Summary

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.

Overall design

Researchers combined scRNA-seq, mass cytometry, and scATAC-seq to compare immune cells from young, old, and COVID-19 patients. They found age reprogrammed the immune landscape, with T cell polarization towards effector, cytotoxic, and exhausted states, along with increases in late NK cells, age-associated B cells, and inflammatory monocytes. Age-specific gene expression linked to coronavirus susceptibility was also upregulated. COVID-19 further promoted these age-related immune changes, suggesting that immu

Contributors

Yingfeng Zheng†, Xiuxing Liu†, Wenqing Le†, Lihui Xie†, He Li†, Wen Wen†, Si Wang†, Jing Qu✉️, Hongyang Wang✉️, Guang-Hui Liu✉️, Wenru Su✉️

Contact

qujing@ioz.ac.cn (Jing Qu), hywangk@vip.sina.com (Hongyang Wang), ghliu@ioz.ac.cn (Guang-Hui Liu), suwenru@gzzoc.com (Wenru Su)