Delta sub-variant: what is AY.4.2 and is it contributing to a surge in cases?

·5-min read
Concern is mounting about the trajectory of the coronavirus in the UK, but it's unlikely that AY.4.2 is to blame - Peter Byrne/PA Wire
Concern is mounting about the trajectory of the coronavirus in the UK, but it's unlikely that AY.4.2 is to blame - Peter Byrne/PA Wire

Scientists tracking Sars-Cov-2 are scrambling to understand a new offshoot of the delta variant, known as AY.4.2, which is responsible for a growing proportion of cases across the UK.

The sub-variant accounts for almost 10 per cent of all sequenced infections in the UK, with a briefing from the UK Health Security Agency suggesting that the delta descendent is “on an increasing trajectory” across the country.

Some scientists have warned that AY.4.2 could be 10 to 15 per cent more transmissible than the original delta variant, and expect it could be elevated to the rank of ‘variant of interest’ by the World Health Organization.

Here’s a look at what we know about the delta descendent so far, and the potential implications for the UK.

What’s different about the subvariant?

AY.4.2 is one of 45 sub-lineages of delta that have been recorded across the globe. It carries two mutations in the spike protein – which Sars-Cov-2 uses to latch onto and enter human cells – called Y145H and A222V.

“Both the spike Y145H and A222V mutations have been found in various other Sars-CoV-2 lineages since the beginning of the pandemic, but have remained at low frequency until now,” said Prof Francois Balloux, director of the University College London Genetics Institute.

He added that it is not clear why these mutations – which have not been detected in any of the variants of concern – could make delta more infectious, as neither are “obvious” candidates for increased transmissibility.

Ravi Gupta, a professor of clinical microbiology at the University of Cambridge, told the Telegraph that similar mutations appear to have had only a modest impact on the binding between antibodies and the virus. Analysis of the “non-spike mutations” will be necessary to fully understand how AY.4.2 behaves, he said.

“The thing delta has taught us, really, is that you often can’t predict the effect of mutations,” Prof Gupta added. “But just looking at them, I don’t think they are ones I’m going to worry about.”

Do scientists think it is more infectious?

Yes. Both Prof Balloux and Jeffrey Barrett, director of the Covid-19 Genomics Initiative at the Wellcome Sanger Institute in Cambridge, told the Financial Times that preliminary analysis points towards AY.4.2 being 10 to 15 per cent more transmissible than its ancestor.

But, even if future studies confirm this, experts say a slightly more infectious subvariant will not trigger the same dramatic surge we saw with both delta and alpha (otherwise known as the Kent variant).

The R number of delta is somewhere between five and eight, meaning that (in an uncontrolled outbreak) an infected individual would be expected to pass the virus onto five to eight people. A 10 per cent rise in this figure would not drastically alter the pandemic’s trajectory.

“The emergence of yet another more transmissible strain would be suboptimal,” said Prof Balloux. “Though, this is not a situation comparable to the emergence of alpha and delta that were far more transmissible (50 per cent or more) than any strain in circulation at the time.

“Here we are dealing with a potential small increase in transmissibility that would not have a comparable impact on the pandemic,” he added.

Where has the the subvariant been detected?

AY.4.2 represented 9.4 per cent of all sequenced variants in the week ending October 9, according to the Wellcome Sanger Institute, up from 4.4 percent the previous month.

It is now present in 90 percent of local authorities and the dominant subvariant in at least two – Worthing and East Lindsey.

Outside the UK, AY.4.2 is still rare. Three cases have so far been detected in the United States, while its frequency is decreasing in Denmark – known for its thorough genome sequencing – after peaking at two per cent of new infections.

Is AY.4.2 behind the surge in cases in the UK?

Probably not. Concern is mounting about the trajectory of the coronavirus in the UK, as cases have risen by 16.1 per cent in the last week.

Britain’s infection rate, which stands at 620 per million people, is around six times higher than its neighbours in western Europe and Scandinavia. And globally, only the United States – with a population roughly six times larger – has seen more new cases in the last week (582,000 compared to 283,000), according to the World Health Organization.

But it’s unlikely that AY.4.2 is to blame. The subvariant, while rising in prevalence, remains at a fairly low level in the UK – and a 10 per cent increase in transmissibility “could have caused only a small number of additional cases”, said Prof Balloux.

So what is to blame for the UK's Covid surge?

A number of factors – from waning vaccine immunity and a slow booster shot rollout, to the lifting of nearly all measures, especially in schools – have been linked to the UK's high case load.

“The reason the cases are high is because we released all restrictions on July 19 when there was still a lot of transmission,” said Prof Gupta. “We can’t blame the virus for what’s going on, it’s just a numbers game.

“Releasing all restrictions when cases were so high was very risky, given vaccinations had only reached 70 per cent of all adults and schools hadn’t gone back,” he added.

Martin McKee, professor of public health at the London School of Hygiene and Tropical Medicine, also suggested the UK's current predicament can be traced to July, and suggested the government has been out of step with the rest of Europe.

“We removed restrictions at a much earlier stage than other countries,” he said. Denmark, for instance, lifted restrictions when cases were hovering at around 90 per million people. In the UK, measures were abolished when the infection rate stood at 670.

“I think that was the mistake,” Prof McKee said. “Had we waited a bit longer we might be in a much better position. I think some of this comes down to British exceptionalism... and we’re still out of step with other countries… on face masks, ventilation, vaccinating children.”

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