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Tracking SARS-CoV-2 variants

Tracking SARS-CoV-2 variants

 

All viruses, including SARS-CoV-2, the virus that causes COVID-19, change over time. Most changes have little to no impact on the virus’ properties. However, some changes may affect the virus’s properties, such as how easily it spreads, the associated disease severity, or the performance of vaccines, therapeutic medicines, diagnostic tools, or other public health and social measures. 

WHO, in collaboration with partners, expert networks, national authorities, institutions and researchers have been monitoring and assessing the evolution of SARS-CoV-2 since January 2020. During late 2020, the emergence of variants that posed an increased risk to global public health prompted the characterisation of specific Variants of Interest (VOIs) and Variants of Concern (VOCs), in order to prioritise global monitoring and research, and ultimately to inform the ongoing response to the COVID-19 pandemic.  

WHO and its international networks of experts are monitoring changes to the virus so that if significant amino acid substitutions are identified, we can inform countries and the public about any changes that may be needed to respond to the variant, and prevent its spread. Globally, systems have been established and are being strengthened to detect “signals” of potential VOIs or VOCs and assess these based on the risk posed to global public health. National authorities may choose to designate other variants of local interest/concern. 

Reducing transmission through established and proven disease control methods/measures, as well as avoiding introductions into animal populations, are crucial aspects of the global strategy to reduce the occurrence of mutations that have negative public health implications.

Current strategies and measures recommended by WHO continue to work against virus variants identified since the start of the pandemic. Evidence from multiple countries with extensive transmission of VOCs has indicated that public health and social measures (PHSM), including infection prevention and control (IPC) measures, have been effective in reducing COVID-19 cases, hospitalizations and deaths. National and local authorities are encouraged to continue strengthening existing PHSM and IPC measures. Authorities are also encouraged to strengthen surveillance and sequencing capacities and apply a systematic approach to provide a representative indication of the extent of transmission of SARS-CoV-2 variants based on the local context, and to detect unusual epidemiological events.

This content is last updated on 29 November 2022.

Naming SARS-CoV-2 variants

The established nomenclature systems for naming and tracking SARS-CoV-2 genetic lineages by GISAID, Nextstrain and Pango are currently and will remain in use by scientists and in scientific research. To assist with public discussions of variants, WHO convened a group of scientists from the WHO Virus Evolution Working Group (now called the Technical Advisory Group on Virus Evolution), the WHO COVID-19 reference laboratory network, representatives from GISAID, Nextstrain, Pango and additional experts in virological, microbial nomenclature and communication from several countries and agencies to consider easy-to-pronounce and non-stigmatising labels for VOI and VOC. At the present time, this expert group convened by WHO has recommended using letters of the Greek Alphabet, i.e., Alpha, Beta, Gamma, Delta which will be easier and more practical to be discussed by non-scientific audiences. When using this naming scheme and referring to the genomic sequence of SARS-CoV-2 identified from the first cases (December 2019), the term ‘index virus’ should be used.

 

SARS-CoV-2 variants, working definitions and actions taken

Given the continuous evolution of the virus that leads to SARS-CoV-2 and the constant developments in our understanding of the impacts of variants, these working definitions may be periodically adjusted. When necessary, variants not otherwise meeting all criteria outlined in these definitions may be designated as VOCs/VOIs/VUMs, and those posing a diminishing risk relative to other circulating variants may be reclassified, in consultation with the Technical Advisory Group on Virus Evolution (formally called the Virus Evolution Working Group).  

Updates on SARS-CoV-2 classifications, the geographic distribution of VOCs, and summaries of their phenotypic characteristics (transmissibility, disease severity, risk of reinfection, and impacts on diagnostics and vaccine performance) based on published studies, are regularly provided in the WHO Weekly Epidemiological Updates. 

Variants of concern (VOC)

Working definition:

A SARS-CoV-2 variant that meets the definition of a VOI (see below) and, through a comparative assessment, has been demonstrated to be associated with one or more of the following changes at a degree of global public health significance: 

  • Increase in transmissibility or detrimental change in COVID-19 epidemiology; OR
  • Increase in virulence or change in clinical disease presentation; OR
  • Decrease in effectiveness of public health and social measures or available diagnostics, vaccines, therapeutics.  

 

Currently circulating variants of concern (VOCs):

WHO label 

 Pango  
lineage•		 GISAID clade Nextstrain clade  Additional amino acid changes monitored° Earliest documented  
samples 		 Date of designation 
Omicron* B.1.1.529 GR/484A

 

21K, 21L, 21M, 22A, 22B, 22C, 22D

 

+S:R346K

+S:L452X

+S:F486V

 Multiple countries, Nov-2021

VUM: 24-Nov-2021

VOC: 26-Nov-2021

* Includes BA.1, BA.2, BA.3, BA.4, BA.5 and descendent lineages. It also includes BA.1/BA.2 circulating recombinant forms such as XE. WHO emphasizes that these descendant lineages should be monitored as distinct lineages by public health authorities and comparative assessments of their virus characteristics should be undertaken.

