COVID-19: How worried should we be about the AY.4.2 Delta variant?

A descendant of the Delta variant of SARS-CoV-2, which is the virus that causes COVID-19, is spreading rapidly in England. This has led to concerns that the new variant, called AY.4.2, may be partly responsible for the high rate of infections in the United Kingdom. Based on what we know so far, however, the new variant is unlikely to be the main culprit.

Someone walking past a COVID-19 vaccination hub in Manchester city centre in the United Kingdom on October 20, 2021

Over the past year, the evolution of new, increasingly infectious variants of SARS-CoV-2 has fueled surges in the number of COVID-19 cases and deaths around the world.

In the U.K., the Alpha variant caused a spike in infections during the winter of 2020, and the Delta variant caused another spike in the spring of 2021.

Alpha was around 50%Trusted Source more transmissible than earlier variants of the virus. And unpublished research by Public Health England showed that Delta has a further 64% higher odds of being transmitted within a household than Alpha.

Over the past 28 days, the U.K. has recorded one of the highest absolute number of new cases in any country, second only to the United States.

The number of new daily cases per million people in the U.K. is rising sharply and is already higher than the figures in the U.S., Germany, France, and Italy.

So the announcement last week from the U.K. Health Security Agency that a new subtype of Delta — called AY.4.2 — is spreading in England has raised concerns that this may ratchet up infection rates even further.

The agency reported that the variant accounted for 6% of all genetic sequences of SARS-CoV-2 in the week beginning September 27, 2021, the latest week for which complete sequencing data was available.

The strain is “on an increasing trajectory,” said the agency.

AY.4.2 could be around 10% more transmissible than the original Delta variant, according to Prof. Francois Balloux, director of the University College London (UCL) Genetics Institute.

On Twitter, Professor Balloux emphasized that, for now, AY.4.2 appears to be mostly confined to the U.K. and “remains exceptionally rare anywhere else.”

Mutations in spike protein

The new subvariant of the virus is distinguished by two mutations in its spike protein, called Y145H and A222V.

However, neither mutation is in the receptor binding domain, which is the part of the spike that binds to a particular receptor on human cells to infect them.

This suggests that the mutations are unlikely to cause major increases in transmissibility or help the virus evade the immune system.

In an update on Twitter, Prof. Balloux wrote: “Even if AY.4.2 is genuinely [around] 10% more transmissible, it does not explain much of the recent case rises in the U.K.”

He explained that if the new variant is 10% more transmissible and has a frequency of 10% in the population, this equates to only 1% more cases every 5 days.

As such, AY.4.2 could not have driven the recent increase in case numbers in the U.K., he explained.

In other words, the emergence of AY.4.2 is not on a par with the emergence of either Alpha or Delta, in terms of increased transmissibility.