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CDC - SARS-CoV-2 Variant Classifications and Definitions (Updated April 27, 2021)

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  • CDC - SARS-CoV-2 Variant Classifications and Definitions (Updated April 27, 2021)

    SARS-CoV-2 Variant Classifications and Definitions


    Updated Apr. 27, 2021
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    Key Points:
    • Genetic variants of SARS-CoV-2 have been emerging and circulating around the world throughout the COVID-19 pandemic.
    • Viral mutations and variants in the United States are routinely monitored through sequence-based surveillance, laboratory studies, and epidemiological investigations.
    • A US government interagency group developed a Variant Classification scheme that defines three classes of SARS-CoV-2 variants:
    • The B.1.526, B.1.526.1, B.1.525, and P.2 variants circulating in the United States are classified as variants of interest.
    • The B.1.1.7, B.1.351, P.1, B.1.427, and B.1.429 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.
    • In laboratory studies, specific monoclonal antibody treatments may be less effective for treating cases of COVID-19 caused by variants with the L452R or E484K substitution in the spike protein.
      • L452R is present in B.1.526.1, B.1.427, and B.1.429.
      • E484K is present in B.1.525, P.2, P.1, and B.1.351, but only some strains of B.1.526 and B.1.1.7.

    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.

    In collaboration with the SIG, CDC established a classification scheme that defines three classes of variants of SARS-CoV-2. These classes include definitions and attributes of the variants. Resulting public health actions are also described in the sections below.
    Notes: Each classification of variant includes the possible attributes of lower classes (e.g., VOC includes the possible attributes of VOI); variant status might escalate or deescalate based on 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 since the importance of variants may differ by location.

    See Variant Proportions in the U.S.
    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 in the table below. The table will be updated when a new variant of interest is identified.
    Spike: (L5F*), T95I, D253G, (S477N*), (E484K*), D614G, (A701V*) 20C/S:484K United States (New York) ? November 2020
    • 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 sera 22, 24
    Spike: D80G, ?144, F157S, L452R, D614G, (T791I*), (T859N*), D950H 20C United States (New York) ? October 2020
    • Potential reduction in neutralization by some EUA monoclonal antibody treatments 7, 14
    • Potential reduction in neutralization by convalescent and post-vaccination sera22
    Spike: A67V, ?69/70, ?144, E484K, D614G, Q677H, F888L 20A/S:484K United Kingdom/Nigeria ? December 2020
    • Potential reduction in neutralization by some EUA monoclonal antibody treatments 7, 14
    • Potential reduction in neutralization by convalescent and post-vaccination sera 22
    Spike: E484K, (F565L*), D614G, V1176F 20J Brazil ? April 2020
    • Potential reduction in neutralization by some EUA monoclonal antibody treatments 7, 14
    • Reduced neutralization by post-vaccination sera 22, 23
    (*) = detected in some sequences but not all

    +These variants share one specific mutation called D614G. This mutation was one of the first documented in the US in the initial stages of the pandemic, after having initially circulated in Europe[13]. There is evidence that variants with this mutation spread more quickly than viruses without this mutation [12].

    a ? Phylogenetic Assignment of Named Global Outbreak (PANGO) Lineages is software tool developed by members of the Rambaut Lab. The associated web application was developed by the Centre for Genomic Pathogen Surveillance in South Cambridgeshire and is intended to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the PANGO nomenclature.

    b ? Nextstrain, a collaboration between researchers in Seattle, USA and Basel, Switzerland, provides open-source tools for visualizing the genetics of outbreaks. The goal is to support public health surveillance by facilitating understanding of the spread and evolution of pathogens.

    c ? The Biodefense and Emerging Infections Research Resources (BEI Resources) is a NIAID-funded repository to provide reagents, tools, and information to the research community. The reference viruses proposed here facilitate the harmonization of information among all stakeholders in the COVID-19 pandemic research community. Please note that the reference viruses provided in the tables below are based on what is currently available through the BEI Resources.
    Top of PageVariant 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 table below. The table will be updated when a new variant of concern is identified.
    ?69/70, ?144, (E484K*), (S494P*), N501Y, A570D, D614G, P681H, T716I, S982A, D1118H (K1191N*) 20I/501Y.V1 United Kingdom NR-54000external icon
    • ~50% increased transmission 5
    • Potential increased severity based on hospitalizations and case fatality rates 6
    • No impact on susceptibility to EUA monoclonal antibody treatments 7,14
    • Minimal impact on neutralization by convalescent and post-vaccination sera 8,9,10,11,12,13,19
    L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, D614G, H655Y, T1027I 20J/501Y.V3 Japan/
    Brazil
    NR-54982external icon
    • Significant decrease in 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 sera 15
    D80A, D215G, ?241/242/243, K417N, E484K, N501Y, D614G, A701V 20H/501.V2 South Africa NR-54009external icon
    • ~50% increased transmission16
    • Significant decrease in 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 sera 8,12,18,19,20
    L452R, D614G 20C/S:452R United States-(California)
    • ~20% increased transmissibility 21
    • Modest decrease in susceptibility to the combination of bamlanivimab and etesevimab; however, the clinical implications of this decrease are not known.7 Alternative monoclonal antibody treatments are available.14
    • Reduced neutralization by convalescent and post-vaccination sera 21
    S13I, W152C, L452R, D614G 20C/S:452R United States-(California)
    • ~20% increased transmissibility 21
    • Modest decrease in susceptibility to the combination of bamlanivimab and etesevimab; however, the clinical implications of this decrease are not known.7 Alternative monoclonal antibody treatments are available.14
    • Reduced neutralization by convalescent and post-vaccination sera 21
    (*) = detected in some sequences but not all
    +These variants share one specific mutation called D614G. This mutation was one of the first documented in the US in the initial stages of the pandemic, after having initially circulated in Europe[13]. There is evidence that variants with this mutation spread more quickly than viruses without this mutation [12].

