Title

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

Authors

Susan R. Conway, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
Christopher A. Lazarski, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
Naomi E. Field, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
Mariah Jensen-Wachspress, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
Haili Lang, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
Vaishnavi Kankate, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
Jessica Durkee-Shock, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
Hannah Kinoshita, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
William Suslovic, Division of Pathology and Laboratory Medicine, Children's National Hospital, Washington, DC, United States.
Kathleen Webber, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
Karen Smith, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Jeffrey I. Cohen, Laboratory of Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
Peter D. Burbelo, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, United States.
Anqing Zhang, Division of Biostatistics and Study Methodology, Children's National Hospital, Washington, DC, United States.
Stephen J. Teach, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Trisha Ibeh, Center for Translational Research, Children's National Hospital, Washington, DC, United States.
Meghan Delaney, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Roberta L. DeBiasi, Department of Pediatrics, George Washington University School of Medicine and Health Sciences, Washington, DC, United States.
Michael D. Keller, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.
Catherine M. Bollard, Center for Cancer and Immunology Research, Children's National Hospital, Washington, DC, United States.

Document Type

Journal Article

Publication Date

1-1-2021

Journal

Frontiers in immunology

Volume

12

DOI

10.3389/fimmu.2021.793197

Keywords

COVID-19; MIS-C; SARS-CoV-2; T cell; pediatric

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.

Department

Pediatrics

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