The BA.2 variant: What you need to know about the strain known as 'stealth omicron' in Arizona

·15 min read

As much of the country sets aside mask mandates and other pandemic restrictions, another version of the omicron coronavirus variant, known as BA.2, accounts for an increasing percentage of samples sequenced in Arizona.

While scientists aren’t ready to say it’s the dominant strain in the state, they say that the trend appears to be heading in that direction.

The omicron variant of the coronavirus appeared in November and became dominant around the world in just a matter of weeks. But “omicron” is really more like a branch on a family tree, encompassing several genetically related but similarly-behaving subvariants that scientists have labeled BA.1, BA.1.1, BA.2, and BA.3.

You’re probably most familiar with BA.1, the strain that broke the ceiling on case counts and quickly outpaced the delta variant, including in Arizona. Still, labs here and around the country have been also detecting BA.2 for several weeks now. That’s despite BA.2’s other moniker, “stealth omicron,” which referenced the challenges its mutations posed to testing technology.

BA.2 is not yet causing a rise in cases in Arizona like it is in other parts of the world. Nevertheless, scientists here are keeping a careful watch on the subvariant to see whether it sets off a small spike or even a surge. They’re also waiting to see how BA.2 will square up against natural and vaccine-induced immunity, new treatments like antivirals and other factors in our arsenal of pandemic defenses.

And many are standing by for more clinical data, hoping to better understand the potential long-term effects of the millions of omicron infections we saw this winter. At the same time, they say, the increased use of home-testing kits rather than PCR lab tests means they have less data they can use to keep tabs on which variants are circulating in communities.

Here’s what we know so far.

What is BA.2? Is it a new variant? How is it different from BA.1 (the “original” omicron)?

The BA.2 variant of the coronavirus is a “sister lineage” to BA.1, explained Efrem Lim, an assistant professor at Arizona State University’s Biodesign Institute whose lab sequences SARS-CoV-2 genomes.

The Biodesign Institute building A on ASU's Tempe campus as seen on Feb. 15, 2019. It opened in 2018.
The Biodesign Institute building A on ASU's Tempe campus as seen on Feb. 15, 2019. It opened in 2018.

Just as you might share a last name with your sibling, BA.1 and BA.2 are genetically related and both called by the same Greek letter, omicron. Nevertheless, these two strains are distinct versions of the virus that causes COVID-19. In fact, Lim says BA.2’s mutation profile is “quite different” — by his estimate, it has at least 28 mutations that differ from BA.1.

Early data suggests that BA.2’s unique characteristics give it a clear advantage over BA.1. Scientists are still trying to figure out why, but many, including Lim, suspect increased transmissibility may have something to do with it.

BA.1 and BA.2 were detected around the same time, in November. But David Engelthaler, director of the pathogen & microbiome division at TGen, says they diverged from each other well before that. All omicron subvariants are descended from a much older version of the coronavirus than, say, the delta variant, but what happened in the intervening months before omicron took off remains unknown.

“We don't know where (omicron) had been hiding out this whole time. That's a real mystery right now,” he said.

Is BA.2 the same thing as “deltacron”?

No. “Deltacron” refers to cases where the genetic code of a sample has components of both omicron and delta. Lim says that’s called recombination, and it usually happens in an individual who has been infected by both delta and omicron (not necessarily at the same time).

Lim said that he has seen at least two credible case reports of recombination between delta and omicron, but added that those cases have been rare and relatively isolated.

How many COVID-19 cases in Arizona are of the BA.2 variant? How fast is BA.2 spreading?

Lim’s lab reported that for the week of March 14, BA.2 accounted for about 67% of cases sequenced — a jump from the previous week, when it accounted for about 18% of cases. However, he noted that it is also important to take numbers into account, not just percentages.

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“Even though the proportion is shifting, we are not seeing an increase, a spike or a surge in cases of the data so far,” Lim said. To put it another way, the number of coronavirus cases may be staying flat for now; it’s just that more of those cases are starting to be caused by BA.2 instead of BA.1. This process, in which an older strain loses traction as a new strain takes hold, occurs every time we see a variant appear with a competitive advantage.

TGen’s tracking dashboard is reporting 60% BA.2 and 40% BA.1 for the week of March 13. As they were at Lim’s lab, those percentages only represent a small number of cases sequenced – 12 of the former and 8 of the latter.

“It's not so much that BA.2 is becoming more dominant. It's that the original omicron strain is becoming less and less dominant,” Engelthaler said. "It’s been estimated that somewhere between 40 and 60% of the population was infected with omicron … that really got us to very high levels of community immunity, which now means that there's just fewer and fewer susceptible people for the remaining stream (BA.2) left to infect."

