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新冠病毒变体的分类和定义SARS-CoV-2 Variant Classifications & Definitions
发布时间:2021-07-09

Viruses constantly change through mutation, and new variants of a virus are expected to occur. Sometimes new variants emerge and disappear. COVID-19疫情自2019年底被发现以来,造成大量人群的感染。伴随着感染人数的增加和疫情的持续,SARS-CoV-2不断进化和变异,产生了大量的病毒变异株,其中一些变异株的传播能力和致病性明显提高,还有一些毒株出现抗原逃逸现象,这些变异株引起了公共卫生部门和民众的关注。Other times, new variants persist. Multiple variants of the virus that causes COVID-19 have been documented in the United States and globally during this pandemic. Genetic variants of SARS-CoV-2 have been emerging and circulating around the world throughout the COVID-19 pandemic. A US government SARS-CoV-2 Interagency Group (SIG) interagency group developed a Variant Classification scheme that defines three classes of SARS-CoV-2 variants:

    The B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 (Delta), and P.1 (Gamma), variants circulating in the United States are classified as variants of concern.

  • To date, no variants of high consequence have been identified in the United States.

  • Laboratory studies suggest specific monoclonal antibody treatments may be less effective for treating cases of COVID-19 caused by variants with certain substitutions or combinations of substitutions in the spike protein.

    • L452R is present in B.1.526 (Iota), B.1.427 (Epsilon), and B.1.429 (Epsilon) lineages, as well as the B.1.617 (Kappa, Delta) lineages and sub-lineages.


    • E484K is present in B.1.525 (Eta), P.2 (Zeta), P.1 (Gamma), and B.1.351 (Beta), but only some strains of B.1.526 (Iota) and B.1.1.7 (Alpha).


    • The combination of K417N, E484K, and N501Y substitutions is present in B.1.351 (Beta).


    • The combination of K417T, E484K, and N501Y substitutions is present in P.1 (Gamma).


Viruses constantly change through mutation. A variant has one or more mutations that differentiate it from other variants in circulation. As expected, multiple variants of SARS-CoV-2 have been documented in the United States and globally throughout this pandemic. To inform local outbreak investigations and understand national trends, scientists compare genetic differences between viruses to identify variants and how they are related to each other.

Variant classifications

The US Department of Health and Human Services (HHS) established a SARS-CoV-2 Interagency Group (SIG) to improve coordination among the Centers for Disease Control and Prevention (CDC), National Institutes of Health (NIH), Food and Drug Administration (FDA), Biomedical Advanced Research and Development Authority (BARDA), and Department of Defense (DoD). This interagency group is focused on the rapid characterization of emerging variants and actively monitors their potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics.

Notes: Each classification of variant includes the possible attributes of lower classes (i.e., VOC includes the possible attributes of VOI); variant status might escalate or deescalate based on emerging scientific evidence. This page will be updated as needed to show the variants that belong to each class. The World Health Organizationexternal icon (WHO) also classifies variant viruses as Variants of Concern and Variants of Interest; US classifications may differ from those of WHO because the importance of variants may differ by location. To assist with public discussions of variants, WHO proposed using labels consisting of the Greek Alphabet, i.e., Alpha, Beta, Gamma, as a practical way to discuss variants by non-scientific audiences. The labels assigned to each variant are provided in the tables below.

See Variant Proportions in the U.S.  2019-nCoV 新型冠状病毒变异株和突变序列

Variant of Interest

A variant with specific genetic markers that have been associated with changes to receptor binding, reduced neutralization by antibodies generated against previous infection or vaccination, reduced efficacy of treatments, potential diagnostic impact, or predicted increase in transmissibility or disease severity.

Possible attributes of a variant of interest:

  • Specific genetic markers that are predicted to affect transmission, diagnostics, therapeutics, or immune escape.

  • Evidence that it is the cause of an increased proportion of cases or unique outbreak clusters.

  • Limited prevalence or expansion in the US or in other countries.

