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 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, 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, 320, (1) pp. L158-L163. ISSN 1040-0605 (2021) [Refereed Article]
Lungs of smokers and chronic obstructive pulmonary disease (COPD) are severely compromised and are susceptible to severe
acute 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-converting
enzyme-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. The
study design was cross-sectional and involved lung resections from 39 patients in total, which included 19 patients with Global
Initiative for Chronic Obstructive Lung Disease (GOLD) stage I or GOLD stage II COPD, of which 9 were current smokers with
COPD (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 for
ACE2, EEA1, RAB7, and cathepsin-L expression pattern is provided for the patient groups. Furthermore, staining intensity for
LAMP-1 lysosomes was measured as the ratio of the LAMP-1-stained areas per total area of epithelium or subepithelium, using
Image ProPlus v7.0 software. LAMP-1 expression showed a positive correlation to patient smoking history while in COPD LAMP-1
negatively correlated to lung function. The active presence of ACE2 protein along with endocytic vacuoles such as early/late
endosomes and lysosomes in the small airways of smokers and COPD patients provides evidence that these patient groups
could be more susceptible to COVID-19.