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Intranasal exposure of African green monkeys to SARS-CoV-2 results in acute phase pneumonia with shedding and lung injury still present in the early convalescence phase.
Virology Journal ( IF 4.0 ) Pub Date : 2020-08-18 , DOI: 10.1186/s12985-020-01396-w
Robert W Cross 1, 2 , Krystle N Agans 1, 2 , Abhishek N Prasad 1, 2 , Viktoriya Borisevich 1, 2 , Courtney Woolsey 1, 2 , Daniel J Deer 1, 2 , Natalie S Dobias 1, 2 , Joan B Geisbert 1, 2 , Karla A Fenton 1, 2 , Thomas W Geisbert 1, 2
Affiliation  

We recently reported the development of the first African green monkey (AGM) model for COVID-19 based on a combined liquid intranasal (i.n.) and intratracheal (i.t.) exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we followed up on this work by assessing an i.n. particle only route of exposure using the LMA mucosal atomization device (MAD). Six AGMs were infected with SARS-CoV-2; three animals were euthanized near the peak stage of virus replication (day 5) and three animals were euthanized during the early convalescence period (day 34). All six AGMs supported robust SARS-CoV-2 replication and developed respiratory disease. Evidence of coagulation dysfunction as noted by a transient increases in aPTT and circulating levels of fibrinogen was observed in all AGMs. The level of SARS-CoV-2 replication and lung pathology was not quite as pronounced as previously reported with AGMs exposed by the combined i.n. and i.t. routes; however, SARS-CoV-2 RNA was detected in nasal swabs of some animals as late as day 15 and rectal swabs as late as day 28 after virus challenge. Of particular importance to this study, all three AGMs that were followed until the early convalescence stage of COVID-19 showed substantial lung pathology at necropsy as evidenced by multifocal chronic interstitial pneumonia and increased collagen deposition in alveolar walls despite the absence of detectable SARS-CoV-2 in any of the lungs of these animals. These findings are consistent with human COVID-19 further demonstrating that the AGM faithfully reproduces the human condition.

中文翻译:


非洲绿猴鼻内接触 SARS-CoV-2 会导致急性期肺炎,并在恢复期早期仍存在脱落和肺损伤。



我们最近报道了第一个针对 COVID-19 的非洲绿猴 (AGM) 模型的开发,该模型基于液体鼻内 (in) 和气管内 (it) 联合暴露于严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2)。在这里,我们通过使用 LMA 粘膜雾化装置 (MAD) 评估仅颗粒内的暴露途径来跟进这项工作。六位年度股东大会感染了 SARS-CoV-2;三只动物在病毒复制高峰期(第 5 天)附近被安乐死,三只动物在恢复期早期(第 34 天)被安乐死。所有六次 AGM 均支持 SARS-CoV-2 的强劲复制并发展为呼吸道疾病。在所有 AGM 中都观察到了凝血功能障碍的证据,即 aPTT 和纤维蛋白原循环水平短暂增加。 SARS-CoV-2 复制和肺部病理水平并不像之前报道的通过联合 in 和 it 途径暴露的 AGM 那样明显;然而,最晚在病毒攻击后第 15 天,在一些动物的鼻拭子中检测到 SARS-CoV-2 RNA,最晚在病毒攻击后第 28 天在直肠拭子中检测到 SARS-CoV-2 RNA。对本研究特别重要的是,直到 COVID-19 恢复期早期为止的所有 3 个 AGM 在尸检时都显示出大量的肺部病理学,如多灶性慢性间质性肺炎和肺泡壁胶原沉积增加所证明,尽管没有可检测到的 SARS-CoV -2 在这些动物的任何肺部。这些发现与人类 COVID-19 一致,进一步证明 AGM 忠实地再现了人类状况。
更新日期:2020-08-18
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