A variant of interest might require one or more appropriate public health actions, including enhanced sequence surveillance, enhanced laboratory characterization, or epidemiological investigations to assess how easily the virus spreads to others, the severity of disease, the efficacy of therapeutics and whether currently authorized vaccines offer protection.

Current variants of interest in the United States that are being monitored and characterized are listed below. This will be updated when a new variant of interest is identified.

Selected Characteristics of SARS-CoV-2 Variants of Interest

B.1.427 (Pango lineageexternal icon)a

Spike Protein Substitutions: L452R, D614G

Name (Nextstrainexternal icon)b: 20C/S:452R

WHO Label: Epsilon

First Identified: United States-(California) 美国加州变异株

Attributes:

  • ~20% increased transmission21

  • Modest decrease in susceptibility to the combination of bamlanivimab and etesevimab; however, the clinical implications of this decrease are not known.Alternative monoclonal antibody treatments are available.14

  • Reduced neutralization by convalescent and post-vaccination sera21

  • Deescalated from a VOC on June 29, 2021, due to the significant decrease in the proportion of B.1.427 lineage viruses circulating nationally and available data indicating that vaccines and treatments are effective against this variant.


B.1.429 (Pango lineageexternal icon)a

Spike Protein Substitutions: S13I, W152C, L452R, D614G

Name (Nextstrainexternal icon)b: 20C/S:452R

WHO Label: Epsilon

First Identified: United States-(California) 美国加州变异株

Attributes:

  • ~20% increased transmission21

  • Reduced susceptibility to the combination of bamlanivimab and etesevimab; however, the clinical implications of this decrease are not known.Alternative monoclonal antibody treatments are available.14

  • Reduced neutralization by convalescent and post-vaccination sera21.

  • Deescalated from a VOC on June 29, 2021, due to the significant decrease in the proportion of B.1.429 lineage viruses circulating nationally and available data indicating that vaccines and treatments are effective against this variant.


B.1.525 (Pango lineageexternal icon)a

Spike Protein Substitutions: A67V, 69del, 70del, 144del, E484K, D614G, Q677H, F888L

Name (Nextstrainexternal icon)b: 20A/S:484K

WHO Label: Eta

First Identified: United Kingdom/Nigeria – December 2020  尼日利亚变异株

Attributes:

  • Potential reduction in neutralization by some Emergency Use Authorization (EUA) monoclonal antibody treatments 7, 14

  • Potential reduction in neutralization by convalescent and post-vaccination sera22


B.1.526 (Pango lineageexternal icon)a

Spike Protein Substitutions: L5F, (D80G*), T95I, (Y144-*), (F157S*), D253G, (L452R*), (S477N*), E484K, D614G, A701V, (T859N*), (D950H*), (Q957R*)

Name (Nextstrainexternal icon)b: 20C/S:484K

WHO Label: Iota

First Identified: United States (New York) – November 2020 美国纽约变异株

BEI Reference IsolatecNR-55359external icon

Attributes:

  • Reduced susceptibility to the combination of bamlanivimab and etesevimab monoclonal antibody treatment; however, the clinical implications of this are not known.7 Alternative monoclonal antibody treatments are available.14

  • Reduced neutralization by convalescent and post-vaccination sera22, 24

  • B.1.526.1 sublineage has been consolidated with this parent lineage


B.1.617.1 (Pango lineageexternal icon)a

Spike Protein Substitutions: (T95I), G142D, E154K, L452R, E484Q, D614G, P681R, Q1071H

Name (Nextstrainexternal icon)b: 20A/S:154K

WHO Label: Kappa

First Identified: India – December 2020 印度变异株

Attributes:

  • Potential reduction in neutralization by some EUA monoclonal antibody treatments7, 14

  • Potential reduction in neutralization by post-vaccination sera26


B.1.617.3 (Pango lineageexternal icon)a

Spike Protein Substitutions: T19R, G142D, L452R, E484Q, D614G, P681R, D950N

Name (Nextstrainexternal icon)b: 20A

First Identified: India – October 2020 印度变异株

Attributes:

