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ACE2 expression is elevated in airway epithelial cells from older and male healthy individuals but reduced in asthma.
Wark, Peter A B; Pathinayake, Prabuddha S; Kaiko, Gerard; Nichol, Kristy; Ali, Ayesha; Chen, Ling; Sutanto, Erika N; Garratt, Luke W; Sohal, Sukhwinder S; Lu, Wenying; Eapen, Mathew S; Oldmeadow, Christopher; Bartlett, Nathan; Reid, Andrew; Veerati, Punnam; Hsu, Alan C-Y; Looi, Kevin; Iosifidis, Thomas; Stick, Stephen M; Hansbro, Philip M; Kicic, Anthony.
  • Wark PAB; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
  • Pathinayake PS; Department of Respiratory and Sleep Medicine, John Hunter Hospital, Newcastle, NSW, Australia.
  • Kaiko G; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
  • Nichol K; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
  • Ali A; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
  • Chen L; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
  • Sutanto EN; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
  • Garratt LW; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
  • Sohal SS; School of Public Health, Curtin University, Perth, WA, Australia.
  • Lu W; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
  • Eapen MS; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.
  • Oldmeadow C; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.
  • Bartlett N; Respiratory Translational Research Group, Department of Laboratory Medicine, School of Health Sciences, College of Health and Medicine, University of Tasmania, Launceston, TAS, Australia.
  • Reid A; Clinical Research Design and Statistics, Hunter Medical Research Institute, Newcastle, NSW, Australia.
  • Veerati P; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
  • Hsu AC; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, NSW, Australia.
  • Looi K; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
  • Iosifidis T; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute and School of Medicine and Public Health, University of Newcastle, Newcastle, NSW, Australia.
  • Stick SM; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
  • Hansbro PM; School of Public Health, Curtin University, Perth, WA, Australia.
  • Kicic A; Telethon Kids Institute, University of Western Australia, Perth, WA, Australia.
Respirology ; 26(5): 442-451, 2021 05.
Article in English | MEDLINE | ID: covidwho-1032419
ABSTRACT
BACKGROUND AND

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Asthma / Gene Expression Regulation / Peptidyl-Dipeptidase A / Epithelial Cells / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Female / Humans / Male / Middle aged Country/Region as subject: Oceania Language: English Journal: Respirology Year: 2021 Document Type: Article Affiliation country: Resp.14003

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Asthma / Gene Expression Regulation / Peptidyl-Dipeptidase A / Epithelial Cells / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Observational study / Prognostic study Limits: Female / Humans / Male / Middle aged Country/Region as subject: Oceania Language: English Journal: Respirology Year: 2021 Document Type: Article Affiliation country: Resp.14003