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bioRxiv · 10.1101/2024.02.28.582510

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

Volcic, M.·Nchioua, R.·Pastorio, C.·Zech, F.·Read, C.·Walther, P.·Kirchhoff, F.
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Abstract

Many COVID-19 patients suffer from gastrointestinal symptoms and impaired intestinal barrier function may play a key role in 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, mucus-secreting HT29 cells and human Raji cells. This gut epithelial model allows efficient differentiation of Caco-2 cells into microfold-like cells, faithfully mimics intestinal barrier function, and is highly permissive to SARS-CoV-2 infection. 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 fewer 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.

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Volcic, M., Nchioua, R., Pastorio, C., Zech, F., Read, C., Walther, P., Kirchhoff, F.. 2024-02-28. Attenuated replication and damaging effects of SARS-CoV-2 Omicron in an intestinal epithelial barrier model. https://doi.org/10.1101/2024.02.28.582510

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