Smoking Upregulates Angiotensin-Converting Enzyme-2 Receptor: A Potential Adhesion Site for Novel Coronavirus SARS-CoV-2 (Covid-19)

Brake, Samuel James; Barnsley, Kathryn; Lu, Wenying; McAlinden, Kielan Darcy; Eapen, Mathew Suji; Sohal, Sukhwinder Singh

An early suggestion is that ACE2 is upregulated on the airway epithelium of smokers. Guoshuai Cai recently reported higher ACE2 gene expression in smoker samples compared to never-smokers. Zhao et al. observed that ACE2 is expressed explicitly in type-2 pneumocytes, in which genes regulating viral reproduction and transmission are highly expressed [31] . This indicates that smokers may be more susceptible to infection by SARS-CoV-2, and possibly Covid-19. We recently identified enhanced ACE2 expression in resected lung tissue from patients with COPD and healthy lung function smokers, albeit comparably less in the latter, while entirely absent in heathy non-smoking individuals ( Figure 1 ). ACE2 expression was quite evident in the type-2 pneumocytes, alveolar macrophages, and the apical end of the small airway epithelium. COPD patients showed significantly higher levels of ACE2, suggesting that COPD further exaggerates ACE2 and potential SARS-CoV-2 adhesion site. ACE2 expression could also be true for patients with another chronic lung disease such as idiopathic pulmonary fibrosis [32] . The attachment of the virus to cell surface ACE2 protects them from immune surveillance mechanisms, leaving them tagged to the host for relatively longer periods, thus making them an efficient carrier and vulnerable host for future infections and spread. The eventual engulfment of ACE2 further provides the virus access to the host cells system, thus providing a flourishing environment, not just to sustain and proliferate but also to mutate and modify host evasion mechanisms. Previous observations using in vivo knockout mice models suggest that SARS-CoV-2 adhesion on ACE2 could also downmodulate the expression of ACE2 itself. This, in turn, increases the production and activation of other related ACE enzymes. This differential modulation and the drastic reduction in ACE2 results in severe acute respiratory failure [33, 34] .