A gateway for SARS-CoV-2 infection in the human olfactory neuroepithelium

Various reports indicate an association between COVID-19 and anosmia, suggesting an infection of the olfactory sensory epithelium, and thus a possible direct virus access to the brain. To test this hypothesis, we generated RNA-seq libraries from human olfactory neuroepithelia, in which we found substantial expression of the genes coding for the virus receptor angiotensin-converting enzyme-2 (ACE2), and for the virus internalization enhancer TMPRSS2. We analyzed a human olfactory single-cell RNA-seq dataset and determined that sustentacular cells, which maintain the integrity of olfactory sensory neurons, express ACE2 and TMPRSS2. We then observed that the ACE2 protein was highly expressed in a subset of sustentacular cells in human and mouse olfactory tissues. Finally, we found ACE2 transcripts in specific brain cell types, both in mice and humans. Sustentacular cells thus represent a potential entry door for SARS-CoV-2 in a neuronal sensory system that is in direct connection with the brain. With the aim of exploring the potential expression of ACE2 and TMPRSS2 in olfactory sensory tissue, we collected biopsies via nasal endoscopic surgery from 4 adult patients. Samples of both nasal respiratory and olfactory sensory epithelia were harvested. Bulk tissue RNA was extracted, libraries generated, and sequenced