  • Potential reduction in neutralization by some EUA monoclonal antibody treatments7, 14

  • Potential reduction in neutralization by post-vaccination sera26


P.2 (Pango lineageexternal icon)a

Spike Protein Substitutions: E484K, (F565L*), D614G, V1176F

Name (Nextstrainexternal icon)b: 20J

WHO Label: Zeta

First Identified: Brazil – April 2020 巴西变异株

Attributes:

  • Potential reduction in neutralization by some EUA monoclonal antibody treatments7, 14

  • Reduced neutralization by post-vaccination sera22, 23

 

Variant of Concern

A variant for which there is evidence of an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), significant reduction in neutralization by antibodies generated during previous infection or vaccination, reduced effectiveness of treatments or vaccines, or diagnostic detection failures.

Possible attributes of a variant of concern:

In addition to the possible attributes of a variant of interest

  • Evidence of impact on diagnostics, treatments, or vaccines

    • Widespread interference with diagnostic test targets

    • Evidence of substantially decreased susceptibility to one or more class of therapies

    • Evidence of significant decreased neutralization by antibodies generated during previous infection or vaccination

    • Evidence of reduced vaccine-induced protection from severe disease

  • Evidence of increased transmissibility

  • Evidence of increased disease severity

Variants of concern might require one or more appropriate public health actions, such as notification to WHO under the International Health Regulations, reporting to CDC, local or regional efforts to control spread, increased testing, or research to determine the effectiveness of vaccines and treatments against the variant. Based on the characteristics of the variant, additional considerations may include the development of new diagnostics or the modification of vaccines or treatments.

Current variants of concern in the United States that are being closely monitored and characterized by federal agencies are included in the below. This table will be updated when a new variant of concern is identified.

Selected Characteristics of SARS-CoV-2 Variants of Concern

B.1.1.7 (Pango lineageexternal icon)a

Spike Protein Substitutions: 69del, 70del, 144del, (E484K*), (S494P*), N501Y, A570D, D614G, P681H, T716I, S982A, D1118H (K1191N*)

Name (Nextstrainexternal icon)b: 20I/501Y.V1

WHO Label: Alpha

First Identified: United Kingdom 英国变异株 N501Y.V1

BEI Reference IsolatecNR-54000external icon

Attributes:

  • ~50% increased transmission5

  • Potential increased severity based on hospitalizations and case fatality rates6

  • No impact on susceptibility to EUA monoclonal antibody treatments7,14

  • Minimal impact on neutralization by convalescent and post-vaccination sera8-13,19


B.1.351 (Pango lineageexternal icon)a

Spike Protein Substitutions: D80A, D215G, 241del, 242del, 243del, K417N, E484K, N501Y, D614G, A701V

Name (Nextstrainexternal icon)b: 20H/501.V2

WHO Label: Beta

First Identified: South Africa 南非变异株  N501Y.V2

BEI Reference IsolatecNR-55282external icon

Attributes:

  • ~50% increased transmission16

  • Significantly reduced susceptibility to the combination of bamlanivimab and etesevimab monoclonal antibody treatment,7 but other EUA monoclonal antibody treatments are available 14

  • Reduced neutralization by convalescent and post-vaccination sera8,12,18,19,20


B.1.617.2 (Pango lineageexternal icon)a

Spike Protein Substitutions: T19R, (V70F*), T95I, G142D, E156-, F157-, R158G, (A222V*), (W258L*), (K417N*), L452R, T478K, D614G, P681R, D950N

Name (Nextstrainexternal icon)b: 20A/S:478K

WHO Label: Delta

First Identified: India   印度德尔塔变异株

Attributes:

  • Increased transmissibility 29

  • Potential reduction in neutralization by some EUA monoclonal antibody treatments 7, 14

  • Potential reduction in neutralization by post-vaccination sera 21

  • AY.1 and AY.2 are currently aggregated with B.1.617.2. As data are available, CDC will continue to evaluate the independent classification of AY.1 and AY.2.


