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

Protein Cell. 2020 Oct;11(10):740-770. doi: 10.1007/s13238-020-00762-2. Epub 2020 Aug 11.


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.

Keywords: COVID-19; aging; blood; immune cells; single-cell sequencing.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / immunology*
  • Betacoronavirus*
  • CD4-Positive T-Lymphocytes / metabolism
  • COVID-19
  • Cell Lineage
  • Chromatin Assembly and Disassembly
  • Coronavirus Infections / immunology*
  • Cytokine Release Syndrome / etiology
  • Cytokine Release Syndrome / immunology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Disease Susceptibility
  • Flow Cytometry / methods
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Gene Rearrangement
  • Humans
  • Immune System / cytology
  • Immune System / growth & development
  • Immune System / immunology*
  • Immunocompetence / genetics
  • Inflammation / genetics
  • Inflammation / immunology
  • Mass Spectrometry / methods
  • Middle Aged
  • Pandemics*
  • Pneumonia, Viral / immunology*
  • SARS-CoV-2
  • Sequence Analysis, RNA
  • Single-Cell Analysis*
  • Transcriptome
  • Young Adult


  • Cytokines