Variant of concern

The term variant of concern (VOC) for SARS-CoV-2, which causes COVID-19, is a category used for variants of the virus where mutations in their spike protein receptor binding domain (RBD) substantially increase binding affinity (e.g., N501Y) in RBD-hACE2 complex (genetic data), while also being linked to rapid spread in human populations (epidemiological data).[1]

SARS-CoV-2, the virus that causes COVID-19

Before this, an emerging variant may have been labeled a variant of interest,[2] or in some countries a variant under investigation.[3] During or after fuller assessment as a variant of concern the variant is typically assigned to a lineage in the PANGOLIN nomenclature system[4] and to clades in the Nextstrain[5] and GISAID[6] systems.

During the COVID-19 pandemic, the SARS-CoV-2 virus has been observed to mutate, with certain combinations of specific point mutations proving to be more concerning than others.[7] This was principally for reasons of transmissibility and virulence, and also with regard to the possible emergence of escape mutations.

Criteria

Several national and international health organisations (e.g. Centers for Disease Control and Prevention (CDC) (US), Public Health England (PHE) and the COVID-19 Genomics UK Consortium for the UK, and the Canadian COVID Genomics Network (CanCOGeN)) use some or all of the following criteria to assess variants:[8][9]

  • Increased transmissibility
  • Increased morbidity
  • Increased mortality
  • Increased risk of "long COVID"
  • Ability to evade detection by diagnostic tests
  • Decreased susceptibility to antiviral drugs (if and when such drugs are available)
  • Decreased susceptibility to neutralizing antibodies, either therapeutic (e.g., convalescent plasma or monoclonal antibodies) or in laboratory experiments
  • Ability to evade natural immunity (e.g., causing reinfections)
  • Ability to infect vaccinated individuals
  • Increased risk of particular conditions such as multisystem inflammatory syndrome or long-haul COVID.
  • Increased affinity for particular demographic or clinical groups, such as children or immunocompromised individuals.

Variants that appear to meet one or more of these criteria may be labeled "variants of interest" or "variants under investigation" ('VUI') pending verification and validation of these properties. Once validated, variants of interest /VUI may be renamed "variants of concern" by monitoring organizations, such as the CDC.[3][7][10] A related category is "variant of high consequence", used by the CDC if there is clear evidence that the effectiveness of prevention or intervention measures for a particular variant is substantially reduced.[11]

Classifications by country

World Health Organization

The WHO maintains a list of variants of global concern.[2] On 26 November 2021, the WHO added a fifth variant of concern, the Omicron variant, previously known as B.1.1.529.[12] Omicron joins the Alpha, Beta, Gamma, and Delta variants.

Africa

The NICD in South Africa maintains a list of variants and testing facilities locally in collaboration with KRISP.[13][14]

Europe

As of November 2021, the European Centre for Disease Prevention and Control declared four variants to be 'variants of concern': Beta, Gamma, Delta, and B.1.1.529 (named 'Omicron' after the reference was updated); Mu, Lambda and AY.4.2 were named as Variants of Interest (VOI), while there were 9 'Variants under monitoring'. 25 variants were described as 'de-escalated'.[15]

United Kingdom

As of November 2021, the United Kingdom has fifteen variants on its 'watch list', 4 with 'VOC' status and 11 rated as 'VUI'. Those designated 'VOC' were Alpha, Beta, Gamma, and Delta. In early December 2021, Omicron was added to the VOCs. Among the Variants under investigation is 'VUI-21OCT-01/ A.Y 4.2'.[16]

North America

Canada (via health-infobase.canada.ca)[17] and the United States (via the CDC)[18] also maintain lists of variants of concern. As of early December, Canada was monitoring five variants of concern: Alpha, Beta, Gamma, Delta, and Omicron, while the US was monitoring two: Delta and Omicron.[19]

References
  1. Shahhosseini, Nariman; Babuadze, George (Giorgi); Wong, Gary; Kobinger, Gary P. (May 2021). "Mutation Signatures and In Silico Docking of Novel SARS-CoV-2 Variants of Concern". Microorganisms. 9 (5): 926. doi:10.3390/microorganisms9050926. PMC 8146828. PMID 33925854.
  2. "Tracking SARS-CoV-2 variants". www.who.int. Retrieved 28 November 2021.
  3. "Variants: distribution of cases data". GOV.UK. 28 January 2021. At "Differences between a Variant of Concern and Variant Under Investigation". Retrieved 19 February 2021. SARS-CoV-2 variants, if considered to have concerning epidemiological, immunological, or pathogenic properties, are raised for formal investigation. At this point they are designated Variant Under Investigation (VUI) with a year, month, and number. Following a risk assessment with the relevant expert committee, they may be designated Variant of Concern (VOC)
  4. Rambaut, A.; Holmes, E.C.; O’Toole, Á.; et al. (2020). "A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology". Nature Microbiology. 5 (11): 1403–1407. doi:10.1038/s41564-020-0770-5. PMC 7610519. PMID 32669681. S2CID 220544096.
  5. Bedford, Trevor; Hodcroft, Emma B; Neher, Richard A (6 January 2021). "Updated Nextstrain SARS-CoV-2 clade naming strategy". nextstrain.org/blog. Retrieved 19 January 2021.
  6. "clade tree (from 'Clade and lineage nomenclature')". www.gisaid.org. 4 July 2020. Retrieved 7 January 2021.
  7. Griffiths, Emma; Tanner, Jennifer; Knox, Natalie; Hsiao, Will; Van Domselaar, Gary (15 January 2021). "CanCOGeN Interim Recommendations for Naming, Identifying, and Reporting SARS-CoV-2 Variants of Concern" (PDF). CanCOGeN (nccid.ca). Retrieved 25 February 2021.
  8. Lucey, Daniel R. (2 February 2021). "COVID "Mega-variant" and eight criteria for a template to assess all variants". Science Speaks: Global ID News. Retrieved 5 June 2022.
  9. CDC (11 February 2020). "Emerging SARS-CoV-2 Variants". Centers for Disease Control and Prevention. Retrieved 4 January 2021. This article incorporates text from this source, which is in the public domain.
  10. Investigation of SARS-CoV-2 variants of concern in EnglandTechnical briefing 6 13 February 2021 (See section: Nomenclature of variants in the UK, P.3) assets.publishing.service.gov.uk, accessed 27 February 2021
  11. CDC (11 February 2020). "Cases, Data, and Surveillance". Centers for Disease Control and Prevention. Retrieved 16 March 2021.
  12. "Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern". World Health Organization. Retrieved 28 November 2021.
  13. "New COVID-19 variant detected in South Africa". NICD. 25 November 2021. Retrieved 29 November 2021.
  14. "Kwazulu-Natal Research Innovation and Sequencing Platform". www.krisp.org.za. Retrieved 29 November 2021.
  15. SARS-CoV-2 variants of concern 26 November 2021 www.ecdc.europa.eu accessed 27 November 2021
  16. Variants of concern or under investigation: data up to 24 November 2021 Updated 26 November 2021, www.gov.uk, accessed 27 November 2021
  17. COVID-19 daily epidemiology update 12 May 2021 health-infobase.canada.ca accessed 13 May 2021
  18. "SARS-CoV-2 Variant Classifications and Definitions". Centers for Disease Control and Prevention. 11 February 2020. Retrieved 30 April 2021.
  19. SARS-CoV-2 Variant Classifications and Definitions Dec. 1, 2021 www.cdc.gov, accessed December 7, 2021
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