ABSTRACT
Background: Multisystem Inflammatory Syndrome in Children (MIS-C) can develop 1-2 mo post SARS-CoV-2 infection. MIS-C is characterized by fever, multiorgan dysfunction requiring hospitalization, and systemic inflammation. To evaluate a potential role for aberrant T-cell responses as a potential mechanism for MIS-C pathogenesis, we quantified SARS-CoV-2 -reactive T cells in children with COVID-19, MIS-C, and healthy children (HC). Methods: Hospitalized children ages 0-20 yrs with COVID-19 (n=13) or MIS-C (n=18) were enrolled from May-Sep 2020. Peripheral blood mononucle ar cells (PBMC) were obtained from convalescent phase of infection (28-54 d from illness onset) for COVID-19 or at hospitalization for MIS-C to approximate similar time since infection. Plasma SARS-CoV-2 receptor binding domain (RBD) antibody titers were determined by ELISA. PBMC from HC (n=20) with undetectable RBD antibodies served as controls. T-cell responses were quantified using activation-induced marker (AIM) assay after stimulation with SARS-CoV-2 peptide “megapools” (MP): CD4 MP-S with 253 spike-spanning peptides, CD4 MP-R with 221 remaining non-spike;spike-containing CD8 MP-A and non-spike CD8 MP-B with 314 each. Frequency of AIM+ T-cells and stimulation index (SI) were compared across donor groups. Results: Among COVID-19, majority had SARS-CoV-2 specific CD4+ (100% spike, 83% non-spike) and CD8+ (85% spike-containing, 83% non-spike) T-cells. There was a trend for lower frequencies of AIM+ T-cells to all peptide MP in MIS-C, with significantly lower responses to non-spike antigens in CD4+ (p<0.05) and CD8+ (p<0.05) T-cells compared to those in COVID-19. In addition, COVID-19 had higher reactivity to stimulation, with significantly greater SI for spike CD4+ T-cell responses compared with HC (4.62 vs 1.93, p<0.05) and non-spike compared to both MIS-C (3.27 vs 1.44, p<0.05) and HC (3.27 vs 1.60, p<0.01). Interestingly, most HC also had detectable CD4+ (70% spike, 50% non-spike) and CD8+ T-cells (90% spike, 75% non-spike) against SARS-CoV-2 antigens, possibly attributable to prior infection by endemic coronaviruses. RBD IgG levels were similar between MIS-C and convalescent COVID-19. Conclusion: We find more robust CD4+ and CD8+ T-cell responses against non-spike SARS-CoV-2 peptides in convalescent COVID-19 compared to MIS-C. Equivalent humoral responses against spike RBD among MIS-C and COVID-19 suggest that impaired SARS-CoV-2-specific T-cell response to non-spike antigens may contribute to the immunopathogenesis of MIS-C.