Exhausted CD8+ T cell (CD8Tex)
In parallel to activation and effector cells expansion, inflammation environment also leads to an occurrence of T cell exhaustion [65]. ScRNA-seq analysis revealed that CD8+ T cell exhaustion, by scoring a core set of exhaustion-associated genes (PDCD1 encoding PD-1, HAVCR2 encoding Tim-3, CD160, LAG3, CD244, and CTLA4), was increased in COVID-19 patients [34] (Figure 1). Similarly, in severe COVID-19 patients, CD8+ T cells expressed higher level of the inhibitory membrane receptors (PD-1, CTLA4, and Tim-3) and type II IFN-γ than those in non-severely ill patients. LAG3+IFN-γ+CD8+ T cells and CTLA4+IL10RA+CD8+T cells might contribute to the T cell exhaustion associated with the severe phenotype of COVID-19 in patients [58, 66]. Clearly, SARS-CoV-2 can drive CD8+ T cell exhaustion, which should be considered during clinical therapy.