COVID-19, caused by SARS-CoV-2, is a virulent pneumonia, with >4,000,000 confirmed cases worldwide and >290,000 deaths as of May 15, 2020. It is critical that vaccines and therapeutics be developed very rapidly. Mice, the ideal animal for assessing such interventions, are resistant to SARS-CoV-2. Here, we overcome this difficulty by exogenous delivery of human ACE2 with a replication-deficient adenovirus (Ad5-hACE2). Ad5-hACE2-sensitized mice developed pneumonia characterized by weight loss, severe pulmonary pathology, and high-titer virus replication in lungs. Type I interferon, T cells, and, most importantly, signal transducer and activator of transcription 1 (STAT1) are critical for virus clearance and disease resolution in these mice. Ad5-hACE2-transduced mice enabled rapid assessments of a vaccine candidate, of human convalescent plasma, and of two antiviral therapies (poly I:C and remdesivir). In summary, we describe a murine model of broad and immediate utility to investigate COVID-19 pathogenesis and to evaluate new therapies and vaccines.

COVID-19 由 SARS-CoV-2 引起，是一种烈性肺炎，截至 2020 年 5 月 15 日，全球确诊病例超过 4,000,000 例，死亡人数超过 290,000 例。疫苗和治疗方法的快速开发至关重要。小鼠是评估此类干预措施的理想动物，对 SARS-CoV-2 具有抵抗力。在这里，我们通过用复制缺陷型腺病毒（Ad5-hACE2）外源递送人类 ACE2 克服了这一困难。 Ad5-hACE2 致敏小鼠出现肺炎，其特征是体重减轻、严重肺部病变和肺部高滴度病毒复制。 I 型干扰素、T 细胞，以及最重要的信号转导子和转录激活子 1 (STAT1) 对于这些小鼠的病毒清除和疾病解决至关重要。 Ad5-hACE2 转导小鼠能够快速评估候选疫苗、人类恢复期血浆和两种抗病毒疗法（Poly I:C 和瑞德西韦）。总之，我们描述了一种具有广泛和直接用途的小鼠模型，可用于研究 COVID-19 发病机制并评估新疗法和疫苗。