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SARS-CoV-2: WHO Designated Variants

Information and resources on SARS-CoV-2 (the virus that causes COVID-19)

WHO Greek Letter Designated Variants

Alpha
  • First Identified: 9/1/2020 - United Kingdom
  • Other Names: VOC 202012/01; 20I/501Y.V1
  • Pango: B.1.1.7
  • VOC: 12/8/2020
  • Previous VOC: 3/9/2022

Beta
  • First Identified: 12/18/2020 - South Africa
  • Other Names: 20H/501Y.V2;  501.V2; 20C/501Y.V2; VOC-202012/02
  • Pango: B.1.351
  • VOC: 12/18/2020
  • Previous VOC: 3/9/2022

Gamma
  • First Identified: 1/21/2021 - Brazil
  • Other Names: 20J/501Y.V3;  VOC-202101/02
  • Sublineage:  B.1.1.28
  • Pango: P.1
  • VOC: 1/11/2021
  • Previous VOC: 3/9/2022

Delta
  • First Identified: 3/1/2021 - India
  • Other Names: G/452R.V3; 21A/S:478K
  • Pango: B.1.617.2
  • VOI: 4/4/2021
  • VOC: 5/11/2021
  • Previous VOC: 6/7/2022

Epsilon
  • First Identified: California, USA
  • Other Names: CAL.20C; CA VUI1; 20C/S:452R
  • Pango: B.1.427/B.1.429
  • VOI: 3/5/2021
  • Previous VOI: 7/6/2021

Zeta
  • First Identified: 4/1/2020 - Rio de Janerio, Brazil
  • Other Names:
  • Sublineage:  B.1.1.28
  • Pango: P.2
  • VOI: 3/17/2021
  • Previous VOI: 7/6/2021

Eta
  • First Identified: 12/1/2020 - Nigeria
  • Other Names: VUI-202102/03; 20A/S:484K
  • Pango: B.1.525
  • VOI: 3/17/2021
  • Previous VOI: 9/20/2021

Theta
  • First Identified: 3/13/2021 - Philippines
  • Other Names: VUI-21MAR-02
  • Pango: P.3
  • VOI: 3/24/2021
  • Previous VOI: 7/6/2021

Iota
  • First Identified: 11/1/2020 - NYC, USA
  • Pango: B.1.526
  • VOI: 3/24/2021
  • Previous VOI: 9/20/2021

Kappa
  • First Identified: 10/1/2020 - India
  • Other Names: 21A/S:154K
  • Pango: B.1.617.1
  • VOI: 4/4/2021
  • Previous VOI: 9/20/2021

Lambda
  • First Identified: 8/1/2020 - Peru
  • Pango: C.37
  • VOI: 6/14/2021
  • Previous VOI: 3/9/2022

Mu
  • First Identified: 1/1/2021 - Colombia
  • Pango: B.1.621
  • VOI: 8/30/2021
  • Previous VOI: 3/9/2022

Omicron
  • First Identified: 11/26/2021 - South Africa
  • Other Names: BA.1
  • Pango: B.1.1.529
  • VUM: 11/24/2021
  • VOC: 11/26/2021
  • Previous VOC: 3/15/2023

WHO Variant Monitoring

WHO SARS-CoV-2 Variant Tracking
Updated working definitions and primary actions for SARS-CoV-2 variants
15 March 2023 | Technical Report

On 15 March 2023, WHO announced that, going forward, the Greek letters will only be assigned to VOCs, while VOIs will be referred to using established scientific nomenclature systems such as those used by Nextstrain and Pango (e.g. XBB.1.5/23A for the latest VOI). WHO and TAGVE will undertake regular risk assessments for both VOIs and VOCs.

