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SARS-CoV-2 infection and replication in human gastric organoids.
Giobbe, Giovanni Giuseppe; Bonfante, Francesco; Jones, Brendan C; Gagliano, Onelia; Luni, Camilla; Zambaiti, Elisa; Perin, Silvia; Laterza, Cecilia; Busslinger, Georg; Stuart, Hannah; Pagliari, Matteo; Bortolami, Alessio; Mazzetto, Eva; Manfredi, Anna; Colantuono, Chiara; Di Filippo, Lucio; Pellegata, Alessandro Filippo; Panzarin, Valentina; Thapar, Nikhil; Li, Vivian Sze Wing; Eaton, Simon; Cacchiarelli, Davide; Clevers, Hans; Elvassore, Nicola; De Coppi, Paolo.
  • Giobbe GG; Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK. g.giobbe@ucl.ac.uk.
  • Bonfante F; Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy.
  • Jones BC; Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK.
  • Gagliano O; Veneto Institute of Molecular Medicine (VIMM), Padova, Italy.
  • Luni C; Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai, China.
  • Zambaiti E; Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK.
  • Perin S; Veneto Institute of Molecular Medicine (VIMM), Padova, Italy.
  • Laterza C; Dept. Women's and Children's Health, University of Padova, Padova, Italy.
  • Busslinger G; Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK.
  • Stuart H; Veneto Institute of Molecular Medicine (VIMM), Padova, Italy.
  • Pagliari M; Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Utrecht, Netherlands.
  • Bortolami A; Veneto Institute of Molecular Medicine (VIMM), Padova, Italy.
  • Mazzetto E; Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy.
  • Manfredi A; Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy.
  • Colantuono C; Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy.
  • Di Filippo L; Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
  • Pellegata AF; Next Generation Diagnostic srl, Pozzuoli, Italy.
  • Panzarin V; Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
  • Thapar N; Next Generation Diagnostic srl, Pozzuoli, Italy.
  • Li VSW; Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
  • Eaton S; Next Generation Diagnostic srl, Pozzuoli, Italy.
  • Cacchiarelli D; Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK.
  • Clevers H; Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy.
  • Elvassore N; Gastroenterology, Hepatology and Liver Transplant, Queensland Children's Hospital, Brisbane, Australia.
  • De Coppi P; Stem Cell and Cancer Biology Lab, the Francis Crick Institute, London, UK.
Nat Commun ; 12(1): 6610, 2021 11 16.
Article in English | MEDLINE | ID: covidwho-1521737
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Stomach / Virus Replication / Organoids / SARS-CoV-2 / COVID-19 / Intestinal Mucosa Topics: Long Covid Limits: Aged / Animals / Child / Child, preschool / Humans / Infant / Middle aged Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-26762-2

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Stomach / Virus Replication / Organoids / SARS-CoV-2 / COVID-19 / Intestinal Mucosa Topics: Long Covid Limits: Aged / Animals / Child / Child, preschool / Humans / Infant / Middle aged Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-26762-2