What Has the COVID-19 Pandemic Taught Us so Far? Addressing the Problem from a Hepatologist’s Perspective

Méndez-Sánchez, Nahum; Valencia-Rodríguez, Alejandro; Qi, Xingshun; Yoshida, Eric M.; Romero-Gómez, Manuel; George, Jacob; Eslam, Mohammed; Abenavoli, Ludovico; Xie, Weifen; Teschke, Rolf; Carrion, Andres F.; Keaveny, Andrew P.

To better understand the current pandemic, we have to start by analyzing the mechanisms that COVID-19 possesses to infect humans and cause disease. We can observe the close similarity of SARS-CoV-2 with the SARS-CoV virus of 2002, that shares the same interaction between the viral protein Spike (commonly referred to as 'S') and the angiotensinconverting enzyme-2 receptor (ACE2) in the host. 2 ACE2 is a protein with an important role in the regulation of cardiovascular, renal and liver function. It is highly expressed in the lungs and in other tissues, such as the liver (discussed later), intestine, and oral mucosa. 3 Further, ACE2 is expressed more in Asian males compared to females and to other ethnic groups, possibly contributing to the susceptibility of Asians for developing respiratory infections by coronavirus species. 4 Interestingly, in SARS-CoV there was a correlation between the susceptibility to infection of airway epithelia with the state of cell differentiation, and with ACE2 expression and location. SARS-CoV replication has been observed in polarized epithelia, exiting mainly in the apical zone. 2 In this context, tobacco use is strongly associated with many lung diseases and cancer development. Although, strictly speaking no relationship has yet been proven to exist between COVID-19 and tobacco use, smoking is well-recognized to upregulate the expression of the epidermal growth factor receptor in polarized airway epithelial cells. It may therefore increase the susceptibility to infection by SARS-CoV-2 by deregulating the ACE2 receptor. 4 Considering that the European Region has the highest prevalence of tobacco use (29%) worldwide, 5 this may provide a possible explanation for the significant burden of COVID-19, as opposed to asymptomatic or mildly symptomatic infection seen in other parts of the world.