Inactivated SARS-CoV-2 induces acute respiratory distress syndrome in human A CE2-transgenic mice  

作　　者：Zhenfei Bi Weiqi Hong Haiying Que Cai He Wenyan Ren Jingyun Yang Tianqi Lu Li Chen Shuaiyao Lu Xiaozhong Peng Xiawei Wei 

机构地区：[1]Laboratory of Aging Research and Cancer Drug Target,State Key Laboratory of Biotherapy,National Clinical Research Center for Geriatrics,West China Hospital,Sichuan University,No.17,Block 3,Southern Renmin Road,Chengdu,Sichuan 610041,PR China [2]National Kunming High-level Biosafety Primate Research Center,Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming,Yunnan,China

出　　处：《Signal Transduction and Targeted Therapy》2022年第1期310-321,共12页信号转导与靶向治疗（英文）

基　　金：This work is supported by the National Natural Science Foundation Regional Innovation and Development(No.U19A2003);National Major Scientific and Technological Special Project for"Significant New Drugs Development"(No.2018ZX09733001);the Excellent Youth Foundation of Sichuan Scientific Committee Grant in China(No.2019JDJQ008);the Development Program of China(No.2016YFA0201402).

摘　　要：The development of animal models for COVID-19 is essential for basic research and drug/vaccine screening.Previously reported COVID-19 animal models need to be established under a high biosafety level condition for the utilization of live SARS-CoV-2,which greatly limits its application in routine research.Here,we gen erate a mouse model of COVID-19 un der a gen eral laboratory condition that captures multiple characteristics of SARS-CoV-2-induced acute respiratory distress syndrome(ARDS)observed in huma ns.Briefly,human ACE2-tra nsge nic(MCE2)mice were in tratracheally in stilled with the formaldehyde-inactivated SARS-CoV-2,resulting in a rapid weight loss and detrimental changes in lung structure and function.The pulmonary pathologic changes were characterized by diffuse alveolar damage with pulmonary consolidation,hemorrhage,necrotic debris,and hyaline membrane formation.The production of fatal cytokines(IL-β,TNF-α,and IL-6)and the infiltration of activated neutrophils,inflammatory monocyte-macrophages,and T cells in the lung were also determined,suggesting the activation of an adaptive immune response.Therapeutic strategies,such as dexamethasone or passive antibody therapy,could effectively ameliorate the disease progression in this model.Therefore,the established mouse model for SARS-CoV-2-induced ARDS in the current study may provide a robust tool for researchers in the standard open laboratory to investigate the pathological mechanisms or develop new therapeutic strategies for COVID-19 and ARDS.

关 键 词：DISTRESS LUNG ROUTINE 

分 类 号：R563.8[医药卫生—呼吸系统]