The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself. Our understanding on the humoral immunity induced by SARS-CoV-2 is still lacking. Here the authors analyze B cell responses at the single cell level to find that, in severe COVID-19 patients, plasmablasts shift from IFN to TGFβ instruction to produce IgA antibodies that are not specific to dominant SARS-CoV-2 antigens.
【저자키워드】 antibodies, viral infection, Antimicrobial responses, Next-generation sequencing, 【초록키워드】 SARS-CoV-2, Pathogenesis, Gene Expression, intensive care, severe COVID-19, interferon, lung, Spike protein, Humoral immunity, Seroconversion, plasmablasts, Lungs, SARS-CoV-2 spike protein, Patient, IFN, Adaptive immune response, expression, COVID-19 patients, Blood, IgG1, SARS-CoV-2 antigens, IL-21, TGF-β, Deceased, COVID-19 patient, Trigger, B cell response, IgA antibodies, B cell responses, severe COVID-19 patients, plasmablast, TGFβ, Express, single cell level, immune reaction, gene signature, IgA2, dominant, gene signatures, bind, instruction, sustained, inefficient, reflect, IgA antibody, dominant antigen, 【제목키워드】 SARS-CoV-2, immune response, induce,