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 LiSimon Eaton, Davide Cacchiarelli, Hans Clevers, Nicola Elvassore, Paolo De Coppi

Research output: Contribution to journal/periodicalArticleScientificpeer-review

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.

Original languageEnglish
Pages (from-to)6610
JournalNature Communications
Volume12
Issue number1
DOIs
Publication statusPublished - 16 Nov 2021

Keywords

  • Aborted Fetus
  • Aged
  • Animals
  • COVID-19/pathology
  • Cell Line
  • Child
  • Child, Preschool
  • Chlorocebus aethiops
  • Humans
  • Infant
  • Intestinal Mucosa/pathology
  • Middle Aged
  • Organoids/pathology
  • SARS-CoV-2/isolation & purification
  • Stomach/pathology
  • Virus Replication/physiology

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