Background: Anosmia is a frequent symptom in coronavirus disease 2019 (COVID-19) patients that generally resolves within weeks. In contrast, the anosmia caused by other upper respiratory infections affects a small proportion of patients and may take months to resolve or never resolve. The mechanisms behind COVID-19-induced olfactory dysfunction remain unknown. Here, we address the unique pathophysiology of COVID-19-associated olfactory dysfunction. Methods: The expression of ACE2 (virus binding receptor) and TMPRSS2 and Furin (host cell proteases facilitating virus entry) was examined in the nasal mucosa, composed of respiratory mucosa (RM), olfactory mucosa (OM), and olfactory bulb (OB) of mouse and human tissues using immunohistochemistry and gene analyses. Results: Co-expression of ACE2, TMPRSS2, and Furin was observed in the RM and in the OM, especially in the supporting cells of the olfactory epithelium and the Bowman glands. Notably, the olfactory receptor neurons (ORNs) in the OM were positive for ACE2 but almost negative for TMPRSS2 and Furin. Cells in the OB expressed ACE2 strongly and Furin weakly, and did not express TMPRSS2. All three gene expressions were confirmed in the nasal mucosa and OB. Conclusions: ACE2 was widely expressed in all tissues, whereas TMPRSS2 and Furin were expressed only in certain types of cells and were absent in the ORNs. These findings, together with clinical reports, suggest that COVID-19-related anosmia occurs mainly through sensorineural and central dysfunction and, to some extent, conductive olfactory dysfunction. The expression of ACE2, but not TMPRSS2 or Furin, in ORNs may explain the early recovery from anosmia.

中文翻译：

---

了解COVID-19中的嗅觉功能障碍：人和小鼠鼻子和嗅球中ACE2，TMPRSS2和弗林蛋白酶的表达

背景：厌食症是2019年冠状病毒病（COVID-19）患者的常见症状，通常可在数周内消退。相比之下，由其他上呼吸道感染引起的厌氧症会影响一小部分患者，可能要花费数月的时间才能解决或永远无法解决。COVID-19诱导的嗅觉功能障碍的机制尚不清楚。在这里，我们解决了与COVID-19相关的嗅觉功能障碍的独特病理生理。方法：检测由呼吸道黏膜（RM），嗅觉黏膜（OM）和嗅球（OB）组成的鼻黏膜中ACE2（病毒结合受体），TMPRSS2和Furin（促进病毒进入的宿主细胞蛋白酶）的表达。使用免疫组织化学和基因分析检测小鼠和人体组织。结果：在RM和OM中观察到ACE2，TMPRSS2和Furin的共表达，特别是在嗅觉上皮和鲍曼腺的支持细胞中。值得注意的是，OM中的嗅觉受体神经元（ORN）对ACE2呈阳性，但对TMPRSS2和弗林蛋白酶几乎呈阴性。OB中的细胞强烈表达ACE2，弗林蛋白酶较弱表达，不表达TMPRSS2。在鼻粘膜和OB中均证实了全部三个基因表达。结论：ACE2在所有组织中广泛表达，而TMPRSS2和Furin仅在某些类型的细胞中表达，而在ORN中不存在。这些发现以及临床报告表明，与COVID-19相关的失眠主要通过感觉神经和中枢功能障碍以及某种程度上的传导性嗅觉障碍引起。在ORN中ACE2的表达，而非TMPRSS2或Furin的表达，可能解释了失眠的早期恢复。