Comparison οf Immune Responses Through Multiparametric T cell Cytokine Expression Profile Between Children With Convalescent COVID-19 Or Multisystem Inflammatory Syndrome

Abstract

The immunological pathways that cause Multisystem Inflammatory Syndrome after SARS-CoV-2 infection in children(MIS-C) remain under investigation. Aim of this study was to prospectively compare T-cell cytokine expression profile in unvaccinated children with acute MIS-C(MIS-C_A) before immunosuppression, convalescent MIS-C(one month after syndrome onset, MIS-C_C), convalescent COVID-19(one month after hospitalization) and healthy, unvaccinated controls. Intracellular expression of IL-4, IL-2, IL-17, IFN-γ, TNF-α and Granzyme B, post SARS-CoV-2-Spike antigenic mix stimulation of T cell subsets was analyzed by 13-colour Flow Cytometry. Twenty children with median age(IQR): 11.5(7.25-14) years were included in the study. From the comparison of the flow cytometry analysis of the 14 markers of MIS-C_A with the other 3 groups(MIS-C_C, post-COVID-19 and controls), significant differences were identified for: 1. CD4+IL-17+/million CD3+: 293.0(256.4-870.9) vs 50.7(8.4-140.5); P-value:0.03, vs 96.7(89.2-135.4); P-value:0.03 and vs 8.7(0.0-82.4); P-value:0.03, respectively, 2. CD8+IL-17+/million CD3+: 335.2(225.8-429.9) vs 78.0(31.9-128.9) vs 84.1(0.0-204.6) vs 33.2(0.0-114.6); P-value:0.05, respectively 3. CD8+IFN-γ+/million CD3+: 162.2(91.6-273.4) vs 41.5(0.0-77.4); P-value:0.03 vs 30.3(0.0-92.8); P-value:0.08, respectively. In children presenting with MIS-C one month after COVID-19 infection, T cells were found to be polarized towards IL-17 and IFN-γ production compared to those with uncomplicated convalescent COVID-19, a finding that could provide possible immunological biomarkers for MIS-C detection.