Abstract

Background

A physiological small-animal model that resembles COVID-19 with low mortality is lacking.

Methods

Molecular docking on the binding between angiotensin-converting enzyme 2 (ACE2) of common laboratory mammals and the receptor-binding domain of the surface spike protein of SARS-CoV-2 suggested that the golden Syrian hamster is an option. Virus challenge, contact transmission, and passive immunoprophylaxis studies were performed. Serial organ tissues and blood were harvested for histopathology, viral load and titer, chemokine/cytokine level, and neutralizing antibody titer.

Results

The Syrian hamster could be consistently infected by SARS-CoV-2. Maximal clinical signs of rapid breathing, weight loss, histopathological changes from the initial exudative phase of diffuse alveolar damage with extensive apoptosis to the later proliferative phase of tissue repair, airway and intestinal involvement with viral nucleocapsid protein expression, high lung viral load, and spleen and lymphoid atrophy associated with marked chemokine/cytokine activation were observed within the first week of virus challenge. The mean lung virus titer was between 10⁵ and 10⁷ TCID₅₀/g. Challenged index hamsters consistently infected naive contact hamsters housed within the same cages, resulting in similar pathology but not weight loss. All infected hamsters recovered and developed mean serum neutralizing antibody titers ≥1:427 14 days postchallenge. Immunoprophylaxis with early convalescent serum achieved significant decrease in lung viral load but not in lung pathology. No consistent nonsynonymous adaptive mutation of the spike was found in viruses isolated from the infected hamsters.

Conclusions

Besides satisfying Koch’s postulates, this readily available hamster model is an important tool for studying transmission, pathogenesis, treatment, and vaccination against SARS-CoV-2.

中文翻译：

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在金色叙利亚仓鼠模型中模拟冠状病毒病2019（COVID-19）的临床和病理表现：对疾病发病机理和传播性的影响。

摘要

背景

缺乏类似于COVID-19且死亡率低的生理小动物模型。

方法

常见实验室哺乳动物的血管紧张素转换酶2（ACE2）与SARS-CoV-2表面突突蛋白的受体结合域之间的结合分子对接表明，金色叙利亚仓鼠是一种选择。进行了病毒攻击，接触传播和被动免疫预防研究。收集连续的器官组织和血液用于组织病理学，病毒载量和滴度，趋化因子/细胞因子水平和中和抗体滴度。

结果

叙利亚仓鼠可能一直受到SARS-CoV-2的感染。快速呼吸，体重减轻，组织病理学改变的最大临床体征，从弥漫性肺泡损害的初期渗出期伴有广泛的细胞凋亡，到组织修复，气道和肠道受病毒核衣壳蛋白表达，高肺病毒载量和脾脏累及的后期增殖期在病毒攻击的第一周内观察到与明显的趋化因子/细胞因子激活相关的淋巴萎缩。肺病毒平均滴度在TCID ₅₀为10 ⁵至10 ⁷之间/G。挑战指数仓鼠持续感染同一笼中的幼稚接触仓鼠，导致相似的病理但体重减轻。攻击后14天，所有感染的仓鼠均恢复并发展出平均血清中和抗体滴度≥1：427。早期恢复性血清的免疫预防可显着降低肺病毒载量，但并未降低肺病理。从感染的仓鼠中分离出的病毒中没有发现一致的非高峰的自适应峰值突变。

结论

除了满足Koch的假设外，这种随时可用的仓鼠模型是研究针对SARS-CoV-2的传播，发病机制，治疗和疫苗接种的重要工具。