Enhanced replication of SARS-CoV-2 Omicron BA.2 in human forebrain and midbrain organoids  

作　　者：Yuxin Hou Chang Li Chaemin Yoon On Wah Leung Sikun You Xiaoming Cui Jasper Fuk-Woo Chan Duanqing Pei Hoi Hung Cheung Hin Chu 

机构地区：[1]State Key Laboratory of Emerging Infectious Diseases,Department of Microbiology,School of Clinical Medicine,Li Ka Shing Faculty of Medicine,The University of Hong Kong,and Centre for Virology,Vaccinology and Therapeutics,Hong Kong Science and Technology Park,Hong Kong Special Administrative Region,China [2]State Key Laboratory of Emerging Infectious Diseases,Department of Microbiology,School of Clinical Medicine,Li Ka Shing Faculty of Medicine,The University of Hong Kong [3]Centre for Virology,Vaccinology and Therapeutics,Hong Kong Science and Technology Park,Hong Kong Special Administrative Region,China

出　　处：《Signal Transduction and Targeted Therapy》2022年第12期4257-4260,共4页信号转导与靶向治疗（英文）

基　　金：Health and Medical Research Fund(CID-HKU1–5,COVID1903010–7 and-14,and 20190652);Food and Health Bureau,the Government of the Hong Kong Special Administrative Region,General Research Fund(14104321,14109920,14121618,14169717,17118621,and 17123920);Collaborative Research Fund(C7060-21GF);Theme-Based Research Scheme(T11-709/21-N),Research Grants Council,the Government of the Hong Kong Special Administrative Region;Health@InnoHK,Innovation and Technology Commission,the Government of the Hong Kong Special Administrative Region;National Natural Science Foundation of China Excellent Young Scientists Fund(Hong Kong and Macao)(32122001);the Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Diseases and Research Capability on Antimicrobial Resistance for Department of Health of the Hong Kong Special Administrative Region Government;Emergency Collaborative Project(EKPG22-01)of Guangzhou Laboratory;Emergency COVID-19 Project(2021YFC0866100),Major Projects on Public Security,National Key Research and Development Program;Sanming Project of Medicine in Shenzhen,China(SZSM201911014);the High Level-Hospital Program,Health Commission of Guangdong Province,China;the University of Hong Kong Outstanding Young Researcher Award;the University of Hong Kong Research Output Prize(Li Ka Shing Faculty of Medicine).

摘　　要：Dear Editor,Coronavirus Disease 2019(COVID-19)is associated with a variety of neurological complications,including encephalopathy,encephalitis,dementia,and others.1 The pathogenic mechanism of these neurological manifestations remains incompletely understood but may be due to factors such as coagulation problem,immune-mediated response,or direct viral invasion into the central nervous system(CNS).2 We and others previously reported that ancestral SARS-CoV-2 could infect and replicate in human brain organoids.3,4 More recently,SARS-CoV-2 Omicron BA.1 emerged in late 2021 and demonstrated altered virological features including increased immunoevasion and attenuated pathogenicity comparing to SARS-CoV-2 wildtype(WT)and previous variants.5 However,the neuroinvasiveness of Omicron sublineages remain unexplored.Here,we investigated the neuroinvasion and neurotoxicity of Omicron BA.1 and BA.2,and compared the findings with those of SARS-CoV-2 WT and Delta in human forebrain and midbrain organoids.Our results demonstrated that BA.2 replicated more efficiently while triggered lower levels of type I interferon response than that of SARS-CoV-2 WT,Delta,and BA.1 in both human forebrain and midbrain organoids.In addition,BA.2 triggered substantially higher levels of apoptosis in the infected human forebrain and midbrain organoids.Together,these findings suggest that BA.2 may be different from SARS-CoV-2 WT and previous variants in its capacity in targeting and causing diseases in the human brain.

关 键 词：INVASION finding INCOMPLETE 

分 类 号：R373[医药卫生—病原生物学]