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Multisystem inflammatory syndrome in children (MIS-C) can complicate infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but differences in the immune responses during MIS-C compared to coronavirus disease 2019 (COVID-19) are poorly understood. We longitudinally compared the amounts and avidity of plasma anti-nucleocapsid (N) and spike (S) antibodies, phenotypes of B cells and numbers of virus-specific antibody-secreting cells in circulation of children hospitalized with COVID-19 (N=10) and with MIS-C (N=12). N-specific IgG was higher early after presentation for MIS-C than COVID-19 patients and avidity of N- and S-specific IgG at presentation did not mature further during follow up as it did for COVID-19. Both groups had waning proportions of B cells in circulation and decreasing but sustained production of virus-specific antibody-secreting cells for months. Overall, B cell responses were similar, but those with MIS-C demonstrated a more mature antibody response at presentation, suggesting a postinfectious entity compared to COVID-19.

B-Cell Responses in Hospitalized Severe Acute Respiratory Syndrome Coronavirus 2–Infected Children With and Without Multisystem Inflammatory Syndrome