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.

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. 

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: 

 

 

* 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:

*Includes all descendent lineages.

 

 

 

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 “VOC lineages under monitoring” (VOC-LUM) 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.

 

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.

*VOC-LUMs 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.

# these lineages have identical constellation of mutations in the spike and the following differences outside the spike: BA.4: ORF7b:L11F, N:P151S; BA.5: M:D3N. Both have reversions at nsp4: L438 and ORF6:D61

§these lineages have identical constellation of mutations in the spike and the following differences outside the spike:  BA.2.9.1: ORF3a:H78Y, N: P67S, N: S412I

**additional mutation outside the spike protein: ORF1a:S2519P

 

 

A SARS-CoV-2 variant : 

 

*Includes all descendent lineages. 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/

 

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.

For each variant, the profile of amino acid changes compared to the wild-type virus (GISAID Accession ID: EPI_ISL_402124) was created based on the first 1,000 genomes (for Theta, it is based on 544 genomes) available in GISAID (genomes with less than 29,000 nucleotides and >5% Ns were excluded). Amino acid changes that are present in ≥ 85% of the analyzed sequences are shown. Of note, relevant amino acid changes may be present in other regions of the SARS-CoV-2 genome, and not all amino acid changes in the spike protein are associated to potential changes in the characteristics of the virus variant.

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. 

 

Former VOCs/VOIs/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.

   

 

*Includes all descendent lineages. See the cov-lineages.org and the Pango network websites for further details.

 

 

 

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.

 

 

 

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