SARS-CoV-2 Immune Complex-Mediated Neutrophil Activation.

Understanding disease pathogenesis is essential to developing therapies in patients with infections that cause critical illness. Herein, we show that SARS-CoV-2-specific antibody levels and markers of neutrophil activation are associated with disease severity in patients hospitalized with COVID-19. We also provide a link between the adaptive and innate immune response by demonstrating an association between antibody levels and multiple markers of neutrophil degranulation and NETosis. We further demonstrate through a series of in vitro assays that SARS-CoV-2 antigen-antibody immune complexes can stimulate NETosis. Last, we discuss how this NETosis is more strongly associated with IgA immune complexes than IgG and can be ameliorated with spleen tyrosine kinase inhibition.