(A) Representative flow cytometry plots of the gating strategy for CD4 T cell subsets. (B) Frequencies of CD4 T cell subsets as indicated. (C) Frequencies of KI67+ cells; green line at upper decile of healthy donors (HD). Representative flow cytometry plots. (D) KI67+ cells from non-naïve CD4 T cells versus non-naïve CD8 T cells, Spearman correlation of COVID-19 patients. (E) Frequencies of HLA-DR+CD38+ cells; green line at upper decile of healthy donors (HD). Representative flow cytometry plots. (F) HLA-DR+CD38+ cells from non-naïve CD4 versus non-naïve CD8 T cells, Spearman correlation of COVID-19 patients. (G) (Top) Global viSNE projection of non-naïve CD4 T cells for all subjects pooled, non-naïve CD4 T cells from HD, RD, and COVID-19 patients concatenated and overlaid. (Bottom) viSNE projections of indicated protein expression. (H) viSNE projection of non-naïve CD4 T cell clusters identified by FlowSOM clustering. (I) Mean fluorescence intensity (MFI) as indicated, column-scaled z-score. (J) Percentage of non-naïve CD4 T cells from each cohort in each FlowSOM cluster. Boxes represent IQR. (B, C, E, J) Each dot represents an individual healthy donor (HD; green), recovered donor (RD; blue), or COVID-19 patient (red). Significance determined by unpaired Wilcoxon test with BH correction: *p < 0.05, **p < 0.01, ***p < 0.001, and ****p < 0.0001.