Kate Ellingson, an infectious disease epidemiologist at the University of Arizona, said BA.2’s impact on overall case numbers will depend on several other factors, including underlying immunity from previous infection and vaccination and how much people take precautions.

“I think that we are likely to see cases rise again, (but) what is sort of harder to predict is the magnitude of that rise,” she said.

How do BA.2 cases in Arizona compare to cases in the rest of the U.S.? The rest of the world?

According to the CDC’s Nowcast tracker, BA.2 accounts for just over 50% of cases in the Northeast. The West and Southwest, including Arizona, is showing a slightly smaller proportion at 40%, while the Midwest and South are hovering in the 20-30% range.

Engelthaler noted that those variations in numbers across the country may represent availability of both testing and sequencing rather than any significant differences in BA.2’s spread. “There’s more home testing available, and there's just going to be less and less testing in the laboratories. We're going to lose some of our ability to continue to gather intel on this virus. So that is a bit of a concern,” he said.

Beyond domestic testing efforts, many epidemiologists and public health officials have been looking to the U.K. throughout the pandemic for hints at what may be to come in the U.S. Recently, BA.2 has caused case counts to rise there. With the caveat that Britain isn’t a perfect analog for the U.S. — their vaccination rates are higher than ours — Ellingson agreed that what’s happening across the pond could provide clues to what may happen here in a few weeks.

Amber Whitaker performs genome sequencing on positive COVID-19 tests in a research lab, Oct. 4, 2021, at TGen North in Flagstaff, Arizona.
Amber Whitaker performs genome sequencing on positive COVID-19 tests in a research lab, Oct. 4, 2021, at TGen North in Flagstaff, Arizona.

“Like Arizona, they have repealed a lot of the mitigation measures or scaled back significantly a lot of mitigation. There's been a lot of omicron transmission there, so there are enough parallels that I think it makes sense to at least pay attention to what's going on there,” Ellingson said.

What are the symptoms of BA.2? How does its severity compare to the symptoms of COVID-19 caused by the BA.1 and delta variants?

Engelthaler said that the preprints he’s seen so far indicate “essentially no clinical differences” between COVID-19 cases caused by BA.1 and those caused by BA.2. Lim said he is waiting for more data on both BA.1 and BA.2’s longer-term effects and connections to long COVID, which is in itself a poorly understood condition.

Nevertheless, Lim said that his lab is not seeing significant numbers of BA.2 showing up in sequences that come from hospitals. That might be a clue to BA.2’s clinical effects, but Lim also pointed out that lower hospitalization numbers could be due to a wide range of factors, such as prior infection and vaccination, which make it difficult to draw any conclusions about BA.2’s true severity.

Do vaccines work against BA.2? What about boosters?

A recent report from the UK Health Security Agency suggested that “vaccine effectiveness against symptomatic disease was similar for BA.1 and BA.2 sublineagues of Omicron.” If that’s the case, our existing vaccines will be substantially less effective against omicron than they were against previous variants — but a booster can significantly decrease the risk of severe disease.

“Our immune system is pretty complex, and we think about it as multiple layers working together,” said Lim, who explained that longer-term T-cell responses can hold strong after B-cell responses wane. “That's the reason why vaccination still protects you from severe disease.”

But for the immunologically vulnerable, infection can still be a serious risk. So while both Pfizer and Moderna have announced plans to develop vaccines tailored to the omicron variant, those companies last week also requested FDA approval for additional booster shots of the existing formulation. Pfizer asked for authorization for adults 65 and over, while Moderna requested authorization for all adults.

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Experts are still debating how much additional protection a fourth shot of the existing formulation might provide for a healthy individual. In the meantime, Ellingson said that for the general public, the focus should still be on increasing access to a first booster dose.

“We still do not have enough people boosted here, even though our rates of people who receive their primary series have increased,” Ellingson said. She added that the public health community should focus on “getting the booster to as many people as possible, because that will make a difference.”

If I recently had COVID-19, do I have natural immunity against BA.2?

Lim said that so far, the data suggests that immune responses developed after infection with BA.1 also protect against BA.2. That’s in line with a February statement from the World Health Organization on BA.2, which said that “reinfection with BA.2 following infection with BA.1 has been documented” but that “initial data from population-level reinfection studies suggest that infection with BA.1 provides strong protection against reinfection with BA.2, at least for the limited period for which data are available.”

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If you live in Arizona and have had COVID-19 since the beginning of 2022, there’s a good chance you were infected with the BA.1 omicron strain. It’s not a guarantee that you won’t get reinfected, but on a population level, the apparent immunity overlap between BA.1 and BA.2 is a promising sign to scientists monitoring variants of concern.

