SARS-CoV-2 Induces a More Robust Innate Immune Response and Replicates Less Efficiently Than SARS-CoV in the Human Intestines: An Ex Vivo Study With Implications on Pathogenesis of COVID-19Summary

• Published in: Cellular and molecular gastroenterology and hepatology 2021-01, Vol.11 (3), p.771-781
• Main Authors: Hin Chu, Jasper Fuk-Woo Chan, Yixin Wang, Terrence Tsz-Tai Yuen, Yue Chai, Huiping Shuai, Dong Yang, Bingjie Hu, Xiner Huang, Xi Zhang, Yuxin Hou, Jian-Piao Cai, Anna Jinxia Zhang, Jie Zhou, Shuofeng Yuan, Kelvin Kai-Wang To, Ivan Fan-Ngai Hung, Tan To Cheung, Ada Tsui-Lin Ng, Ivy Hau-Yee Chan, Ian Yu-Hong Wong, Simon Ying-Kit Law, Dominic Chi-Chung Foo, Wai-Keung Leung, Kwok-Yung Yuen
• Format: Article
• Language: English
• Subjects: COVID-19; Immune Activation; Intestine; Replication; SARS-CoV; SARS-CoV-2
• ISSN: 2352-345X; 2352-345X

Background and Aims: Besides prominent respiratory involvement, gastrointestinal manifestations are commonly reported in Coronavirus Disease 2019 (COVID-19) patients. We compared infection of ex vivo human intestinal tissues by SARS-CoV-2 and SARS-CoV with respect to their replication kinetics and immune activation profile. Methods: Human intestinal tissues were obtained from patients while undergoing surgical operations at Queen Mary Hospital, Hong Kong. Upon surgical removal, the tissues were immediately processed and infected with SARS-CoV-2 or SARS-CoV. Replication kinetics were determined with immunohistochemistry, qRT-PCR, and plaque assays. Immune activation in the infected intestinal tissues was assessed by detecting the gene expression of interferons and representative pro-inflammatory cytokines and chemokines. Results: SARS-CoV-2 could infect and productively replicate in the ex vivo human intestinal tissues with release of infectious virus particles, but not in ex vivo human liver and kidney tissues. Importantly, SARS-CoV-2 replicated less efficiently than SARS-CoV, induced less cytopathology in the human intestinal epithelium, and induced a more robust innate immune response including the activation of both type I and type III interferons, than SARS-CoV in human intestinal tissues. Conclusion: Using the ex vivo human intestinal tissues as a physiologically relevant model, our data indicated that SARS-CoV-2 could productively replicate in the human gut and suggested that the gastrointestinal tract might serve as an alternative route of virus dissemination. SARS-CoV-2 replicated less efficiently and induced less cytopathology than SARS-CoV in keeping with the clinical observations reported for COVID-19 and SARS, which might be the result of a more robust immune activation by SARS-CoV-2 than SARS-CoV in the human intestine.