Variant Under Monitoring (VUM)
  • A SARS-CoV-2 variant with genetic changes that are suspected to affect virus characteristics and early signals of growth advantage relative to other circulating variants (e.g. growth advantage which can occur globally or in only one WHO region), but for which evidence of phenotypic or epidemiological impact remains unclear, requiring enhanced monitoring and reassessment pending new evidence
Variant of Interest (VOI)
  • A SARS-CoV-2 variant with genetic changes that are predicted or known to affect virus characteristics such as transmissibility, virulence, antibody evasion, susceptibility to therapeutics and detectability; AND
  • Identified to have a growth advantage over other circulating variants in more than one WHO region with increasing relative prevalence alongside increasing number of casesover time, or other apparent epidemiological impacts to suggest an emerging risk to global public health.
Variant of Concern (VOC)

A SARS-CoV-2 variant that meets the definition of a VOI (see above) and, through a risk assessment, conducted by WHO TAG-VE, and determined to be associated with a moderate or high level of confidence, meets at least one of the following criteria when compared with other variants:

  • Detrimental change in clinical disease severity; OR
  • Change in COVID-19 epidemiology causing substantial impact on the ability of health systems to provide care to patients with COVID-19 or other illnesses and therefore requiring major public health interventions; OR
  • Significant decrease in the effectiveness of available vaccines in protecting against severe disease.

WHO Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE)

XBB.1.16 Initial Risk Assessment
17 April 2023

XBB.1.16 is a descendent lineage of XBB, a recombinant of two BA.2 descendent lineages. XBB.1.16 was first reported on 09 January 2023, and designated a variant under monitoring (VUM) on 22 March 2023. On 17 April 2023, XBB.1.16 was designated a variant of interest (VOI). XBB.1.16 has a similar genetic profile as the VOI XBB.1.5, with the additional E180V and K478R amino acid mutations in the spike protein compared to their parent XBB.1.

As of 17 April 2023, 3648 sequences of the Omicron XBB.1.16 variant have been reported from 33 countries (GISAID, XBB.1.16 searched using variant defining nucleotide mutations T12730A, T28297C, A28447G). The majority of the XBB.1.16 sequences are from India (63.4%, 2314 sequences). The other countries with at least 50 sequences include the United States of America (10.9%, 396 sequences), Singapore (6.9%, 250 sequences), Australia (3.9%, 143 sequences), Canada (2.6%, 94 sequences), Brunei (2.4%, 89 sequences), Japan (2.0%, 73 sequences) and the United Kingdom (2.1%, 75 sequences).

Globally, there has been a weekly rise in the prevalence of XBB.1.16. During epidemiological week 13 (27 March to 2 April 2023), the global prevalence of XBB.1.16 was 4.15%, an increase from 4 weeks prior (epidemiological week 9, 27 February to 5 March 2023), when the global prevalence was 0.52%.

  Indicator Level of Risk Level of Confidence
Growth Advantage

Comparing the month of February and the month of March 2023 in India, the proportion of XBB1.16 relative to other circulating variants rose from 15.3% (137/895) to 58.6% (2,130/3,636). Similarly for countries with more than 100
sequences, the prevalence of XBB.1.16 rose from 0.04 to 1.09 for the United States of America (USA), 1.2% (12/992) to 11.6% (223/1,929) for Singapore, and 0.07% (2/3,331) to 3.7% (154/4,180) for Australia.

From WHO’s internal variant growth rate analysis, similarly used by the UKHSA, XBB.1 family of variants, which includes XBB.1.16, have the fastest growth over
other circulating variants in AMRO, EURO, SEARO and WPRO. US CDC Nowcast model-based projections predict a rise of the XBB.1.16 variant to 7.2% (95% predictive interval 4.5- 1.3%) by 15 Apr 20236.

Nextstrain has designated XBB.1.16 a new clade 23B based on a criteria of “>0.05 per day growth in frequency and >5% regional frequency”, whereby from their
estimates XBB.1.16 represented ~10% of all sequences collected mid-March in Asia, had a simple logistical growth rate advantage of ~9% in all of Asia, and relative growth against all of XBB* variants of ~5% in India.

