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Generation of a Broadly Useful Model for COVID-19 Pathogenesis, Vaccination, and Treatment.
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.
  • Sun J; 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.
  • Zhuang Z; 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.
  • Zheng J; Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
  • Li K; Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
  • Wong RL; Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
  • Liu D; 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.
  • Huang J; Guangzhou Customs District Technology Center, Guangzhou 510700, China.
  • He J; Guangzhou Regenerative Medicine and Health-Guangdong Laboratory (GRMH-GDL), Guangzhou 510530, China.
  • Zhu A; 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.
  • Zhao J; 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.
  • Li X; Guangzhou Customs District Technology Center, Guangzhou 510700, China.
  • Xi Y; 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.
  • Chen R; Shenzhen Institute of Respiratory Disease, First Affiliated Hospital of South University of Science and Technology of China (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
  • Alshukairi AN; King Faisal Specialist Hospital and Research Centre, Jeddah, Kingdom of Saudi Arabia.
  • Chen Z; 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.
  • Zhang Z; 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.
  • Chen C; 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.
  • Huang X; 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.
  • Li F; 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.
  • Lai X; 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.
  • Chen D; 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.
  • Wen L; 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.
  • Zhuo J; 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.
  • Zhang Y; 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.
  • Wang Y; 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.
  • Huang S; Guangzhou Customs District Technology Center, Guangzhou 510700, China.
  • Dai J; Guangzhou Customs District Technology Center, Guangzhou 510700, China.
  • Shi Y; Guangzhou Customs District Technology Center, Guangzhou 510700, China.
  • Zheng K; Guangzhou Customs District Technology Center, Guangzhou 510700, China.
  • Leidinger MR; Department of Pathology, University of Iowa, Iowa City, Iowa 52242, USA.
  • Chen J; Guangzhou Regenerative Medicine and Health-Guangdong Laboratory (GRMH-GDL), Guangzhou 510530, China; Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
  • Li Y; 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.
  • Zhong N; 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.
  • Meyerholz DK; Department of Pathology, University of Iowa, Iowa City, Iowa 52242, USA.
  • McCray PB; Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA; Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA. Electronic address: paul-mccray@uiowa.edu.
  • Perlman S; Department of Microbiology and Immunology, University of Iowa, Iowa City, Iowa 52242, USA; Department of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA. Electronic address: stanley-perlman@uiowa.edu.
  • Zhao J; 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; Institute of Infectious Disease, Guangzhou Eighth Peop
Cell ; 182(3): 734-743.e5, 2020 08 06.
Article in English | MEDLINE | ID: covidwho-592236
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 IC 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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Vaccination / Coronavirus Infections / Disease Models, Animal / Pandemics / Betacoronavirus Type of study: Experimental Studies / Observational study / Prognostic study Topics: Traditional medicine / Vaccines Limits: Animals / Female / Humans / Male Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.06.010

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Vaccination / Coronavirus Infections / Disease Models, Animal / Pandemics / Betacoronavirus Type of study: Experimental Studies / Observational study / Prognostic study Topics: Traditional medicine / Vaccines Limits: Animals / Female / Humans / Male Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.06.010