Attenuated replication and damaging effects of SARS-CoV-2 Omicron variants in an intestinal epithelial barrier model

Published: 16 February 2024| Version 1 | DOI: 10.17632/n2cyh3pk4h.1
Meta Volcic, Frank Kirchhoff, Rayhane Nchioua, Chiara Pastorio, Fabian Zech, Clarissa Read, paul walther


Many COVID-19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function may play a key role in harmful inflammatory responses and Long COVID. Despite its importance, the impact of SARS-CoV-2 on intestinal epithelia is poorly understood. To address this, we established an intestinal barrier model integrating epithelial Caco-2 cells and mucus-secreting HT29 cells in the presence or absence of human Raji cells. We show that this gut epithelial model allows efficient differentiation of Caco-2 cells into M (microfold) cell-like cells and faithfully mimics intestinal barrier function. It is highly permissive to SARS-CoV-2 infection due to high expression of the viral entry factors ACE2 and TMPRSS2. Early strains of SARS-CoV-2 and the Delta variant replicated with high efficiency, severely disrupted barrier function and depleted tight junction proteins, such as claudin-1, occludin and ZO-1. In comparison, Omicron subvariants also depleted ZO-1 from tight junctions but had less damaging effects on mucosal integrity and barrier function. Remdesivir and the TMPRSS2 inhibitor Camostat prevented SARS-CoV-2 replication and thus epithelial barrier damage, while the Cathepsin inhibitor E64d was ineffective. Our results support that SARS-CoV-2 disrupts intestinal barrier function but further suggest that circulating Omicron variants are less damaging than earlier viral strains.



Intestine, Tight Junction, Severe Acute Respiratory Syndrome Coronavirus 2, Intestinal Mucosal Barrier


Deutsche Forschungsgemeinschaft