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Distinct immune signatures discriminate between asymptomatic and presymptomatic SARS-CoV-2^(pos)subjects

查看全文 作　　者：Shanhe [1,3]Yu;Caixia [2,3]Di;Shijun [1]Chen;Mingquan [4]Guo;Jiayang [2,3]Yan;Zhaoqin [4]Zhu;Li [5]Liu;Ruixue [1]Feng;Yinyin [1]Xie;Ruihong [1]Zhang;Juan [1]Chen;Mengxi [1]Wang;Dong [3,6]Wei;Hai [1]Fang;Tong [1]Yin;Jinyan [1]Huang;Saijuan [1]Chen;Hongzhou [5]Lu;Jiang [1,3]Zhu;Jieming [2,3,7]Qu 高影响力作者 机构地区：[1]Shanghai Institute of Hematology,State Key Laboratory of Medical Genomics,National Research Center for Translational Medicine at Shanghai,Collaborative Innovation Center of Hematology,Ruijin Hospital affiliated to Shanghai Jiao-Tong University School of Medicine,Shanghai,China;[2]Department of Respiratory and Critical Care Medicine,Ruijin Hospital,Institute of Respiratory Diseases,School of Medicine,Shanghai Jiao-Tong University,Shanghai,China;[3]Key Laboratory of Emergency Prevention,Diagnosis and Treatment of Respiratory Infectious Diseases,Shanghai,China;[4]Department of Laboratory Medicine,Shanghai Public Health Clinical Center,Fudan University,Shanghai,China;[5]Department of Infectious Diseases and Immunology,Shanghai Public Health Clinical Center,Fudan University,Shanghai,China;[6]Department of Infectious Disease,Research Laboratory of Clinical Virology,Ruijin Hospital,School of Medicine,Shanghai Jiao-Tong University,Shanghai,China;[7]National Research Center for Translational Medicine at Shanghai,Shanghai,China高影响力机构 出　　处：《Cell Research》索引2021年第31卷第11期,共15页高影响力期刊 基　　金：This work was supported by Key Laboratory of Emergency Prevention,Diagnosis and Treatment of Respiratory Infectious Diseases in Shanghai(20dz2261100);the National Major Scientific and Technological Special Project(2018ZX09101001);Cultivation Project of Shanghai Major Infectious Disease Research Base(20dz2210500);the National Natural Science Foundation of China(NSFC)(81430002,81770206,81900148);the National Innovative Research Team of High-level Local Universities in Shanghai,Shanghai Collaborative Innovation Program on Regenerative Medicine and Stem Cell Research(2019CXJQ01);the National Research Center for Translational Medicine at Shanghai,RiHjin Hospital Affiliated to Shanghai Jiao-Tong University School of Medicine[NRCTM(SH)-2019-02];the National Key R&D Program of China(2018YFA0107802);Shanghai Rising-Star Program(20QC1400100);Samuel Waxman Cancer Research Foundation,Novo Nordisk Hemophilia Research Fund in China and Emergency Project of Shanghai Science and Technology Commission(20411950502). 摘　　要：Increasing numbers of SARS-CoV-2-positive(SARS-CoV-2^(pos))subjects are detected at silent SARS-CoV-2 infection stage(SSIS).Yet,SSIS represents a poorly examined time-window wherein unknown immunity patterns may contribute to the fate determination towards persistently asymptomatic or overt disease.Here,we retrieved blood samples from 19 asymptomatic and 12 presymptomatic SARS-COV-2^(pos)subjects,47 age/gender-matched patients with mild or moderate COVID-19 and 27 normal subjects,and interrogated them with combined assays of 44-plex CyTOF,RNA-seq and Olink.Notably,both asymptomatic and presymptomatic subjects exhibited numerous readily detectable immunological alterations,while certain parameters including more severely decreased frequencies of CD107a^(low)classical monocytes,intermediate monocytes,non-classical monocytes and CD62L^(hi)CD8^(+)Tnaive cells,reduced plasma STC1 level but an increased frequency of CD4^(+)NKT cells combined to distinguish the latter.Intercorrelation analyses revealed a particular presymptomatic immunotype mainly manifesting as monocytic overactivation and differentiation blockage,a likely lymphocyte exhaustion and immunosuppression,yielding mechanistic insights into SSIS fate determination,which could potentially improve 5ARS-CoV-2 management. 关 键 词：ASYMPTOMATIC immunity alterations
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