What is the AY.4.2 COVID variant under investigation in the UK?

Jolyon Attwooll

26/10/2021 4:56:07 PM

The potentially more transmissible strain is descended from the main Delta variant and has already been identified in Australia.

Graphic of SARS-CoV-2 cell
AY.4.2 has two additional genetic mutations, Y145H and A222V, which affect the spike protein.

The Communicable Diseases Genomics Network (CDGN) has confirmed a new Delta variant being carefully monitored overseas has been detected in Australia.
The AY.4.2 variant, which accounted for 9.6% of COVID-19 cases in the UK over the past four weeks, has become so common that the UK Health Security Agency (UKHSA) recently labelled it a ‘variant under investigation’.
But while scientists have said it may be up to 10–15% more transmissible than the main Delta B.1.617.2 variant, they suggest it is unlikely to be behind the recent surge of cases in the UK.
‘The increase … doesn’t seem region-specific, which may suggest AY.4.2 is intrinsically more transmissible, rather than being carried by a demographic event,’ Professor Francois Balloux, Director of the University College London Genetics Institute said.
‘[But] as AY.4.2 is still at fairly low frequency, a 10% increase in its transmissibility could have caused only a small number of additional cases.
‘As such it hasn’t been driving the recent increase in case numbers in the UK.’
Professor Balloux also stated the strain is unlikely to cause a surge in other parts of the world.
‘The emergence of yet another more transmissible strain would be suboptimal,’ he said.
‘Though, this is not a situation comparable to the emergence of Alpha and Delta that were far more transmissible [50% or more] than any strain in circulation at the time.’
The variant has been linked to 15,120 cases in England, according to the most recent statistics, but so far appears to be rare outside of the UK. The UKHSA said that as of last Wednesday (20 October), there were 33 countries, including Australia, which had recorded the variant on the international data-sharing platform GISAID.
The CDGN confirmed to newsGP there has been one genome identified through SARS-CoV-2 sequencing in Australia. Since UKHSA released those figures, the Israeli Health Ministry has said the presence of the genome has been recorded in that country too.

But while seemingly more transmissible, AY.4.2 does not seem to be more virulent or resistant to vaccination than the main dominant Delta strain,  a statement put out by the UKHSA indicates.
‘Evidence is still emerging [but] so far it does not appear this variant causes more severe disease or renders the vaccines currently deployed any less effective,’ it reads.
How does it differ from Delta?
Writing in The Conversation, Northumbria University scientists Dr Matthew Bashton and Darren Smith, a Senior Fellow in Computational Biology and Professor of Bacteriophage Biology respectively, said AY.4.2 is a descendant of AY.4, another sublineage of Delta.
‘There are now 75 AY lineages identified, each with different additional defining mutations in their genome,’ they wrote.
The scientists are unsure if the mutations give the AY.4 sublineage an advantage over others or whether the increasing number of cases is due to a so-called ‘founder effect’.
‘This is when a subset of viruses get separated from the overall viral population, and then reproduce in isolation,’ they explained.
‘In the area where the separated viruses are, all subsequent viruses will therefore be descendants of this subset.’
Meanwhile, Dr Bashton and Professor Smith said AY.4.2 has two additional genetic mutations, Y145H and A222V, which affect the spike protein.
‘Whether its two mutations offer the virus a selective advantage is unclear,’ they wrote.
‘But it’s … possible the Y145H mutation could give the virus an even greater ability to escape immunity by making this supersite less recognisable to antibodies.’
They also noted the variant has not yet taken hold in other European countries, saying it could either be a sign that it does not have any enhanced ability to dodge immunity or that there may not be enough of the AY.4.2 virus present in these places to take hold.
Likewise, it is too early to tell if AY.4.2 is likely to be the next dominant lineage, or whether it will have an increased capacity to escape immunity.
‘Clearly, though, its emergence shows that there’s a continued need for genomic surveillance of the virus,’ they wrote.
The UKHSA currently lists four variants of concern, including Alpha, Beta, Gamma and Delta, alongside five other variants under investigation – which now include the AY.4.2 strain.
The same variants of concern are listed by the Australian CDGN as well as the World Health Organization.
Dr Jenny Harries, Chief Executive of the UKHSA, said the emergence of a new variant under investigation is not a surprise.
‘Viruses mutate often and at random, and it is not unexpected that new variants will continue to arise as the pandemic goes on, particularly while the case rate remains high,’ she said.
While Dr Harries praised colleagues for identifying and tracking the variant so quickly, she said it ‘should serve as objective evidence that this pandemic is not over’.
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Dr Robert Paul Brown   27/10/2021 3:29:28 PM

As I'm a Queensland GP with minimal Covid in the State, I would like to know how GP practices in Victoria and NSW deal with Covid infections, possibly on a daily basis? I'm alluding to patient flow, use of EPP, access to ambulance service etc