SARS-CoV-2 Variant Classifications and Definitions

SARS-CoV-2 Variant Classifications and Definitions
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Key point –

SARS-CoV-2 Variant Classifications and Definitions

  • Genetic lineages of SARS-CoV-2 have been emerging and circulating the world since the beginning of the COVID-19 pandemic.
  • SARS-CoV-2 genetic lineages in the United States are routinely monitored through epidemiological investigations, virus genetic sequence-based surveillance, and laboratory studies.
  • The US government SARS-CoV-2 Interagency Group (SIG) added a new class of SARS-CoV-2 variants designated as Variants Being Monitored.
    • This class includes variants with substitutions of concern, including previously designated Variants of Interest (VOIs) or Variants of Concern (VOCs), that is no longer detected or are circulating at very low levels in the United States, and as such, do not pose a significant or imminent risk to public health in the United States.
  • The SIG Variant classification scheme defines four classes of SARS-CoV-2 variants:
  • Alpha (B.1.1.7, Q.1-Q.8), Beta (B.1.351, B.1.351.2, B.1.351.3), and Gamma (P.1, P.1.1, P.1.2) have been downgraded from Variants of Concern to Variants Being Monitored based on significant and sustained reduction in national and regional proportions.
  • Eta (B.1.525), Iota (B.1.526), Kappa (B.1.617.1), and B.1.617.3 have been downgraded from Variants of Interest to Variants Being Monitored based on significant and sustained reduction in national and regional proportions.
  • Additional Variants Being Monitored include Epsilon (B.1.427 and B.1.429) and Zeta (P.2) based on their previous classification as Variants of Concern or Variants of Interest.
  • To date, no variants of high consequence have been identified in the United States.
  • Due to the increasing number of sublineages that are associated with Alpha, Delta, and Gamma, unless otherwise specified, CDC will refer to the sublineages collectively as Q sublineages (Alpha), AY sublineages (Delta), and P.1 sublineages (Gamma).
  • Vaccines approved and authorized for use in the United States are effective against these variants and effective therapeutics are available. CDC continues to monitor all variants circulating within the United States.
  • CDC will no longer provide unweighted proportions of substitutions of concern for SARS-CoV-2 monoclonal antibody therapies. Clinicians seeking advice on the use of monoclonal antibody products authorized for emergency use in the United States for the treatment of SARS-CoV-2 should consult the NIH COVID-19 Treatment Guidelinesexternal icon and the FDA Fact Sheets for Health Care Providers for the three anti-SARS-CoV-2 monoclonal antibody treatments with FDA Emergency Use Authorization (EUA) for the treatment of COVID-19:
Delta Variant (SARS-CoV-2 Variant Classifications and Definitions)

The Delta variant causes more infections and spreads faster than earlier forms of the virus that causes COVID-19. It might cause more severe illness than previous strains in unvaccinated people.

  • Vaccines continue to reduce a person’s risk of contracting the virus that causes COVID-19, including this variant.
  • Vaccines continue to be highly effective at preventing hospitalization and death, including against this variant.
  • Fully vaccinated people with breakthrough infections from this variant appear to be infectious for a shorter period.
  • Get vaccinated and wear masks indoors in public spaces to reduce the spread of this variant.

Viruses like SARS-CoV-2 continuously evolve as mistakes (genetic mutations) occur during the replication of the genome. A lineage is a genetically closely related group of virus variants derived from a common ancestor.  A variant has one or more mutations that differentiate it from other variants of the SARS-CoV-2 viruses. 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. 

SARS-CoV-2 Variant Classifications and Definitions

How Variants Are Classified 

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. 

The SIG meets regularly to evaluate the risk posed by SARS-CoV-2 variants circulating in the United States and to make recommendations about the classification of variants. This evaluation is undertaken by a group of subject matter experts who assess available data, including variant proportions at the national and regional levels and the potential or known impact of the constellation of mutations on the effectiveness of medical countermeasures, the severity of disease, and ability to spread from person to person. Given the continuous evolution of SARS-CoV-2 and our understanding of the impact of variants on public health, variants may be reclassified based on their attributes and prevalence in the United States.  