Moderate High
Antibody Escape

Similar to XBB.1 and XBB.1.5, XBB.1.16 neutralization assays have demonstrated resistance to BA.2 and BA.5 breakthrough infection sera.

The sensitivity of XBB.1.16 to convalescent sera of XBB.1-infected hamsters was comparable to those of XBB.1 and XBB.1.5, which points at a similar ability of these variants to evade immunity.

Moderate Low
Severity and Clinical Considerations

An analysis of infections from India did not report any differences in hospitalization and oxygen requirement for XBB.1.16 as compared to other circulating lineages (Dr. Rajesh Karyakarte’s, BJ Government Medical College, Pune).

In terms of clinical considerations, there has been a slight rise in bed occupancy in some states in India (2-4%). However, these levels are much lower compared to the level recorded during the Delta wave or Omicron BA.1/BA.2 wave.

Disease severity is not higher compared to previously circulating variants. In India, >70% of the population have received a booster vaccine dose.

The antiviral sotrovimab exhibits antiviral activity against XBB.1.16, similar to other XBB subvariants.

Low Moderate

Overall Risk Assessment

 

Low

Based on its genetic features, immune escape characteristics and growth rate estimates, XBB.1.16 may spread globally and drive an increase in case incidence.

From reports from India and other countries, no early signals of increases in severity have been observed. As XBB.1.16 has spread to 33 countries, disease severity is being monitored carefully.

Taken together, available evidence does not suggest that XBB.1.16 has additional public health risks relative to the other currently circulating Omicron descendent lineages.

XBB.1.5 Updated Risk Assessment
24 February 2023

XBB.1.5 is a descendent lineage of XBB, which is a recombinant of two BA.2 descendent lineages.

From 22 October 2022 to 21 February 2023, 45,193 sequences of the Omicron XBB.1.5 variant have been made available from 74 countries. Most of these sequences are from the United States of America (72.2%). The other countries include the United Kingdom (7.3%), Canada (5.0%), Germany (2.7%), Austria (1.8%). Denmark (1.1%), and France (1.0%).

Based on its genetic characteristics and available growth rate estimates, XBB.1.5 is likely to further contribute to increases in case incidence globally. There is high-strength of evidence for increased risk of transmission and moderate-strength of evidence for immune escape. The number of cases associated with XBB.1.5 is still low in many countries, and from reports by several countries, no early signals of changes or increases in severity have been observed. At this time, because there is limited data currently available globally, a full assessment of the severity of XBB.1.5 cannot yet be confidently assessed. Taken together, available information does not suggest that XBB.1.5 has additional public health risk relative to the other currently circulating Omicron descendent lineages.

This updated risk assessment below is based on currently available evidence and will be revised regularly as more evidence and data from additional countries become available.

  Indicator Confidence in Assessment
Growth Advantage

In the United States of America (USA), XBB1.5 currently represents 23-86% of circulating variants across the different regions within the country.

From 1 February 2023 to date and for countries with more than 100 sequences, such as the United Kingdom (UK), Canada, Germany, Austria and Denmark, XBB.1.5 represents 13-36% of submitted sequences to GISAID.

In the EURO region, between week 01-2023 and week 05-2023, the median proportion of all nationally sequenced XBB.1.5 virus isolates was 5.0% (range: 0.3-13.9%, from 16 countries or areas). In the AFRO region, South Africa has reported a strong increase in XBB.1.5 from 1% in December 2022, to 10% in January 2023, and 76% as of the latest report from February 2023.

The amino acid change to 486P contributes to a higher ACE-2 binding affinity, and suggests a mechanism for XBB.1.5 to have a higher growth advantage as compared to its parent lineage XBB.1.

High
Antibody Escape

Using pseudotyped virus neutralization assays, XBB.1.5 is shown to be as immune evasive as XBB.1, and one of the Omicron subvariants with the highest immune escape to date.

