The SARS-CoV-2 pandemic continues to spread relentlessly, associated with a high frequency of respiratory failure and mortality. Children experience largely asymptomatic disease, with rare reports of a Multisystem Inflammatory Syndrome in Children (MIS-C). Identifying immune mechanisms that result in these disparate clinical phenotypes in children could provide critical insights into COVID-19 pathogenesis. Using Systems Serology, here we observed in 25 children with acute mild COVID a functional phagocyte and complement activating IgG response to SARS-CoV-2, comparable to the acute responses generated in adults with mild disease. Conversely, IgA and neutrophil responses were significantly expanded in adults with severe disease. Moreover, weeks after the resolution of SARS-CoV-2 infection, children who develop MIS-C maintained highly inflammatory monocyte activating SARS-CoV-2 IgG antibodies distinguishable from acute disease in children but with antibody levels comparable to convalescent adults. Collectively, these data provide unique insights into the potential mechanisms of IgG and IgA that may underlie differential disease severity as well as unexpected complications in SARS-CoV-2 infected children.
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