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Figure1.Phylogenetic Relationship of CSMC Samples to Global SARS-CoV-2 Genomes
CSMC Samples to Global SARS-CoV-2 Genomes Phylogenetic Relationship of

Phylogenetic tree of 185 Cedars-Sinai Medical Center(CSMC)SARS-CoV-2 isolates and aglobal subsampling of 1480 isolates collected from December2019to January2021 reveals anover subcluster within20C that share5 mutations(ORF1a:I4205V,ORF1b:D1183Y,S:S13I;W152C;L452L/CAgnas.S.452R)。The phylogenetic tree shows the relationship of CAL.20C to other circulating lineages.The branch length(x-axis)reflects numbers of mutations accumulated before being discovered,and clades are designated based on Nextstrain nomenclature.The UK variant(501Y。V1),South African variant(501Y。V2),and Brazil variant(501Y。V3)are shown。

Figure2.Timeline for the Emergence of a Novel Southern California Variant,CAL.20C,Among All SARS-COV-2 Circulating Variants Observed
Timeline for the Emergence of a Novel Southern California Variant,CAL.20C,Among All SARS-Cov-2 Circulating Variants Observed

Diagrammatic representation of circulating SARS-COV-2variant frequencies.A,Includes10 431samples from the state of California。B,Includes4829samples from Southern California。

Nancy E.Messonnier,MD is director of the National Center for Immunization and Respiratory Diseases(NCIRD)at the Centers for Disease Control and Prevention(CDC)and leads the CDC’s efforts on COVID-19vaccination。Shejoins JAMA's Q&A series to discuss the agency's response to emerging coronavirus variants,the FDA advisory hearings on the new Johnson&Johnson vaccine,。。。

1。
张扬,张扬W,GovindavariJP,DavisBD、,et al.Analysis of genomic characteristics and transmission routes of patients with confirmed SARS-Cov-2in Southern California during the early stage of the US COVID-19pandemic。 JAMA Netw Open.2020;3(10):e2024191。doi:10.1001/jamanetworkopen.2020.24191PubMedGoogle Scholar
2。
LauringAS,HodcroftEB。Genetic variants of SARS-Cov-2—what do they mean? JAMA.Published online January62021。doi:10.1001/jama.2020.27124PubMedGoogle Scholar
3。
TangJW,TambyahPA,HuiDS。Emergence of a new SARS-Cov-2variant in the UKJ Infect.Published online December282020。doi:10.1016/j.jinf.2020.12.024PubMedGoogle Scholar
4。
HadfieldJ,MegillC,BellSM,et al.Nextstrain:real-time tracking of pathogen evolution。 Bioinformatics.2018;34(23):4121-4123。doi:10.1093/bioinformatics/bty407PubMedGoogle ScholarCrossref
5。
ShuY,McCauleyJ。GISAID:Global Initiative on Sharing All Influenza Data—from vision to reality。 Euro Surveill.2017;22(13):30494。doi:10.2807/1560-7917.ES.2017.22.13.30494PubMedGoogle ScholarCrossref
6。
LiQ,WuJ,NieJ,et al.The impact of mutations in SARS-CoV-2spike on viral infectivity and antigenicity。 中心,中心.2020;182(5):1284-1294。doi:10.1016/j.cell.2020.07.012PubMedGoogle ScholarCrossref
1 Comment for this article
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Spread of Infection With Tokyo-type SARS-COV-2 Variant(E484K)
Takuma Hayashi,MBBS,DMSci,GMRC,PhDNational Hospital Organization Kyoto Medical Center
SARS-Cov-2variants,which are spreading in the United Kingdom and Europe,have been found in infected individuals in Japan。正规ly,the virus mutates to make it easier to live in the host in the process of repeating proliferation in the living body of the host including humans.As a result,the viral mutants acquire strong proliferative potential in the host and become high ly pathogenic.From around March 2021,the number of people infected with SARS-CoV-2variant(E484K),which is different from SARS-CoV-2variants,which are spreading in the United Kingdom,South Africa,and Brazil,is increasing in the Tokyo metropolitan area.It has been pointed out that the effectiveness of antiviral immunity and vaccine effect may be low in persons infected with Tokyo-type SARS-CoV-2variant(E484K)。

