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-19

• Published in: Cellular and molecular gastroenterology and hepatology 2021-01, Vol.11 (3), p.771-781
• Main Authors: Chu, Hin, Chan, Jasper Fuk-Woo, Wang, Yixin, Yuen, Terrence Tsz-Tai, Chai, Yue, Shuai, Huiping, Yang, Dong, Hu, Bingjie, Huang, Xiner, Zhang, Xi, Hou, Yuxin, Cai, Jian-Piao, Zhang, Anna Jinxia, Zhou, Jie, Yuan, Shuofeng, To, Kelvin Kai-Wang, Hung, Ivan Fan-Ngai, Cheung, Tan To, Ng, Ada Tsui-Lin, Hau-Yee Chan, Ivy, Wong, Ian Yu-Hong, Law, Simon Ying-Kit, Foo, Dominic Chi-Chung, Leung, Wai-Keung, Yuen, Kwok-Yung
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; COVID-19; COVID-19 - immunology; COVID-19 - virology; Female; Humans; Immune Activation; Immunity, Innate - immunology; In Vitro Techniques; Intestinal Mucosa - virology; Intestine; Male; Middle Aged; Original Research; Replication; SARS Virus - pathogenicity; SARS-CoV; SARS-CoV-2; SARS-CoV-2 - immunology; SARS-CoV-2 - pathogenicity; Virus Replication - immunology; Virus Replication - physiology
• ISSN: 2352-345X; 2352-345X
• DOI: 10.1016/j.jcmgh.2020.09.017

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. 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. 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. 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. [Display omitted]