Why call it BA.2.12.1? A Guide to the Confused Omicron Family

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

In the coming period, the coronavirus SARS-CoV-2 will continue to develop into new variants that lead to waves of infections. In 2020 and 2021, the World Health Organization (WHO) announced the emergence of variants of concern by: by giving them names from the Greek alphabet† But this year, Omicron has remained in the spotlight, with members of its family — subvariants — fueling spikes because they evade antibodies humans have generated from previous infections and vaccines. For example, the Omicron subvariant BA.2.12.1 is gaining ground in North America, and now accounts for about 26% of the SARS-CoV-2 genomes submitted to the GISAID data initiative, and BA.4 and BA. 5 spreading rapidly in South Africacomprising more than 90% of the sequenced genomes.

Given the increasing dominance of the subvariants, Nature spoke to researchers to understand the current shaky names and to find out why the WHO hasn’t given them Greek nicknames that might spur policymakers to take stronger action.

How do scientists first identify a variant?

SARS-CoV-2 acquires mutations as it replicates in cells. Technically, that means there are probably millions of variants emerging every day. But most mutations don’t improve the virus’s ability to survive and reproduce, so these variants are lost over time — outnumbered by fitter versions.

However, a small part of the variants are gaining traction. When this happens, researchers conducting genomic surveillance tag samples that all have the same set of different mutations. To find out whether these samples represent a new branch of the SARS-CoV-2 family tree, they are contacting bioinformatics scientists who have established nomenclature systems for the virus. A popular group called Pango consists of about two dozen evolutionary biologists and bioinformatics scientists who compare the sequences of the samples with hundreds of others using phylogenetic software.

The group’s name is derived from a software program 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, it means they are clear lineage from the coronavirus boom. In determining whether to name the lineage, Pango considers whether the variants have appeared more frequently over time and whether their mutations are in parts of the virus that could give it a competitive advantage. At present, a parentage label does not indicate any risk. Instead, scientists can keep an eye on a variant and learn more.

“We want to name anything that catches our eye at an early stage so we can define it and track it, and see if it’s growing quickly relative to other genera,” said Andrew Rambaut, an evolutionary biologist at the University of Edinburgh. and member of Pango. “You probably won’t hear from most of the genera we list,” he says, because they couldn’t compete with other versions of SARS-CoV-2 and are gone.

What are variants called?

When naming a variant, the Pango Commission uses a hierarchical system that indicates the evolutionary history of the variant and when it was detected relative to others. The initials in the name indicate when Pango labeled the lineage, in an order from A to Z, then AA to AZ, BA to BZ, and so on. Separated by a period, the following numbers indicate the order of the branches of that lineage. For example, BA.1, BA.2, BA.3, BA.4, and BA.5 are the first five branches descended from an original Omicron ancestor. And BA.2.12.1 is the 12th line branching off from BA.2, and 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 lines belong to a larger grouping, such as Omicron.

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

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

Source: GISAID

Given all these variants, does SARS-CoV-2 evolve faster than other viruses?

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

Still, Rambaut says, many questions remain about how SARS-CoV-2 develops, as sequencing is almost absent in some parts of the world and some countries with raging outbreaks are scaling back genomic surveillance.

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

Yes, although it hasn’t happened yet. Some researchers argue that the Omicron subvariants currently causing spikes, such as BA.4 and BA.2.12.1, deserve simpler names to facilitate communication with governments and the public at a time when COVID-19 control measures are taken into account. , such as face masks, is decreasing. They also point out that unlike the subvariants of Delta – which have not been discussed much in the media – BA.4 and BA.2.12.1 can overcome the immunity caused by previous infections with other Omicron subvariants. This was unexpected, says Houriiyah Tegally, a bioinformatician at the Center for Epidemic Response and Innovation in Stellenbosch, South Africa. “Everyone thought that only new variants would create new waves, but now that we see that Omicron can do it, we may need to change the naming system,” she suggests.

But the WHO has so far resisted this idea. WHO virologist Lorenzo Subissi says immune evasion ability is not vastly different between Omicron subvariants. He adds that the agency’s assessment could change if future studies prove that an Omicron subvariant causes more serious disease than other Omicron varieties. The technical leader of WHO’s COVID-19 response, Maria Van Kerkhove, adds that the agency also does not recommend swapping a tech label for a Greek name in hopes of urging leaders to take the ongoing pandemic more seriously to take. “This is already a scary virus, it’s still killing huge numbers of people unnecessarily,” she says, suggesting world leaders should be on the lookout now.

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