Vaccine and antiviral development against SARS-CoV-2 infection or COVID-19 disease would benefit from validated small animal models. Here, we show that transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) by the human cytokeratin 18 promoter (K18 hACE2) represent a susceptible rodent model. K18 hACE2 transgenic mice succumbed to SARS-CoV-2 infection by day 6, with virus detected in lung airway epithelium and brain. K18 ACE2 transgenic mice produced a modest TH1/2/17 cytokine storm in the lung and spleen that peaked by day 2, and an extended chemokine storm that was detected in both lungs and brain. This chemokine storm was also detected in the brain at day 6. K18 hACE2 transgenic mice are, therefore, highly susceptible to SARS-CoV-2 infection and represent a suitable animal model for the study of viral pathogenesis, and for identification and characterization of vaccines (prophylactic) and antivirals (therapeutics) for SARS-CoV-2 infection and associated severe COVID-19 disease.

针对 SARS-CoV-2 感染或 COVID-19 疾病的疫苗和抗病毒药物开发将受益于经过验证的小动物模型。在这里，我们展示了通过人细胞角蛋白 18 启动子 (K18 hACE2) 表达人血管紧张素转换酶 2 (hACE2) 的转基因小鼠代表了易感啮齿动物模型。K18 hACE2 转基因小鼠在第 6 天死于 SARS-CoV-2 感染，并在肺气道上皮和大脑中检测到病毒。K18 ACE2 转基因小鼠在肺和脾中产生适度的 TH1/2/17 细胞因子风暴，并在第 2 天达​​到峰值，并在肺和脑中检测到延长的趋化因子风暴。在第 6 天的大脑中也检测到了这种趋化因子风暴。因此，K18 hACE2 转基因小鼠对 SARS-CoV-2 感染高度敏感，是研究病毒发病机制以及疫苗鉴定和表征的合适动物模型针对 SARS-CoV-2 感染和相关严重 COVID-19 疾病的（预防）和抗病毒（治疗）药物。