Delta sub-variant: What we know as it ‘expands’ throughout England

Experts have speculated AY.4.2 could be 15 per cent more transmissible than original Delta variant but do not believe its emergence will be ‘catastrophic’ for UK

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An offshoot of the Delta coronavirus variant which appears to be more transmissible than its predecessor is beginning to spread throughout England, scientists have said.

Little is known about the AY.4.2 sub-variant, but data suggest it was responsible for almost 10 cent of new infections at the beginning of October. A briefing from the UK Health Security Agency said AY.4.2 is “expanding” and “on an increasing trajectory”.

Experts have speculated that it could be 10 to 15 per cent more transmissible than the original Delta variant, which has come to dominate across the world.

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Dr Jeffrey Barrett, director of the Covid-19 Genomics Initiative at the Wellcome Sanger Institute, said this “would be annoying but not catastrophic” for the UK in the coming months.

However, he wrote on Twitter, “what is perhaps more worrying is that it suggests the virus still has evolutionary paths to higher transmissibility open to it, and there are millions of Delta cases around the world without much sequencing coverage.”

Aris Katzourakis, a professor of evolution and genomics at Oxford University, said it was concerning that the “evolutionary trajectory of delta is still ongoing, and there is plenty of space for further adaptation to human transmission.”

Downing Street said it was keeping “a very close eye” on the Delta sub-variant. "There's no evidence to suggest that this variant... the AY.4.2 one... is more easily spread,” the prime minister’s spokesperson said. “But as you would expect, we're monitoring it closely and won't hesitate to take action if necessary."

Professor Francois Balloux, director of the Genetics Institute at University College London, said the recent spike in UK cases could not be attributed to AY.4.2 alone.

“As AY.4.2 is still at fairly low frequency, a 10 per cent increase [in] its transmissibility could have caused only a small number of additional cases,” he said. “As such it hasn’t been driving the recent increase in case numbers in the UK.”

The Covid-19 Genomics UK Consortium (COG-UK), which tracks new variants, said AY.4.2 “is likely to become dominant” in Britain if it is found to be more infectious. However, it said there is no evidence to support this yet, with tests underway to determine its “biological properties”.

The sub-variant carries two mutations in its spike protein, called Y145H and A222V, which have emerged independently in other variants, suggesting they may prove to be overly problematic.

“Neither mutation is a priori an obvious candidate for increased viral transmissibility, but we have learnt that mutations can have different, sometimes unexpected, effects in different strains,” Prof Balloux said.

Delta will be the branch from which a good number of things grow now.

Dr Stephen Griffin, virologist at Leeds University

Ravi Gupta, a professor of clinical microbiology at the University of Cambridge, told the Guardian that similar mutations to Y145H had been seen in other variants which had a modest effect on the antibody response.

For now, AY.4.2 remains rare outside of the UK. Three cases of the sub-variant have been detected in the US so far, while Denmark – renowned for its genomic surveillance – has also picked up a low number of AY.4.2 infections, said Prof Balloux.

Although he described the emergence of the sub-variant as “sub-optimal”, he said “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.”

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

Dr Barrett said it could be simply be a “fluke” that AY.4.2 has managed to establish itself in the UK but not elsewhere, adding that it would need “to really get established somewhere” to avoid burning out.

“That is, landing 20 Delta infections in a place with only Alpha almost guarantees that it will go on to complete replacement, whereas 20 AY.4.2 landing in an existing Delta epidemic may well fizzle,” he said.

Testing is meanwhile underway to ascertain whether this new sub-variant may be less well recognised by the body’s antibodies and better at evading the immune response generated by vaccination or previous infection.

Both the Alpha and Delta variants generated a large surge in cases during the earlier stages of the pandemic. But with infections once again on the rise – nearly 50,000 people tested positive for Covid on Monday – there is a fear that the emergence of AY.4.2 could be just beginning of a new wave of Delta sub-variants.

“It is a worry,” said Dr Stephen Griffin, a virologist at Leeds University. “Delta will be the branch from which a good number of things grow now.”