SARS-CoV-2 receptors and entry genes are expressed in the human olfactory neuroepithelium and brain

Fodoulian, Leon; Tuberosa, Joel; Rossier, Daniel; Boillat, Madlaina; Kan, Chenda; Pauli, Véronique; Egervari, Kristof; Lobrinus, Johannes A.; Landis, Basile N.; Carleton, Alan; Rodriguez, Ivan

Reports indicate an association between COVID-19 and anosmia, as well as the presence of SARS-CoV-2 virions in the olfactory bulb. To test whether the olfactory neuroepithelium may represent a target of the virus, 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. 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.