A human circulating immune cell landscape in aging and COVID-19

Zheng, Yingfeng; Liu, Xiuxing; Le, Wenqing; Xie, Lihui; Li, He; Wen, Wen; Wang, Si; Ma, Shuai; Huang, Zhaohao; Ye, Jinguo; Shi, Wen; Ye, Yanxia; Liu, Zunpeng; Song, Moshi; Zhang, Weiqi; Han, Jing-Dong J.; Belmonte, Juan Carlos Izpisua; Xiao, Chuanle; Qu, Jing; Wang, Hongyang; Liu, Guang-Hui; Su, Wenru

Age-associated changes in immune cells have been linked to an increased risk for infection. However, a global and detailed characterization of the changes that human circulating immune cells undergo with age is lacking. Here, we combined scRNA-seq, mass cytometry and scATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with COVID-19. We found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector, cytotoxic, exhausted and regulatory cells, along with increased late natural killer cells, age-associated B cells, inflammatory monocytes and age-associated dendritic cells. In addition, the expression of genes, which were implicated in coronavirus susceptibility, was upregulated in a cell subtype-specific manner with age. Notably, COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular senescence. Therefore, these findings suggest that a dysregulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13238-020-00762-2) contains supplementary material, which is available to authorized users.