Objectives/Hypothesis: Intracellular entry of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) depends on the interaction between its spike protein with the cellular receptor angiotensin‐converting enzyme 2 (ACE2) and depends on Furin‐mediated spike protein cleavage and spike protein priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). As the expression of ACE2, TMPRSS2, and Furin in the middle and inner ear remain unclear, we analyzed the expression of these proteins in mouse ear tissues.Study Design: Animal Research.Methods: We performed immunohistochemical analysis to examine the distribution of ACE2, TMPRSS2, and Furin in the Eustachian tube, middle ear spaces, and cochlea of mice.Results: ACE2 was present in the nucleus of the epithelium of the middle ear and Eustachian tube, as well as in some nuclei of the hair cells in the organ of Corti, in the stria vascularis, and the spiral ganglion cells. ACE2 was also expressed in the cytoplasm of the stria vascularis. TMPRSS2 was expressed in both the nucleus and cytoplasm in the middle spaces, with the expression being stronger in the nucleus in the mucosal epithelium of the middle ear spaces and Eustachian tube. TMPRSS2 was present in the cytoplasm in the organ of Corti and stria vascularis and in the nucleus and cytoplasm in the spiral ganglion. Furin was expressed in the cytoplasm in the middle ear spaces, Eustachian tube, and cochlea.Conclusions: ACE2, TMPRSS2, and Furin are diffusely present in the Eustachian tube, middle ear spaces, and cochlea, suggesting that these tissues are susceptible to SARS‐CoV‐2 infection.Level of Evidence: NA Laryngoscope, 131:E2013–E2017, 2021

Objective: Patients with coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), exhibit not only respiratory symptoms but also symptoms of chemo‐sensitive disorders. Cellular entry of SARS‐CoV‐2 depends on the binding of its spike protein to a cellular receptor named angiotensin‐converting enzyme 2 (ACE2), and the subsequent spike protein‐priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 is considered to enhance the invading capacity of SARS‐CoV‐2.Methods: To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS‐CoV‐2, we investigated the expression of ACE2 and TMPRSS2 proteins using immunohistochemistry, in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, and lung of rats.Results: Co‐expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal epithelium, trachea, bronchioles, and alveoli with varying degrees of expression. Remarkably, TMPRSS2 expression was more distinct in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID‐19, such as the loss of taste, loss of olfaction, and respiratory dysfunction.Conclusions: A wide range of organs have been speculated to be affected by SARS‐CoV‐2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID‐19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID‐19.Level of Evidence: NA Laryngoscope, 131:E932–E939, 2021

Objective: We examined the influence of liquid thickness levels on the frequency of liquid penetration‐aspiration in patients with dysphagia and evaluated the clinical risk factors for penetration‐aspiration and aspiration pneumonia development.Study Design: A case series.Setting: Single‐institution academic center.Methods: We reviewed medical charts from 2018 to 2019. First, we evaluated whether liquid thickness levels influence the frequency of liquid penetration‐aspiration in patients with dysphagia. Penetration‐aspiration occurrence in a videofluoroscopic swallowing study was defined as Penetration‐Aspiration Scale (PAS) scores ≥3. Second, the association between liquid thickness level and penetration‐aspiration was analyzed, and clinical risk factors were identified. Moreover, clinical risk factors for aspiration pneumonia development within 6 months were investigated.Results: Of 483 patients, 159 showed penetration‐aspiration. The thickening of liquids significantly decreased the incidence of penetration‐aspiration (P <. 001). Clinical risk factors for penetration‐aspiration were vocal fold paralysis (odds ratio [OR], 1.99), impaired laryngeal sensation (OR, 5.01), and a history of pneumonia (OR, 2.90). Twenty‐three patients developed aspiration pneumonia while undertaking advised dietary changes, including liquid thickening. Significant risk factors for aspiration pneumonia development were poor performance status (OR, 1.85), PAS score ≥3 (OR, 4.03), and a history of aspiration pneumonia (OR, 7.00).Conclusion: Thickening of liquids can reduce the incidence of penetration‐aspiration. Vocal fold paralysis, impaired laryngeal sensation, and history of aspiration pneumonia are significant risk factors of penetration‐aspiration. Poor performance status, PAS score ≥3, and history of aspiration pneumonia are significantly associated with aspiration pneumonia development following recommendations on thickening liquids.Level of Evidence: 3.

Objective: Patients with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit not only respiratory symptoms but also symptoms of chemo-sensitive disorders and kidney failure. Cellular entry of SARS-CoV-2 depends on the binding of its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2), and the subsequent spike protein-priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 are considered to enhance the invading capacity of SARS-CoV-2. Methods: To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, lung, and kidney of rats through immunohistochemistry. Results: Strong co-expression of ACE2 and TMPRSS2 proteins was observed in the nasal respiratory epithelium, trachea, bronchioles, alveoli, kidney, and taste buds of the tongue. Remarkably, TMPRSS2 expression was much stronger in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID-19, such as the loss of taste, loss of olfaction, respiratory dysfunction, and acute nephropathy. Conclusions: A wide range of organs have been speculated to be affected by SARS-CoV-2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID-19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID-19. Level of Evidence: NA

Systemic sclerosis (SSc) is often associated with dysphagia and esophageal dysmotility; however, only a few clinical studies on this topic have been conducted. Patients with SSc who underwent swallowing examinations and esophagography at our institution between 2010 and 2022 were included. A retrospective evaluation of the patients’ backgrounds, autoantibody positivity, swallowing function, and esophageal motility was performed using medical charts. The association between dysphagia and esophageal dysmotility in patients with SSc and respective risk factors was investigated. Data were collected from 50 patients. Anti-topoisomerase I antibodies (ATA) and anti-centromere antibodies (ACA) were detected in 21 (42%) and 11 (22%) patients, respectively. Dysphagia was present in 13 patients (26%), and esophageal dysmotility in 34 patients (68%). ATA-positive patients had a higher risk for dysphagia (p = 0.027); ACA-positive patients had a significantly lower risk (p = 0.046). Older age and laryngeal sensory deficits were identified as risk factors for dysphagia; however, no risk factors for esophageal dysmotility were identified. No correlation was found between dysphagia and esophageal dysmotility. Esophageal dysmotility is more common in patients with SSc than in those with dysphagia. Autoantibodies can be predictors of dysphagia, and dysphagia must be carefully considered in ATA-positive and elderly patients with SSc.