SARS-CoV-2-Specific T-Cell Responses are Amplified in Children with Multisystem Inflammatory Syndrome in Children

Background: Despite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. The cause of these differences in presentation may relate to differences in the host response to infection between adults and children. We thus set out to measure the SARS-CoV-2-specific T cell (CST) response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection. Methods: CSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay. Findings: Twenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses were significantly increased in adults versus children with uncomplicated SARS-CoV-2 infection (P=0.008), while children with MIS-C displayed a CST response that was similar to convalescent adults. Interpretation: Age-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults. Children with MIS-C have T cell immunity to SARS-CoV-2 that is similar to convalescent adults and greater than children with uncomplicated SARS-CoV-2, despite near uniform seropositivity. Funding: This study was funded by the Board of Visitors of Children’s National Hospital, the Connor Family Foundation, the Katzen Foundation, the National Institute of Allergy and Infectious Diseases, and the National Institute of Dental and Craniofacial Research. Declaration of Interest: C.M.B. is a co-founder and on the scientific advisory boards for Catamaran Bio and Mana Therapeutics with stock and/or ownership, is on the Board of Directors for Caballeta Bio with stock options and has stock in Neximmune and Repertoire Immune Medicines. M.D.K. is on a scientific advisory panel for Enzyvant. The other authors declare that there are no conflicts of interest. Ethical Approval: Peripheral blood mononuclear cells (PBMCs) were obtained from participants recruited from Children’s National Hospital (Washington, DC) and the National Institutes of Health under informed consent approved by the Institutional Review Board of both institutions in accordance with the Declaration of Helsinki.