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SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids
Giovanni Giuseppe Giobbe; Francesco Bonfante; Elisa Zambaiti; Onelia Gagliano; Brendan C. Jones; Camilla Luni; Cecilia Laterza; Silvia Perin; Hannah T. Stuart; Matteo Pagliari; Alessio Bortolami; Eva Mazzetto; Anna Manfredi; Chiara Colantuono; Lucio Di Filippo; Alessandro Filippo Pellegata; Vivian S.W. Li; Simon Eaton; Nikhil Thapar; Davide Cacchiarelli; Nicola Elvassore; Paolo De Coppi.
Afiliación
  • Giovanni Giuseppe Giobbe; University College London - GOS Institute of Child Health
  • Francesco Bonfante; izsvenezie
  • Elisa Zambaiti; University College London - GOS Institute of Child Health
  • Onelia Gagliano; VIMM
  • Brendan C. Jones; University College London - GOS Institute of Child Health
  • Camilla Luni; ShanghaiTech University
  • Cecilia Laterza; VIMM
  • Silvia Perin; University College London - GOS Institute of Child Health
  • Hannah T. Stuart; VIMM
  • Matteo Pagliari; izsvenezie.it
  • Alessio Bortolami; izsvenezie
  • Eva Mazzetto; izsvenezie
  • Anna Manfredi; TIGEM
  • Chiara Colantuono; TIGEM
  • Lucio Di Filippo; Next Generation Diagnostic srl
  • Alessandro Filippo Pellegata; University College London - GOS Institute of Child Health
  • Vivian S.W. Li; The Francis Crick Institute
  • Simon Eaton; University College London - GOS Institute of Child Health
  • Nikhil Thapar; University College London - GOS Institute of Child Health
  • Davide Cacchiarelli; TIGEM
  • Nicola Elvassore; University College London - GOS Institute of Child Health
  • Paolo De Coppi; University College London - GOS Institute of Child Health
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-167049
ABSTRACT
Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global public health emergency. COVID-19 typically manifests as a respiratory illness but an increasing number of clinical reports describe gastrointestinal (GI) symptoms. This is particularly true in children in whom GI symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. By contrast, fetuses seem to be rarely affected by COVID-19, although the virus has been detected in placentas of affected women. These observations raise the question of whether the virus can infect and replicate within the stomach once ingested. Moreover, it is not yet clear whether active replication of SARS-CoV-2 is possible in the stomach of children or in fetuses at different developmental stages. Here we show the novel derivation of fetal gastric organoids from 8-21 post-conception week (PCW) fetuses, and from pediatric biopsies, to be used as an in vitro model for SARS-CoV-2 gastric infection. Gastric organoids recapitulate human stomach with linear increase of gastric mucin 5AC along developmental stages, and expression of gastric markers pepsinogen, somatostatin, gastrin and chromogranin A. In order to investigate SARS-CoV-2 infection with minimal perturbation and under steady-state conditions, we induced a reversed polarity in the gastric organoids (RP-GOs) in suspension. In this condition of exposed apical polarity, the virus can easily access viral receptor angiotensin-converting enzyme 2 (ACE2). The pediatric RP-GOs are fully susceptible to infection with SARS-CoV-2, where viral nucleoprotein is expressed in cells undergoing programmed cell death, while the efficiency of infection is significantly lower in fetal organoids. The RP-GOs derived from pediatric patients show sustained robust viral replication of SARS-CoV-2, compared with organoids derived from fetal stomachs. Transcriptomic analysis shows a moderate innate antiviral response and the lack of differentially expressed genes belonging to the interferon family. Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. However, the virus can efficiently infect gastric epithelium in pediatric patients, suggesting that the stomach might have an active role in fecal-oral transmission of SARS-CoV-2.
Licencia
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Observational_studies / Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Observational_studies / Prognostic_studies Idioma: En Año: 2020 Tipo del documento: Preprint