Why call it BA.2.12.1? A guide to the tangled Omicron family

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Before naming a new variant of the SARS-CoV-2 coronavirus, researchers assess whether it represents a new lineage in the virus family tree.Credit: National Institutes of Health/Science Photo Library

For the foreseeable future, the SARS-CoV-2 coronavirus will continue to evolve into new variants that lead to waves of infections. In 2020 and 2021, the World Health Organization (WHO) announced the emergence of worrying variants by giving them names from the Greek alphabet. But this year, Omicron has remained in the spotlight, with members of its family – subvariants – fueling surges as they evade the antibodies people have generated from past infections and vaccines. For example, the Omicron BA.2.12.1 subvariant is gaining traction in North America, now representing approximately 26% of SARS-CoV-2 genomes submitted to the GISAID data initiative, and BA.4 and BA. 5 are spreading rapidly in South Africa, comprising more than 90% of sequenced genomes.

Given the growing dominance of sub-variants, Nature spoke to researchers to make sense of the current wonky names and to find out why the WHO didn’t give them Greek nicknames that could prompt policymakers to take stronger action.

How do scientists first identify a variant?

SARS-CoV-2 acquires mutations during its replication in cells. Technically, this means that probably millions of variants appear every day. But the majority of mutations do not improve the virus’s ability to survive and reproduce, and so these variants are lost to time – overtaken by more adapted versions.

A small part of the variants are, however, gaining ground. When this happens, researchers doing genomic surveillance flag samples that all have the same set of distinct mutations. To find out if these samples constitute a new branch of the SARS-CoV-2 family tree, they contact bioinformaticians who have established nomenclature systems for the virus. One popular group, called Pango, consists of about two dozen evolutionary biologists and bioinformaticians who compare sample sequences to hundreds of others using phylogenetic software.

The group’s name derives from software called Pangolin, originally created by bioinformatician Áine O’Toole at the University of Edinburgh, UK. If the analysis suggests the new samples come from the same recent common ancestor, that means they are a separate lineage on the coronavirus tree. To determine whether to name the lineage, Pango considers whether the variants have appeared more frequently over time and whether their mutations are in regions of the virus that could give it a competitive advantage. At this point, a lineage tag does not indicate risk. Rather, it allows scientists to keep tabs on a variant and learn more.

“We want to name everything that jumps out at us at an early stage so that we can define and track it, and see if it develops quickly compared to other lineages,” says Andrew Rambaut, evolutionary biologist at the University of Edinburgh. and member of Pango. “You probably won’t hear about most of the lineages we name,” he says, because they couldn’t compete with other versions of SARS-CoV-2 and died out.

How are the variants named?

When nominating a variant, the Pango committee uses a hierarchical system that indicates the evolutionary history of the variant and when it was detected relative to others. The initial letters of the name reflect when Pango gave the lineage a label, following a sequence from A to Z, then AA to AZ, BA to BZ, and so on. Separated by a dot, the following numbers indicate the order of the branches of this lineage. For example, BA.1, BA.2, BA.3, BA.4 and BA.5 are the first five branches descended from an original ancestor of Omicron. And BA.2.12.1 is the 12th lineage to branch off from BA.2, then the first named branch on that 12th bush. All subvariants are variants, but researchers use the first term when they want to imply that the lineages belong to a larger group, such as Omicron.

If a variant evades the immune system much more efficiently than others in circulation, causes more severe disease, or is much more transmissible, the WHO could determine it as a “variant of concern” and change its name to a Greek letter. For example, multiple mutations in a variant labeled B.1.1.529 last year, coupled with its rapid rise, prompted the WHO to change its name to Omicron in November 2021. While Pango’s technical names are intended To help researchers track SARS-CoV-2 evolution, the WHO system prioritizes ease of communication to the public.

EVOLUTION OF A VIRUS.  Graph showing the evolution of the 5 SARS-CoV-2 variants of concern according to the WHO.

Source: GISAID

Given all these variants, is SARS-CoV-2 evolving faster than other viruses?

Not necessarily, says Rambaut. Researchers are discovering an incredible amount of diversity in SARS-CoV-2, but they are also sequencing this virus at an unprecedented rate. A record 11 million SARS-CoV-2 genomes have been uploaded to the popular data platform GISAID since January 2020. In contrast, researchers have uploaded around 1.6 million influenza virus sequences to the GISAID EpiFlu database since May 2008.

Yet, Rambaut says, many questions remain about the evolution of SARS-CoV-2, as sequencing is nearly absent in some parts of the world, and some countries with rampaging epidemics are reducing genomic surveillance.

Could Omicron sub-variants, such as BA.4, possibly be given Greek names?

Yes, although it hasn’t happened yet. Some scholars argue that the Omicron subvariants currently powering surges, such as BA.4 and BA.2.12.1, deserve simpler names to facilitate communication with governments and the public at a time when the consideration is given to COVID-19 control measures, such as face masks. , is in decline. They also point out that unlike Delta subvariants – which haven’t been discussed much in the media – BA.4 and BA.2.12.1 can overcome immunity provided by previous infections with other subvariants. of Omicron. This was unexpected, says Houriiyah Tegally, a bioinformatician at the Center for Epidemic Response and Innovation in Stellenbosch, South Africa. “Everyone thought only new variants would cause new waves, but now that we see that Omicron can do that, maybe we should adapt the naming system,” she suggests.

But the WHO has so far resisted this idea. WHO virologist Lorenzo Subissi says immune evasion ability is not significantly different between Omicron subvariants. He adds that the agency’s assessment could change if future studies prove that a subvariant of Omicron causes more severe disease than other varieties of Omicron. The technical lead for the WHO’s COVID-19 response, Maria Van Kerkhove, adds that the agency also does not recommend replacing a technical label with a Greek name in the hope of prompting leaders to take more seriously. the ongoing pandemic seriously. “It’s already a scary virus, it’s still killing a lot of people unnecessarily,” she says, suggesting that world leaders should already pay attention.

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