With the world already grappling with the highly infectious Omicron variant of Covid, the discovery of a new sub-lineage at the end of last year gripped the attention of scientists and health officials.
Identified as BA.2, this sub-lineage of Omicron has so far been found in at least 40 countries, including scores of cases in the US. In the UK it now accounts for more new cases than Delta — around 300 in the last week.
The emergence of BA.2 highlights both the importance of tracking new variants and the inconsistency with how they are handled. The sub-lineage has formally been identified as a “variant under investigation” by the UK’s Health Security Agency, but it has so far not been classified as a “variant of concern” by the World Health Organisation (WHO).
The discrepancy comes from the fact there is no one agency organising the search for new variants during the pandemic. The WHO may highlight potentially problematic variants to its member states, but responsibility for testing and genome sequencing falls on the healthcare systems in individual countries and regions.
“Mutations arise randomly and frequently in the Sars-CoV-2 virus,” explains Dr Norelle Sherry, a clinical microbiologist at the University of Melbourne involved in genome sequencing in Australia.
“Most of the time these mutations don’t make any difference to the way that the virus behaves,” she tells The Independent. “[But] sometimes the mutations can give the virus a survival advantage over the other circulating viruses - that is, more transmissible, causing more severe disease, or evading the immune system or vaccinations.
“Identifying a handful of cases with a particular pattern of mutations is not that helpful, but when clusters of cases with the same viral sequence are identified by genomic surveillance, this gives us a clue that there might be something about this particular strain of virus that could make it a variant of concern.”
When a team like Dr Sherry’s identifies a potential new variant, they are encouraged to share the data with the open science initiative Gisaid (founded in 2008 as the Global Initiative on Sharing Avian Influenza Data). Though unaffiliated with the WHO, it has become the go-to “international genomic surveillance programme” and accumulated the world’s largest database of Covid sequencing data.
The programme allows genomic experts to access past sequencing data, analyse the variations in RNA sequences to look at different facets of the virus, including tracking the spread of variants of concern like Alpha, Delta and Omicron through different countries and regions, explains Dr Sherry.
“Other uses for the genomic data from Gisaid include identifying mutations that may [have an] impact on diagnostic testing or vaccine efficacy,” she says.
So, when the virus lineage that later became Delta was first identified (B.1.617.2), it was first seen as a handful of cases that were slightly different from its parent lineage (B.1.617), says Dr Sherry.
“However, when the number of cases of B.1.617.2 started to grow much faster than other circulating lineages in multiple countries, the international public health and scientific community (including the WHO) directed their attention to this lineage, resulting in many critical early investigations, and B.1.617.2 being declared a variant of concern.”
The WHO’s main role with new variants is to inform member states on how much of a threat they are — and it is certainly not ignoring BA.2. The agency has asked officials in member states to monitor it closely, saying that “investigations into the characteristics of BA.2, including immune escape properties and virulence, should be prioritised independently and comparatively to BA.1 (the more widely-spread version of Omicron).”
Dr Maria Van Kerkhove, an epidemiologist and the WHO’s Covid-19 technical lead, tells The Independent that before determining whether a new mutation poses a threat to the general public, the WHO looks at three sets of parameters.
First, “we first look at the mutations themselves,” she says. “And we look at the mutations in the spike protein. We also look at mutations outside of spike protein,” which plays a role in determining the transmissibility of the variant.
The second thing the WHO looks at is whether the new mutation is spreading. “So, the emergence of a variant is not the only factor. It has to spread, it has to be circulating,” says Dr Van Kerkhove.
“The third thing we look at is any data… that suggests these mutations are responsible for any changes in transmissibility, immuno-escape [ability to evade the body’s defences], severity or effectiveness [against] our counter-measures, diagnostic, therapeutics, vaccines.”
But the process of labelling a variant as concerning does not have a pre-fixed threshold of an exact number of infections or mutations, says Dr Van Kerkhove, adding that “it is dynamic”.
With Omicron, she notes, there were a large number of mutations. “About 30 [mutations] in the spike protein itself.”
It was labeled as a variant of concern following advice from the Technical Advisory Group of Virus Evolution (TAG-VE) after scientists observed a significant growth rate in cases. “What that meant was, [Omicron] was spreading rapidly,” she says, adding it not just had increased transmissibility but also had the property of immuno-escape.
The WHO has so far issued alerts for 64 different Covid variants, but not all of them have been named in their own right using letters of the Greek alphabet. The global health body assigns these labels only to those variants that are designated variants of interest or variants of concern.
The process involves real-time evaluation, research and consultation with researchers before the WHO labels a new variant, the experts said.
The TAG-VE holds regular teleconferences and video conferences with groups around the world who present to the WHO their ongoing research and findings, says Dr Van Kerkhove. “This happens in real-time. It is before any pre-print is available, even before any reports are drafted.”
So, the IHU variant with 46 mutations seen in France was evaluated by the WHO and it was aware of its circulation from September 2021, says Dr Van Kerkhove, adding that it was listed as a variant under monitoring before the pre-print study was published in December last year which was then reported widely in the media.
“With regards to the variants, we are in a pretty good place to be able to process this in real-time, even before the information gets into the scientific paper,” she says. “And that’s what the public should want and should expect from us.”