  • Variants Being Monitored (VBM) – View current VBM in the United States that continue to be monitored and characterized by federal agencies 
  • A variant of Interest (VOI) – Currently, there are no SARS-CoV-2 variants that are designated as Variants of Interest 
  • A variant of Concern (VOC) – View current VOC in the United States that are being closely monitored and characterized by federal agencies 
  • A variant of High Consequence (VOHC) – Currently there are no SARS-CoV-2 variants that rise to the level of high consequence 

SARS-CoV-2 Variant Classifications and Definitions

Notes: Each variant classification includes the possible attributes of lower classes (e.g., 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 Organization (WHO)external icon also classifies variant viruses as Variants of Concern and Variants of Interest; US classifications may differ from those of WHO because the impact of variants may differ by location. To assist with public discussions of variants, WHO proposed using labels consisting of the Greek Alphabet, e.g., 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. 

 

Variants Being Monitored (VBM)

SARS-CoV-2 Variant Classifications and Definitions

CDC monitors all variants circulating in the United States. The variants designated as Variants Being Monitored include variants for which data are indicating a potential or clear impact on approved or authorized medical countermeasures or that has been associated with more severe disease or increased transmission but are no longer detected or are circulating at very low levels in the United States, and as such, do not pose a significant and imminent risk to public health in the United States.

A Variant of Interest or a Variant of Concern may be downgraded to this list when there has been a significant and sustained reduction in its national and regional proportions over time, or other evidence indicates that a variant does not pose a significant risk to public health in the United States.   

These variants continue to be closely monitored to identify changes in their proportions and new data is continually being analyzed. If the data indicate that a VBM warrants more concern, the classification will be changed based on the SIG assessment of the attributes of the variant and the risk to public health in the United States.  

Variants Being Monitored
WHO Label  Pango Lineage Date of Designation
Alpha B.1.1.7Q.1-Q.8 VOC:  December 29, 2020 VBM:  September 21, 2021
Beta B.1.351B.1.351.2, B.1.351.3 VOC:  December 29, 2020 VBM:  September 21, 2021
Gamma P.1P.1.1, P.1.2 VOC:  December 29, 2020 VBM:  September 21, 2021
Epsilon B.1.427
B.1.429
VOC:  March 19, 2021 VOI:  February 26, 2021
VOI: June 29, 2021
VBM: September 21, 2021
Eta B.1.525 VOI:  February 26, 2021 VBM:  September 21, 2021
Iota B.1.526 VOI:  February 26, 2021 VBM:  September 21, 2021
Kappa B.1.617.1 VOI:  May 7, 2021 VBM:  September 21, 2021
N/A B.1.617.3 VOI:  May 7, 2021 VBM:  September 21, 2021
Zeta P.2 VOI:  February 26, 2021 VBM:  September 21, 2021
Mu B.1.621B.1.621.1 VBM: September 21, 2021

A variant of Interest (VOI)

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 are predicted to affect the 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 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 approved or authorized vaccines offer protection.

A variant of Concern (VOC)

A variant for which there is evidence of an increase in transmissibility, more severe disease (e.g., increased hospitalizations or deaths), a 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 classes of therapies
    • Evidence of significantly 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 are listed below. This table will be updated when a new variant of concern is identified.

Characteristics of Selected SARS-CoV-2 Variants

WHO Label: Delta

Pango Lineage: B.1.617.2 and all AY sublineages (Pango lineage eternal icon)a

Spike Protein SubstitutionsT19R, (V70F*), T95I, G142D, E156-, F157-, R158G, (A222V*), (W258L*), (K417N*), L452R, T478K, D614G, P681R, D950N 

Next strain clade (Nextstrainexternal icon)b: 21A/S:478K

First Identified: India

Attributes:

  • Increased transmissibility29 
  • Potential reduction in neutralization by some EUA monoclonal antibody treatments7, 14 
  • Potential reduction in neutralization by post-vaccination sera21 

A variant of High Consequence (VOHC)

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 diagnostic test targets
    • Evidence to suggest a significant reduction in vaccine effectiveness, a disproportionately high number of infections in vaccinated persons, 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 the transmission, and recommendations to update treatments and vaccines. 

 

 

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