SARS-CoV-2 infection and recovery in children: Distinct T cell responses in MIS-C compared to COVID-19
Ksenia Rybkina, Joseph Bell, Marissa C. Bradley, Teddy John Wohlbold, Marika Scafuro, Wenzhao Meng, Rebecca C. Korenberg, Julia Davis‐Porada, Brett R. Anderson, Rachel Weller, Joshua D. Milner, Anne Moscona, Matteo Porotto, Eline T. Luning Prak, Kalpana Pethe, Thomas J. Connors, Donna L. Färber
Abstract
SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.