Age-related rhesus macaque models of COVID-19

Age-related rhesus macaque models of COVID-19
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DOI:
10.1002/ame2.12108
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发表时间:
2020-03-01
影响因子:
3.7
通讯作者:
Qin, Chuan
Qin, Chuan
中科院分区:
其他
文献类型:
--
作者:
Yu, Pin;Qi, Feifei;Qin, Chuan

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背景自2019年12月以来,中国武汉爆发的由严重急性呼吸综合征冠状病毒(SARS-CoV-2)引起的2019年冠状病毒病(COVID-19)已成为国际关注的突发公共卫生事件。 SARS-CoV-2引起的老年病例高病死率需要用非人灵长类动物模型探讨可能与年龄相关的现象。方法对3只3-5岁和两只15岁恒河猴进行气管内感染SARS-CoV-2,然后通过临床体征、病毒复制、胸部X线、组织病理学变化和免疫反应进行分析。结果鼻咽拭子、肛拭子的病毒复制SARS-CoV-2 攻击后 14 天,年老猴子的拭子和肺部比年轻猴子更加活跃。猴子出现典型的间质性肺炎,其特征是肺泡间隔增厚,伴有炎症和水肿,尤其是老年猴表现出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在老年猴中引起的间质性肺炎比幼猴中更严重。感染 SARS-CoV-2 的恒河猴模型提供了对致病机制的深入了解,并促进了针对 SARS-CoV-2 感染的疫苗和治疗方法的开发。
BackgroundSince 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.MethodsThree 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.ResultsViral 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.ConclusionSARS-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.