Single-cell epigenomic landscape of peripheral immune cells reveals establishment of trained immunity in individuals convalescing from COVID-19

Nat Cell Biol. 2021 Jun;23(6):620-630. doi: 10.1038/s41556-021-00690-1. Epub 2021 Jun 9.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection often causes severe complications and even death. However, asymptomatic infection has also been reported, highlighting the difference in immune responses among individuals. Here we performed single-cell chromatin accessibility and T cell-receptor analyses of peripheral blood mononuclear cells collected from individuals convalescing from COVID-19 and healthy donors. Chromatin remodelling was observed in both innate and adaptive immune cells in the individuals convalescing from COVID-19. Compared with healthy donors, recovered individuals contained abundant TBET-enriched CD16+ and IRF1-enriched CD14+ monocytes with sequential trained and activated epigenomic states. The B-cell lineage in recovered individuals exhibited an accelerated developmental programme from immature B cells to antibody-producing plasma cells. Finally, an integrated analysis of single-cell T cell-receptor clonality with the chromatin accessibility landscape revealed the expansion of putative SARS-CoV-2-specific CD8+ T cells with epigenomic profiles that promote the differentiation of effector or memory cells. Overall, our data suggest that immune cells of individuals convalescing from COVID-19 exhibit global remodelling of the chromatin accessibility landscape, indicative of the establishment of immunological memory.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity
  • Adolescent
  • Adult
  • Aged
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / virology
  • COVID-19 / genetics*
  • COVID-19 / immunology
  • COVID-19 / metabolism
  • COVID-19 / virology
  • Case-Control Studies
  • Cell Differentiation
  • Chromatin Assembly and Disassembly
  • Epigenesis, Genetic*
  • Epigenomics*
  • Female
  • Gene Expression Profiling
  • Genes, T-Cell Receptor*
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Immunologic Memory*
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Lymphocyte Subsets / virology
  • Male
  • Middle Aged
  • Monocytes / immunology*
  • Monocytes / metabolism
  • Monocytes / virology
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / pathogenicity
  • Single-Cell Analysis*
  • Young Adult