Single-cell analyses reveal SARS-CoV-2 interference with intrinsic immune response in the human gut

Mol Syst Biol. 2021 Apr;17(4):e10232. doi: 10.15252/msb.202110232.


Exacerbated pro-inflammatory immune response contributes to COVID-19 pathology. However, despite the mounting evidence about SARS-CoV-2 infecting the human gut, little is known about the antiviral programs triggered in this organ. To address this gap, we performed single-cell transcriptomics of SARS-CoV-2-infected intestinal organoids. We identified a subpopulation of enterocytes as the prime target of SARS-CoV-2 and, interestingly, found the lack of positive correlation between susceptibility to infection and the expression of ACE2. Infected cells activated strong pro-inflammatory programs and produced interferon, while expression of interferon-stimulated genes was limited to bystander cells due to SARS-CoV-2 suppressing the autocrine action of interferon. These findings reveal that SARS-CoV-2 curtails the immune response and highlights the gut as a pro-inflammatory reservoir that should be considered to fully understand SARS-CoV-2 pathogenesis.

Keywords: SARS-CoV-2; human intestinal epithelial cells; interferon; intrinsic immune response; single-cell RNA sequencing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / virology
  • Gastrointestinal Microbiome
  • Humans
  • In Situ Hybridization, Fluorescence
  • Intestines / immunology*
  • Organoids / metabolism
  • SARS-CoV-2 / physiology*
  • Sequence Analysis, RNA
  • Single-Cell Analysis*

Associated data

  • figshare/13703752.v1