Factors Associated with the Expression of ACE2 in Human Lung Tissue: Pathological Evidence from Patients with Normal FEV1 and FEV1/FVC

Abstract

Background Whether COVID-19 comorbidities and risk factors such as old age, male gender, smoking, obesity, eosinophils and blood types have direct contact with expression of ACE2 and pro-inflammation cytokines in human lung tissues were still unclear. Patients and Methods Sixty-four patients with normal FEV 1 and FEV 1 /FVC underwent thoracotomy for pulmonary nodules were included. Blinded histological assessments were performed by two pathologists. Clinical features and results of the immunohistochemical staining of ACE2 were collected and analyzed. Results ACE2 expressed in alveolar macrophages (most obvious), alveolar epithelia and vascular endothelia, but not in small-airway epithelia. ACE2 expressions are positively related to age ( r =0.26, P =0.040), weight ( r =0.43, P <0.001), as well as BMI ( r = 0.38, P =0.002), and male patients show higher expressions of ACE2 in lungs ( P <0.05). ACE2 expressions are negatively related to peripheral eosinophils ( r = −0.30, P =0.017). There was no correlation between ABO blood types and ACE2 expression in normal lung tissues ( P > 0.05). IL-13 and IL-6R expression in lung tissue increased with age ( r =0.26, P <0.05, for both). Conclusion Our pathological evidences showed that the alveolar epithelia, vascular endothelia, and alveolar macrophages are susceptible in human lungs for SARS-CoV-2 infection. The risk factors such as high body weight/BMI, old age, male gender, and eosinopenia may be related to ACE2 expression in human lungs, and associated with more chance to develop the severe cases. IL-6R expression in lung tissue also increased with age. Therefore, weight control and smoking cessation are essential to reduce the susceptibility of SARS-CoV-2 infection, especially in obesity, old or male patients. Peripheral eosinophils monitor is also quite necessary to detect severe tendency in COVID-19 patients.

Further comments on the role of ACE‐2 positive macrophages in human lung

“…In agreement with these studies, our current studies have demonstrated ACE2 protein expression on alveolar, lipopolysaccharide (LPS)‐treated and other tissue macrophages [ 1 ]. These findings are consistent with other reports [ 2 , 4 , 5 , 6 , 7 ]. For alveolar macrophages, there are different subpopulations with different phenotypes [ 20 , 21 ].…”

“…The ACE2 expression on the surface of macrophages have been well established by studies such as ACE2 on alveolar macrophages [ 2 , 3 , 4 , 5 , 6 ], blood monocyte‐derived macrophages [ 7 , 8 , 9 ], and macrophages of atherosclerotic carotid arteries [ 10 ]. Specifically, the ACE2 protein expression on alveolar macrophages has been demonstrated by different studies with lung tissues from normal human and COVID‐19 patients (Table 1 ).…”

Angiotensin converting enzyme 2 level and its significance in COVID‐19 and other diseases patients

“…The studies that reported ACE2 expression in patients with different diseases were included 5,7,12–43 . Following the removal of duplicate datasets, the unique datasets were collected.…”

Role of SARS-CoV-2 Virus in Brain Cells: A Brief Review

“…To entry into cells, the virus binds via its S1 spike protein to angiotensin converting enzyme 2 (ACE2) (19,20). In human, the ACE2 RNA expression, even though shown chiefly in lung tissues (21), heart, gastrointestinal (GI) system, and kidney (22), has been detected in both brain tissues and cerebrospinal fluid (CSF) (23,24); thus, the nervous system -both the neurons and glial cells of the brain -can be damaged by COVID-19 infection (25). Incidentally, a blood circulatory pathway has been proposed by which this virus-SARS-CoV-2-directly infects the CNS (26), thereby escalating the permeability of the blood brain barrier (BBB).…”