No abstract

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

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.

Introduction: Multiple system atrophy (MSA) has detrimental effects on swallowing function. The swallowing function of patients with MSA has not been systematically characterized and the underlying pathophysiological mechanisms of dysphagia remain poorly understood.Objectives: To investigate the characteristics of swallow function in MSA using high-resolution manofluorography (HRMF).Methods: We conducted a retrospective review of twenty-five MSA patients who underwent HRMF from 2016 to 2017. HRMF was utilized on patients with only oral diet (Functional Oral Intake Scale (FOIS) >3). Pharyngoesophageal and proximal esophageal pressure profiles were evaluated and compared to established normative data. The frequency and characteristics of upper esophageal sphincter (UES) and proximal esophageal abnormalities during rest and swallow were calculated.Results: The ages of patient cohort in our study ranged from 48–81 years (median 65 years) with male predominance (68%). We observed a distinct abnormal deglutitive proximal esophageal contraction (ADPEC) in 14 (56% of patients), which appears to reflect a discoordinated response of the striated muscle esophagus. Deficient UES relaxation duration, impaired UES relaxation, hypertensive resting UES pressure and hypotensive resting UES pressure were detected in 8 patients (32%), 3 patients (12%), 1 patient (4%), and 11 patients (44%) respectively.Conclusions: In patients with MSA, abnormal UES resting pressure is common. A discoordinated proximal esophageal pressure response was identified and may be a pathognomonic manometry finding for MSA. These findings may serve as indications of early stage swallowing dysfunction in patients with MSA.