Gut as an Alternative Entry Route for SARS-CoV-2: Current Evidence and Uncertainties of Productive Enteric Infection in COVID-19

Clerbaux, Laure-Alix; Mayasich, Sally A.; Muñoz, Amalia; Soares, Helena; Petrillo, Mauro; Albertini, Maria Cristina; Lanthier, Nicolas; Grenga, Lucia; Amorim, Maria João

doi:10.3390/jcm11195691

Cited by 18 publications

(19 citation statements)

References 187 publications

(285 reference statements)

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“…Differentiation of Caco-2 cells to M-like cells can be induced by co-culture with Raji cells and is relevant for nanoparticles uptake in related intestinal models (Cabellos et al, 2017). The gut has been suggested as an alternative entry site of SARS-CoV-2 and may be infected both directly or by systemic spread of the virus from the lung and other organs (Clerbaux et al, 2022; Guo et al, 2021). Thus, we challenged the gut epithelium model with the virus from both the top and the bottom.…”

Section: Resultsmentioning

confidence: 99%

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

Volcic,

Nchioua,

Pastorio

et al. 2024

Preprint

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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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Section: Resultsmentioning

confidence: 99%

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

Volcic,

Nchioua,

Pastorio

et al. 2024

Preprint

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“…The four workshop reports published for externals or circulated internally ( 14 , 25 ) were conceived as ways of sharing the progress of the project within the CIAO community and with a wider audience following the workshops. At first, the authorship was restricted to members of the coordination group.…”

Section: Resultsmentioning

confidence: 99%

CIAO: a living experiment in interdisciplinary large-scale collaboration facilitated by the Adverse Outcome Pathway framework

Carusi¹,

Filipovska

Wittwehr

et al. 2023

Front. Public Health

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IntroductionThe CIAO project was launched in Spring 2020 to address the need to make sense of the numerous and disparate data available on COVID-19 pathogenesis. Based on a crowdsourcing model of large-scale collaboration, the project has exploited the Adverse Outcome Pathway (AOP) knowledge management framework built to support chemical risk assessment driven by mechanistic understanding of the biological perturbations at the different organizational levels. Hence the AOPs might have real potential to integrate data produced through different approaches and from different disciplines as experienced in the context of COVID-19. In this study, we aim to address the effectiveness of the AOP framework (i) in supporting an interdisciplinary collaboration for a viral disease and (ii) in working as the conceptual mediator of a crowdsourcing model of collaboration.MethodsWe used a survey disseminated among the CIAO participants, a workshop open to all interested CIAO contributors, a series of interviews with some participants and a self-reflection on the processes.ResultsThe project has supported genuine interdisciplinarity with exchange of knowledge. The framework provided a common reference point for discussion and collaboration. The diagram used in the AOPs assisted with making explicit what are the different perspectives brought to the knowledge about the pathways. The AOP-Wiki showed up many aspects about its usability for those not already in the world of AOPs. Meanwhile their use in CIAO highlighted needed adaptations. Introduction of new Wiki elements for modulating factors was potentially the most disruptive one. Regarding how well AOPs support a crowdsourcing model of large-scale collaboration, the CIAO project showed that this is successful when there is a strong central organizational impetus and when clarity about the terms of the collaboration is brought as early as possible.DiscussionExtrapolate the successful CIAO approach and related processes to other areas of science where the AOP could foster interdisciplinary and systematic organization of the knowledge is an exciting perspective.

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“…Immunomodulator use was associated with a higher risk of anxiety [ 6 ]. Clerbaux et al performed a literature review and found that SARS-CoV-2 could induce intestinal inflammation by binding to ACE2 and infecting intestinal bacteria [ 7 , 8 ]. In addition, Serban et al and Łykowska-Szuber et al examined the literature to show the relationships between acute mesenteric ischemia and deranged liver tests among hospitalized COVID-19 patients [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

COVID-19 and Gastrointestinal Disease: Current Insights and Future Management

Kopel

Goyal²

2023

JCM

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Gut as an Alternative Entry Route for SARS-CoV-2: Current Evidence and Uncertainties of Productive Enteric Infection in COVID-19

Cited by 18 publications

References 187 publications

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

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

CIAO: a living experiment in interdisciplinary large-scale collaboration facilitated by the Adverse Outcome Pathway framework

COVID-19 and Gastrointestinal Disease: Current Insights and Future Management

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