Increased Hepatic ACE2 Expression in NAFL and Diabetes—A Risk for COVID-19 Patients?

The current pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced disease (coronavirus disease 2019 [COVID-19]) is a major global threat. Although most infected patients have a mild course, a relevant proportion of approximately 20% develop a severe and often lethal condition. Recent findings demonstrate that COVID-19 is a multiorgan disease. In addition to the characteristic pneumonia, it affects heart, kidney, pancreas, the coagulation system, and liver. Major risk factors for severe COVID-19 with multiorgan complications include male sex, older age (>65 years), cardiovascular and chronic lung disease, and especially diabetes (1,2). However, it is still unclear why these conditions predispose to a severe course of COVID-19.To enter the target cell, SARS-CoV-2 requires the binding of its spike protein to the angiotensin-converting enzyme 2 (ACE2) receptor (3). The entry is additionally facilitated by subsequent priming and cleavage of the spike protein through proteases such as transmembrane serine protease 2 (TPMRSS2) and furin (3). While the ACE2 receptor is mainly expressed in heart, lungs, endothelial cells, kidney, and the gastrointestinal tract, expression has also been detected in cholangiocytes and in lower amounts in hepatocytes (4). Of note, hepatic ACE2 expression was found to be increased upon chronic liver damage in rodents as well as in humans.Nonalcoholic fatty liver (NAFL) is the most prevalent liver disorder in people with type 2 diabetes and is present in …