The full list of Pango lineages can be found here: https://cov-lineages.org/lineage_list.html; for FAQ, visit: https://www.pango.network/faqs/

° Only found in a subset of sequences

Previously circulating VOCs:

WHO label 

 Pango  
lineage•		 GISAID clade Nextstrain clade  Earliest documented  
samples 		 Date of designation 

Alpha 

B.1.1.7 

GRY

20I (V1) 

United Kingdom,  
Sep-2020 

VOC: 18-Dec-2020

Previous VOC: 09-Mar-2022
Beta 

B.1.351 

 GH/501Y.V2  20H (V2) South Africa,  
May-2020 

VOC: 18-Dec-2020

Previous VOC: 09-Mar-2022
Gamma 

P.1 

 GR/501Y.V3  20J (V3) Brazil,  
Nov-2020 

VOC: 11-Jan-2021

Previous VOC: 09-Mar-2022
Delta  B.1.617.2 G/478K.V1 21A, 21I, 21J India,  
Oct-2020 

VOI: 4-Apr-2021 
VOC: 11-May-2021

Previous VOC: 7-Jun-2022

 

*Includes all descendent lineages.

22 February 2022
Statement

Statement on Omicron sublineage BA.2

VOC-defining constellation of mutations

For each variant, the profile of amino acid changes compared to the index virus (GISAID Accession ID: EPI_ISL_402124) was created using outbreak.info and covariants.org.

VOC profiles of Spike amino acid changes

VOC profiles of amino acid changes in other proteins

Actions taken by WHO and Member States: 

Primary actions by WHO for a potential VOC: 

  • Comparative assessment of variant characteristics and public health risks by WHO and the Technical advisory Group on Virus Evolution.

  • If determined necessary, coordinate additional laboratory investigations with Member States and partners. 

  • Communicate new designations and findings with Member States and public through established mechanisms.  

  • Evaluate WHO guidance through established WHO mechanisms and update, if necessary.  

  • Facilitate sharing of virus isolates via WHO Biohub

 

Primary actions by a Member State, if a VOC is identified: 

  • Submit complete genome sequences and associated metadata to a publicly available database, such as GISAID.
  • Report initial cases/clusters associated with VOC infection to WHO through the IHR mechanism. 
  • Where capacity exists and in coordination with the international community, perform field investigations and laboratory assessments to improve understanding of the potential impacts of the VOC on COVID-19 epidemiology, severity, effectiveness of public health and social measures, diagnostic methods, immune responses, antibody neutralization, or other relevant characteristics. 
  • Share virus isolates via WHO Biohub and/or other virus sharing initiatives 

 

 

Omicron subvariants under monitoring (as of 29 November 2022)

 

Latest VOCs have largely replaced other co-circulating SARS-CoV-2 variants. Delta reached almost 90% of all viral sequences submitted on GISAID by October 2021, and Omicron is currently the dominant variant circulating globally, accounting for >98% of viral sequences shared on GISAID after February 2022. As transmission of these VOCs has been sustained, this has led to significant intra-VOC evolution. Since its designation as a VOC by WHO on 26 November 2021, viruses part of the Omicron complex have continued to evolve, leading to descendent lineages with different genetic constellations of mutations. Each constellation may or may not differ in the public health risk it poses, and each lineage that includes substitutions in key sites may need further investigation to assess whether its characteristics diverge or not from those that define the variant of concern they stem from.

In light of the widespread transmission of the Omicron VOC across the globe and the subsequent expected increased viral diversity, WHO has added a new category to its variant tracking system, termed “Omicron subvariants under monitoring" to signal to public health authorities globally, which VOC lineages may require prioritized attention and monitoring. The main objective of this category is to investigate if these lineages may pose an additional threat to global public health as compared to other circulating viruses. If any of these lineages is proven to have distinct characteristics as compared to the original VOC it belongs to, the TAG-VE will convene and may advice WHO to give it a separate WHO label.

 

Working definition:

A variant that, according to phylogenetic analysis, belongs to a currently circulating VOC

AND

shows signals of transmission advantage compared to other circulating VOC lineages

AND

has additional amino acid changes that are known or suspected to confer the observed change in epidemiology and fitness advantage as compared to other circulating variants.

