A ‘Stealth’ Omicron Subvariant Is Now Spreading, Worrying Experts

Cases of the Omicron variant are on the decline in U.S. and worldwide—but a different version of Omicron is now gaining traction. This so-called stealth variant, officially known as BA.2, is armed with even higher transmission potential, and possibly a greater ability to evade the immune response, than the original Omicron, leading experts to fear it could further prolong the COVID-19 pandemic.

The World Health Organization does not yet consider BA.2 to be a distinct “variant of concern” but is continuing to monitor its spread. BA.2 is beginning to replace the original Omicron strain in many countries. It is now the dominant variant in Denmark, which recorded more than 50,000 new infections in just one day last week. BA.2 also appears to be the major Omicron lineage in parts of India and the Philippines. It has already caused about 250 cases in the United States and been identified in more than half the states.

The BA.2 subvariant likely arose from a common ancestor around the same time as the original Omicron, also known as BA.1, so it is not a descendent but a sibling, says Cornelius Römer, a bioinformatician at the Biozentrum of the University of Basel in Switzerland.

“I would hypothesize that BA.1 dominated first simply because it started spreading earlier, and now BA.2 is catching up,” says Jesse Bloom, an evolutionary virologist at the Fred Hutchinson Cancer Research Center and a Howard Hughes Medical Institute investigator.

However, BA.2 has been sometimes dubbed a stealth variant because it is missing key mutations in its spike protein that are necessary for rapid PCR tests to distinguish it from previous variants, such as Delta. This difference also may be why BA.2 escaped attention earlier.

In fact, the two Omicron lineages have greater evolutionary divergences from each other than the differences between the original virus and the Alpha variant, the first variant of concern. “BA.2 shares over 30 mutations with BA.1, but it also has 28 unique mutations,” says Shay Fleishon, an evolutionary geneticist and advisor to the Central Virology Laboratory in Israel.

This suggests that the common ancestor of both Omicron subvariants spread for quite some time, evolving into distinct subvariants before BA.1 was detected by a stroke of luck: A pair of mutations deleted two amino acids from its spike protein, making BA.1 easier to distinguish from Delta in rapid tests.

Still, BA.2 is “just as detectable by PCR as any other variant,” says Römer, referring to the “gold standard” tests that rely on time-consuming but highly accurate genetic techniques.

What makes BA.2 different?

Most of the differences between BA.2 and BA.1 are in the spike protein of the virus, which it uses to anchor to and infect human cells. BA.2 also has a large number of mutations in other parts of its viral sequence that are not well understood.

Early estimates by Denmark’s State Serum Institute suggest BA.2 is about 50 percent more transmissible than the previous BA.1 strain. The Danish study, which is not yet peer reviewed, looked into the way COVID-19 spread in 8,541 households between late December and early January. About a quarter were BA.2 cases, and the data show that even fully vaccinated people are more susceptible to catching BA.2 than BA.1.

The United Kingdom Health Security Agency also estimates that BA.2 is more transmissible, though it puts the figure at roughly 30 percent higher than BA.1.

The genetic basis behind BA.2’s transmission advantage is not yet understood, says Bloom, who has combined computational and experimental methods to study the evolution of the SARS-CoV-2 virus and understand how specific mutations influence infection.

But the good news is that experts think it’s unlikely BA.2 will cause a spike in severe infections.

Another study that is not yet peer reviewed bolsters the case that the BA.1 version of Omicron causes less severe disease than previous variants, especially Delta; only half a percent of 52,297 Omicron cases in Southern California required hospital admissions. Similarly in the U.K., most admissions to the intensive care unit were caused by Delta until January 19, 2022, when the most recent data are available.

Although BA.2 looks quite different from the original Omicron, there is no evidence yet to suggest that it is any more severe than the previous variant. Neither the Danish nor the U.K. data show any difference in hospitalizations between BA.1 and BA.2 variants. And in other countries where BA.2 is now spreading, the WHO reports that hospitalizations are not rising any faster than what would otherwise be expected.

“We expect antibodies elicited by BA.1 will neutralize BA.2 fairly well, since the viruses are relatively similar in their [binding regions],” says Bloom. For this reason, Bloom thinks it is unlikely that massive BA.2 waves will follow in regions that just suffered from an Omicron surge.

Will vaccines protect against BA.2?

However, the results from preliminary data are mixed as to whether current vaccines will be more or less protective against BA.2 compared to BA.1, which has experts concerned about more potential breakthrough infections. For context, BA.1 is already very efficient at dodging previous immunity. It also reduces the efficacy of two doses of the Pfizer-BioNtech mRNA vaccine, though a third dose at least partially restores it.

The U.K. Health Security Agency estimates that existing vaccines are equally effective at preventing symptomatic disease caused by BA.2 and BA.1, though their data are based on a relatively small number of cases. The U.K. data showed that a booster dose administered two weeks after the second shot of a vaccine was 63 percent effective at preventing symptomatic disease from BA.1 and 70 percent effective for BA.2.

Preliminary studies with lab-synthesized versions of the coronavirus also suggest that neutralizing antibodies collected from the blood of vaccinated people are equally capable of blocking BA.1 and BA.2. And Fred Hutchinson’s Bloom and others have done modelling based on the subvariant’s specific mutations, and they predict that BA.2 won’t be as good as BA.1 at evading antibodies from vaccines.

By contrast, the Danish study is based on a larger case sample, and their data suggest the BA.2 subvariant is even better at evading immune protection provided by vaccines than the original version.

For now, it’s tough to say anything for sure until more real-world data come in. “Obviously, there are not yet direct experimental measurements for BA.2,” Bloom notes, “so we will know more soon.”