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What You Need to Know About the Omicron BA.2.12.1 Subvariant

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Key Takeaways

  • BA.2.12.1 is set to become the dominant COVID-19 variant in the United States.
  • The variant appears to be more transmissible than BA.2, but there is no evidence yet that it causes more severe disease.
  • Experts say to expect that such minor mutations in Omicron will continue throughout the next few months of the pandemic.

An offshoot of the Omicron variant, BA.2.12.1, will likely be the dominant COVID-19 strain in the United States soon. This subvariant is currently responsible for 42.6% of the new cases and it is on track to over take BA.2, demonstrating its transmission advantage.

BA.2.12.1 is already accounting for a majority of the new cases in northeastern U.S. Since it was first spotted in November 2021, the subvariant has been detected in at least 70 countries.

Omicron has continued to evolve and splinter into a smattering of subvariants that have become more transmissible, and experts believe that more new versions of Omicron may crop up in coming months.

Scientists around the world have found more than 70 Omicron off-shoots, according to a variant database. Two of those—BA.4 and BA.5—are circulating at low levels in some parts of southern Africa and Europe, the World Health Organization said.

Early signs from South Africa suggest that these new subvariants are no more likely to cause severe disease than the earlier versions of Omicron.

What Makes BA.2.12.1 Different

With each evolution of COVID-19, the virus tends to become incrementally transmissible than the last version. The original Omicron carried a whopping 30 mutations in the spike protein, which helps attach the virus to the cells and increase its transmissibility.

BA.2.12.1 contains about 20 of the same mutations seen in the original Omicron, plus seven new ones, said Benjamin tenOever, PhD, a professor of microbiology and medicine at New York University and an affiliate member of the New York Genome Center.

“It is likely that the sub-sub-variants will now start taking prominence in the space, but they’re not their own variant yet,” tenOever told Verywell. “They’re still basically Omicron—they just have a few more spike mutations.”

COVID-19’s spike protein targets ACE2 receptors, which allow the virus to access human cells. Since Omicron’s mutated spike protein is more eager to attach to the ACE2 receptors right when it enters the body, the infection remains largely in the upper respiratory tract and doesn’t always get a chance to move deeper into the lungs. Therefore, the enhancement of the spike protein seen in the Omicron subvariants indicates that these versions may also cause relatively mild illness, tenOever said.

He said he’s relieved to see that most of the changes are in the spike protein rather than the other internal components of the virus, which might make it more adept at evading immune defenses.

BA.2.12.1 carries a mutation in a section of its spike protein called L452Q. Genetic swaps in L452 have helped other COVID-19 variants, including Delta and Lambda, to attach more tightly to ACE2 and become more transmissible.

Scientists don’t yet know exactly what makes the new subvariant more transmissible. tenOever said some of the other new mutations may help the virus to glom onto ACE2, allow it to enter a cell more quickly after attaching to ACE2, or reduce its dependence on certain enzymes called proteases to replicate.

These changes may mean that an individual can become infected more quickly with less exposure.

“Someone can now give you the virus by breathing less virus on you—that’s really new,” tenOever said. “The virus is getting much more efficient at being able to jump from one person to another person, which means that [infection] happens earlier, it happens faster, and probably most importantly, it happens even before most people know they’re sick or test positive.”

Expect to See More Versions of Omicron

The influx of COVID-19 variants seems to mirror the genetic “drift” that scientists often see when tracking influenza and other viruses.

Future variants in the U.S. are likely to accumulate minor genetic mutations on top of prior Omicron subvariants, causing a “flu-like drift,” Trevor Bedford, PhD, a professor of biostatistics, bioinformatics, and epidemiology at Fred Hutchinson Cancer Center, told an FDA panel earlier this month.

In a tweet thread, Bedford said that because BA.2 is the dominant strain worldwide, new variants will likely be slightly more transmissible versions of that particular subvariant.

A less likely scenario, Bedford said, was that a new divergent variant could evolve to mostly evade our immune responses, causing a surge in cases as was the case when Omicron overtook Delta.

tenOever said it’s likely that Omicron will keep adjusting to be more transmissible, until it runs out of ways to improve the spike protein. In the meantime, he said being fully vaccinated and receiving a booster shot are the best ways to protect yourself and others from Omicron and its subvariants.   

“I’m not saying it’s a harmless virus, but it’s not as serious as the ones before, especially amongst those people who have had been vaccinated or have some pre-existing immunity—which many do now,” tenOever said. “At this moment in time, I think there’s lots of room for optimism and hopefully it stays that way.”

What This Means For You

New York State Health Commissioner Mary T. Bassett, MD, MPH, said that the tools to combat COVID-19 variants remain the same: getting fully vaccinated and boosted, getting tested after potential exposure, and wearing a mask in public indoor spaces.

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.

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2 Sources
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  1. Centers for Disease Control and Prevention. COVID data tracker: variant proportions.

  2. Tchesnokova V, Kulasekara H, Larson L, et al. Acquisition of the L452R mutation in the ACE2-binding interface of spike protein triggers recent massive expansion of sars-CoV-2 variants. J Clin Microbiol. 2021;59(11):e0092121. doi:10.1128/JCM.00921-21