Expression of Ace2, Tmprss2, and Furin in mouse ear tissue

ObjectivesIntracellular entry of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) depends on the interaction between its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2) and depends on Furin-mediated spike 23 protein cleavage and spike protein priming by host cell proteases including 24 transmembrane protease serine 2 (TMPRSS2). Tmprss1, Tmprss3, and Tmprss5 are expressed in the spiral ganglion neurons and the organ of Corti in the inner ear; however, Ace2, Tmprss2, and Furin expression profiles in the middle ear remain unclear. Therefore, this study aimed to analyze Ace2, Tmprss2, and Furin expression in the middle and inner ear of mice. Study DesignAnimal research. SettingDepartment of Otolaryngology and Head and Neck Surgery, University of Tokyo. MethodsWe performed immunohistochemical analysis to examine the distribution of Ace2, Tmprss2, and Furin in the eustachian tube, middle ear space, and cochlea of mice. ResultsAce2 was expressed in the cytoplasm in the middle ear epithelium, eustachian tube epithelium, stria vascularis, and spiral ganglion. Tmprss2 and Furin were widely expressed in the middle ear spaces and the cochlea. ConclusionCo-expression of Ace2, Tmprss2, and Furin in the middle ear indicates that the middle ear is susceptible to SARS-CoV-2 infections, thus warranting the use of personal protective equipment during mastoidectomy for coronavirus disease (COVID-19) patients.

Longer latency of sensory response to intravenous odor injection predicts olfactory neural disorder.

A near loss of smell may result from conductive and/or neural olfactory disorders. However, an olfactory test to selectively detect neural disorders has not been established. We investigated whether onset latency of sensory response to intravenous odor injection can detect neural disorders in humans and mice. We showed that longer preoperative onset latency of odor recognition to intravenous odor in patients with chronic rhinosinusitis predicted worse recovery of olfactory symptoms following sinus surgery. The onset latency of the olfactory sensory neuron (OSN) response to intravenous odor using synaptopHluorin signals from OSN axon terminals was delayed in mice with reduced numbers of OSNs (neural disorder) but not with increased mucus or blocked orthonasal pathways (conductive disorders). Moreover, the increase in onset latency correlated with the decrease in mature OSN numbers. Longer onset latency to intravenous odor injection is a useful biomarker for presence and severity of olfactory disorders with neural etiology.