A prominent clinical symptom of 2019-novel coronavirus (nCoV) infection is hyposmia/anosmia (decrease or loss of sense of smell), along with general symptoms such as fatigue, shortness of breath, fever and cough. The identity of the cell lineages that underpin the infection-associated loss of olfaction could be critical for the clinical management of 2019-nCoV-infected individuals. Recent research has confirmed the role of angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) as key host-specific cellular moieties responsible for the cellular entry of the virus. Accordingly, the ongoing medical examinations and the autopsy reports of the deceased individuals indicate that organs/tissues with high expression levels of ACE2, TMPRSS2 and other putative viral entry-associated genes are most vulnerable to the infection. We studied if anosmia in 2019-nCoV-infected individuals can be explained by the expression patterns associated with these host-specific moieties across the known olfactory epithelial cell types, identified from a recently published single-cell expression study. Our findings underscore selective expression of these viral entry-associated genes in a subset of sustentacular cells (SUSs), Bowman’s gland cells (BGCs) and stem cells of the olfactory epithelium. Co-expression analysis of ACE2 and TMPRSS2 and protein–protein interaction among the host and viral proteins elected regulatory cytoskeleton protein-enriched SUSs as the most vulnerable cell type of the olfactory epithelium. Furthermore, expression, structural and docking analyses of ACE2 revealed the potential risk of olfactory dysfunction in four additional mammalian species, revealing an evolutionarily conserved infection susceptibility. In summary, our findings provide a plausible cellular basis for the loss of smell in 2019-nCoV-infected patients.

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Among the prominent clinical symptoms such as fatigue, shortness of breath, fever, and cough, 2019-nCoV infected individuals often experience hyposmia/anosmia (decrease or loss of sense of smell). Angiotensin I Converting Enzyme 2 (ACE2), a key host receptor has now been established as an important moiety for the entry of 2019-nCoV into the host cells. A multitude of studies estimated the expression of ACE2 in multiple organs including heart, kidney, intestines, lungs, buccal cavity, etc. The ongoing medical examinations and the autopsy reports of the diseased individuals strongly corroborate these organ/tissue-level molecular insights. Olfactory mucosa harbors multiple functionally distinct cell types. Zeroing in on the cell lineages that underpin infection associated loss of olfaction may provide new leads for diagnostics/clinical management of 2019-nCoV infected individuals. Our pointed bioinformatic analysis of single-cell expression profiles underscored selective expression of ACE2 in a subset of horizontal basal cells (HBCs) and sustentacular cells (SUSs) of the olfactory mucosa in humans. Inspection of the ACE2 levels in the olfactory mucosa of 4 additional mammalian species revealed comparable expression patterns, indicating the risk of olfactory dysfunction in these species. In summary, our findings pinpoint the molecular rationale of loss of smell in 2019-nCoV infected patients.