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

Coloured transmission electron micrograph of SARS-CoV-2 coronavirus particles (blue) emerging from a cell cultured in a lab.

Earlier than naming a brand new variant of the SARS-CoV-2 coronavirus, researchers assess whether or not it represents a brand new lineage on the virus’s household tree.Credit score: Nationwide Institutes of Well being/Science Picture Library

For the foreseeable future, the coronavirus SARS-CoV-2 will proceed evolving into new variants that result in waves of infections. In 2020 and 2021, the World Well being Group (WHO) introduced the emergence of variants of concern by giving them names from the Greek alphabet. However this yr, Omicron has remained within the highlight, with members of its household — subvariants — fuelling surges as they evade antibodies that folks have generated from earlier infections and vaccines. For instance, the Omicron subvariant BA.2.12.1 is gaining floor in North America, now accounting for about 26% of the SARS-CoV-2 genomes submitted to the GISAID information initiative, and BA.4 and BA.5 are spreading quickly in South Africa, comprising greater than 90% of genomes sequenced.

Given the subvariants’ growing dominance, Nature spoke to researchers to make sense of the present wonky names, and to be taught why the WHO hasn’t given them Greek monikers that might spur policymakers to take stronger motion.

How do scientists first establish a variant?

SARS-CoV-2 acquires mutations because it replicates in cells. Technically, because of this hundreds of thousands of variants in all probability come up on daily basis. However the majority of mutations don’t enhance the virus’s means to outlive and reproduce, and so these variants are misplaced to time — outcompeted by fitter variations.

A small portion of variants do, nonetheless, acquire traction. When this occurs, researchers conducting genomic surveillance flag samples that each one have the identical set of distinct mutations. To search out out whether or not these samples represent a brand new department on the SARS-CoV-2 household tree, they contact bioinformaticians who’ve established nomenclature programs for the virus. One common group, referred to as Pango, consists of about two-dozen evolutionary biologists and bioinformaticians who evaluate the samples’ sequences to lots of of others utilizing phylogenetic software program.

The group’s title derives from a software program programme referred to as Pangolin, initially created by bioinformatician Áine O’Toole on the College of Edinburgh, UK. If the evaluation means that the brand new samples derived from the identical latest widespread ancestor, it implies that they’re a definite lineage on the coronavirus tree. In figuring out whether or not to call the lineage, Pango considers whether or not the variants have appeared extra continuously over time, and whether or not their mutations are in areas of the virus which may give it a aggressive edge. At this level, a lineage label doesn’t point out danger. Fairly, it permits scientists to control a variant and be taught extra.

“We wish to title all the things that jumps out at us at an early stage in order that we are able to outline it and observe it, and see whether it is rising rapidly relative to different lineages,” says Andrew Rambaut, an evolutionary biologist on the College of Edinburgh and a member of Pango. “You in all probability gained’t hear of a lot of the lineages we title,” he says, as a result of they couldn’t compete with different variations of SARS-CoV-2 and have disappeared.

How are variants named?

When naming a variant, the Pango committee makes use of a hierarchical system that signifies the variant’s evolutionary historical past and when it was detected relative to others. The preliminary letters within the title mirror when Pango gave the lineage a label, following in a sequence from A to Z, then from AA to AZ, BA to BZ, and so forth. Separated by a full cease, the following numbers point out the order of branches from that lineage. For instance, BA.1, BA.2, BA.3, BA.4 and BA.5 are the primary 5 branches descending from an authentic Omicron ancestor. And BA.2.12.1 is the twelfth lineage to department off from BA.2, after which the primary named department on that twelfth bush. All subvariants are variants, however researchers use the previous time period after they wish to indicate that the lineages belong to a bigger grouping, similar to Omicron.

If a variant evades the immune system way more successfully than others in circulation, causes extra extreme illness or is way more transmissible, the WHO may decide it to be a ‘variant of concern’ and alter its title to a Greek letter. For example, the a number of regarding mutations in a variant labelled as B.1.1.529 final yr, coupled with its fast rise, prompted the WHO to vary its title to Omicron in November 2021. Whereas Pango’s technical names are supposed to assist researchers observe SARS-CoV-2 evolution, the WHO’s system locations a precedence on the benefit of communication to the general public.

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

Supply: GISAID

Given all these variants, is SARS-CoV-2 evolving extra quickly than different viruses?

Not essentially, Rambaut says. Researchers are discovering an unbelievable quantity of variety in SARS-CoV-2, however they’re additionally sequencing this virus at an unprecedented fee. A file 11 million SARS-CoV-2 genomes have been uploaded to the favored GISAID information platform since January 2020. In contrast, researchers have uploaded about 1.6 million sequences of the influenza virus to GISAID’s EpiFlu database since Might 2008.

Nonetheless, Rambaut says, many questions stay about how SARS-CoV-2 is evolving, as a result of sequencing is sort of absent in some elements of the world, and a few nations with raging outbreaks are scaling again genomic surveillance.

May Omicron’s subvariants, similar to BA.4, finally obtain Greek names?

Sure, though it hasn’t occurred but. Some researchers argue that the Omicron subvariants at the moment fuelling surges, similar to BA.4 and BA.2.12.1, deserve less complicated names to help communication with governments and the general public at a time when regard for COVID-19 management measures, similar to face masks, is waning. Additionally they level out that not like Delta’s subvariants — which weren’t mentioned a lot within the media — BA.4 and BA.2.12.1 can overcome immunity offered by earlier infections with different Omicron subvariants. This was surprising, says Houriiyah Tegally, a bioinformatician on the Centre for Epidemic Response and Innovation in Stellenbosch, South Africa. “Everybody thought that solely new variants would trigger new waves, however now that we’re seeing that Omicron can do it, perhaps we must always adapt the system of naming,” she suggests.

However the WHO is to date resisting this concept. WHO virologist Lorenzo Subissi says that the capability for immune evasion isn’t wildly totally different between Omicron subvariants. He provides that the company’s evaluation might change if future research show that an Omicron subvariant causes extra extreme illness than different Omicron varieties. The technical lead of the WHO’s COVID-19 response, Maria Van Kerkhove, provides that the company additionally doesn’t advocate swapping a technical label for a Greek title within the hope of spurring leaders to take the continuing pandemic extra significantly. “That is already a scary virus, it’s nonetheless killing big numbers of individuals unnecessarily,” she says, suggesting that world leaders ought to already be paying consideration.

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