Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19

Nat Commun. 2022 Jan 21;13(1):440. doi: 10.1038/s41467-021-27716-4.


Dysregulated immune responses against the SARS-CoV-2 virus are instrumental in severe COVID-19. However, the immune signatures associated with immunopathology are poorly understood. Here we use multi-omics single-cell analysis to probe the dynamic immune responses in hospitalized patients with stable or progressive course of COVID-19, explore V(D)J repertoires, and assess the cellular effects of tocilizumab. Coordinated profiling of gene expression and cell lineage protein markers shows that S100Ahi/HLA-DRlo classical monocytes and activated LAG-3hi T cells are hallmarks of progressive disease and highlights the abnormal MHC-II/LAG-3 interaction on myeloid and T cells, respectively. We also find skewed T cell receptor repertories in expanded effector CD8+ clones, unmutated IGHG+ B cell clones, and mutated B cell clones with stable somatic hypermutation frequency over time. In conclusion, our in-depth immune profiling reveals dyssynchrony of the innate and adaptive immune interaction in progressive COVID-19.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptive Immunity / drug effects
  • Adaptive Immunity / genetics
  • Adaptive Immunity / immunology*
  • Aged
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • COVID-19 / genetics
  • COVID-19 / immunology*
  • COVID-19 Drug Treatment
  • Cells, Cultured
  • Female
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Humans
  • Immunity, Innate / drug effects
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology*
  • Male
  • RNA-Seq / methods
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • SARS-CoV-2 / drug effects
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • Single-Cell Analysis / methods*


  • Antibodies, Monoclonal, Humanized
  • Receptors, Antigen, B-Cell
  • Receptors, Antigen, T-Cell
  • tocilizumab