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

David H. Brann, Tatsuya Tsukahara, Caleb Weinreb, Marcela Lipovsek, Koen Van Den Berge, Boying Gong, Rebecca Chance, Iain C. Macaulay, Hsin Jung Chou, Russell B. Fletcher, Diya Das, Kelly Street, Hector Roux De Bezieux, Yoon Gi Choi, Davide Risso, Sandrine Dudoit, Elizabeth Purdom, Jonathan Mill, Ralph Abi Hachem, Hiroaki MatsunamiDarren W. Logan, Bradley J. Goldstein, Matthew S. Grubb, John Ngai, Sandeep Robert Datta

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

Abstract

Altered olfactory function is a common symptom of COVID-19 (coronavirus disease 2019), but its etiology is unknown. A key question is whether SARS-CoV-2 (severe acute respiratory syndrome coronavirus 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, by perturbing support cells. Bulk and single-cell RNA sequencing revealed that support and stem cells in the human and mouse olfactory epithelium and vascular pericytes in the mouse olfactory bulb express angiotensin-converting enzyme 2 (ACE2), which is essential for CoV-2 cell entry. In contrast, ACE2 was not detected in either olfactory sensory neurons or olfactory bulb neurons. Immunostaining confirmed these results and revealed pervasive expression of ACE2 protein in dorsally located olfactory epithelial sustentacular cells and mouse olfactory bulb pericytes. These findings suggest that CoV-2 infection of non-neuronal cell types leads to olfactory dysfunction in patients with COVID-19.

Original languageEnglish (US)
Article numberabc5801
JournalScience Advances
Volume6
Issue number31
DOIs
StatePublished - Jul 2020
Externally publishedYes

ASJC Scopus subject areas

  • General

Fingerprint

Dive into the research topics of 'Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia'. Together they form a unique fingerprint.

Cite this