Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters
Age-Dependent Progression of SARS-CoV-2 Infection in Syrian Hamsters
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DOI：
10.3390/v12070779
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发表时间：
2020-07-01
期刊：
影响因子：
4.7
通讯作者：
Trimpert, Jakob
中科院分区：
文献类型：
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作者：
Osterrieder, Nikolaus;Bertzbach, Luca D.;Trimpert, Jakob
2019年底，一种新型冠状病毒SARS-CoV-2引起的严重呼吸道疾病爆发，导致受感染人群的发病率和死亡率很高。全面了解COVID-19是由SARS-CoV-2引起的多方面疾病，需要合适的小动物模型，疫苗和抗病毒药物的开发和评估也是如此。由于在人类中发现了COVID-19的年龄依赖性差异，我们比较了年轻和老年叙利亚仓鼠的SARS-CoV-2感染过程。我们发现，病毒复制在上呼吸道和下呼吸道是独立的动物的年龄。然而，年龄较大的仓鼠表现出更明显和一致的体重减轻。在肺原位杂交确定病毒RNA在支气管上皮细胞，肺泡上皮细胞I型和II型，和巨噬细胞。组织学显示出明显的年龄依赖性差异，年轻仓鼠比老年仓鼠更早和更强的免疫细胞流入。后者出现明显的肺泡和血管周围水肿，表明血管渗漏。相比之下，我们只在年轻仓鼠中观察到感染后第14天的快速肺恢复。我们建议，在年轻与老年仓鼠的SARS-CoV-2疫苗和治疗的比较评估可能会产生有价值的信息，因为这种小动物模型似乎反映了人类患者的年龄依赖性差异。
In late 2019, an outbreak of a severe respiratory disease caused by an emerging coronavirus, SARS-CoV-2, resulted in high morbidity and mortality in infected humans. Complete understanding of COVID-19, the multi-faceted disease caused by SARS-CoV-2, requires suitable small animal models, as does the development and evaluation of vaccines and antivirals. Since age-dependent differences of COVID-19 were identified in humans, we compared the course of SARS-CoV-2 infection in young and aged Syrian hamsters. We show that virus replication in the upper and lower respiratory tract was independent of the age of the animals. However, older hamsters exhibited more pronounced and consistent weight loss. In situ hybridization in the lungs identified viral RNA in bronchial epithelium, alveolar epithelial cells type I and II, and macrophages. Histopathology revealed clear age-dependent differences, with young hamsters launching earlier and stronger immune cell influx than aged hamsters. The latter developed conspicuous alveolar and perivascular edema, indicating vascular leakage. In contrast, we observed rapid lung recovery at day 14 after infection only in young hamsters. We propose that comparative assessment in young versus aged hamsters of SARS-CoV-2 vaccines and treatments may yield valuable information, as this small-animal model appears to mirror age-dependent differences in human patients.