Omicron’s BA.2 subvariant raises new questions about the puzzling virus evolution behind COVID-19

BA.2 caught the attention of virologists once it began to rise in several countries, including early signals of a slight increase here in Canada, suggesting it may be even more transmissible than its predecessor.

“There is a competition,” said Nathalie Grandvaux, a researcher and professor in the Department of Biochemistry and Molecular Medicine at the University of Montreal. “It feels a bit like Delta vs. Alpha…does that mean we’ll get another wave? That’s not something we can say right now.”

Denmark in particular is reporting an increase in BA.2 infections, with the sub-variant accounting for almost half of all Omicron cases by the second week of January, up from around 20% at the end of 2021.

“During the same period, the relative frequency of BA.1 dropped,” said the Statens Serum Institut (SSI), a Danish research agency, reported on January 20.

The UK is also watching BA.2 closely, and officials noted in a technical briefing mid-January that this sub-variant is often able to fly under the radar. While BA.1 lacks one of the three target genes used in large-scale SARS-CoV-2 testing, making it easy to spot – a process known as S-BA gene target failure .2 cannot be detected in the same way.

The same report noted that as of January 1, BA.2 accounted for 5% of positive S gene tests in the UK – and that figure is growing.

This means that the rapid S gene failure method of catching Omicron infections “is no longer sufficient to assess the spread of Omicron as a whole,” he continued.

‘No big alarm bells’ so far

In contrast, for much of the first year of the pandemic, it was much easier to track and manage the evolution of this virus.

That first changed when the B117 variant – later dubbed Alpha by the World Health Organization – burst onto the scene in late 2020, boosting the number of cases thanks to a set of mutations that helped it to spread rapidly around the world.

As the number of cases increased, this evolutionary process apparently accelerated, causing variant after variant.

Surprisingly, the differences between BA.1 and BA.2 are even greater than the differences between the original SARS-CoV-2 strain and the Alpha variant, Denmark’s SSI noted.

Monday, the World Health Organization has declared research into BA.2 operation should be “prioritized independently” of other Omicron sub-variants.

There are global signals that the BA.2 subvariant is a bit more transmissible, echoing the early days of Omicron’s spread, said Jesse Shapiro, associate professor of microbiology and immunology at McGill University. .

While it’s possible it could also prolong this wave of infections, he said, “there are no big alarm bells ringing yet.”

Immune Evasion Questions

Still, questions remain about BA.2’s ability to re-infect growing numbers of people who have already treated an Omicron infection. Could its dramatic evolutionary change allow it to escape weeks-old immunity for the millions infected since late 2021?

There are a few documented cases of reinfections in Norway, so it’s possible that BA.2 is infecting some of those who have already recovered from BA.1 and increasing the number of cases, said Anders Fomsgaard, chief medical officer and researcher on virus at ISS, during a recent interview with Danish media.

But Matthew Miller, associate professor of infectious diseases and immunology at McMaster, expects those types of reinfections to be unlikely. More concerning, he suggested, are the impacts of a “little sister” to Omicron spreading among unprotected populations.

“People who have received only two doses of vaccine, or no dose of vaccine, or [are] incompletely vaccinated, they may be as susceptible to BA.2 as they were to Omicron,” he said.

What is reassuring about BA.2 – at least for now – is that the initial analysis of the SSI shows no difference in hospitalizations compared to BA.1. Further research is underway to understand the impact of the subvariant on vaccine effectiveness, the SSI noted, but the vaccines should continue to provide protection against serious disease.

The subvariant also represents only a small percentage of the total number of known COVID-19 cases in Canada, according to federal data, although it appears to be increasing.

Omicron infections account for more than 90% of recent cases in Canada – and almost all remain BA.1. But BA.2 infections totaled about 1% of reported cases in early January, down from just 0.2% in late December, with data for that period still accumulating.

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Angela Rasmussen, a virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan, pointed out that these small numbers may not change, unlike the situation in Denmark, where the potential takeover of BA.2 is concerning.

“The important takeaway here is that Denmark is not Canada. Denmark is a different population, with different vaccination coverage, different medical backgrounds and demographics,” he said. she declared. “So what happens in Denmark is not necessarily going to automatically translate to Canada.”

Surveillance efforts will be crucial going forward to catch BA.2 cases and bring its spread under control, Grandvaux noted, but she said it has likely been a trickier task given its stealthy nature.

“We have to keep the sequencing going,” she said. “We need to know the behavior of this virus.”

Scientists intrigued by the origins of Omicron

Darren Martin, a virologist at the University of Cape Town in South Africa, the country that alerted the world to the existence of Omicron, also said it was crucial to understand why and how this variant evolved.

“We need to get serious, quickly uncover the conditions Omicron was born into, the mechanisms involved in assembling its complement of mutations, and figure out how we can minimize the likelihood of those conditions reoccurring,” he said. said in an email interview. with CBC News.

“The last thing any of us want is another new hyper-evolved [variant of concern] popping up every few months.”

Martin and a team of researchers recently shared first discoveries regarding the original Omicron lineage, noting that more than a dozen high number of BA.1 mutations are very rare, suggesting that they would not necessarily be useful to an evolving virus.

Instead, these unique quirks are part of a constellation of mutations that seem to grant Omicron the uncanny ability to spread rapidly between human hosts, leaving other variants in its dust.

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What is concerning, Martin said, is not just this confusing original Omicron lineage, but the fact that BA.2 and other lines also exist – all closely related, but with unique properties, raising questions. on how each evolved fast enough to be discovered. by scientists around the same time.

“How did a virus with a much lower mutation rate than viruses like HIV and influenza manage, in a linear, stepwise process, to string together such large sets of interactive mutations, while each mutation alone would have reduced his ability? asked Martin.

“The conditions under which this evolution occurred might have to be quite different from those of a normal, short-term SARS-CoV-2 infection.”

Some scientists have speculated that Omicron developed during a long-lasting infection in an immunocompromised patient or in animal hosts before suddenly spreading to humans with explosive force.

Regardless of how Omicron was born, its existence – and continued shapeshifting – hints at the ability of this virus to evolve drastically if infections remain at high levels around the world.

“He behaves as we could predict,” said Grandvaux. “It mutates while transmitting.”