Expression of the SARS-CoV-2 Entry Proteins, ACE2 and TMPRSS2, in Cells of the Olfactory Epithelium: Identification of Cell Types and Trends with Age

ACS Chem Neurosci. 2020 Jun 3;11(11):1555-1562. doi: 10.1021/acschemneuro.0c00210. Epub 2020 May 19.


The COVID-19 pandemic revealed that there is a loss of smell in many patients, including in infected but otherwise asymptomatic individuals. The underlying mechanisms for the olfactory symptoms are unclear. Using a mouse model, we determined whether cells in the olfactory epithelium express the obligatory receptors for entry of the SARS-CoV-2 virus by using RNAseq, RT-PCR, in situ hybridization, Western blot, and immunocytochemistry. We show that the cell surface protein ACE2 and the protease TMPRSS2 are expressed in sustentacular cells of the olfactory epithelium but not, or much less, in most olfactory receptor neurons. These data suggest that sustentacular cells are involved in SARS-CoV-2 virus entry and impairment of the sense of smell in COVID-19 patients. We also show that expression of the entry proteins increases in animals of old age. This may explain, if true also in humans, why individuals of older age are more susceptible to the SARS-CoV-2 infection.

Keywords: ACE2 expression; COVID-19; SARS-CoV-2; aging; anosmia; olfactory epithelium.

MeSH terms

  • Age Factors
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Betacoronavirus / metabolism*
  • COVID-19
  • Coronavirus Infections
  • Gene Expression
  • Gene Expression Profiling
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice
  • Olfaction Disorders
  • Olfactory Mucosa / cytology
  • Olfactory Mucosa / metabolism*
  • Olfactory Receptor Neurons / metabolism*
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics*
  • Peptidyl-Dipeptidase A / metabolism
  • Pneumonia, Viral
  • RNA-Seq
  • Reverse Transcriptase Polymerase Chain Reaction
  • SARS-CoV-2
  • Serine Endopeptidases / genetics*
  • Serine Endopeptidases / metabolism
  • Virus Internalization


  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Angiotensin-Converting Enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, mouse