• Cell · Aug 2020

    Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment.

    • Jing Sun, Zhen Zhuang, Jian Zheng, Kun Li, Roy Lok-Yin Wong, Donglan Liu, Jicheng Huang, Jiangping He, Airu Zhu, Jingxian Zhao, Xiaobo Li, Yin Xi, Rongchang Chen, Abeer N Alshukairi, Zhao Chen, Zhaoyong Zhang, Chunke Chen, Xiaofang Huang, Fang Li, Xiaomin Lai, Dingbin Chen, Liyan Wen, Jianfen Zhuo, Yanjun Zhang, Yanqun Wang, Shuxiang Huang, Jun Dai, Yongxia Shi, Kui Zheng, Mariah R Leidinger, Jiekai Chen, Yimin Li, Nanshan Zhong, David K Meyerholz, Paul B McCray, Stanley Perlman, and Jincun Zhao.
    • State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510182, China.
    • Cell. 2020 Aug 6; 182 (3): 734-743.e5.

    AbstractCOVID-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.Copyright © 2020 Elsevier Inc. All rights reserved.

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