Yet another version of the coronavirus is getting global attention, this one dubbed AY.4.2. It appears that it could be slightly more transmissible than the Delta variant — a marginal difference that experts say is more of a headache than a devastating gamechanger in the scope of the pandemic. Still, the emergence of AY.4.2 offers lessons about the ongoing evolution of the pathogen.
AY.4.2 has caused some alarm because its prevalence is building up in the United Kingdom, where it’s even gained ground on the remarkably transmissible Delta variant. It now accounts for about 10% of sequenced virus samples in England.
Scientists are still trying to determine what, if any, competitive advantage the newer form of the virus has over Delta, and there are a number of possible explanations for AY.4.2’s increasing frequency.
One option is that AY.4.2 isn’t actually a better spreader, but by chance, it’s the virus that’s circulating in populations or parts of the country where cases are rising fastest. Perhaps the mutations it has picked up do make it inherently more transmissible than Delta. Maybe it’s able to get around people’s immune protection to a greater extent, causing reinfections or breakthrough infections at higher rates than Delta. Or it could be some combination of those factors.
“A high observed growth rate may be due to a biological change in the virus (transmissibility or immune escape) or to epidemiological context, such as being introduced into an area or population subgroup with high existing levels of transmission,” said a report last week from the UK Health Security Agency. “It is still uncertain whether AY.4.2 is growing due to a biological difference.”
Studies that examine how well our immune systems, primed by vaccines or past infections, fight off AY.4.2 could help answer that question, and scientists are also waiting to see if the pattern in the United Kingdom repeats if and when AY.4.2 establishes a beachhead in other countries.
To determine if AY.4.2 is indeed more transmissible, “you need to see the difference in more geographies, and is it sustained over a long period,” said Jeremy Kamil, a virologist at Louisiana State University Health Shreveport.
Still, some scientists estimate AY.4.2 has perhaps a 10% to 15% transmission advantage over Delta, which, in the grand scheme of the pandemic, wouldn’t lead to drastically more infections.
AY.4.2 is itself a descendant of the original Delta variant and is sometimes called “Delta Plus.” It’s appeared as Delta has continued to circulate around the world, branching into a number of sublineages as it has acquired additional mutations.
Below, STAT outlines three takeaways and questions about AY.4.2 and what its emergence signals about the ongoing and future evolution of the SARS-CoV-2 virus.
The coronavirus can still potentially find new ways to enhance its transmissibility
Some scientists had wondered whether Delta was so transmissible that it had reached some peak spreading capacity. Or they speculated that if Delta were to gain any new spreading prowess, it might have to cede some other feature, such as how often it causes severe disease. After all, mutation combinations that confer certain traits sometimes come at the expense of others.
But if AY.4.2 does in fact have an edge over Delta, it disproves that theory. On top of potentially being more transmissible than the original Delta strain, the preliminary evidence out of the U.K. indicates Delta Plus carries the same risk of hospitalization and death as its parent virus (though that is based on limited data).
Whether Delta itself causes more severe disease on average than earlier forms of the virus remains an open question; in some countries, researchers have reported that Delta was causing higher rates of hospitalizations among people with Covid-19, though other research — including a report last week from the Centers for Disease Control and Prevention — did not find a difference in disease severity.
The daughters of Delta
Earlier in the pandemic, different worrisome variants popped up, like Alpha in the U.K., Beta in South Africa, Gamma in Brazil, and Delta in India (or at least, those were the countries where the strains were first noticed). Those variants shared some of the same mutations, but they all emerged independently.
Now, with Delta so dominant globally, experts anticipate that future variants that raise alarms will almost certainly be descendants of the original Delta strain — just like AY.4.2.
Something unexpected could happen, of course. Maybe one of the non-Delta variants that accounts for just a fraction of cases right now could stumble upon some mutations that would allow it to outcompete Delta over time. Scientists are also keeping an eye out as SARS-2 circulates in different animal species; perhaps a new troublesome variant emerges out of transmission in, say, minks, and spills back into people.
Still, it seems most likely that the variants you’ll be hearing about going forward will derive from Delta.
What does Delta Plus mean for the United States?
It’s perhaps not a surprise that the U.K. noticed AY.4.2 so quickly. The country has an incredible sequencing system in place to monitor genetic changes in the virus, and researchers there have been among the global leaders in characterizing different mutations and forms of the virus. It’s possible that other Delta sublineages have similar growth rates to AY.4.2, but they’re in parts of the world where it will take longer for scientists to detect.
“Not everyone is as on top of it as the U.K. is,” Kamil said.
The U.S. sequencing network has improved throughout the pandemic, and right now it’s indicating that AY.4.2 accounts for just a smidgen of cases — less than 1% — and is not igniting outbreaks.
“We have on occasion identified the sublineage here in the United States, but not with recent increased frequency or clustering to date,” CDC Director Rochelle Walensky said at a briefing last week.
It’s possible that whatever transmission advantage AY.4.2 has over Delta is so narrow that it will take a while for it to start to gain on its parent strain in places beyond the United Kingdom. Also, there’s a lot of randomness when a new form of a pathogen gets introduced into an area — many imported cases simply die out without setting off a transmission chain. If AY.4.2 has just a small edge over Delta, then probability dictates it would require more imported cases for some to take off than if something much more transmissible arrived.
Some variants also don’t circulate everywhere — a lot depends on what other versions of the virus are out there, and what the local environment looks like. The Alpha and Delta variants were so much more transmissible than the other iterations of the virus that were present when they emerged and encountered so many susceptible people that they became dominant. The Beta and Gamma variants, however, only caused issues in the regions where they emerged; there were cases detected elsewhere, but they never drove outbreaks globally.
At this point, it’s too early to say what impact, if any, AY.4.2 will have in the United States. It takes higher levels of population immunity to slow more transmissible pathogens, but between vaccinations and past infections, the country has a big wall of protection out there, with vulnerable pockets interspersed. For now, U.S. modeling still indicates a continued ebbing of the epidemic.