To gain more insights, we applied global high-dimensional mapping of the 27-parameter flow cytometry data. A tSNE representation of the data highlighted key regions of non-naïve CD8 T cells found preferentially in COVID-19 patients (Fig. 2G). A major region of this tSNE map present in COVID-19 patients, but not HD or RD, were CD8 T cells that enriched for expression of CD38, HLA-DR, KI67, CD39, and PD1 (Fig. 2G), highlighting the co-expression of these activation markers with other features including CD95 (i.e., FAS). Notably, although non-naïve CD8 T cells from RD were highly similar to those from HD, subtle differences existed, including in the lower region highlighted by T-bet and CX3CR1 (Fig. 2G). To further define and quantify these differences between COVID-19 patients and controls, we performed FlowSOM clustering (Fig. 2H) and compared expression of fourteen CD8 T cell markers to identify each cluster (Fig. 2I). This approach identified an increase in cells in several clusters including Clusters 1, 2, and 5 in COVID-19 patients, reflecting CD45RA+CD27−CCR7− TEMRA-like populations that expressed CX3CR1 and varying levels of T-bet (Fig. 2, I and J). Clusters 12 and 14 contained CD27+HLA-DR+CD38+KI67+PD-1+ activated, proliferating cells and were more prevalent in COVID-19 disease (Fig. 2, I and J, and fig. S2F). In contrast, the central Eomes+CD45RA−CD27+CCR7− EM1-like Cluster 6 and T-bethiCX3CR1+ Cluster 11 were decreased compared to HD (Fig. 2, I and J, and fig. S2F). Thus, CD8 T cell responses in COVID-19 patients were characterized by populations of activated, proliferating CD8 T cells in a subgroup of patients.