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, Paolo De Coppi
Author Information
Giovanni Giuseppe Giobbe: Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK. g.giobbe@ucl.ac.uk. ORCID
Francesco Bonfante: Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy. ORCID
Brendan C Jones: Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK. ORCID
Onelia Gagliano: Veneto Institute of Molecular Medicine (VIMM), Padova, Italy.
Camilla Luni: Shanghai Institute for Advanced Immunochemical Studies (SIAIS), ShanghaiTech University, Shanghai, China. ORCID
Elisa Zambaiti: Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK. ORCID
Silvia Perin: Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK. ORCID
Cecilia Laterza: Veneto Institute of Molecular Medicine (VIMM), Padova, Italy.
Georg Busslinger: Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Utrecht, Netherlands. ORCID
Hannah Stuart: Veneto Institute of Molecular Medicine (VIMM), Padova, Italy.
Matteo Pagliari: Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy.
Alessio Bortolami: Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy. ORCID
Eva Mazzetto: Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy. ORCID
Anna Manfredi: Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
Chiara Colantuono: Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
Lucio Di Filippo: Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
Alessandro Filippo Pellegata: Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK. ORCID
Valentina Panzarin: Lab. of Experimental Animal Models, Division of Comparative Biomedical Sciences, Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Italy.
Vivian Sze Wing Li: Stem Cell and Cancer Biology Lab, the Francis Crick Institute, London, UK. ORCID
Simon Eaton: Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK. ORCID
Davide Cacchiarelli: Telethon Institute of Genetics and Medicine (TIGEM), Armenise/Harvard Laboratory of Integrative Genomics, Pozzuoli, Italy.
Hans Clevers: Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center (UMC) Utrecht, Utrecht, Netherlands. ORCID
Nicola Elvassore: Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK. n.elvassore@ucl.ac.uk. ORCID
Paolo De Coppi: Stem Cell and Regenerative Medicine Section, GOS Institute of Child Health, University College London, London, UK. p.decoppi@ucl.ac.uk. ORCID
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.
