Why are there so many Omicron subvariants and why have BA.4 and BA.5 taken hold?

·7-min read
<span>Photograph: Asanka Ratnayake/Getty Images</span>
Photograph: Asanka Ratnayake/Getty Images

On 28 November, the World Health Organization designated the variant B.1.1.529 a variant of concern, naming it Omicron. By February 2022, it overtook the Delta variant to become the dominant strain circulating in Australia and worldwide.

Since then subvariants of Omicron have emerged, the key ones being BA.1, BA.2, BA.4, and BA.5. Both BA.5 and, to a lesser extent, BA.4, rapidly replaced other Omicron subvariants and are now dominant in Australia and worldwide, causing concerning spikes in hospitalisations and deaths.

According to the World Health Organization, the proportion of reported cases of BA.4 globally rose from 11% of cases in the week ending 25 June to 14% in the week ending 7 July. BA.5 rose from 42% to 50% of cases in the same period.

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All Omicron subvariants are considered “variants of concern” by WHO, which means they show increased transmissibility, virulence or change in clinical disease, and a decreased effectiveness of public health and social measures, such as vaccination.

While there are many Covid-19 subvariants, not all are concerning, and most contain changes that aren’t helpful to the survival of the virus, so these variants die out before even being identified.

So what is Omicron, why are there so many subvariants in its family, and why have lineages BA.4 and BA.5 taken hold?

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Why do some variants become primary?

New variants will always turn up as long as they have a chance to continue to infect people, the Kirby Institute virologist, Prof Stuart Turville, says. But he says the most significant changes to the Covid virus seems to occur when someone is immunocompromised and chronically ill with Covid-19.

This gives the virus more opportunity to change, and that is when we see new variants identified. The WHO names these variants after letters of the Greek alphabet to keep track of them.

“Person-to-person transfer within the community may lead to a few changes per month in the genome – [the genetic material of the virus],” Turville says. “But a chronic infection in someone for a long period of time is thought to lead to a variant that appears in the community with more changes than we expect, for example, Delta or Omicron.”

More changes do not always mean more chance the virus will be more transmissible, or more able to evade immunity, or both. But it was the case for Omicron.

Changes that occur in the spike protein, which is the part of the virus that latches onto and infects human cells and which vaccines target, seem to be key to the virus becoming fitter.

Ensuring vaccine equity worldwide will be key to stopping problematic variants emerging.

What are the differences between subvariants?

Turville says the Delta variant, dominant in Australia until around November, contained seven key changes in its spike protein compared to the original strain first identified in Wuhan, China. The Kappa variant, which triggered a lockdown in Victoria in June 2021, had only two key changes in the spike protein.

The first Omicron subvariant to emerge, BA.1, had 53 changes in its genome compared to the original strain, and 36 of those were within the spike protein.

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“This was a seismic shift,” Turville says. “Then when we look at BA.2, it has 31 changes in the spike compared to the Wuhan strain. While 20 of these changes are shared with BA.1, 11 are not.”

Some infectious diseases experts and epidemiologists have argued that the changes to BA.1 and BA.2 were significant enough to warrant their own Greek alphabet letters, given both also drove new waves of the virus. BA.2 cases in Australia peaked in April. BA.4 and BA.5 appear to be offshoots of BA.2, and are very similar to it.

“Their shift is small from their parent BA.2, with only four key changes, but in the right places to influence their phenotype – [the way they behave],” Turville says.

Why are BA.4 and BA.5 spoken about together?

According to Dr Michael Lydeamore, a research fellow in infectious diseases at Monash University, the two are extremely similar, and emerged at around the same time – BA.4 in January and BA.5 in February.

In a department of health primary care Covid-19 update on 11 July, the deputy chief health officer, Prof Michael Kidd, said in the three weeks prior, 46.4% of all Covid-19 cases sequenced in Australia were BA.5, 38.8% BA.2, and much of the rest BA.4.

“When we say BA.4 and BA.5 are similar, we mean they’ve got the same mutations on the spike protein, which is an important part of the virus and because of this, they behave very similarly,” Lydeamore says.

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It means BA.4 and BA.5 infect cells similarly, and evade immunity similarly. While vaccines are very effective at preventing severe disease and death, they’re not so good at preventing infection and symptoms from BA.4 and BA.5 altogether. Infection with BA.4 or BA.5 is possible just 28 days after being infected with other variants, such as BA.1 or BA.2, or Delta.

The Kirby Institute’s Turville says BA.4 and BA.5 have differences in their mutations outside of the spike protein, which is why they have different names.

But the spike protein mutations and similarities are those most well understood by scientists.

What is BA.2.75?

This is yet another Omicron subvariant, first detected in India in early May. Cases of BA.2.75 in the UK have since sharply risen, and it has been detected elsewhere including in Canada, Australia, the US and the Netherlands.

While this subvariant has been given the nickname “Centaurus” on social media, a name also adopted by news outlets, it is not an official WHO name.

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“It has a whole heap of mutations, but in places that we don’t normally see,” Lydeamore says. “That’s why there’s a lot of interest and concern about exactly what that’s going to do because we haven’t really seen widespread transmission of variants with these mutations yet.”

There are very few publicly available samples of this subvariant that have been analysed in laboratories (genomically sequenced), so it is too early to say how BA.2.75 will impact infections and disease severity.

Turville says laboratories are watching it closely. “It is important to study variants like 2.75 early so we will know what we need to plan for if it does supplant BA.5, but we don’t know if it will yet.”

Is Covid changing more rapidly than other viruses?

“It seems quick if you compare it to other diseases like flu, but there are so many more people that have Covid, and that means more opportunity for it to mutate,” Lydeamore says. “I don’t think it’s actually that fast compared to other viruses. But it is very good at finding its niche, which at the moment for BA.4/5 is immune-evasion.”

Immune evasion means the antibodies we’ve developed aren’t as effective in neutralising the virus. “It doesn’t mean we have no protection at all, just that the protection we do have is less than previously,” he says.