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

To determine whether genes relevant to CoV-2 entry are expressed in OSNs or other cell types in the OE, we examined published datasets in which RNA-Seq was independently performed on mouse whole olfactory mucosa (WOM) and on purified populations of mature OSNs (39) (40) (41) . The CoV-2 receptor Ace2 and the protease Tmprss2 were expressed in WOM, as were the cathepsins Ctsb and Ctsl (Figures 2A-B ) (39) . However, expression of these genes (with the exception of Ctsb) was much lower and Ace2 expression was nearly absent in purified OSN samples (Figure 2A , see Legend for counts, see Methods). Genes used for cell entry by other CoVs (except St3gal4) were also expressed in WOM, and de-enriched in purified OSNs. These samples reflected the presence of expected cell types, as the WOM sequencing data included gene expression profiles associated with a wide variety of RE and OE cells, while the purified OSN samples were specifically enriched for markers of mature OSNs. The de-enrichment of Ace2 and Tmprss2 in OSNs relative to WOM was also observed in two other mouse RNA-Seq datasets (40, 41) ( Figure S1A ).