SARS-CoV-2 and the digestive tract - Organoids to model gastrointestinal infection

Abstract

SARS-CoV-2 is a novel human pathogenic coronavirus whose predilection for the respiratory tract has given rise to a rapid pandemic spread via airborne particles. Organ-specific susceptibility is substantially determined by the density of cell surface expression of ACE2, which is exploited by viral spike protein as a receptor molecule to mediate adhesion and, thus, to permit internalization of the viral genome into the host cell. Based on an ample data set derived from clinical studies and case reports, evidence suggests that distinct cell populations of the digestive and olfactory-gustatory system are equally equipped with membrane-bound ACE2, rendering them "vulnerable" to SARS-CoV-2. Numerous reports on concomitant gastrointestinal complaints and laboratory abnormalities are thought to reflect a relevant degree of organ dysfunction and underscore the tropism of SARS-CoV-2 for the digestive tract. Organoids are three-dimensional in vitro replicas of organ tissue which, owing to their organotypic complex cellular composition and functional resemblance to primary cells, are particularly appreciated for basic research in the field of infectious diseases. This review specifically addresses the involvement of digestive organs by SARS-CoV-2 and outlines the significant contribution of organoid- and primary-cell culture-based models to gaining a deeper understanding of the underlying pathophysiological processes.