Antibody titers against XBB.1 were mostly absent in individuals with a history of vaccination with index virus-based vaccines (2-4 doses), were higher in those who recently received a bivalent (BA.5) vaccine booster, and highest in individuals with hybrid immunity.

Antibody titers to XBB.1.5 in bivalent mRNA boosted individuals declined to pre-booster levels after 3 months, while antibody titers to other Omicron lineages declined less strikingly. However, cross-reactive T cell responses, which were present prior to boosting, are likely to continue to provide protection against severe disease.

Moderate
Severity and Clinical Considerations

Severity assessments in human populations are ongoing.

An analysis from India did not report any differences in clinical severity of XBB and its descendent lineages, as compared to other Omicron lineages. A preliminary analysis from the US reports that there is no difference in number of deaths per hospital admissions of patients with XBB.1.5 compared to other Omicron lineages.

Indicators such as the number of hospital admissions per case and the number of deaths per case are difficult to estimate and interpret because of the current case under-ascertainment in most countries, and which tend to overestimate severity of currently circulating variants as compared to previously circulating variants.

There are currently no data on real world vaccine effectiveness against severe disease or death.

XBB.1.5 does not carry any known mutation(s) associated with potential changes in severity (such as S:P681R).

A recent study reported that antivirals remdesivir, molnupiravir, nirmatrelvir, and ensitrelvir remain efficacious against both XBB.1.5 and XBB in vitro, while monoclonal antibodies imdevimab– casirivimab, tixagevimab–cilgavimab, sotrovimab, and bebtelovimab might not be effective against XBB.1.5 in the clinical setting.

Low
Risk Assessment

Based on its genetic characteristics and growth rate estimates, XBB.1.5 is likely to contribute to further increases in case incidence globally.

There is high-strength of evidence for increased risk of transmission and moderate-strength of evidence for immune escape.

From reports by several countries, no early signals of increases in severity have been observed.

Taken together, available information does not suggest that XBB.1.5 has additional public health risks relative to the other currently circulating Omicron descendent lineages.

XBB.1.5 Updated Rapid Risk Assessment
25 January 2023

Following a TAG-VE meeting on 23 January 2023, the WHO has revised the confidence level of the risk assessment for XBB.1.5 from “Low” (assessed on 11 January 2023) to “Moderate” (25 January 2023), using additional reports from countries on prevalence and growth advantage, and laboratory-based studies.

Based on its genetic characteristics and growth rate estimates, XBB.1.5 is likely to contribute to increases in case incidence globally. There is moderate-strength evidence for increased risk of transmission and immune escape. From reports by several countries, no early signals of increases in severity have been observed. The number of cases associated with XBB.1.5 is still low and thus severity cannot yet be confidently assessed. Taken together, available information does not suggest that XBB.1.5 has additional public health risk relative to the other currently circulating Omicron descendent lineages.

The rapid risk assessment below is based on currently available evidence and will be revised regularly as more evidence and data from additional countries become available.

  Indicator Confidence in Assessment
Growth Advantage

In the United States of America, XBB1.5 is increasing in many regions (the prevalence of XBB.1.5 in some regions is predicted to be 80%, while in others, 20-50%).

In the United Kingdom, growth advantage relative to BQ.1.1 was estimated to 38.9%, with high uncertainty due to the small number of sequenced XBB.1.5 cases.

Further, the ECDC has reported growth of XBB.1.5 in several countries, including Iceland where it has increased to 8.7% in week 2 of 2023.

The amino acid change to 486P contributes to higher ACE-2 binding affinity, and suggests a mechanism for XBB.1.5 to have a higher growth advantage as compared to its parent lineage XBB.1.

Moderate
Antibody Escape

Along with BQ.1* variants, XBB* variants are the most antibody-resistant variants to date. XBB.1.5 is shown to be equally immune evasive as XBB.1, the Omicron subvariant with the highest immune escape to date.

