Characterization of the SARS-CoV-2 Host Response in Primary Human Airway Epithelial Cells from Aged Individuals

Viruses. 2021 Aug 12;13(8):1603. doi: 10.3390/v13081603.

Abstract

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), a global pandemic characterized by an exaggerated immune response and respiratory illness. Age (>60 years) is a significant risk factor for developing severe COVID-19. To better understand the host response of the aged airway epithelium to SARS-CoV-2 infection, we performed an in vitro study using primary human bronchial epithelial cells from donors >67 years of age differentiated on an air-liquid interface culture. We demonstrate that SARS-CoV-2 infection leads to early induction of a proinflammatory response and a delayed interferon response. In addition, we observed changes in the genes and pathways associated with cell death and senescence throughout infection. In summary, our study provides new and important insights into the temporal kinetics of the airway epithelial innate immune response to SARS-CoV-2 in older individuals.

Keywords: COVID-19; SARS-CoV-2; aging; airway epithelium; air–liquid interface; immune response; inflammation; innate immunity.

Publication types

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

MeSH terms

  • Aged
  • Aging / immunology
  • Bronchi / cytology
  • Bronchi / immunology*
  • Bronchi / metabolism
  • Bronchi / virology*
  • COVID-19 / immunology
  • Cell Death / genetics
  • Cells, Cultured
  • Cellular Senescence / genetics
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism
  • Epithelial Cells / virology
  • Female
  • Humans
  • Immunity, Innate*
  • Inflammation
  • Interferons / biosynthesis
  • Interferons / genetics
  • Male
  • RNA-Seq
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / virology*
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • Signal Transduction / genetics

Substances

  • Cytokines
  • Interferons