Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, including hepatic dysfunction observed in over 50% of COVID-19 patients. This study demonstrates hepatocyte susceptibility to infection using humanized ACE2 mice and primary human hepatocytes. SARS-CoV-2 spike and RBD bind to hepatocyte ACE2, causing metabolic reprogramming towards glycolysis and impaired mitochondrial activity. Steatosis and inflammation increase vulnerability. Renin-angiotensin system inhibition increases susceptibility, while metformin reduces infection. The study suggests metformin as a potential therapeutic option for SARS-CoV-2 infection in patients with fatty liver.

Maria Mercado-Gómez, Endika Prieto-Fernández, Naroa Goikoetxea-Usandizaga, Laura Vila-Vecilla, Mikel Azkargorta, Miren Bravo, Marina Serrano-Maciá, Leire Egia-Mendikute, Rubén Rodríguez-Agudo, Sofia Lachiondo-Ortega, So Young Lee, Alvaro Eguileor Giné, Clàudia Gil-Pitarch, Irene González-Recio, Jorge Simón, Petar Petrov, Ramiro Jover, Luis Alfonso Martínez-Cruz, June Ereño-Orbea, Teresa Cardoso Delgado, Felix Elortza, Jesús Jiménez-Barbero, Ruben Nogueiras, Vincent Prevot, Asis Palazon, María L. Martínez-Chantar