新型冠状病毒肺炎的年龄相关性恒河猴模型。
Age-related rhesus macaque models of COVID-19.
作者信息
Yu Pin, Qi Feifei, Xu Yanfeng, Li Fengdi, Liu Peipei, Liu Jiayi, Bao Linlin, Deng Wei, Gao Hong, Xiang Zhiguang, Xiao Chong, Lv Qi, Gong Shuran, Liu Jiangning, Song Zhiqi, Qu Yajin, Xue Jing, Wei Qiang, Liu Mingya, Wang Guanpeng, Wang Shunyi, Yu Haisheng, Liu Xing, Huang Baoying, Wang Wenling, Zhao Li, Wang Huijuan, Ye Fei, Zhou Weimin, Zhen Wei, Han Jun, Wu Guizhen, Jin Qi, Wang Jianwei, Tan Wenjie, Qin Chuan
机构信息
Key Laboratory of Human Disease Comparative Medicine Chinese Ministry of Health Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases Institute of Laboratory Animal Science Chinese Academy of Medical Sciences and Comparative Medicine Center Peking Union Medical College Beijing China.
MHC Key Laboratory of Biosafety National Institute for Viral Disease Control and Prevention China CDC Beijing China.
出版信息
Animal Model Exp Med. 2020 Mar 30;3(1):93-97. doi: 10.1002/ame2.12108. eCollection 2020 Mar.
BACKGROUND
Since December 2019, an outbreak of the Corona Virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) in Wuhan, China, has become a public health emergency of international concern. The high fatality of aged cases caused by SARS-CoV-2 was a need to explore the possible age-related phenomena with non-human primate models.
METHODS
Three 3-5 years old and two 15 years old rhesus macaques were intratracheally infected with SARS-CoV-2, and then analyzed by clinical signs, viral replication, chest X-ray, histopathological changes and immune response.
RESULTS
Viral replication of nasopharyngeal swabs, anal swabs and lung in old monkeys was more active than that in young monkeys for 14 days after SARS-CoV-2 challenge. Monkeys developed typical interstitial pneumonia characterized by thickened alveolar septum accompanied with inflammation and edema, notably, old monkeys exhibited diffuse severe interstitial pneumonia. Viral antigens were detected mainly in alveolar epithelial cells and macrophages.
CONCLUSION
SARS-CoV-2 caused more severe interstitial pneumonia in old monkeys than that in young monkeys. Rhesus macaque models infected with SARS-CoV-2 provided insight into the pathogenic mechanism and facilitated the development of vaccines and therapeutics against SARS-CoV-2 infection.
背景
自2019年12月以来，中国武汉爆发了由严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起的2019冠状病毒病（COVID-19），已成为国际关注的突发公共卫生事件。SARS-CoV-2导致老年病例的高死亡率，因此有必要用非人灵长类动物模型探索可能的年龄相关现象。
方法
对3只3 - 5岁和2只15岁的恒河猴进行气管内感染SARS-CoV-2，然后通过临床症状、病毒复制、胸部X光、组织病理学变化和免疫反应进行分析。
结果
在SARS-CoV-2攻击后14天内，老年猴子鼻咽拭子、肛门拭子和肺中的病毒复制比年轻猴子更活跃。猴子出现典型的间质性肺炎，其特征为肺泡间隔增厚并伴有炎症和水肿，值得注意的是，老年猴子表现为弥漫性严重间质性肺炎。病毒抗原主要在肺泡上皮细胞和巨噬细胞中检测到。
结论
SARS-CoV-2在老年猴子中引起的间质性肺炎比年轻猴子更严重。感染SARS-CoV-2的恒河猴模型为致病机制提供了见解，并促进了针对SARS-CoV-2感染的疫苗和治疗方法的开发。
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