Age-determined expression of priming protease TMPRSS2 and localization of SARS-CoV-2 in lung epithelium

J Clin Invest. 2021 Jan 4;131(1):e140766. doi: 10.1172/JCI140766.


The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel coronavirus 2019 (COVID-19) global pandemic has led to millions of cases and hundreds of thousands of deaths. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.

Keywords: Expression profiling; Pulmonology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aging
  • Alveolar Epithelial Cells / enzymology*
  • Alveolar Epithelial Cells / pathology
  • Alveolar Epithelial Cells / virology
  • Animals
  • COVID-19 / enzymology*
  • COVID-19 / metabolism*
  • COVID-19 / pathology
  • Child, Preschool
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Infant
  • Male
  • Mice
  • SARS-CoV-2 / metabolism*
  • Serine Endopeptidases / biosynthesis*


  • Serine Endopeptidases
  • TMPRSS2 protein, human
  • TMPRSS2 protein, mouse