Comparison οf Immune Responses Through Multiparametric T-Cell Cytokine Expression Profile Between Children with Convalescent COVID-19 or Multisystem Inflammatory Syndrome

Abstract

Background/objectives: The immunological pathways that cause Multisystem Inflammatory Syndrome after SARS-CoV-2 infection in children (MIS-C) remain under investigation. Methods: The aim of this study was to prospectively compare the T-cell cytokine expression profile in unvaccinated children with acute MIS-C (MISC_A) before immunosuppression, convalescent MIS-C (one month after syndrome onset, MISC_C), convalescent COVID-19 (one month after hospitalization), and in healthy, unvaccinated controls. The intracellular expression of IL-4, IL-2, IL-17, IFNγ, TNF-α and Granzyme B, and the post SARS-CoV-2-Spike antigenic mix stimulation of T-cell subsets was analyzed by 13-color flow cytometry. Results: Twenty children with a median age (IQR) of 11.5 (7.25–14) years were included in the study. From the comparison of the flow cytometry analysis of the 14 markers of MISC_A with the other three groups (MISC_C, post-COVID-19 and controls), significant differences were identified as follows: 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+IFNγ+/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. Conclusions: In children presenting with MIS-C one month after COVID-19 infection, T cells were found to be polarized towards IL-17 and IFNγ production compared to those with uncomplicated convalescent COVID-19, a finding that could provide possible immunological biomarkers for MIS-C detection.