Omicron subvariants under monitoring (as of 20 November 2022)

Pango lineage# (+ mutation) GISAID clade Nextstrain  
clade 		 Relationship to circulating VOC lineages Spike genetic features Earliest documented  
samples 
BA.5** (+R346X or +K444X or +V445X or +N450D or +N460X)

GRA

 22B, 22E

BA.5 sublineages (e.g. BF.7, BF.14, BQ.1, BQ.1.1)

BA.5 + one or more of these mutations:

S:R346X, S:K444X, S:V445X , S:N450D or S:N460X

07-02-2022

BA.2.75***

GRA

22D

BA.2 sublineage

BA.2.75: BA.2 + S:K147E, S:W152R, S:F157L, S:I210V, S:G257S, S:D339H, S:G446S, S:N460K, S:Q493R reversion


BA.2.75.2: BA.2.75 + S:R346T, S:F486S, S:D1199N

31-12-2021
BA.4.6 GRA 22A BA.4 sublineage BA.4+S:R346T, S:N658S 20-07-2020
XBB$   - Recombinant of BA.2.10.1 and BA.2.75 sublineages, i.e. BJ1 and BM.1.1.1, with a breakpoint in S1 BA.2+ S:V83A, S:Y144-, S:H146Q, S:Q183E, S:V213E, S:G252V, S:G339H, S:R346T, S:L368I, S:V445P, S:G446S, S:N460K, S:F486S, S:F490S 13-08-2022
BA.2.3.20§ GRA 21L BA.2 sublineage BA.2+ S:M153T, S:N164K, S:H245N, S:G257D, S:K444R, S:N450D, S:L452M, S:N460K, S:E484R 15-08-2022

 

* these subvariants are tracked under Omicron unless/until sufficient evidence arises that the virus characteristics are substantially different from what is known about the VOC they belong to. If this evidence arises, WHO will decide, in consultation with the TAG-VE, if designation of the emerging variant warrants a separate WHO label. 

# includes descendent lineages

** additional mutations outside of the spike protein: N:G30-, N:S33F, N:E136D, ORF1a:Q556K, ORF1a:L3829F, ORF1b:Y264H, ORF1b:M1156I, ORF9b:P10F, ORF9b:D16G, ORF9b:M26-, ORF9b:A29I, ORF9b:V30L.

*** additional mutation outside the spike protein: ORF1a:S1221L, ORF1a:P1640S, ORF1a:N4060S; ORF1b:G662S; E:T11A

$ additional mutations outside of the spike protein: E:T11A, ORF1a:K47R, ORF1b:G662S, ORF1b:S959P, ORF8:G8*

§ additional mutations outside of the spike protein: ORF1a:T727I, ORF1a:I1714T, ORF1a:M2169V, ORF1a:T2174I, ORF1a:T2648I, ORF1a:A2909V, ORF1a:Q3922R, ORF1b:T1404M, ORF3a:L140F, ORF9b:D89E

 


 

Primary actions by WHO for a VOC-subvariant under monitoring

  • Review global epidemiology of VOC-subvariant under monitoring
  • Monitor and track global spread of VOC-subvariant under monitoring
  • If determined necessary, coordinate additional laboratory investigations with Member States and partners
  • Facilitate sharing of virus isolates via WHO Biohub
  • In consultation with the TAG-VE, review characteristics of the VOC-subvariant under monitoring as compared to the VOC it belongs to, and provide a separate label in case those are substantially different.

Primary actions by a Member State, if a VOC-subvariant under monitoring is identified:

  • Inform WHO through established WHO Country or Regional Office reporting channels with supporting information.
  • Submit complete genome sequences and associated metadata to a publicly available database, such as GISAID. 
  • Perform field investigations to improve understanding of the potential impacts of the VOC-subvariant under monitoring on COVID-19 epidemiology, severity, effectiveness of public health and social measures, or other relevant characteristics. 
  • Perform laboratory assessments according to capacity or contact WHO for support to conduct laboratory assessments on the impact of the VOC-subvariant under monitoring on relevant virus characteristics. 
  • Share virus isolates via WHO Biohub and/or other virus sharing initiatives.

 

 

Variants of interest (VOI)

Working definition

A SARS-CoV-2 variant : 

  • with genetic changes that are predicted or known to affect virus characteristics such as transmissibility, disease severity, immune escape, diagnostic or therapeutic escape; AND 
  • Identified to cause significant community transmission or multiple COVID-19 clusters, in multiple countries with increasing relative prevalence alongside increasing number of cases over time, or other apparent epidemiological impacts to suggest an emerging risk to global public health.  

There is no currently circulating variant of interest (VOI).

Previously circulating VOIs

 

Actions taken by WHO and Member States: 

Primary actions by WHO for a potential VOI: 

  • Comparative assessment of variant characteristics and public health risks by WHO. 

  • If determined necessary, coordinated laboratory investigations with Member States and partners.  

  • Review global epidemiology of VOI. 

