Aging and CMV Infection Affect Pre-existing SARS-CoV-2-Reactive CD8+ T Cells in Unexposed Individuals
Norihide Jo, Rui Zhang, Hideki Ueno, Takuya Yamamoto, Daniela Weiskopf, Miki Nagao, Shinya Yamanaka, Yoko Hamazaki
Abstract
Age is a major risk factor for COVID-19 severity, and T cells play a central role in anti-SARS-CoV-2 immunity. Because SARS-CoV-2-cross-reactive T cells have been detected in unexposed individuals, we investigated the age-related differences in pre-existing SARS-CoV-2-reactive T cells. SARS-CoV-2-reactive CD4 + T cells from young and elderly individuals were mainly detected in the central memory fraction and exhibited similar functionalities and numbers. Naïve-phenotype SARS-CoV-2-reactive CD8 + T cell populations decreased markedly in the elderly, while those with terminally differentiated and senescent phenotypes increased. Furthermore, senescent SARS-CoV-2-reactive CD8 + T cell populations were higher in cytomegalovirus seropositive young individuals compared to seronegative ones. Our findings suggest that age-related differences in pre-existing SARS-CoV-2-reactive CD8 + T cells may explain the poor outcomes in elderly patients and that cytomegalovirus infection is a potential factor affecting CD8 + T cell immunity against SARS-CoV-2. Thus, this study provides insights for developing effective therapeutic and vaccination strategies for the elderly.