Children with Multi-System Inflammatory Syndrome (MIS-C) develop functionally competent T cell memory against SARS-CoV-2 following recovery

Abstract

Abstract While pediatric SARS-CoV-2 infection is largely spared from severe COVID-19, a small fraction of children develop a life-threatening condition known as MIS-C, which is associated with an aberrant peripheral blood immunophenotype; namely within adaptive immune cell populations. Little is known about how MIS-C impacts memory generation that would be imperative for future SARS-CoV-2 responses. Here, we used high dimensional flow cytometry and TCR sequencing to assess the peripheral blood T cell profile during acute MIS-C (n=17), following recovery (MIS-C-R) up to 9 months post-MIS-C (n=9), and relative to age-matched convalescent, mild pediatric COVID-19 (non-MIS-C; n=5) and uninfected controls (n=3). We also applied antigen-specific analyses to determine the magnitude and functional capacity of SARS-CoV-2-specific T cells in MIS-C-R (n=10) and non-MIS-C children (n=16). Flow cytometry showed unique T cell composition in MIS-C which resolved in recovery: lacking persistence of exhausted CD8+ T cells observed during MIS-C, and reestablishment of the naïve T cell pool. TCR sequencing showed decreased clonal diversity and distinct TCR Vβ usage in acute MIS-C compared to MIS-C-R. Results from antigen-specific analyses show that while T cell memory is similar phenotypically, MIS-C-R children have greater frequencies of SARS-CoV-2-specific CD4+ T cells than non-MIS-C up to 9 months since diagnosis. Meanwhile, SARS-CoV-2-specific CD8+ T cells in MIS-C children were more cytokine-producing, while more cytotoxic in non-MIS-C children. Together, these results reveal a restoration in global T cell phenotype in MIS-C-R children, as well as the robust production of functionally competent SARS-CoV-2 specific T cell memory. This work is supported by grants from NIH (K23 AI141686, 3U01 AI100119-10S1)