P.1 (Pango lineageexternal icon)a

Spike Protein Substitutions: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I

Name (Nextstrainexternal icon)b: 20J/501Y.V3

WHO Label: Gamma

First Identified: Japan/Brazil  巴西变异株 N501Y.V3

BEI Reference IsolatecNR-54982external icon

Attributes:

  • Significantly reduced susceptibility to the combination of bamlanivimab and etesevimab monoclonal antibody treatment,7 but other EUA monoclonal antibody treatments are available 14

  • Reduced neutralization by convalescent and post-vaccination sera15


Variant of High Consequence

A variant of high consequence has clear evidence that prevention measures or medical countermeasures (MCMs) have significantly reduced effectiveness relative to previously circulating variants.

Possible attributes of a variant of high consequence:

In addition to the possible attributes of a variant of concern

  • Impact on Medical Countermeasures (MCM)

    • Demonstrated failure of diagnostics

    • Evidence to suggest a significantly reduction in vaccine effectiveness, a disproportionately high number of vaccine breakthrough cases, or very low vaccine-induced protection against severe disease

    • Significantly reduced susceptibility to multiple Emergency Use Authorization (EUA) or approved therapeutics

    • More severe clinical disease and increased hospitalizations

A variant of high consequence would require notification to WHO under the International Health Regulations, reporting to CDC, an announcement of strategies to prevent or contain transmission, and recommendations to update treatments and vaccines.

Currently, there are no SARS-CoV-2 variants that rise to the level of high consequence.

 

Treatment considerations for healthcare providers

Substitutions of Concern for SARS-CoV-2 Monoclonal Antibody Therapies

In the United States, there are three anti-SARS-CoV-2 monoclonal antibody treatments with FDA Emergency Use Authorization (EUA) for the treatment of COVID-19: bamlanivimab plus etesevimabexternal iconcasirivimab plus imdevimab,external icon, and sotrovimabexternal icon.

CDC’s national genomic surveillance program identifies new and emerging SARS-CoV-2 variants to determine implications for COVID-19 diagnostics, treatments, or vaccines authorized for use in the United States. Sequences with similar genetic changes are grouped into lineages, and multiple lineages can have the same substitutions. For example, the E484K substitution is found in lineages B.1.351, P.1, B.1.526, and many others. Genomic surveillance efforts provide the capability to detect viruses that have reduced susceptibility to treatments more quickly.

In laboratory studies, SARS-CoV-2 variants that contain certain substitutions in the spike protein cause a marked reduction in susceptibility to bamlanivimab and may have reduced sensitivity to etesevimab and casirivimab. The L452R substitution found in the B.1.427 and B.1.429 lineages has been shown to cause a significant reduction in susceptibility to bamlanivimab and a modest decrease in susceptibility to the combination of bamlanivimab and etesevimab, although the clinical implications of this modest decrease are not known. 7 The E484K substitution found in the B.1.351, P.1, and B.1.526 lineages also results in a marked reduction in susceptibility to bamlanivimab, as well as the combination of bamlanivimab and etesevimab.7  Laboratory studies also suggest that the K417N and K417T substitutions, which are present in the B.1.351 and P.1 variants, respectively, along with the E484K mutation, reduces virus susceptibility to casirivimab, although the combination of casirivimab and imdevimab appears to retain activity.14 There is no reported reduction in susceptibility of variants to sotrovimab.28

The data below shows the national and regional unweighted proportions of SARS-CoV-2 that contain the L452R or E484K substitution, individually, as well as the unweighted proportions of SARS-CoV-2 that contain the combination of K417N, E484K, and N501Y substitutions or the combination of K417T, E484K, and N501Y substitutions. As new data become available, additional substitutions may be added below. 

