Activation or exhaustion of CD8(+) T cells in patients with COVID-19

In addition to CD4(+) T cells and neutralizing antibodies, CD8(+) T cells contribute to protective immune responses against SARS-CoV-2 in patients with coronavirus disease 2019 (COVID-19), an ongoing pandemic disease. In patients with COVID-19, CD8(+) T cells exhibiting activated phenotypes are commonly observed, although the absolute number of CD8(+) T cells is decreased. In addition, several studies have reported an upregulation of inhibitory immune checkpoint receptors, such as PD-1, and the expression of exhaustion-associated gene signatures in CD8(+) T cells from patients with COVID-19. However, whether CD8(+) T cells are truly exhausted during COVID-19 has been a controversial issue. In the present review, we summarize the current understanding of CD8(+) T-cell exhaustion and describe the available knowledge on the phenotypes and functions of CD8(+) T cells in the context of activation and exhaustion. We also summarize recent reports regarding phenotypical and functional analyses of SARS-CoV-2-specific CD8(+) T cells and discuss long-term SARS-CoV-2-specific CD8(+) T-cell memory.