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.

Lungs of smokers and COPD are severely compromised and are susceptible to SARS-CoV-2 attack. The lethal 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 lysosome-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 GOLD stage I or stage II COPD, of which 9 were current smokers with COPD (COPD-CS), and 10 ex-smokers with COPD (COPD-ES), 10 normal lung function smokers (NLFS) and 10 were never smoking normal controls (NC). 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. Further, staining intensity for LAMP-1 lysosomes was measured as the ratio of the LAMP-1 stained areas per total area of epithelium or sub-epithelium, using Image ProPlus 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.