Why Are There So Many Omicron Subvariants—And What Can They Tell Us About the Future of the Pandemic?

What to know as two new subvariants—BA.4 and BA.5—are now on the rise throughout the U.S.

Young Scientist Working in The Laboratory test SARS-COV-2 pcr diagnostics kit.
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Fact checked on June 22, 2022 by Ebyan Abdigir, a multimedia journalist, producer, and fact-checker with nearly a decade of experience.

Two new Omicron subvariants—BA.4 and BA.5, first identified in South Africa between January and February—are gaining steam in the United States, according to the latest estimates by the Centers for Disease Control and Prevention (CDC). Together, they represent 34.9% of all new COVID-19 cases in the U.S., with BA.5 alone making up 23.5%.

It's been a quick rise for the subvariants. In the beginning of May, BA.4 and BA.5 only made up about 1% of all COVID-19 cases—and just like Omicron subvariants of the past, the new ones are set to outcompete the previously dominant subvariants.

This all begs the question: Why are there so many versions of Omicron? Numerous Omicron subvariants have popped up since the original Omicron variant—B.1.1.529—was identified in November 2021: BA.1, BA.1.1, BA.2, BA.2.12.1, BA.3, BA.4, and BA.5 are among the most important subvariants.

What many don't realize, however, is that the Delta variant had subvariants, too—we just weren't as aware of them. "The difference is that the Delta subvariants petered out," Shishi Luo, PhD, associate director of bioinformatics and infectious diseases at Helix, a genomics company that monitors emerging SARS-CoV-2 variants, told Health. "They never really dominated the previous Delta subvariant."

But it's different with Omicron: As new subvariants emerge, they are managing to outcompete the previous ones, ultimately becoming the dominant form of the virus in the population.

Virus Evolution and Naming Structure, Explained

Viruses are always mutating and generating new variants, but most of them go unnoticed. They do that in order to adapt to their environment and spread more efficiently.

When scientists identify that one of these variants, having accumulated enough mutations, changes the virus' ability to transmit or cause severe disease, they give it a new name. If a new lineage comes along that doesn't seem to be a descendant of any main branch in the tree, that's when the scientific community classifies it as a new variant, naming it after a Greek letter.

If the new lineage seems to be closely related to an existing variant, it is considered a subvariant. "That's why we continue to use the BA nomenclature for the Omicron subvariants," said Luo. "Because we can see in the tree that they're more similar to the BA.1 variant than any other existing lineage."

Scientists believe that SARS-CoV-2 may be accelerating its evolutionary rate for short periods of time to accumulate mutations and give rise to new subvariants. Researchers at the University of Melbourne who studied this acceleration pattern compare this behavior with that of marathon runners who occasionally benefit from short sprints.

But regarding Omicron specifically, it's not yet clear if the emergence of so many subvariants means it's mutating more quickly. "The number of mutations the original Omicron had was higher than anyone anticipated, given the amount of time SARS-CoV-2 had been around," said Luo. "Since then, though, I don't think there have been major jumps in the Omicron sublineages in terms of the number of mutations."

Omicron Subvariants Have a Keen Ability to Escape Immunity

Omicron subvariants' abilities to outcompete prior subvariants hinge largely on their ability to evade immunity from both previous infections and immunization.

A preliminary study from early May looked at BA.4 and BA.5 subvariants' abilities to escape immunity from previous BA.1 infections—both with and without vaccination—and found that, because of the two subvariants' abilities to evade immunity, the emergence of BA.4 and BA.5 could result in a new wave of infection.

A recent analysis conducted by Helix also looked into an Omicron subvariant's ability to evade prior immunity, even from infection by another Omicron subvariant. Researchers identified 788 participants who had COVID-19 reinfections during the Omicron BA.2 wave (April and May 2022); of those participants, 146 had also been infected with the virus during the BA.1 wave (January and February 2022). These data suggest that a previous Omicron infection doesn't entirely protect you from other Omicron subvariants.

Although even vaccines don't promise complete protection against infection or reinfection from the SARS-CoV-2 virus, there is some good news: Vaccines are still effective in protecting people from severe disease. According to a March 2022 study published in the BMJ, three doses of an mRNA vaccine was 86% effective in preventing Omicron-related hospital admissions.

"The vaccine efficacy against death is still pretty strong, which means you're seeing more infections, but you're seeing fewer people hospitalized and fewer people dying," Carlos del Rio, MD, a distinguished professor of medicine in the Division of Infectious Diseases at Emory University School of Medicine, told Health.

So far, the Omicron subvariants are causing less severe disease than previous variants in general. And, when comparing the different subvariants with each other, their symptoms have been pretty homogeneous, according to Dr. del Rio.

Can Omicron's Many Subvariants Tell Us Anything About the Future of COVID-19?

Is the fact that SARS-CoV-2 has been evolving into new subvariants of Omicron instead of generating completely new variants good or bad news? That's not yet clear, according to experts.

"The hard thing about this is that using what's happened in the past has not proven to be very useful in predicting the future," said Luo. One possibility would be that the virus will continue to change, but not cause more severe disease, as has been the case with Omicron and its various subvariants. "But we have no evidence to prove that would be the case other than the fact it hasn't happened for the past few months," she noted.

It is also difficult to extrapolate data from other countries to try to predict what will happen in the U.S. In South Africa, for example, the BA.4 and BA.5 subvariants led to a new surge of COVID-19, but the wave was more modest than previous ones. But in Portugal, which also had a BA.4 and BA.5 wave, there was a spike of COVID-19 cases and deaths. "Once you see that evidence, you have to assume that both scenarios could happen in the U.S. and that every region is different," said Luo.

According to Dr. del Rio, the quick emergence of Omicron subvariants means that COVID-19 is likely here to stay—at least for a while. "We will continue to have infections, and it's going to become very common that people will get reinfected," he said. "But hopefully, if you're vaccinated and boosted, you're not going to get very ill."

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