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A potentially faster-spreading “sub-lineage” of the coronavirus Delta variant named AY.4.2 has been spotted by labs in at least 8 states, and health authorities in the United Kingdom say they are investigating a growing share of cases from this strain of the virus.
Labs in California, Florida, Maryland, Massachusetts, Nevada, North Carolina, Rhode Island and Washington state, plus the District of Columbia, have so far spotted at least one case of AY.4.2.
While it may spread somewhat faster, health authorities have not found evidence of more severe illness caused by the variant, and they say current vaccines remain effective against it.
The sub-lineage has remained a small fraction of circulating cases in the U.S. for several weeks, but American health officials say they are already ramping up efforts to study the new Delta variant descendant.
“We have teams that are constantly reviewing the genetic sequence data and looking for blips, an increase in a certain proportion or just something that’s completely new,” says Dr. Summer Galloway, executive secretary of the U.S. government’s SARS-CoV-2 Interagency Group.
Galloway, who also serves as policy lead on the CDC’s laboratory and testing task force, said U.S. labs began preparing last month to prioritize tests to assess whether AY.4.2 can evade antibodies from vaccinated Americans, or from currently authorized monoclonal antibody treatments for the virus.
That process can take up to four weeks, Galloway said, across several laboratories that will run tests with harmless “pseudoviruses” designed to impersonate the variant’s characteristic mutations.
Scientists have already turned up worrying combinations of mutations in other sub-lineages of Delta called AY.1 and AY.2, which like AY.4.2 have also sometimes been interchangeably called “Delta plus” variants.
Last month, the Biden administration temporarily halted distribution of a monoclonal antibody treatment in Hawaii after estimated cases of AY.1 climbed up to 7.7% in the state. The Food and Drug Administration said lab experiments with AY.1 suggested it was “unlikely” the drug would be effective against the variant.
The state has since resumed use of the antibody treatment, after AY.1 dropped below 5% in Hawaii. Nationwide, AY.1 has hovered around 0.1% of cases.
“Right now, I think there’s not a lot that we know. But in terms of the risk that it poses to public health, the prevalence is very low in the U.S. and we don’t really anticipate that the substitutions [of AY.4.2] are going to have a significant impact on either the effectiveness of our vaccines or its susceptibility to monoclonal antibody treatments,” said Galloway.
In the U.K., AY.4.2 has climbed to more than 11% of cases of the Delta variant. Health officials there say the variant does not appear to have led to a “significant reduction” in vaccine effectiveness or an uptick in hospitalizations, but it could be spreading faster because of “slightly increased biological transmissibility.”
“Estimated growth rates remain slightly higher for AY.4.2 than for Delta, and the household secondary attack rate is higher for AY.4.2 cases than for other Delta cases,” said a report published Friday by the U.K. Health Security Agency.
The Centers for Disease Control and Prevention estimates that AY.4.2 has made up less than 0.05% of circulating cases in the U.S. for several weeks, according to an agency spokesperson. Grouped together, CDC estimates that the Delta variant and its sub-lineages has been virtually 100% of cases in the U.S. for months.
“Even based on the data in the U.K., if you look at the transmission advantage, it looks smaller. It’s not like Delta, which as soon as they came in, it was almost a 50[%] to 60% advantage over all previous lineages,” says Dr. Karthik Gangavarapu, a postdoctoral researcher at UCLA’s Suchard group.
Gangavarapu was part of the team to lead Scripps Research’s variant tracking effort at Outbreak.info, which has tracked variants like AY.4.2 as they have emerged in an international database of “sequenced” viruses maintained by a group called the GISAID Initiative.
“It could have a slight transmission advantage, but it could also have other factors that are important. For example, how is the population immunity in a given location? What is the vaccination rate? Those may have some sort of impact on how the variant is spreading,” said Gangavarapu.
The largest share of circulating virus in the U.S. remains closely related to the original Delta variant, among samples reported to GISAID. Scientists have speculated that the next major variant of concern could emerge as a mutation from the Delta variant, though Gangavarapu cautioned that highly-contagious strains have arisen largely independently from one another.
Delta variant sub-lineages like AY.25, AY.3, and AY.44 also currently make up large U.S. proportions of cases, though not necessarily because they have an advantage over their siblings.
Outbreak.info had previously counted AY.4.2 sightings in at least 35 states. However, Gangavarapu said a bug in the “Pangolin” system used to generate reports of variants had resulted in some false positives for the sub-lineage showing up in some tallies.
New sub-lineages are frequently re-categorized by scientists to “help researchers track the virus” clustered in certain regions, even when they sport mutations that end up having no meaningful impact on the public health risk of the variant.
“Probably over the next month or so we will get more data to actually see if there is the same sort of increase in prevalence that we see in the U.K. in the U.S. as of now,” says Gangavarapu.