While individual patients can’t see the genetic mapping of their own COVID-19 samples, Lim’s lab receives patient data for every test. “We're not seeing many people that had BA.1 and then got a second BA.2 infection. And so that's looking good so far,” Lim said.

How do treatments like antiviral pills and monoclonal antibodies fare against BA.2?

Antivirals such as Paxlovid and molnupiravir appear to remain effective against BA.2, according to a news release from the University of Wisconsin-Madison. Even so, Ellingson said antivirals are most effective if the virus is caught early, which relies on early and accurate testing measures.

“If people have early access to accurate testing, and we have access to these antivirals and monoclonal antibodies, then we have a chance to protect the vulnerable in this surge,” said Ellingson, noting that challenges remain to effectively deploying many of the medications that could be a lifeline for the vulnerable. “Given that we don't have perfect access to those (treatments), we do have people who will be at risk in the context of scaled back mitigation.”

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One recent preprint about Evusheld, the preventative monoclonal antibody cocktail for the immunocompromised, originally suggested that BA.2 would evade neutralization by monoclonal antibodies but has since been updated to indicate evidence that Evusheld may work against the subvariant. AstraZeneca, which makes Evusheld, has also announced that the cocktail may still work against BA.2, based on preprint evidence from an independent lab study.

However, a news article in Nature stated that early data suggests other antibody treatments such as sotrovimab may lose potency against BA.2, highlighting the challenges for drugmakers trying to ensure that treatments keep pace with the virus as it evolves.

Does BA.2 change masking or other public health measures?

Local officials have not yet made any moves to reinstate masking guidelines in Arizona, though global leaders have emphasized that places with fewer mitigation measures will see more community spread. “Continued local outbreaks and surges are to be expected, particularly in areas where measures to prevent transmission have been lifted,” said Dr. Tedros Adhanom Ghebreyesus, director-general of the World Health Organization, in a press conference on March 16.

But rising case counts aren’t solely dependent on public health measures — they are also a factor of population-level immunity, which Engelthaler said is very high in Arizona and across the U.S. after the last omicron surge.

Ellingson acknowledged that it can be a challenge for leaders to reimpose policies once they have been lifted. “I think it's very difficult for public health officials and government officials to reinstate mitigation measures soon after they've rolled them back,” she said. She added that as an epidemiologist, she hopes public health measures will align with science.

She said that she has made the individual choice to continue masking indoors and in large groups for now, even if it feels awkward to be doing so when others are not. “Social norms are incredibly powerful. And so of course, I think we are in such a tricky space here. (But) we still have vulnerable people in our communities,” she said.

Ellingson said she would hesitate to give a specific number at which she would feel comfortable taking off her mask, because accurate numbers are contingent on the amount and accuracy of testing. “I do not see us wearing masks forever,” she said.

Still, she is aware that benchmarks for “low” community transmission have changed. Organizations like the CDC have increased the threshold for an acceptable amount of spread.

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While she appreciates that the data now incorporates hospitalizations as well as overall case numbers, she still believes that those changes can engender a false sense of security. She is particularly mindful of the potential effects mitigation measures can have on elderly, immunocompromised or otherwise high-risk populations.

“I want (the pandemic) to be over just as badly as I imagine almost everybody in this country (does). This has lasted a lot longer than any of us wanted, but we still have to own the realities of what's happening out in the world, of the epidemiology that we're living in,” Ellingson said.

Can I get a test to tell me if I’ve been infected with BA.2 or a different variant?

Not yet, though Lim hopes to see that change. He said that the technology is already in place, but that regulatory and ethical considerations will have to be addressed before the general public can access personalized coronavirus sequencing results.

But he sees people’s interest in individualized information, and thinks such testing could play a role in the future. “The population is vested and interested in these kinds of questions. And if we have this technology, can we … help people be more educated? Seeing the information (at) their fingertips is what makes all of us in a better place as a society moving forward in public health,” he said.

What about long COVID?

It’s still too early to know what impact the BA.1 and BA.2 sublineages of omicron will have on long COVID diagnoses, because by its nature, the condition plays out over several weeks or months. But Lim is concerned about the potential effects of the last omicron surge, which infected millions of people.

“If we (knew) before this that there is long COVID, and we know that there are long-term implications, now consider that you have a large part of the U.S. population and around the world that caught omicron,” Lim said. “This issue of long COVID is something that we need to consider seriously.”

Independent coverage of bioscience in Arizona is supported by a grant from the Flinn Foundation.

Melina Walling is a bioscience reporter who covers COVID-19, health, technology, agriculture and the environment. You can contact her via email at mwalling@gannett.com, or on Twitter @MelinaWalling.

This article originally appeared on Arizona Republic: BA.2, the 'stealth omicron,' is gaining prominence in Arizona cases