Integrated single-cell analysis unveils diverging immune features of COVID-19, influenza, and other community-acquired pneumonia

Elife. 2021 Aug 23;10:e69661. doi: 10.7554/eLife.69661.


The exact immunopathophysiology of community-acquired pneumonia (CAP) caused by SARS-CoV-2 (COVID-19) remains clouded by a general lack of relevant disease controls. The scarcity of single-cell investigations in the broader population of patients with CAP renders it difficult to distinguish immune features unique to COVID-19 from the common characteristics of a dysregulated host response to pneumonia. We performed integrated single-cell transcriptomic and proteomic analyses in peripheral blood mononuclear cells from a matched cohort of eight patients with COVID-19, eight patients with CAP caused by Influenza A or other pathogens, and four non-infectious control subjects. Using this balanced, multi-omics approach, we describe shared and diverging transcriptional and phenotypic patterns-including increased levels of type I interferon-stimulated natural killer cells in COVID-19, cytotoxic CD8 T EMRA cells in both COVID-19 and influenza, and distinctive monocyte compositions between all groups-and thereby expand our understanding of the peripheral immune response in different etiologies of pneumonia.

Keywords: COVID-19; PBMC; Pneumonia; human; immunology; infectious disease; inflammation; microbiology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • COVID-19 / immunology*
  • Community-Acquired Infections / immunology*
  • Female
  • Humans
  • Influenza, Human / immunology*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • Single-Cell Analysis*

Associated data

  • GEO/GSE164948