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

Abstract

Wuping Bao,1,* Xue Zhang,1,* Yubiao Jin,2,* Huijuan Hao,1 Fu Yang,3 Dongning Yin,1 Xi Chen,3 Yishu Xue,1 Lei Han,1 Min Zhang1 1Department of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pathology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Min ZhangDepartment of Respiratory and Critical Care Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Road, Shanghai, 200080, People’s Republic of ChinaEmail [email protected]: 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 FEV1 and FEV1/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.Keywords: ACE2, risk factor, BMI, age, sex, eosinophils

Keywords

• ace2
• risk factor
• bmi
• age
• sex
• eosinophils