In the Tokyo metropolitan area,the number of persons infected with SARS-CoV-2variants is shown below。
March10221,SARS-Cov-2variant infected rate1.18%
[UK type(20I/501Y.V1/B.1.1.7)4cases/Overall340cases]
April62021,SARS-Cov-2variant infected rate3.38%[British type
(20I/501Y.V1/B.1.1.7)2cases,Tokyo-type SARS-COV-2variant(E484K)10cases/Overall355cases]
April72021,SARS-Cov-2variant infected rate4.26%[British type
(20I/501Y.V1/B.1.1.7):2cases,Tokyo-type SARS-COV-2variant
(E484K)15Example/Overall399cases]

Since April2021,the number of people infected with the Tokyo-type SARS-CoV-2variant(E484K)has been increasing in the Tokyo metropolitan area。At hospitals in the Tokyo metropolitan area,COVID-19patients are admitted to the hospital room that has been designated for each SARS-CoV-2variant.Compared to the infectivity of conventional SARS-CoV-2,infectivity of Tokyo-type SARS-CoV-2variant(E484K)is belied to venot。The virological and medical properties of the Tokyo-type SARS-COV-2variant(E484K)have not been clarified。Further clinical research is required to clarify the properties of the Tokyo-type SARS-COV-2variant(E484K)。

Dr.Takuma Hayashi,Dr.Ikuo Konishi
CONFLICT OF INTEREST: 无报告
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Research Letter
February112021

Emergence of a Novel SARS-CoV-2 Variant in Southern California

Author Affiliations
  • 1个路径和Laboratory Medicine,Cedars-Sinai Medical Center,Los Angeles,California
  • 2Biomedical Sciences,Cedars-Sinai Medical Center,Los Angeles,California
JAMA。2021;325(13):1324-1326。doi:10.1001/jama.2021.1612

Aspike in COVID-19 has occurred in Southern California since October2020.Analysis of SARS-CoV-2 in Southern California prior to October indicated most isolates originated from clade20C that likely emerged from New York via Europe early in the pandemic。1个Since then,novel variants of SARS-Cov-2including those seen in the UK(20I/501Y。V1/B.1.1.7),South Africa(20H/501Y。V2/B.1.351),and Brazil(P.1/20J/501Y。V3/B.1.1.248)have emerged,with the concern of increased infectivity and virulence。2单击功能区上,3Thus,we analyzed variants of SARS-CoV-2in Southern California to establish whether one of these known strains or anovel variant had emerged。

Methods

Regulatory review with waiver of consent was completed by Cedars-Sinai Medical Center(CSMC)。从同步存储器和ambulatory存储器,primary care,and employee health)that tested positive for SARS-CoV-2 collected from November 222020,to December 282020,at CSMC with cycle threshold values less less less than 30,a random sample from selected runs and dates within the collection period was sequenced and analyzed(eMethods in the支持,支持)。In addition,phylogenetic analysis was conducted with CSMC samples and globally representative genomes on January112021,by utilizing Nextstrain,a collection of open-source tools for visualizing the genetics behind the spread of viral outbreaks。4个全球Initiative on Sharing All Influenza Data,viral genomic data,5collected between December212019,and January112021(eMethods in the支持,支持)。

从以下CSMC中选择,collected between March4200and January222021.Southern California was defined as including the following counties:Imperial,Kern,Los Angeles,Orange,Riverside,San Bernardino,San Diego,San Luis Obispo,Santa Barbara,and Ventura。

结果,结果

Of2311 samples at CSMC,192 were selected and 185(67 inpatient;118outpatient)underwent phylogenetic analysis,along with1480representative genomes using Nextstrain.A diverse set of lineages with2main clusters was identified(火焰1)。The smaller of the 2 clusters was from the 20G lineage and accounted for22%(40of185)of the samples。The larger cluster(36%;67 of 185)consisted of a novel variant descended from cluster20C,defined by5 mutations(ORF1a:I4205V,ORF1b:D1183Y,S:S13I;W152C;L452R)and designated CAL.20C(20C/S:452R;/B.1.429)。

Analysis of 10 431 samples from California,including4829 from Southern California,revealed that CAL.20Cwas first observed in July2020in1 of 1247 samples from Los Angeles County and not detected in Southern California again until Octover.Since then,this variant’s prevalence has increased in the state of California and in Southern California California,35%(86 of 247)和44%(37 of 85)of all samples collected in January,respectively(火焰2)。

