Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia.
Respirology. 2021 May;26(5):442-451. doi: 10.1111/resp.14003. Epub 2021 Jan 17.
COVID-19 is complicated by acute lung injury, and death in some individuals. It is caused by SARS-CoV-2 that requires the ACE2 receptor and serine proteases to enter AEC. We determined what factors are associated with ACE2 expression particularly in patients with asthma and COPD.
We obtained lower AEC from 145 people from two independent cohorts, aged 2-89 years, Newcastle (n = 115) and Perth (n = 30), Australia. The Newcastle cohort was enriched with people with asthma (n = 37) and COPD (n = 38). Gene expression for ACE2 and other genes potentially associated with SARS-CoV-2 cell entry was assessed by qPCR, and protein expression was confirmed with immunohistochemistry on endobronchial biopsies and cultured AEC.
Increased gene expression of ACE2 was associated with older age (P = 0.03) and male sex (P = 0.03), but not with pack-years smoked. When we compared gene expression between adults with asthma, COPD and healthy controls, mean ACE2 expression was lower in asthma patients (P = 0.01). Gene expression of furin, a protease that facilitates viral endocytosis, was also lower in patients with asthma (P = 0.02), while ADAM-17, a disintegrin that cleaves ACE2 from the surface, was increased (P = 0.02). ACE2 protein expression was also reduced in endobronchial biopsies from asthma patients.
Increased ACE2 expression occurs in older people and males. Asthma patients have reduced expression. Altered ACE2 expression in the lower airway may be an important factor in virus tropism and may in part explain susceptibility factors and why asthma patients are not over-represented in those with COVID-19 complications.
COVID-19 可导致急性肺损伤，某些患者还会死亡。其由需要 ACE2 受体和丝氨酸蛋白酶才能进入 AEC 的 SARS-CoV-2 引起。我们确定了与 ACE2 表达相关的因素，尤其是在哮喘和 COPD 患者中。
我们从澳大利亚纽卡斯尔（n = 115）和珀斯（n = 30）的两个独立队列中获得了 145 人的下气道细胞，年龄在 2-89 岁之间。纽卡斯尔队列中富集了哮喘（n = 37）和 COPD（n = 38）患者。通过 qPCR 评估 ACE2 和其他可能与 SARS-CoV-2 细胞进入相关的基因的基因表达，并通过免疫组织化学在支气管活检和培养的 AEC 上验证蛋白表达。
ACE2 基因表达增加与年龄较大（P = 0.03）和男性（P = 0.03）相关，但与吸烟包年数无关。当我们比较哮喘、COPD 和健康对照成人之间的基因表达时，哮喘患者的 ACE2 表达较低（P = 0.01）。哮喘患者的 furin 基因表达（一种促进病毒内吞的蛋白酶）也较低（P = 0.02），而从表面切割 ACE2 的 ADAM-17 则增加（P = 0.02）。哮喘患者的支气管活检中 ACE2 蛋白表达也减少。
ACE2 表达增加见于老年人和男性。哮喘患者的表达减少。下气道中 ACE2 表达的改变可能是病毒嗜性的重要因素，部分解释了易感性因素，以及为什么哮喘患者在 COVID-19 并发症患者中并不多见。
