Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia
Science Advances, 2020
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 Matsunami, Darren W. Logan, Bradley J. Goldstein, Matthew S. Grubb, John Ngai and Sandeep Robert Datta. (2020). Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia. Science Advances 6:eabc5801. https://doi.org/10.1126/sciadv.abc5801
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.