Tu163 - Alterations in γδ T Cells and the Effect of IVIG in Multisystem Inflammatory Syndrome After SARS CoV-2 Infection in Children

Ayantika Sen – Stanford University School of Medicine; Jing Guo – Stanfod University School of Medicine; Anika Shah – Stanford University School of Medicine; Mahil Rao – Stanford University School of Medicine; Yueh-hsui Chien – Stanford University School of Medicine; Sheri Krams – Stanford University School of Medicine; Olivia Martinez – Stanford University School of Medicine

Abstract Text: Multisystem Inflammatory Syndrome in Children (MIS-C) is a late onset severe hyperinflammatory condition associated with SARS CoV-2. As part of the Pediatric Research Immune Network on SARS-CoV-2 and MIS-C (PRISM) trial, we collected whole blood from children at baseline prior to treatment, and at 28 days, 6 months, and 12 months post-diagnosis (n=33 MIS-C and n=25 COVID). Analysis of 37 cell immune subsets by mass cytometry demonstrated significant increases in B cells (p=0.0002), CD4+ T cells (p=0.0193) and non-classical monocytes (NCMo) (CD11c+HLA-DR+CD14-CD38-) (p=0.0026) in MIS-C. The proportions of T cells (p=0.0145), dendritic cells (DC) (p=0.0001), and classical monocytes (p=0.0162) were significantly decreased in MIS-C patients. By 28 days post-diagnosis immune cell subsets in MIS-C patients had returned to the levels in COVID patients. Although the proportion of γδ T cells (γδT) in the MIS-C and COVID groups were similar at diagnosis, γδT were significantly elevated in MIS-C at 28 days and 180 days (p=0.0068, p=0.0058). Further analysis of γδT identified four subclusters of effector memory phenotypes dysregulated in MIS-C patients. Immune cell subsets before or after treatment with IVIG were analyzed. DC (p=0.0445), γδT (p=.0003) and NCMo (p=0.0010) were all significantly decreased after treatment. There were no changes in other T cell or B cell populations and all populations returned to baseline levels by 28 days post-treatment. Thus, IVIG, an effective treatment for MIS-C, rapidly decreases DC, NCMo and γδT in the circulation. Further, our study suggests an unappreciated role for γδ T cells in MIS-C.