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

Authors: Sun, Jing; Zhuang, Zhen; Zheng, Jian; Li, Kun; Wong, Roy Lok-Yin; Liu, Donglan; Huang, Jicheng; He, Jiangping; Zhu, Airu; Zhao, Jingxian; Li, Xiaobo; Xi, Yin; Chen, Rongchang; Alshukairi, Abeer N; Chen, Zhao; Zhang, Zhaoyong; Chen, Chunke; Huang, Xiaofang; Li, Fang; Lai, Xiaomin; Chen, Dingbin; Wen, Liyan; Zhuo, Jianfen; Zhang, Yanjun; Wang, Yanqun; Huang, Shuxiang; Dai, Jun; Shi, Yongxia; Zheng, Kui; Leidinger, Mariah R; Chen, Jiekai; Li, Yimin; Zhong, Nanshan; Meyerholz, David K; McCray Jr, Paul B; Perlman, Stanley; Zhao, Jincun

Published In Cell, (2020 Aug 06)

Abstract: 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.

PubMed ID: 32643603

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