) is a respiratory viral disease with a wide range of clinical symptoms that emerged in December 2019. Innate immunity serves as a rapid immune system that can fight off pathogens before they can spread and cause an active infection. Neutrophils, the most abundant innate immune cells, are the first cells to migrate to the site of infection, where they defend against invading pathogens. Once activated at the inflammatory site, neutrophils mediate host protection through multiple mechanisms, including the phagocytosis of pathogens, the release of antimicrobial and pro-inflammatory enzymes, the production of reactive oxygen species (ROS), and the extrusion of their chromatin to form neutrophil extracellular traps (NETs) that bind to extracellular pathogens. Furthermore, neutrophils can move toward the source of the stimulus through a mechanism called chemotaxis, which is mediated by adhesion molecules and chemokine-chemokine receptor axes. However, neutrophil overactivation can have deleterious effects on various organs through the induction of cytokine storms, ROS production, and NET formation. Moreover, the contribution of distinct neutrophil subsets and their plasticity over the course of infection and recovery remain poorly understood. This review summarizes the current knowledge of the interplay between neutrophils and SARS-CoV-2, highlighting the most important mechanisms involved in the pathogenesis of COVID-19, to advance our understanding of this disease.