Figure 4. Functional diversity of CD4⁺ T cell responses to SARS-CoV-2 are associated with hospitalization.

(A) The CD4⁺ T cell functionality score (FS) was determined by COMPASS and compared across all 4 stimulation conditions. (B) Two-way correlations of FS were calculated between stimulations. Colored squares indicate a statistically significant correlation (P < 0.05). (C–E) For each stimulation, we examined the association with age (C), sex (D), and hospitalization status (E). The black lines on the scatter plots represent best fit linear regression lines, and the gray-shaded areas represent the 95% CI of the predicted means. (F) CD4 functionality scores for each stimulation were compared in the presence and absence of comorbidities. (G) Background corrected magnitudes of CD4⁺ T cells expressing a CD40L⁺IL-2⁺TNF⁺ functional profile in the presence or absence of IFN-γ are compared between groups after stimulation with S1, S2, and N. CD4 functionality scores were compared using Wilcoxon signed-rank tests or Mann-Whitney U tests, followed by correction for multiple hypothesis testing using the Bonferroni method except for D and F. Supplemental Figure 6 shows all the functional profiles that were compared with obtain P values reported in G. Median, 25th, and 75th quartiles are indicated for violin plots. If not shown, P values were not significantly different. n = 60 in all panels.