TY - JOUR
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
N1 - Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
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.
UR - http://www.scopus.com/inward/record.url?scp=85119159623&partnerID=8YFLogxK
U2 - 10.1038/s41467-021-26762-2
DO - 10.1038/s41467-021-26762-2
M3 - Article
C2 - 34785679
AN - SCOPUS:85119159623
SN - 2041-1723
VL - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 6610
ER -