A damaging inflammatory response is implicated in the pathogenesis of severe coronavirus disease 2019 (COVID-19), but mechanisms contributing to this response are unclear. In two prospective cohorts, early non-neutralizing, afucosylated IgG antibodies specific to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were associated with progression from mild to more severe COVID-19. In contrast to the antibody structures that were associated with disease progression, antibodies that were elicited by mRNA SARS-CoV-2 vaccines were instead highly fucosylated and enriched in sialylation, both modifications that reduce the inflammatory potential of IgG. To study the biology afucosylated IgG immune complexes, we developed an in vivo model that revealed that human IgG-Fc gamma receptor (FcγR) interactions could regulate inflammation in the lung. Afucosylated IgG immune complexes isolated from COVID-19 patients induced inflammatory cytokine production and robust infiltration of the lung by immune cells. By contrast, vaccine-elicited IgG did not promote an inflammatory lung response. Together, these results show that IgG-FcγR interactions are able to regulate inflammation in the lung and may define distinct lung activities associated with the IgG that are associated with severe COVID-19 and protection against infection with SARS-CoV-2. Description Divergent early antibody structures are associated with severe COVID-19 and are functionally distinct from mRNA vaccine-elicited antibodies in vivo.
【초록키워드】 COVID-19, SARS-CoV-2, IgG, Inflammation, coronavirus, Pathogenesis, severe COVID-19, antibody, lung, Antibody structure, progression, SARS-CoV-2 vaccine, Immune complexes, activity, Disease progression, immune complex, IgG antibody, mRNA, Mild, immune cells, receptor, in vivo, mechanism, infiltration, Interaction, Inflammatory response, Inflammatory, regulate, COVID-19 patient, acute respiratory syndrome, severe coronavirus disease, cohorts, FcγR, description, Modification, inflammatory cytokine production, robust, promote, contributing to, reduce, elicited, implicated, in vivo model, infection with SARS-CoV-2, 【제목키워드】 severity, Antibody Response, with COVID-19,