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

Area of Science:

• Immunology
• Gerontology
• Infectious Diseases

Background:

• Age-associated immune system decline increases infection susceptibility.
• A comprehensive understanding of age-related immune cell alterations in humans is needed.
• The impact of aging on immune responses, particularly in the context of viral infections like COVID-19, requires detailed investigation.

Purpose of the Study:

• To globally characterize age-associated changes in human circulating immune cells.
• To investigate how aging affects immune cell populations and gene expression.
• To explore the interplay between aging, immune dysregulation, and COVID-19 severity.

Main Methods:

• Utilized single-cell RNA sequencing (scRNA-seq), mass cytometry, and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq).
• Compared immune cell profiles from peripheral blood of young and old individuals, including COVID-19 patients.
• Analyzed cell type composition, gene expression patterns, and chromatin accessibility.

Main Results:

• Identified significant age-related reprogramming of the immune cell landscape.
• Observed T cell polarization towards effector, cytotoxic, exhausted, and regulatory phenotypes with age.
• Detected increased frequencies of late natural killer cells, age-associated B cells, inflammatory monocytes, and age-associated dendritic cells.
• Found age-dependent upregulation of genes associated with coronavirus susceptibility in a cell subtype-specific manner.
• Demonstrated that COVID-19 exacerbates age-induced immune cell polarization and inflammation-related gene expression.

Conclusions:

• Aging significantly alters circulating immune cell composition and function.
• Age-associated immune dysregulation and increased susceptibility gene expression may contribute to severe COVID-19 in the elderly.
• These findings highlight the immunological basis for increased vulnerability to infections in older populations.