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

doi:10.1038/s41467-021-26762-2

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

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

43 Citations (Scopus)

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 language	English
Pages (from-to)	6610
Journal	Nature Communications
Volume	12
Issue number	1
DOIs	https://doi.org/10.1038/s41467-021-26762-2
Publication status	Published - 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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10.1038/s41467-021-26762-2

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Giobbe, G. G., Bonfante, F., Jones, B. C., Gagliano, O., Luni, C., Zambaiti, E., Perin, S., Laterza, C., Busslinger, G., Stuart, H., Pagliari, M., Bortolami, A., Mazzetto, E., Manfredi, A., Colantuono, C., Di Filippo, L., Pellegata, A. F., Panzarin, V., Thapar, N., ... De Coppi, P. (2021). SARS-CoV-2 infection and replication in human gastric organoids. Nature Communications, 12(1), 6610. https://doi.org/10.1038/s41467-021-26762-2

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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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Giobbe, GG, Bonfante, F, Jones, BC, Gagliano, O, Luni, C, Zambaiti, E, Perin, S, Laterza, C, Busslinger, G, Stuart, H, Pagliari, M, Bortolami, A, Mazzetto, E, Manfredi, A, Colantuono, C, Di Filippo, L, Pellegata, AF, Panzarin, V, Thapar, N, Li, VSW, Eaton, S, Cacchiarelli, D, Clevers, H, Elvassore, N & De Coppi, P 2021, 'SARS-CoV-2 infection and replication in human gastric organoids', Nature Communications, vol. 12, no. 1, pp. 6610. https://doi.org/10.1038/s41467-021-26762-2

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T1 - SARS-CoV-2 infection and replication in human gastric organoids

AU - Giobbe, Giovanni Giuseppe

AU - Bonfante, Francesco

AU - Jones, Brendan C

AU - Gagliano, Onelia

AU - Luni, Camilla

AU - Zambaiti, Elisa

AU - Perin, Silvia

AU - Laterza, Cecilia

AU - Busslinger, Georg

AU - Stuart, Hannah

AU - Pagliari, Matteo

AU - Bortolami, Alessio

AU - Mazzetto, Eva

AU - Manfredi, Anna

AU - Colantuono, Chiara

AU - Di Filippo, Lucio

AU - Pellegata, Alessandro Filippo

AU - Panzarin, Valentina

AU - Thapar, Nikhil

AU - Li, Vivian Sze Wing

AU - Eaton, Simon

AU - Cacchiarelli, Davide

AU - Clevers, Hans

AU - Elvassore, Nicola

AU - De Coppi, Paolo

PY - 2021/11/16

Y1 - 2021/11/16

N2 - 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.

AB - 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.

KW - Aborted Fetus

KW - Aged

KW - Animals

KW - COVID-19/pathology

KW - Cell Line

KW - Child

KW - Child, Preschool

KW - Chlorocebus aethiops

KW - Humans

KW - Infant

KW - Intestinal Mucosa/pathology

KW - Middle Aged

KW - Organoids/pathology

KW - SARS-CoV-2/isolation & purification

KW - Stomach/pathology

KW - Virus Replication/physiology

U2 - 10.1038/s41467-021-26762-2

DO - 10.1038/s41467-021-26762-2

M3 - Article

C2 - 34785679

SN - 2041-1723

VL - 12

SP - 6610

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -

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

Abstract

Keywords

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