Dr José C. Fernandez Checa, from IIBB has been awarded with the COVID-LIVER grant, from Asociación Española para el Estudio del Hígado (AEEH) with the project “Zonal distribution of the SARS CoV-2 receptor ACE2 and its partner TMPRSS2 in chronic liver disease"
Since its debut in December 2019, the COVID-19 has reached pandemic proportions and has become the most critical health issue around the globe. The pathophysiology of the emerging COVID-19 is unknown in almost all aspects, and it is increasingly recognized that besides severe respiratory dystress and systemic overinflammation, as the main causes of death, other organs are also affected, including the liver. In addition, whether existing chronic liver disease facilitates SARS-CoV2 infection is not completely understood. Given the high homology between SARS-CoV-2, the coronovirus triggering COVID-19, and its relative SARS-CoV, responsible for the severe acute respiratory syndrome (SARS) of 2003, ACE2 and its partner TMPRSS2 stand as a crucial mechanism for SARS-CoV-2 infection, which are expressed at high levels in nasal and alveolar epithelial cells. The profile of expression of ACE2/TMRPSS2 in parenchymal and nonparenchymal cells in the liver has not been explored. We hypothesize that chronic diseased hepatocytes may be a significant reservoir of ACE2/TMPRSS2 expression, standing as the gate for SARS-CoV-2 liver infection and a cause for the worsening of preexisting chronic liver disease. Our Project aims to explore the basal and disease-associated expression of ACE2 and its key partner TMPRSS2 in liver, their zonal distribution and regulation by hypoxia and cholesterol in chronic liver diseases. The Project may shed light about the potential susceptibility of patients with fatty liver disease to the novel COVID-19 and may open opportunities of intervention targeting ACE2/TMPRSS2 with cholesterol-modifying agents (e.g. statins).
