FIGURE 4.

Cytokine combinations and polyfunctional N‐specific CD4+ T‐cell response are associated with COVID‐19 progression. (A) N‐specific CD4+ T‐cell response considering the levels of cells producing IL‐2 in the different CD4+ T‐cell subsets, in mild and severe acute patients’ groups. (B) N‐specific CD4+ T‐cell response considering the levels of cells producing TNF‐α in the different CD4+ T‐cell subsets, in mild and severe acute patients’ groups. (C) N‐specific CD4+ T‐cell levels in the different T‐cell subsets of combinations including IL‐2+ and TNF‐α+ cells for five (IFN‐γ, TNF‐α, IL‐2, CD107a and PRF) functions. (D) N‐specific CD4+ T‐cell levels in the different T‐cell subsets of combinations including IL‐2+, TNF‐α+ and IFN‐γ+ T‐cells for five (IFN‐γ, TNF‐α, IL‐2, CD107a and PRF) functions. (E) N‐specific MEM CD4 T‐cell polyfunctionality pie charts. Each sector represents the proportion of N‐specific CD4+ T‐cells producing three (red), two (blue) and one (yellow) function. Arc represents the type of function (IFN‐γ, TNF‐α, IL‐2, CD107a and PRF) expressed in each sector. Permutation test, following the Spice version 6.0 software was used to assess differences between pie charts. (F) Polyfunctional index bar graph of N‐specific MEM CD4+ polyfunctionality, for five functions. The medians with the interquartile ranges are shown. Each dot represents a patient. ROUT method was utilised to identify and discard outliers. *p < 0.05, **p < 0.01, ***p < 0.001. Mann–Whitney U‐test was used for groups’ comparisons. (Mild, n = 11; severe, n = 11)