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

David H. Brann(Harvard University), Tatsuya Tsukahara(Harvard University), Caleb Weinreb(Harvard University), Marcela Lipovsek(King's College London), Koen Van Den Berge(Ghent University), Boying Gong(University of California, Berkeley), Rebecca K. Chance(University of California, Berkeley), Iain C. Macaulay(Norwich Research Park), Hsin-Jung Chou(University of California, Berkeley), Russell B. Fletcher(University of California, Berkeley), Diya Das(University of California, Berkeley), Kelly Street(Harvard University), Hector Roux de Bézieux(University of California, Berkeley), Yoon-Gi Choi(University of California, Berkeley), Davide Risso(University of Padua), Sandrine Dudoit(University of California, Berkeley), Elizabeth Purdom(University of California, Berkeley), Jonathan Mill(University of Exeter), Ralph Abi Hachem(Duke University), Hiroaki Matsunami(Duke University), Darren W. Logan, Bradley J. Goldstein(Duke University), Matthew S. Grubb(King's College London), John Ngai(National Institutes of Health), Sandeep Robert Datta(Harvard University)
Science Advances
July 24, 2020
10.1126/sciadv.abc5801
Cited by 1,237Open Access
Full Text

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.

Related Papers

No related papers found

Powered by citation graph analysis