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SARS-CoV-2-Specific T Cell Responses Are Stronger in Children With Multisystem Inflammatory Syndrome Compared to Children With Uncomplicated SARS-CoV-2 Infection

Susan R. Conway, Christopher A. Lazarski, Naomi E. Field, Mariah Jensen-Wachspress, Haili Lang, Vaishnavi V. Kankate, Jessica Durkee-Shock, Hannah Kinoshita, William Suslovic, Kathleen Webber, Karen Smith, Jeffrey I. Cohen, Peter D. Burbelo, Anqing Zhang, Stephen J. Teach, Trisha Ibeh, Meghan Delaney, Roberta L. DeBiasi, Michael D. Keller, Catherine M. Bollard

2022Frontiers in Immunology23 citationsDOIOpen Access PDF

Abstract

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. We hypothesized that these differences in presentation are related to differences in the magnitude and/or antigen specificity of SARS-CoV-2-specific T cell (CST) responses between adults and children. We therefore set out to measure the 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 in MIS-C patients were significantly higher than children with uncomplicated SARS-CoV-2 infection, but weaker than CST responses in 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 post uncomplicated infection. Children with MIS-C have CST responses that are stronger than children with uncomplicated SARS-CoV-2 infection and weaker than convalescent adults, despite near uniform seropositivity.

Topics & Concepts

MedicineImmunologySevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)AntibodyImmunityCoronavirusCellular immunityImmune systemCoronavirus disease 2019 (COVID-19)Internal medicineInfectious disease (medical specialty)DiseaseKawasaki Disease and Coronary ComplicationsSARS-CoV-2 and COVID-19 ResearchImmune responses and vaccinations