Shared T cell features between severe pathogen-induced RSs highlight the emergence of hyperinflammatory and exhausted subsets in COVID-19s
(A) Comparison of immune features derived from each leukocyte subpopulation between experimental groups. A dot plot displaying the ES calculated in HAP versus COVID-19s (x axis; threshold 0.4) compared with the ES calculated in COVID-19m versus COVID-19s (y axis; threshold 0.3). Each dot represents one immunological feature. The red box highlights immune features, which are associated with severe RS (COVID-19s and HAP), with a focus on changes within the T cell fraction.
(B) UMAP with FlowSOM overlay of total T cells of combined samples. One thousand cells were subsetted from every sample from each cohort. T cell subsets with transparent names do not contain immune features highlighted in (A).
(C) Median frequencies and 25th and 75th percentiles of FlowSOM-generated CD4− CD8− (TCRγδ-enriched) immune cell cluster.
(D) Median expression and 25th and 75th percentiles of PD-1 in FlowSOM-generated immune cell clusters shown in (B).
(E) Median expression of CTLA-4 within CD4+ EM T cell subset of HCs shown in gray, of HAP in blue, and of mild and severe COVID-19 patients across TPs 1–5 shown in red.
(F) Schematic overview of cytokine polarization profile comparing COVID-19s and COVID-19m. UMAP with FlowSOM overlay shows cytokine-producing T cell subpopulations (features reaching ES > 0.3). One thousand T cells were subsetted from every sample from each cohort.
(G) Median frequency and 25th and 75th percentiles of IFN-γ-positive cells in FlowSOM-generated immune cell clusters shown in F.
(H) Median frequency and 25th and 75th percentiles of IL-2-positive cells in FlowSOM-generated immune cell cluster shown in (F).
(I) Correlation between frequency of GM-CSF expressing CD4+ (left panel) and CD8+ (right panel) TEMRA cells and the severity grade of COVID-19 patients in combined TPs 1 and 2.
(J) Heatmap depicting the Z score of each T cell related immune feature (highlighted in A) compared with HCs for every TP. Both negative and positive changes are visualized by intensity of red color scale. MFI, mean fluorescence intensity.
∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, and ∗∗∗∗p < 0.0001, Mann-Whitney test, Benjamini-Hochberg (BH) correction. See also Figure S2.