  • Monitor and track global spread of VOI 

  • Facilitate sharing of virus isolates via WHO Biohub.

 

Primary actions by a Member State, if a new potential VOI is identified: 

  • Inform WHO through established WHO Country or Regional Office reporting channels with supporting information about VOI-associated cases (person, place, time, clinical and other relevant characteristics). 

  • Submit complete genome sequences and associated metadata to a publicly available database, such as GISAID. 

  • Perform field investigations to improve understanding of the potential impacts of the VOI on COVID-19 epidemiology, severity, effectiveness of public health and social measures, or other relevant characteristics. 

  • Perform laboratory assessments according to capacity or contact WHO for support to conduct laboratory assessments on the impact of the VOI on relevant topics. 

  • Share virus isolates via WHO Biohub and/or other virus sharing initiatives 

Previously circulating VOCs/ VOIs

A designated VOC or VOI which has demonstrated to no longer pose a major added risk to global public health compared to other circulating SARS-CoV-2 variants, can be designated as previously circulating VOCs or VOIs. This is undertaken through a critical expert assessment, in collaboration with the Technical Advisory Group on Virus Evolution of several criteria, such as the observed incidence/relative prevalence of variant detections among sequenced samples over time and between geographical locations, the presence/absence of other risk factors, and any ongoing impact on control measures. Member States should continue to monitor variants including previously circulating VOCs and VOIs and flag any upsurge of cases observed linked to these viruses. A designation from currently circulating VOCs and VOIs to previously circulating VOCs VOIs reflects the steep decline in circulation of the variant, but does not exclude a future upsurge of this variant.

Variants under monitoring (VUM)

Working definition 

A SARS-CoV-2 variant with genetic changes that are suspected to affect virus characteristics with some indication that it may pose a future risk, but evidence of phenotypic or epidemiological impact is currently unclear, requiring enhanced monitoring and repeat assessment pending new evidence.  

Note: It is expected that our understanding of the impacts of these variants may fast evolve, and designated Variants under Monitoring may be readily added/removed; therefore, WHO labels will not be assigned at this time. Former VOIs/VOCs may, however, be monitored for an extended period under this category, and will maintain their assigned WHO label until further notice. 

Variants under monitoring (VUMs):

There is currently no variant under monitoring

Member State Actions:

  • Enhance efforts towards a more representative picture of circulating variants in the country. Submit complete genome sequences and associated metadata to a publicly available database, such as GISAID.
  • Perform field investigations to improve understanding of the characteristics of the VUM on COVID-19 epidemiology (infectivity, neutralization, severity etc.).
  • Conduct laboratory investigations to understand the phenotypic implications of the VUM
  • Monitor spread of VUM and interaction with other circulating variants for potential to outcompeting or thrive in the presence of a known dominant VOC/VOI
  • Share virus isolates via WHO Biohub and/or other virus sharing initiatives 

WHO Actions:

  • Comparative assessment of variant characteristics and public health risks by WHO.
  • Monitor and track global spread of VUM.

Formerly monitored variants

Former VUMs, including their descendent lineages, that have been reclassified based on at least one the following criteria: (1) the variant is no longer circulating at levels of global public health significance, (2) the variant has been circulating for a long time without any impact on the overall epidemiological situation, or (3) scientific evidence demonstrates that the variant is not associated with any concerning properties.

Publications

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10 June 2021

2nd Global consultation on assessing the impact of SARS-CoV-2 Variants of Concern on Public Health Interventions

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29 March 2021

Global Consultation on a Decision Framework for Assessing the Impact of SARS-CoV-2 Variants of Concern...

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Genomic sequencing of SARS-CoV-2: a guide to implementation for maximum impact on public health
8 January 2021

Genomic sequencing of SARS-CoV-2: a guide to implementation for maximum impact on public health

Sequencing enabled the world to rapidly identify SARS-CoV-2 and develop diagnostic tests and other tools for outbreak management. Continued genome sequencing...

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SARS-CoV-2 genomic sequencing for public health goals: Interim guidance, 8 January 2021
8 January 2021

SARS-CoV-2 genomic sequencing for public health goals: Interim guidance, 8 January 2021

The growing understanding of how sequence information can contribute to improved public health is driving global investments in sequencing facilities and...

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9 August 2021

Guidance for surveillance of SARS-CoV-2 variants: Interim guidance, 9 August 2021

This document aims to describe a minimum set of surveillance activities recommended at the national level to detect and monitor SARS-CoV-2 variants. It is primarily intended for national and sub-national public health authorities and partners who support implementation of surveillance for SARS-CoV-2 variants, and complements the interim guidance on public health surveillance for COVID-19, which provides overall guidance for public health surveillance of coronavirus disease 2019 (COVID-19) in humans.