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expert comments on the AY.4.2 subvariant

There have been reports in the media of a new Delta descendant designated as AY.4.2, here are some general comments from Professor Francois Balloux in case useful.


Prof Francois Balloux, Professor of Computational Systems Biology and Director, UCL Genetics Institute, UCL, said:

What mutations does AY.4.2 carry?

“A new SARS-CoV-2 lineage has gone up in frequency in the UK. It has been defined as AY.4.2. It is a descendant of the Delta (B.1.167.2) variant. It carries two characteristic mutations in the spike, Y145H and A222V.”

What other variants are they present in? 

“Most SARS-CoV-2 mutations have independently emerged many times in unrelated strains. 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. The first strains carrying both mutations were sequenced in April 2020. Neither are found in any Variant of Concern.

“The A222V was found in the B.1.177 lineage that swept Europe in the summer of 2020, but careful follow-up analyses pointed to the lineage likely having no inherent transmissibility advantage and that its spread was most likely caused by demographic processes.”

What do we know about their effect on transmissibility/severity? 

“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.”

How is it being investigated?

“The AY.4.2 is being closely monitored in the UK and elsewhere. It remains rare outside the UK. There have been only three cases detected in the US so far. In Denmark, the other country that besides the UK has excellent genomic surveillance in place, it reached a 2% frequency but has gone down since. In addition, functional work is underway to test whether it may be less well recognised by antibodies.”

Could it explain the recent rise in UK cases?

“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.”

Should we be concerned?

“The emergence of yet another more transmissible strain would be suboptimal. 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. Here we are dealing with a potential small increase in transmissibility that would not have a comparable impact on the pandemic.”



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Declared interests

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