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Dysregulation of endocytic machinery and ACE2 in small airways of smokers and COPD patients can augment their susceptibility to SARS-CoV-2 (COVID-19) infections

Eapen, MS ORCID: 0000-0003-0570-7059, Lu, W, Hackett, TL, Singhera, GR, Thompson, IE, McAlinden, KD, Hardikar, A, Weber, HC, Haug, G, Wark, PAB, Chia, C and Sohal, SS ORCID: 0000-0001-9627-6498 2021 , 'Dysregulation of endocytic machinery and ACE2 in small airways of smokers and COPD patients can augment their susceptibility to SARS-CoV-2 (COVID-19) infections' , American Journal of Physiology, vol. 320, no. 1 , L158-L163 , doi: 10.1152/ajplung.00437.2020.

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Abstract

Lungs of smokers and chronic obstructive pulmonary disease (COPD) are severely compromised and are susceptible to severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) attack. The dangerous combination of enhanced SARS-CoV-2 attachment receptor protein ACE2 along with an increase in endocytic vacuoles will enable viral attachment, entry, and replication.The objective of the study was to identify the presence of SARS-CoV-2 host attachment receptor angiotensin-convertingenzyme-2 (ACE2) along with endocytic vacuoles, early endosome antigen-1 (EEA1), late endosome marker RAB7, cathepsin-L,and lysosomal associated membrane protein-1 (LAMP-1) as lysosome markers in the airways of smokers and COPD patients. Thestudy design was cross-sectional and involved lung resections from 39 patients in total, which included 19 patients with GlobalInitiative for Chronic Obstructive Lung Disease (GOLD) stage I or GOLD stage II COPD, of which 9 were current smokers withCOPD (COPD-CS) and 10 were ex-smokers with COPD (COPD-ES), 10 were normal lung function smokers, and 10 were neversmoking normal controls. Immunostaining for ACE2, EEA1, RAB7, and cathepsin-L was done. A comparative description forACE2, EEA1, RAB7, and cathepsin-L expression pattern is provided for the patient groups. Furthermore, staining intensity forLAMP-1 lysosomes was measured as the ratio of the LAMP-1-stained areas per total area of epithelium or subepithelium, usingImage ProPlus v7.0 software. LAMP-1 expression showed a positive correlation to patient smoking history while in COPD LAMP-1negatively correlated to lung function. The active presence of ACE2 protein along with endocytic vacuoles such as early/lateendosomes and lysosomes in the small airways of smokers and COPD patients provides evidence that these patient groupscould be more susceptible to COVID-19.

Item Type: Article
Authors/Creators:Eapen, MS and Lu, W and Hackett, TL and Singhera, GR and Thompson, IE and McAlinden, KD and Hardikar, A and Weber, HC and Haug, G and Wark, PAB and Chia, C and Sohal, SS
Keywords: COPD, SARS-CoV-2, ACE2, COVID-19, smoking
Journal or Publication Title: American Journal of Physiology
Publisher: Amer Physiological Soc
ISSN: 1040-0605
DOI / ID Number: 10.1152/ajplung.00437.2020
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Copyright 2021 the American Physiological Society

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