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Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation
Published on: February 2, 2024
SARS-CoV-2 Immune Complex-Mediated Neutrophil Activation
Kiana C Allen1,2, Seth Warner1,2, Heather L Teague1,2
1Critical Care Medicine Department, National Institutes of Health Clinical Center, Bethesda, Maryland, USA.
Abstract:
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.
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