    a ? Phylogenetic Assignment of Named Global Outbreak (PANGO) Lineages is software tool developed by members of the Rambaut Lab. The associated web application was developed by the Centre for Genomic Pathogen Surveillance in South Cambridgeshire and is intended to implement the dynamic nomenclature of SARS-CoV-2 lineages, known as the PANGO nomenclature.

    b ? Nextstrain, a collaboration between researchers in Seattle, USA and Basel, Switzerland, provides open-source tools for visualizing the genetics of outbreaks. The goal is to support public health surveillance by facilitating understanding of the spread and evolution of pathogens.

    c ? The Biodefense and Emerging Infections Research Resources (BEI Resources) is a NIAID-funded repository to provide reagents, tools, and information to the research community. The reference viruses proposed here facilitate the harmonization of information among all stakeholders in the COVID-19 pandemic research community. Please note that the reference viruses provided in the tables below are based on what is currently available through the BEI resources.

    d ? Attributes listed are based on data available from pseudoviruses or recombinant viruses containing combinations of substitutions characteristic of specific lineages or from reference virus isolates.
    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 significant 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.
    Top of PageTreatment considerations for healthcare providers


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

    In the United States, there are two anti-SARS-CoV-2 monoclonal antibody treatments with FDA Emergency Use Authorization (EUA) for the treatment of COVID-19: bamlanivimab plus etesevimabexternal icon and casirivimab plus imdevimab.external 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 the L452R or E484K substitution in the spike protein cause a marked reduction in susceptibility to bamlanivimab and may have lower sensitivity to etesevimab and casirivimab.

    The table below shows the estimated national and regional proportions of SARS-CoV-2 that contain the L452R or E484K substitution. As new data become available, additional substitutions may be added to the table below. The national and regional proportions provided in the table below will be updated every two weeks.
    Resources


    Monoclonal Antibody COVID-19 Infusionexternal icon

    Statement on Anti-SARS-CoV-2 Monoclonal Antibodies EUA | COVID-19 Treatment Guidelines (nih.gov)external icon
    L452R 18.0% Region 1 7.8% B.1.429
    B.1.427
    B.1.526.1
    Region 2 9.4%
    Region 3 11.5%
    Region 4 8.6%
    Region 5 13.1%
    Region 6 10.2%
    Region 7 7.7%
    Region 8 29.5%
    Region 9 50.6%
    Region 10 33.9%
    E484K 10.4% Region 1 13.7% B.1.526
    R.1
    P.1
    P.2
    B.1.351
    B.1
    B.1.525
    B.1.1
    B.1.1.318
    B.1.1.207
    Region 2 25.5%
    Region 3 16.6%
    Region 4 10.4%
    Region 5 6.0%
    Region 6 4.9%
    Region 7 4.1%
    Region 8 3.7%
    Region 9 5.8%
    Region 10 3.6%
    a ? The estimated prevalence of SARS-CoV-2 circulating in the United States that contain the designated substitution, based on >19,000 sequences collected through CDC?s national genomic surveillance during the two-week period ending March 27, 2021.

    b ? The estimated regional prevalence of SARS-CoV-2 circulating in each HHS region that contain the designated substitution, based on >19,000 sequences collected through CDC?s national genomic surveillance during the two-week period ending March 27, 2021.