以上内容转自美国CDChttps://www.cdc.gov/coronavirus/2019-ncov/variants/variant-info.html  



另外可以参考英国Public Health England定期发布的: Technical briefing documents on novel SARS-CoV-2 variants:

https://www.gov.uk/government/publications/investigation-of-novel-sars-cov-2-variant-variant-of-concern-20201201


PANGO Lineages网站:

https://cov-lineages.org/index.html


https://cov-lineages.org/global_report.html


Pango命名规则:
Pango, GISAID,和Nextstrain命名是依据病毒进化距离命名的,其中Pango最为常用 ,如在伦敦首先发现的B.1.1.7,南非最先发现的B.1.352,印度目前在流行的B.1.617.2,均为Pango命名 。Pango命名前面的英文字母代表属于某一个支系 ,后面的点和数字代表来源于前面支系的第几个子代分支。如以B.1.1.7为例,B.1.1.7是B.1.1支系的第七个子代支系,C.1是C支系的第一个子代分支。Pango命名法将谱系名称限制在最多四个层次的祖先,以确保谱系名称不会过长,当某一个支系后面的数字超过3个时,将产生一个新的字母支系。如B.1.1.1的下一个子代支系不叫B.1.1.1.1,而是生成一个新的支系C支系,命名为C1;在巴西传播的关切变异株被称为P.1,而不是B.1.1.28.1。Pango命名能清楚表示出该突变株在进化上位置,以及和其他突变株的亲缘关系的远近。


新冠病毒SARS-CoV-2序列数据库:

https://www.gisaid.org/


GISAID命名规则:

GISAID命名是根据病毒基因组的进化距离来命名的[4]。GISAID命名不是按照字母顺序A,B,C来依次命名,而是依据突变位点的氨基酸变异来命名。2020年2月携带S-D614G突变的毒株在全球迅速传播,这群变异株就被命名为G。大的支系可以继续向下划分,如G支系后续又分支为GH,GR支系[5],支系后面可以标注关键的突变位点。如伦敦突变株B.1.1.7在GISAID命名系统中为GR/501Y.V1”。



https://nextstrain.org/


Nextstrain SARS-CoV-2 resources: https://nextstrain.org/sars-cov-2 


Nextstrain 命名规则:

Nextstrain命名是以年份开头,后续依次按照字母顺序来命名变异株[6],如B.1.1.7在Nextstrain命名规则中命名为“20I(V1)”。Nextrain定义一个新的支系需要满足以下3个条件之一:(1)在全球流行超过2个月且比例超过本时期流行株总数的20%以上;(2)在某个地区流行超过2个月且比例高于本地区同时期流行毒株的30%;(3)出现引起公共卫生风险的变异(如501Y.V1和501Y.V2)。

WHO 命名规则:

  为了便于公众对这些变异株的讨论和认识,WHO推荐使用希腊字母(Alpha,Beta, Gamma)来命名重要毒株。依据这些变异株的传播力、致病力不同,将其分为“关切变异株”(variant of concern, VOC)和“关注变异株”(variant of interest, VOI)。

 关注变异株(Variant of interest, VOI):

VOI毒株需满足以下两个条件之一:相比较参考毒株,变异株基因组的变异引起了病毒表型的改变;变异株引起社区传播或者在多个国家地区传播。目前,WHO公布的VOI主要包括以下几种:


关切变异株(Variant of concern, VOC):

相比较VOI变异株,VOC毒株的公共卫生风险更高,更受大众关注。VOC必须满足以下3个条件之一:① 传播能力增强或者流行特点出现不良方向的改变;② 毒力增强或者临床致病性增加;③ 毒株的变异使公共卫生,社会干预措施,或现有诊断、疫苗、治疗方法的有效性降低。VOI是科学家和普通群众重点关心的变异株,媒体常常报道的伦敦突变株,南非突变株,巴西突变株,和最近出现的印度突变株,均为VOC。


以上转自  京港感染论坛 作者: 邹晓辉、曹彬