Protein & Cell 2020;11(10):740-770

doi:10.1007/s13238-020-00762-2

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

Yingfeng ZHENG 1 ; Xiuxing LIU 1 ; Wenqing LE 2 ; Lihui XIE 1 ; He LI 1 ; Wen WEN 3 ; Si WANG 4 ; Shuai MA 4 ; Zhaohao HUANG 1 ; Jinguo YE 1 ; Wen SHI 1 ; Yanxia YE 5 ; Zunpeng LIU 5 ; Moshi SONG 4 ; Weiqi ZHANG 6 ; Jing-Dong J HAN 7 ; Juan Carlos Izpisua BELMONTE 8 ; Chuanle XIAO 1 ; Jing QU 9 ; Hongyang WANG 10 ; Guang-Hui LIU 11 ; Wenru SU 12

Affiliations

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Keywords

COVID-19; aging; blood; immune cells; single-cell sequencing

Country

China

Language

English

MeSH

Abstract

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.