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

CoV-2like SARS-CoVinfects cells through interactions between its spike (S) protein and the ACE2 protein on target cells. This interaction requires cleavage of the S protein, likely by the cell surface protease TMPRSS2, although other proteases (such as Cathepsin B and L, CTSB/CTSL) may also be involved (4) (5) (6) (28) (29) (30) (31) (32) . Other coronaviruses use different cell surface receptors and proteases to facilitate cellular entry, including DPP4, FURIN and HSPA5 for MERS-CoV, ANPEP for HCoV-229E, TMPRSS11D for SARS-CoV (in addition to ACE2 and TMPRSS2), and ST6GAL1 and ST3GAL4 for HCoV-OC43 and HCoV-HKU1 (6, (33) (34) (35) . It has recently been demonstrated through single cell RNA sequencing analysis (referred to herein as scSeq) that cells from the human upper airwayincluding nasal RE goblet, basal and ciliated cells -express high levels of ACE2 and TMPRSS2, suggesting that these RE cell types may serve as a viral reservoir during CoV-2 infection (36) . However, analyzed samples in that dataset did not include any OSNs or sustentacular cells, suggesting that tissue sampling in these experiments did not access the OE (37, 38) . Here we query both new and previously published bulk RNA-Seq and scSeq datasets from the olfactory system for expression of ACE2, TMRPSS2 and other genes implicated in coronavirus entry. We find that non-neuronal cells in the OE and olfactory bulb, including support, stem and perivascular cells, express CoV-2 entry-associated molecules, raising the possibility that infection of these non-neuronal cell types contributes to anosmia in COVID-19 patients.