Sequence analysis of 405 871global samples on GISAID on January222021,revealed that CAL.20Cwas only found in Southern California in Octover2020(4cases)。In November2020,30cases were also identified in Northern California and individual cases in5additional states.As of January222021,CAL.20C has been detected in26states and other countries(支持,支持)。

Discussion

Anovel variant of SARS-Cov-2,CAL.20C,was identified,which emerged in Southern California contemporaneously with the local surge in cases.Unlike clade20G,currently the largest reported clade in North America,this strain is defined by3mutations in the S protein characterizing it as subclade of 20C.The S protein L452R mutation is within a known receptor binding domain that has been found to be resistant to certain spike(S)protein monoclonal antibodies。6个Because this study was limited to databases of publicly available genomes and a comparatively small set of local samples,the possibility of collection bias cannot be ruled out.Additionally,as clinical outcomes have yet to be established, the functional effect of this strain regarding infectivity and disease severity remains uncertain.Nevertheless,the identification of this novel strain is important to frontline and global surveillance of this evolving virus。

分区编辑器:Jody W.Zylke,MD,Deputy Editor。
后退,后退
区域信息

已接受的发布:February12021。

已发布的联机:February112021.doi:10.1001/jama.2021.1612

核心审计:Jasmine T.Plummer,PhD,Cedars Sinai Medical Center,8700 Beverly Blvd,SSB365,Los Angeles,CA90048(jasmine.plummer@cshs.org)。

Author Contributions:Drs Plummer and Vail had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.Drs Plummer and Vail codirected the study。

Concept and design:Zhang,Plummer,Vail。

Acquisition,analysis,or interpretation of data:All authors。

Drafting of the manuscript:Plummer,Vail。

严重警告:All authors。

统计分析:Zhang,Vail。

Obtained funding:Plummer,Vail。

管理员,技术支持:Davis,Chen,Sincuir Martinez,Plummer,Vail。

超级vision:Plummer,Vail。

接口磁盘:Dr Vail reported receiving personal fees from Illumina outside the submitted work.Noother disclosures were reported。

功能/支持:This project was funded by an internal grant to Dr Plummer provided by the Department of Biomedical Sciences,Cedars-Sinai Medical Center。

Role of the Funder/Sponsor:The funder had no role in the design and conduct of the study;collection,management,analysis,and interpretation of the data;preparation,review,or approval of the manuscript;and decision to submit the manuscript for publication。

其他内容:We thank Yizhou Wang,PhD,Applied Genomics,Computational and Translational Core,for demultiplexing files and Jeffrey Golden,MD,Burns and Allen Research Institute,for assistance with editing.Neither received compensation。

其他信息:Data used in this study have been deposited to GISAID with accession ESP_ISL_824555-824741。

参考,参考
1。
张扬,张扬W,GovindavariJP,DavisBD、,et al.Analysis of genomic characteristics and transmission routes of patients with confirmed SARS-Cov-2in Southern California during the early stage of the US COVID-19pandemic。 JAMA Netw Open.2020;3(10):e2024191。doi:10.1001/jamanetworkopen.2020.24191PubMedGoogle Scholar
2。
LauringAS,HodcroftEB。Genetic variants of SARS-Cov-2—what do they mean? JAMA.Published online January62021。doi:10.1001/jama.2020.27124PubMedGoogle Scholar
3。
TangJW,TambyahPA,HuiDS。Emergence of a new SARS-Cov-2variant in the UKJ Infect.Published online December282020。doi:10.1016/j.jinf.2020.12.024PubMedGoogle Scholar
4。
HadfieldJ,MegillC,BellSM,et al.Nextstrain:real-time tracking of pathogen evolution。 Bioinformatics.2018;34(23):4121-4123。doi:10.1093/bioinformatics/bty407PubMedGoogle ScholarCrossref
5。
ShuY,McCauleyJ。GISAID:Global Initiative on Sharing All Influenza Data—from vision to reality。 Euro Surveill.2017;22(13):30494。doi:10.2807/1560-7917.ES.2017.22.13.30494PubMedGoogle ScholarCrossref
6。
LiQ,WuJ,NieJ,et al.The impact of mutations in SARS-CoV-2spike on viral infectivity and antigenicity。 中心,中心.2020;182(5):1284-1294。doi:10.1016/j.cell.2020.07.012PubMedGoogle ScholarCrossref