Antibody titers against XBB.1 were mostly absent in individuals with a history of vaccination with the index vaccine (2-4 doses), were higher in those who recently received a bivalent (BA.5) vaccine booster, and highest in individuals with hybrid immunity.

There are currently no data on real world vaccine effectiveness against severe disease or death.

Moderate
Severity and Clinical Considerations

Severity assessments in human populations are ongoing. The number of cases associated with XBB.1.5 is still low and thus clinical severity cannot yet be confidently assessed.

XBB.1.5 does not carry any known mutation(s) associated with potential changes in severity.

Low
Risk Assessment

Based on its genetic characteristics and growth rate estimates, XBB.1.5 is likely to contribute to increases in case incidence globally.

There is moderate-strength evidence for increased risk of transmission and immune escape. From reports by several countries, no early signals of increases in severity have been observed. The number of cases associated with XBB.1.5 is still low and thus severity cannot yet be confidently assessed.

Taken together, available information does not suggest that XBB.1.5 has additional public health risks relative to the other currently circulating Omicron descendent lineages.

XBB.1.5 Rapid risk assessment
11 January 2023

Based on its genetic characteristics and early growth rate estimates, XBB.1.5 may contribute to increases in case incidence. To date, the overall confidence in the assessment is low as growth advantage estimates are only from one country, the United States of America.

The rapid risk assessment below is based on currently available evidence and will be revised regularly as more evidence and data from additional countries become available.

  Indicator Confidence in Assessment
Growth Advantage As of the date of publication, available data are available only from one country, and therefore confidence in a global assessment is low. Low
Antibody Escape

Along with BQ.1* variants, XBB* variants are the most antibody-resistant variants to date. XBB.1.5 is shown to be equally immune evasive as XBB.1, the Omicron subvariant with the highest immune escape to date.

There is currently no data on real world vaccine effectiveness against severe disease or death.

Moderate
Severity and Clinical Considerations

No data.

Severity assessments are ongoing. XBB.1.5 does not carry any mutation known to be associated with potential change in severity.

Low
Risk Assessment

Based on its genetic characteristics and early growth rate estimates, XBB.1.5 may contribute to increases in case incidence globally.

To date, the overall confidence in the assessment is low as growth advantage estimates are only from one country, the United States of America.

TAG-VE statement on Omicron sublineages BQ.1 and XBB
27 October 2022

Based on currently available evidence, the TAG-VE does not feel that the overall phenotype of XBB* and BQ.1* diverge sufficiently from each other, or from other Omicron lineages with additional immune escape mutations, in terms of the necessary public health response, to warrant the designation of new variants of concern and assignment of a new label.

This decision will be reassessed regularly. If there is any significant development that warrant a change in public health strategy, WHO will promptly alert Member States and the public.

Overall Summary

The Omicron variant of concern remains the dominant variant circulating globally, accounting for nearly all sequences reported to GISAID. While we are looking at a vast genetic diversity of Omicron sublineages, they currently display similar clinical outcomes, but with differences in immune escape potential.

The potential impact of these variants is strongly influenced by the regional immune landscape. While reinfections have become an increasingly higher proportion of all infections, this is primarily seen in the background of non-Omicron primary infections. With waning immune response from initial waves of Omicron infection, and further evolution of Omicron variants, it is likely that reinfections may rise further.

The role of the TAG-VE is to alert WHO if a variant with a substantially different phenotype (e.g. a variant that can cause a more severe disease or lead to large epidemic waves causing increased burden to the healthcare system) is emerging and likely to pose a significant threat.

Based on currently available evidence, the TAG-VE does not feel that the overall phenotype of XBB* and BQ.1* diverge sufficiently from each other, or from other Omicron sublineages with additional immune escape mutations, in terms of the necessary public health response, to warrant the designation of a new variant of concern and assignment of a new label, but the situation will be reassessed regularly. We note these two sublineages remain part of Omicron, which is a variant of concern with very high reinfection and vaccination breakthrough potential, and surges in new infections should be handled accordingly.