Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (scRNA-seq: olfactory mucosa)

A subset of COVID-19 patients exhibit altered olfactory function. Here we analyze bulk and single cell RNA-Seq datasets to identify cell types in the olfactory epithelium and olfactory bulb that express cell entry molecules that mediate infection by SARS-CoV-2 (CoV-2), the causal agent in COVID-19. We find that samples from whole olfactory mucosa in species including mouse and human express two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, neither olfactory sensory neurons nor olfactory bulb neurons express these genes, which are instead expressed in support cells, stem cells, and perivascular cells. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients. Eight 15 min Drop-seq runs from dissociated whole olfactory mucosa from five adult male C57BL/6 mice (8-12 weeks-old). Additional Drop-Seq data from the olfactory bulb can be found in GSE148360.部分新型冠状病毒肺炎（COVID-19）患者会出现嗅觉功能异常。本研究通过分析批量RNA测序（bulk RNA-Seq）与单细胞RNA测序（single cell RNA-Seq）数据集，对嗅觉上皮与嗅球中表达介导严重急性呼吸综合征冠状病毒2型（SARS-CoV-2，简称CoV-2，即COVID-19致病原）入侵的细胞进入分子的细胞类型进行鉴定。我们发现，包括人类与小鼠在内的多个物种的全嗅觉黏膜样本，均表达两种参与CoV-2入侵的关键基因：血管紧张素转换酶2（ACE2）与跨膜丝氨酸蛋白酶2（TMPRSS2）。但值得注意的是，嗅觉感觉神经元与嗅球神经元均不表达上述基因，此类基因的表达主要定位于支持细胞、干细胞与血管周细胞。上述研究结果表明，CoV-2对非神经元细胞类型的感染，可导致COVID-19患者出现嗅觉丧失及相关嗅觉感知障碍。本研究包含8次时长15分钟的Drop-seq测序，样本取自5只8-12周龄成年雄性C57BL/6小鼠的解离全嗅觉黏膜组织。额外的嗅球Drop-seq数据集可于GSE148360中获取。