What to Know About the New Delta Sublineage

As the now ubiquitous Delta variant continues to mutate, it’s spawned a new descendant that’s spread in the U.K. and made its way to the U.S.

The Delta sublineage, known as AY.4.2, is characterized by two “S-gene mutations” on A222V and Y145H, both located on the gene that encodes the spike glycoprotein of SARS-CoV-2.

CDC Director Rochelle Walensky, MD, acknowledged during the White House’s latest COVID-19 Response Team press briefing that the AY.4.2 sublineage has been identified “on occasion” in the U.S. without increased frequency or clustering to date.

Since August, AY.4.2 with these mutations has appeared in a total of three cases in the U.S.: in California, North Carolina, and Washington, D.C., according to Outbreak.info, which collects COVID-19 sequencing data from GISAID, a global genomic data-sharing initiative.

“At this time, there is no evidence that the sub-lineage AY.4.2 impacts the effectiveness of our current vaccines or therapeutics, and we will continue to follow up,” Walensky said.

Experts think the new Delta sublineage is slightly more transmissible, but say it’s likely less worrisome than its predecessor Alpha or Delta variants, which made bigger jumps in transmissibility. There’s a level of uncertainty over its exact advantage in spreading, however.

“There was a bit of a hope that Delta had, ideally, reached a kind of bound in transmissivity, so that will be a bit of a disappointment,” said Francois Balloux, Ph.D., computational biologist at University College London and director of the UCL Genetics Institute, in an interview.

Balloux predicted that at some point, almost everyone will be exposed to the “already so bloody transmissible” Delta variant, which makes up around 80% of sequenced cases in the U.K. He said AY.4.2 could be up to 15% more transmissible.

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