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SARS-CoV-2 infection and replication in human gastric organoids

Giovanni Giuseppe Giobbe (), Francesco Bonfante, Brendan C. Jones, Onelia Gagliano, Camilla Luni, Elisa Zambaiti, Silvia Perin, Cecilia Laterza, Georg Busslinger, Hannah Stuart, Matteo Pagliari, Alessio Bortolami, Eva Mazzetto, Anna Manfredi, Chiara Colantuono, Lucio Di Filippo, Alessandro Filippo Pellegata, Valentina Panzarin, Nikhil Thapar, Vivian Sze Wing Li, Simon Eaton, Davide Cacchiarelli, Hans Clevers, Nicola Elvassore () and Paolo De Coppi ()
Additional contact information
Giovanni Giuseppe Giobbe: GOS Institute of Child Health, University College London
Francesco Bonfante: Istituto Zooprofilattico Sperimentale delle Venezie
Brendan C. Jones: GOS Institute of Child Health, University College London
Onelia Gagliano: Veneto Institute of Molecular Medicine (VIMM)
Camilla Luni: ShanghaiTech University
Elisa Zambaiti: GOS Institute of Child Health, University College London
Silvia Perin: GOS Institute of Child Health, University College London
Cecilia Laterza: Veneto Institute of Molecular Medicine (VIMM)
Georg Busslinger: Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht
Hannah Stuart: Veneto Institute of Molecular Medicine (VIMM)
Matteo Pagliari: Istituto Zooprofilattico Sperimentale delle Venezie
Alessio Bortolami: Istituto Zooprofilattico Sperimentale delle Venezie
Eva Mazzetto: Istituto Zooprofilattico Sperimentale delle Venezie
Anna Manfredi: Armenise/Harvard Laboratory of Integrative Genomics
Chiara Colantuono: Armenise/Harvard Laboratory of Integrative Genomics
Lucio Di Filippo: Armenise/Harvard Laboratory of Integrative Genomics
Alessandro Filippo Pellegata: GOS Institute of Child Health, University College London
Valentina Panzarin: Istituto Zooprofilattico Sperimentale delle Venezie
Nikhil Thapar: Queensland Children’s Hospital
Vivian Sze Wing Li: the Francis Crick Institute
Simon Eaton: GOS Institute of Child Health, University College London
Davide Cacchiarelli: Armenise/Harvard Laboratory of Integrative Genomics
Hans Clevers: Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht
Nicola Elvassore: GOS Institute of Child Health, University College London
Paolo De Coppi: GOS Institute of Child Health, University College London

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract COVID-19 typically manifests as a respiratory illness, but several clinical reports have described gastrointestinal symptoms. This is particularly true in children in whom gastrointestinal symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. These observations raise the question of whether the virus can replicate within the stomach. Here we generate gastric organoids from fetal, pediatric, and adult biopsies as in vitro models of SARS-CoV-2 infection. To facilitate infection, we induce reverse polarity in the gastric organoids. We find that the pediatric and late fetal gastric organoids are susceptible to infection with SARS-CoV-2, while viral replication is significantly lower in undifferentiated organoids of early fetal and adult origin. We demonstrate that adult gastric organoids are more susceptible to infection following differentiation. We perform transcriptomic analysis to reveal a moderate innate antiviral response and a lack of differentially expressed genes belonging to the interferon family. Collectively, we show that the virus can efficiently infect the gastric epithelium, suggesting that the stomach might have an active role in fecal-oral SARS-CoV-2 transmission.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26762-2

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DOI: 10.1038/s41467-021-26762-2

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