To determine whether the overall phenotypical profile of SARS-CoV-2–responding CD4+ T cells allows discrimination between COVID-19–induced and preexisting cross-reactive CD4 responses, we performed a PCA (Figure 3D) and hierarchical clustering analysis (Supplemental Figure 2D), including 8 parameters (e.g., the proportion of IFN-γ+TNF-α+IL-2+, IFN-γ–TNF-α+IL-2+ IFN-γ–TNF-α+IL-2– cells; the proportion of the early differentiated memory phenotype; and GrB, HLA-DR, CD38, and Ki67 expression). Here, IL2 is linked to COVID-19.