Severe manifestations of COVID-19 are mostly restricted to people with comorbidities. Here we report that induced mild pulmonary morbidities render SARS-CoV-2-refractive CD-1 mice to be susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low-doses of the acute-lung-injury stimulants bleomycin or ricin caused a severe disease in CD-1 mice, manifested by sustained body weight loss and mortality rates of >50%. Further studies revealed markedly higher levels of viral RNA in the lungs, heart and serum of low-dose-ricin pretreated, as compared to non-pretreated mice. Notably, the deleterious effects of SARS-CoV-2 infection were effectively alleviated by passive transfer of polyclonal or monoclonal antibodies generated against SARS-CoV-2 RBD. Thus, viral cell entry in the sensitized mice seems to involve viral RBD binding, albeit by a mechanism other than the canonical ACE2-mediated uptake route. In summary, we present a novel mice-based animal model for the study of comorbidity-dependent severe COVID-19.

中文翻译：

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暴露于SARS-CoV-2后，诱发肺合并症的小鼠表现出严重的肺部炎症和死亡率

COVID-19的严重表现主要限于合并症患者。在这里，我们报道诱导的轻度肺部疾病使SARS-CoV-2-折射CD-1小鼠易感于这种病毒。具体而言，在应用低剂量急性肺损伤刺激剂博来霉素或蓖麻毒蛋白后，SARS-CoV-2感染在CD-1小鼠中引起严重疾病，表现为持续体重减轻和死亡率> 50％。进一步的研究表明，与未预处理的小鼠相比，经预处理的低剂量蓖麻毒蛋白在肺，心脏和血清中的病毒RNA水平明显更高。值得注意的是，通过被动转移针对SARS-CoV-2 RBD产生的多克隆或单克隆抗体，有效减轻了SARS-CoV-2感染的有害影响。从而，致敏小鼠中的病毒细胞进入似乎涉及病毒RBD结合，尽管其机制不同于典型的ACE2介导的摄取途径。总之，我们提出了一种新型的基于小鼠的动物模型，用于研究合并症相关的严重COVID-19。