What We Know About the 'Delta Plus' AY.4.2 COVID Mutations Y145H and A222V

The COVID variant AY.4.2, also being referred to as the new "Delta Plus," continues to spread around the world, and scientists are still trying to figure out exactly how it works.

The variant is an offshoot of the COVID Delta variant AY.4., which itself is an offshoot of the original Delta. Scientists know that AY.4.2 is characterized by two mutations in its spike protein—a spike on the surface of the SARS-CoV-2 virus that allows it to enter human cells.

These two mutations are called Y145H and A222V, and there's not a lot that researchers know about them just yet—though it appears that AY.4.2 may have a "modestly increased" growth rate compared to the normal Delta variant, according to the U.K. Health Security Agency (HSA).

Dr. Scott Wesley Long, Associate Professor of Pathology and Genomic Medicine at Texas' Houston Methodist hospital, told Newsweek that out of AY.4.2's mutations, A222V is the better understood one having been seen before in different COVID variants as far back as the spring of 2020.

"A222V seems to confer a beneficial effect on the spike protein," he said. "The Y145H has been seen much less frequently and it is less understood."

Long thinks it's possible that the rise of AY.4.2 could be credited, at least in part, to a change in virus sequencing technology that was implemented this summer by the Artic viral sequencing network.

The update, from Artic V3 to Artic V4, could have made the technology more able to identify the Y145H mutation, he said, leading to an increase in detections of this particular mutation.

"This could be leading to the apparent increase in AY.4.2, rather than any inherent change in the virus' ability to transmit or infection," he suggested.

Jeffrey Barrett is director of the COVID-19 Genomics Initiative at the Wellcome Sanger Institute and part of a U.K. team at the forefront of AY.4.2 monitoring. They observed a 10 percent growth advantage in AY.4.2 compared to other Delta variants.

"In terms of the mutations, A222V has been seen in a lineage from summer 2020 which spread around Europe pre-Alpha, but there was never strong experimental evidence of what that mutation might do, nor was there consensus it really gave a growth advantage in the wild," he told Newsweek.

"Y145H hasn't really been seen before, but is in a region of the spike protein that has been the subject of lots of evolution in Alpha and Delta. Again, no lab data yet on its possible function."

Javier Jaimes, a postdoctoral associate at the Department of Microbiology and Immunology in the College of Veterinary Medicine at Cornell University, is cautious about the available data on AY.4.2 since variants are mutating all the time.

"I think we need to wait to see more data to even discuss whether this is a case of a new 'more contagious' form of the Delta variant or not," he said. "In my opinion, what we are seeing right now is not conclusive and it's actually creating a little confusion—and some panic—which could be as dangerous as the virus itself."

The U.K. HSA has acknowledged that the variant is accounting for a slowly increasing proportion of COVID cases there and has classed AY.4.2 as a Variant Under Investigation.

The vast majority of the world's 23,407 AY4.2. cases had been recorded in the U.K. as of October 25, though cases appear to be emerging in an increasing number of U.S. states as well, according to variant tracking tool Outbreak.Info.

Former FDA commissioner Scott Gottlieb has referred to AY.4.2 as 'Delta Plus'—a term which earlier this year was used to refer to a different Delta variant with the K417N mutation.

COVID sample
A stock image shows medical workers holding a COVID test swab sample. AY.4.2 has mostly been detected in the U.K. Yeongsik Im/Getty