Non-neural expression of SARS-CoV-2 entry genes in the olfactory epithelium suggests mechanisms underlying anosmia in COVID-19 patients

David Brann; Tatsuya Tsukahara; Caleb Weinreb; Darren W. Logan; Sandeep Robert Datta

Many viruses, including coronaviruses, have been shown to propagate from the nasal epithelium past the cribriform plate to infect the olfactory bulb; this form of central infection has been suggested to mediate olfactory deficits, even in the absence of lasting OE damage (16, 30, (52) (53) (54) (55) . The rodent coronavirus MHV passes from the nose to the bulb, even though rodent OSNs do not express CEACAM1, the main MHV receptor (53, 56) (Figures S1A/C and S2A), suggesting that CoVs in the nasal mucosa can reach the brain through mechanisms independent of axonal transport by sensory nerves; in this case, OB neurons express CEACAM1 ( Figure 4E ), which likely supports the ability of MHV to target these neurons and change odor perception. One speculative possibility is that local seeding of the OE with CoV-2-infected cells can result in OSNindependent transfer of virions from the nose to the bulb, perhaps via the vascular supply shared between the OB and the OSN axons that comprise CN I. Although CN I was not directly queried in our datasets, it is reasonable to infer that vascular pericytes in CN I also express ACE2, which suggests a possible route of entry for CoV-2 from the nose into the brain. Given the absence of ACE2 in OB neurons, we speculate that any central olfactory dysfunction in COVID-19 is the secondary consequence of pericytemediated vascular inflammation (46) .