Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia

Sci Adv. 2020 Jul 31;6(31):eabc5801. doi: 10.1126/sciadv.abc5801. Epub 2020 Jul 24.

Abstract

Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) - the causal agent in COVID-19 - affects olfaction directly, by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing demonstrated that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing revealed that ACE2 is expressed in support cells, stem cells, and perivascular cells, rather than in neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally-located olfactory epithelial sustentacular cells and olfactory bulb pericytes in the mouse. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients.

Publication types

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

MeSH terms

  • Animals
  • Betacoronavirus / physiology
  • Callithrix
  • Coronavirus Infections / pathology*
  • Humans
  • Macaca
  • Mice
  • Olfaction Disorders / genetics
  • Olfaction Disorders / virology*
  • Olfactory Mucosa / cytology
  • Olfactory Mucosa / metabolism
  • Olfactory Receptor Neurons / metabolism
  • Pandemics
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism*
  • Pneumonia, Viral / pathology*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Smell / genetics
  • Smell / physiology*
  • Virus Internalization

Substances

  • Peptidyl-Dipeptidase A
  • angiotensin converting enzyme 2
  • Serine Endopeptidases
  • TMPRSS2 protein, human

Supplementary concepts

  • COVID-19
  • severe acute respiratory syndrome coronavirus 2