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. Overall design: 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