SARS-CoV-2-specific T cell responses in children
(A) Representative flow cytometry plots of SARS-CoV-2-specific interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-2 (IL-2) cytokine production from CD4+ (left) and CD8+ (right) T cells in response to SARS-CoV-2 peptide stimulation. NS: no stimulation, SNM: combined peptide pool of SARS-CoV-2-spike, nucleocapsid and membrane proteins.
(B) Frequency of SARS-CoV-2-specific CD4+ T cells producing any of the measured cytokines (IFN-γ, IL-2 or TNF-α). Children were grouped according to SARS-CoV-2 serostatus (light blue: n = 41 SARS-CoV-2 seropositive; dark blue: n = 30 SARS-CoV-2 seronegative). Bars represent the median of the responders, and median values are indicated. The pie charts represent the proportion of responders with detectable T cell response to SARS-CoV-2 SNM peptides.
(C) Frequency of SARS-CoV-2-specific CD8+ T cells producing any of the measured cytokines (IFN-γ, IL-2 or TNF-α). Children were grouped according to SARS-CoV-2 serostatus (light red: n = 41 SARS-CoV-2 seropositive children; dark red: n = 30 SARS-CoV-2 seronegative children). Statistical comparisons in (B) and (C) were performed using the Mann-Whitney test between seropositive and seronegative children and the Chi-square test to compare the percentage of responders; p values < 0.05 were considered statistically significant and are bolded.
(D) Polyfunctional profile of SARS-CoV-2-specific CD4+ and (E) CD8+ T cells in seropositive and seronegative unvaccinated children. The x axis illustrates each combination which is indicated with a black circle for the presence of IFN-γ, IL-2 and TNF-α. The medians and interquartile range are shown. Each response pattern (any possible combination of IFN-γ, IL-2 and TNF-α production) is color coded and summarized in the pie charts, with each pie slice representing the median contribution of each combination to the total SARS-CoV-2 responses. The permutation test was used to compare the statistical differences between the pie charts and the Mann Whitney Sum Test to compare response patterns between seropositive and seronegative children; p values < 0.05 were considered statistically significant and are bolded.