The coronavirus SARS-CoV-2 is the causative agent of the ongoing severe acute respiratory disease pandemic COVID-19. Tissue and cellular tropism is one key to understanding the pathogenesis of SARS-CoV-2. We investigate the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of human donors using a diverse panel of banked tissues. Here, we report our discovery that the ACE2 receptor protein robustly localizes within the motile cilia of airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during host respiratory transmission. We further determine whether ciliary ACE2 expression in the upper airway is influenced by patient demographics, clinical characteristics, comorbidities, or medication use, and show the first mechanistic evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) does not increase susceptibility to SARS-CoV-2 infection through enhancing the expression of ciliary ACE2 receptor. These findings are crucial to our understanding of the transmission of SARS-CoV-2 for prevention and control of this virulent pathogen.

Background: The characteristics and surgical outcomes of central compartment atopic disease (CCAD) vary by region and race. Therefore, we aimed to identify the risk factors, symptom severity, and prognosis of CCAD in the Asian population. Methods: This case-control study recruited patients diagnosed with chronic rhinosinusitis with nasal polyps who underwent functional endoscopic sinus surgery (FESS) at a tertiary hospital in Taiwan. Patients were classified into CCAD and lateral-dominant nasal polyp (LDNP) groups based on endoscopic and computed tomography imaging findings. The demographic data, symptom severity scores, and surgical outcomes of the 2 groups were analyzed.Results: Our study included 442 patients (CCAD group: n = 51; LDNP group: n = 391). We found that CCAD was strongly related to both asthma (9.8% vs 3.5%, p = 0.04) and allergic rhinitis symptoms (43.3% vs 26.6%, p = 0.01). Higher eosinophil counts were detected in blood serum (5.8% vs 2.8%, p < 0.01) and histopathologic profiles (57.0 vs 17.3, p < 0.01) among patients with CCAD. Improvements in 22item Sino-Nasal Outcome Test (SNOT-22) score and mucociliary clearance time (MCT) after surgical intervention revealed that the CCAD group had a better response to FESS (SNOT-22 score: −31.82 vs −22.66, p < 0.01; MCT: −233.06 vs −191.93 seconds, p = 0.03). The revision FESS rate was not different between the 2 groups. Conclusion:Polyps originating from the central compartment were found to be related to asthma and allergic rhinitis in Taiwanese patients. A higher eosinophil count was suggested in both serum and local nasal tissue from patients with CCAD. FESS serves as an effective treatment for symptom relief in patients with CCAD.

This study showed an association between FESS combined with concurrent SMR/septoplasty and less incidence of revision rate of FESS. Patients with asthma or allergic rhinitis have an increased risk of requiring more revision surgeries after FESS.

We investigated the expression and subcellular localization of the SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE2), within the upper (nasal) and lower (pulmonary) respiratory tracts of healthy human donors. We detected ACE2 protein expression within the cilia organelle of ciliated airway epithelial cells, which likely represents the initial or early subcellular site of SARS-CoV-2 viral entry during respiratory transmission. We further determined whether ACE2 expression in the cilia of upper respiratory cells was influenced by patient demographics, clinical characteristics, co-morbidities, or medication use, and found no evidence that the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARBs) increases ACE2 protein expression.Coronavirus disease 2019 is an ongoing pandemic infection caused by the positivesense RNA virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 1 . The high transmissibility of the virus, along with case fatality estimates ranging from 1% to above 5%, has raised concerns worldwide. Patients with comorbid conditions including hypertension, diabetes, and pulmonary disease are highly represented among hospitalized patients with COVID-19 disease, suggesting the presence of risk factors that may determine susceptibility to SARS-CoV-2 infection [2][3][4][5] .A molecular connection between SARS-CoV-2 and hypertension, in particular, is suggested by the discovery that ACE2 is the major essential receptor for SARS-CoV-2 6,7 . ACE2 plays an important role in the renin-angiotensin-aldosterone system (RAAS), which consists of a cascade of vasoactive peptides that maintain blood pressure and electrolyte homeostasis. ACE2 converts vasoconstrictor peptides, angiotensin (Ang) II and Ang I, into the vasodilator peptides, Ang (1-7) and Ang (1-9), respectively 8 . These actions counterbalance the enzymatic effect of the related ACE, which generates angiotensin II from angiotensin I. ACEI and ARBs are commonly used antihypertensive drugs that target components of the RAAS. Several recent correspondences have raised concerns that ACEI and ARBs may increase expression of ACE2 and thereby elevate the risk of infection by SARS-CoV-2, thus potentially explaining why hypertension is a common comorbidity in patients with COVID-19 9-12 . This hypothesis is also rooted in human and rodent studies showing upregulation of ACE2 mRNA in the heart, kidney, and urine after ACEI/ARB administration [13][14][15] . Notably, however, the effects of ACEI and ARBs on the expression of ACE2 in the respiratory tract are currently unknown. Given SARS-CoV-2 causes respiratory infections, whether ACE2 expression is altered in the airway of patients taking ACEI or ARBs is a critical question that needs to be addressed to support continued clinical use of these antihypertensive drugs.We first determined the expression patterns of the ACE2 protein in the upper and lower respiratory tract. Gene expression analyses have identified ACE2 expression in the nasopharynx, oral muc...