Age-specific nasal epithelial responses to SARS-CoV-2 infection

Nat Microbiol. 2024 May;9(5):1293-1311. doi: 10.1038/s41564-024-01658-1. Epub 2024 Apr 15.

Abstract

Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high. Here we investigate differences in the cellular landscape and function of paediatric (<12 years), adult (30-50 years) and older adult (>70 years) ex vivo cultured nasal epithelial cells in response to infection with SARS-CoV-2. We show that cell tropism of SARS-CoV-2, and expression of ACE2 and TMPRSS2 in nasal epithelial cell subtypes, differ between age groups. While ciliated cells are viral replication centres across all age groups, a distinct goblet inflammatory subtype emerges in infected paediatric cultures and shows high expression of interferon-stimulated genes and incomplete viral replication. In contrast, older adult cultures infected with SARS-CoV-2 show a proportional increase in basaloid-like cells, which facilitate viral spread and are associated with altered epithelial repair pathways. We confirm age-specific induction of these cell types by integrating data from in vivo COVID-19 studies and validate that our in vitro model recapitulates early epithelial responses to SARS-CoV-2 infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Angiotensin-Converting Enzyme 2* / genetics
  • Angiotensin-Converting Enzyme 2* / metabolism
  • COVID-19* / virology
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Epithelial Cells* / virology
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Nasal Mucosa* / virology
  • SARS-CoV-2* / genetics
  • SARS-CoV-2* / pathogenicity
  • SARS-CoV-2* / physiology
  • Serine Endopeptidases* / genetics
  • Serine Endopeptidases* / metabolism
  • Viral Tropism
  • Virus Replication

Substances

  • Angiotensin-Converting Enzyme 2
  • TMPRSS2 protein, human
  • ACE2 protein, human
  • Serine Endopeptidases