    c ? The lineages listed are the most common lineages within CDC?s national genomic surveillance with these substitutions, but this list is not intended to be a complete list of the lineages that contain the spike protein substitutions.
    Top of PageReferences
    1. Zhou, B., Thi Nhu Thao, T., Hoffmann, D. et al. SARS-CoV-2 spike D614G change enhances replication and transmission. Nature (2021). https://doi.org/10.1038/s41586-021-03361-1external icon
    2. Volz E, Hill V, McCrone J, et al. Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity. Cell 2021; 184(64-75). doi: https://doi.org/10.1016/j.cell.2020.11.020external icon
    3. Korber B, Fischer WM, Gnanakaran S, et al. Tracking Changes in SARS-CoV-2 Spike: Evidence that D614G Increases Infectivity of the COVID-19 Virus. Cell 2021; 182(812-7) doi: https://doi.org/10.1016/j.cell.2020.06.043external icon
    4. Yurkovetskiy L, Wang X, Pascal KE, et al. Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant. Cell 2020; 183(3): 739-751. doi: https://doi.org/10.1016/j.cell.2020.09.032external icon
    5. *Davies NG, Abbott S, Barnard RC, et al. Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England. MedRXiv 2021. doi: https://doi.org/10.1101/2020.12.24.20248822external icon
    6. Horby P, Huntley C, Davies N et al. NERVTAG note on B.1.1.7 severity. New & Emerging Threats Advisory Group, Jan. 21, 2021. Retrieved from NERVTAG note on variant severityexternal icon
    7. Fact Sheet For Health Care Providers Emergency Use Authorization (Eua) Of Bamlanivimab And Etesevimab 02092021 (fda.gov)external icon
    8. *Wang P, Nair MS, Liu L, et al. Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7. BioXRiv 2021. doi: https://doi.org/10.1101/2021.01.25.428137external icon
    9. *Shen X, Tang H, McDanal C, et al. SARS-CoV-2 variant B.1.1.7 is susceptible to neutralizing antibodies elicited by ancestral Spike vaccines. BioRxiv 2021. doi: https://doi.org/10.1101/2021.01.27.428516external icon
    10. *Edara VV, Floyd K, Lai L, et al. Infection and mRNA-1273 vaccine antibodies neutralize SARS-CoV-2 UK variant. MedRxiv 2021. doi: https://doi.org/10.1101/2021.02.02.21250799external icon
    11. *Collier DA, DeMarco A, Ferreira I, et al. SARS-CoV-2 B.1.1.7 sensitivity to mRNA vaccine-elicited, convalescent and monoclonal antibodies. MedRxiv 2021. doi: https://doi.org/10.1101/2021.01.19.21249840external icon
    12. *Wu K, Werner AP, Moliva JI, et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. BioRxiv 2021. doi: https://doi.org/10.1101/2021.01.25.427948external icon
    13. Emary KRW, Golubchik T, Aley PK, et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7). 2021. The Lancet. doi: http://dx.doi.org/10.2139/ssrn.3779160external icon
    14. FACT SHEET FOR HEALTH CARE PROVIDERS EMERGENCY USE AUTHORIZATION (EUA) OF REGEN-COV (fda.gov)external icon
    15. *Wang P, Wang M, Yu J, et al. Increased Resistance of SARS-CoV-2 Variant P.1 to Antibody Neutralization. BioRxiv 2021. doi: https://doi.org/10.1101/2021.03.01.433466external icon
    16. Pearson CAB, Russell TW, Davies NG, et al. Estimates of severity and transmissibility of novel South Africa SARS-CoV-2 variant 501Y.V2. Retrieved from: pdf (cmmid.github.io)pdf iconexternal icon
    17. Liu Y, Liu J, Xia H, et al. Neutralizing Activity of BNT162b2-Elicited Serum. 2021. NEJM. DOI: 10.1056/NEJMc2102017
    18. *Madhi SA, Ballie V, Cutland CL, et al. Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa. MedRxiv 2021. doi: https://doi.org/10.1101/2021.02.10.21251247external icon
    19. Novavax COVID-19 Vaccine Demonstrates 89.3% Efficacy in UK Phase 3 Trial | Novavax Inc. ? IR Siteexternal icon
    20. Johnson & Johnson COVID-19 Vaccine Authorized by U.S. FDA For Emergency Use | Johnson & Johnson (jnj.com)external icon
    21. *Deng X, Garcia-Knight MA, Khalid MM, et al. Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation. MedRxiv 2021. doi: https://doi.org/10.1101/2021.03.07.21252647external icon
    22. Xie X, Liu Y, Liu J, et al. SARS-CoV-2 spike E484K mutation reduces antibody neutralisation. The Lancet 2021. doi: https://doi.org/10.1016/S2666-5247(21)00068-9external icon
    23. Garcia-Beltran W, Lam EC, St. Denis K, et al. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell 2021. doi: https://doi.org/10.1016/j.cell.2021.03.013external icon
    24. *Annavajhala MK, Mohri H, Zucker JE, at al. A Novel SARS-CoV-2 Variant of Concern, B.1.526, Identified in New York. MedRxiv 2021. DOI: 10.1101/2021.02.23.21252259external icon

    *Non-peer-reviewed

    Related Resources
    ...
    https://www.cdc.gov/coronavirus/2019...iant-info.html
    "Safety and security don't just happen, they are the result of collective consensus and public investment. We owe our children, the most vulnerable citizens in our society, a life free of violence and fear."
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  • #2
    ****, me who by the mad cow crisis discovered this:
    https://artfl-project.uchicago.edu/c...res-dautrefois

    So the importance of definitions when you want to be a little serious: between noticing that the C.D.C, which has not yet accepted the term syndeme, wants to put some order in the words:

    I smile .

    Are we going to start talking seriously this time, or?

    Comment


    • bertrand789
      bertrand789 commented
      Editing a comment
      we are waiting for the two definitions which will define the sequences:

      - what about the definition of long covid or the consequences of vaccines

      - what about the definition of covid, professional disease
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