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

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...

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Detalles Bibliográficos
Autores principales: 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, Paul B., Perlman, Stanley, Zhao, Jincun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284240/
https://www.ncbi.nlm.nih.gov/pubmed/32643603
http://dx.doi.org/10.1016/j.cell.2020.06.010
Descripción
Sumario: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.

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