Increased expression of SARS-CoV-2 (Covid-19) adhesion sites on type II pneumocytes, small airway epithelium, and alveolar macrophages in smokers and patients with COPD

Abstract

<b>Aim:</b> To perform detailed tissue analysis of SARS-CoV-2 adhesion sites in surgically resected small airway tissue. <b>Methods:</b> This study included 16 patients with COPD, of which 8 were current smokers with COPD (COPD-CS) and 8 ex-smokers with COPD (COPD-ES), 7 normal lung function smokers (NLFS), 9 patients with small airways disease (SAD), and 10 never-smoking normal controls (NC). Immunostaining was performed for ACE2, TMPRSS2, and FURIN. Type II pneumocytes, small airway epithelium (SAE), and alveolar macrophages (AM) were analysed using Image ProPlus 7.0. software. <b>Results:</b> Total number of type II pneumocytes and AM significantly increased in the pathological groups compared to NC (p&lt;0.01), except SAD (p=0.08). Total AM significantly decreased in COPD-ES (p&lt;0.003). ACE2 expression increased in SAE of all the patients compared to NC (p&lt;0.001). ACE2 expressing type II pneumocytes were significantly higher in pathological groups compared to NC (p &lt; 0.003). Similar significant changes were observed for ACE2 positive AM (p &lt; 0.002), except COPD-ES, which had decrease in ACE2 positive AM (p&lt;0.003). ACE2 positive AM and type II pneumocytes showed significant negative correlation with FEF25-75% (p&lt;0.05, p = 0.05). ACE2 positive AM and total AM negatively correlated to DLCO% predicted (p&lt;0.02; p&lt;0.04). A similar staining pattern was observed for TMPRSS2 and FURIN. <b>Conclusion:</b> The increased expression of ACE2 along with TMPRSS2 and FURIN, in the small airways of smokers and COPD patients, provides further evidence that these patient groups could be more susceptible to severe COVID-19 infection.