The Gastrointestinal Tract Is an Alternative Route for SARS-CoV-2 Infection in a Nonhuman Primate Model.
The Gastrointestinal Tract Is an Alternative Route for SARS-CoV-2 Infection in a Nonhuman Primate Model.
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DOI：
10.1053/j.gastro.2020.12.001
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发表时间：
2021-04
期刊：
影响因子：
29.4
通讯作者：
Peng X
中科院分区：
文献类型：
--
作者：
Jiao L;Li H;Xu J;Yang M;Ma C;Li J;Zhao S;Wang H;Yang Y;Yu W;Wang J;Yang J;Long H;Gao J;Ding K;Wu D;Kuang D;Zhao Y;Liu J;Lu S;Liu H;Peng X
2019冠状病毒病（COVID-19）患者的胃肠道（GI）表现越来越多。然而，胃肠道在严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染中的作用尚不完全清楚。我们研究了胃肠道如何参与SARS-CoV-2感染，以阐明COVID-19的发病机制。我们之前建立的COVID-19非人灵长类动物（NHP）模型在本研究中进行了修改，以验证我们的假设。恒河猴在胃内或鼻内感染了SARS-CoV-2。感染后记录临床症状。采用定量逆转录聚合酶链反应测定病毒基因组RNA。通过检查炎症细胞因子、巨噬细胞、组织病理学和粘蛋白屏障完整性来评估宿主对SARS-CoV-2感染的反应。鼻内接种SARS-CoV-2不仅导致呼吸道组织感染和病理改变，而且导致消化组织感染和病理改变。意料之中的是，灌胃接种SARS-CoV-2导致消化组织的生产性感染和肺和消化组织的炎症。两种类型的SARS-CoV-2接种均可诱导炎症细胞因子，与CD68表达增加一致。免疫组织化学和阿利新蓝/周期性酸-希夫染色显示Ki67减少，裂解caspase 3增加，含黏液杯状细胞数量减少，提示这两种类型的SARS-CoV-2接种引起的炎症损害了胃肠道屏障，导致严重感染。在我们的恒河猴模型中，鼻内和胃内接种SARS-CoV-2均可引起肺炎和胃肠道功能障碍。炎症细胞因子可能是SARS-CoV-2在呼吸系统和消化系统之间发病的联系。
Gastrointestinal (GI) manifestations have been increasingly reported in patients with coronavirus disease 2019 (COVID-19). However, the roles of the GI tract in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We investigated how the GI tract is involved in SARS-CoV-2 infection to elucidate the pathogenesis of COVID-19. Our previously established nonhuman primate (NHP) model of COVID-19 was modified in this study to test our hypothesis. Rhesus monkeys were infected with an intragastric or intranasal challenge with SARS-CoV-2. Clinical signs were recorded after infection. Viral genomic RNA was quantified by quantitative reverse transcription polymerase chain reaction. Host responses to SARS-CoV-2 infection were evaluated by examining inflammatory cytokines, macrophages, histopathology, and mucin barrier integrity. Intranasal inoculation with SARS-CoV-2 led to infections and pathologic changes not only in respiratory tissues but also in digestive tissues. Expectedly, intragastric inoculation with SARS-CoV-2 resulted in the productive infection of digestive tissues and inflammation in both the lung and digestive tissues. Inflammatory cytokines were induced by both types of inoculation with SARS-CoV-2, consistent with the increased expression of CD68. Immunohistochemistry and Alcian blue/periodic acid–Schiff staining showed decreased Ki67, increased cleaved caspase 3, and decreased numbers of mucin-containing goblet cells, suggesting that the inflammation induced by these 2 types of inoculation with SARS-CoV-2 impaired the GI barrier and caused severe infections. Both intranasal and intragastric inoculation with SARS-CoV-2 caused pneumonia and GI dysfunction in our rhesus monkey model. Inflammatory cytokines are possible connections for the pathogenesis of SARS-CoV-2 between the respiratory and digestive systems.
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DOI：
10.1080/08998280.2020.1771164
发表时间：
2020-07-01
期刊：
Proceedings (Baylor University. Medical Center)
影响因子：
--
作者：
Gul, Fahad;Lo, Kevin Bryan;Rangaswami, Janani
通讯作者：
Rangaswami, Janani
影响因子：
39.3
作者：
Lu, Shuaiyao;Zhao, Yuan;Peng, Xiaozhong
通讯作者：
Peng, Xiaozhong
影响因子：
56.9
作者：
Lamers, Mart M.;Beumer, Joep;Clevers, Hans
通讯作者：
Clevers, Hans
95例SARS-CoV-2胃肠道症状
影响因子：
24.5
作者：
Lin, Lu;Jiang, Xiayang;Shan, Hong
通讯作者：
Shan, Hong
影响因子：
11.4
作者：
Lukassen, Soeren;Chua, Robert Lorenz;Eils, Roland
通讯作者：
Eils, Roland