What to Know About the Newest, Most Contagious Omicron Subvariants

It only took about a month for BA.2.12.1, an Omicron subvariant, to cause most of the new COVID-19 cases in the U.S. since scientists first spotted it in the country. But even newer iterations of the Omicron variant are spreading rapidly through the U.S. and are poised to outcompete past versions of the virus, reinfect millions of Americans, and extend the country’s current COVID-19 surge.

BA.4 and BA.5 now account for more than 21% of new cases in the U.S., according to U.S. Centers for Disease Control and Prevention (CDC) estimates as of June 11. These two new subvariants evolved from the Omicron lineage to become even more contagious and can bypass immunity from a past infection or vaccination, experts say. This means people can be reinfected even if they had Omicron earlier this year.

Here’s what to know about the latest Omicron subvariants.

They’re built to escape immunity

Omicron BA.4 and BA.5 were first identified in South Africa in January and February 2022, respectively. BA.2.12.1, meanwhile, evolved out of BA.2 in the U.S., and scientists at the New York state health department identified the first cases caused by it in the country in April.

All three subvariants have a similar mutation that distinguishes them from older versions of Omicron, says Marc Johnson, a microbiology and immunology professor at the University of Missouri who leads the state’s wastewater surveillance program. “There’s clearly a convergence on how to get around the immune system,” he says.

These newer versions of Omicron can bypass antibodies created by past vaccination or prior infection, says Paul Bieniasz, a professor at Rockefeller University who studies viral evolution. Several research groups—including a team at Columbia University, a consortium based in Japan, and an international group including South African scientists—have tested antibodies from prior Omicron infections against BA.4 and BA.5. All three studies found that such antibodies offer several times more protection against Omicron BA.1 or BA.2, which are older versions of this variant, than against BA.4 or BA.5.

While these studies have not yet been peer-reviewed, scientists like Bieniasz consider them part of an expected trend in the coronavirus’ continued evolution. Future variants will “acquire more and more mutations that enable them to evade the antibodies we’re generating in response to vaccination and infection,” he says.

Some treatments aren’t as effective against them

The newer subvariants can also bypass monoclonal antibody treatments, which use lab-made immune system proteins developed from earlier strains of ​​SARS-CoV-2. “Most of those antibodies that have been made are now obsolete,” Bieniasz says. Only one such treatment made by Eli Lilly, specifically designed to work against Omicron, is now effective and in use. Still, other treatments like the antiviral drug Paxlovid can help minimize severe symptoms from Omicron infections.

They’re more contagious, but it’s still unclear whether they cause more severe disease

Limited data are available so far on the severity of the newer subvariants, though scientists are optimistic based on reports from South Africa, which had fewer hospitalizations and deaths during its BA.4 and BA.5 waves compared to BA.1.

However, it’s clear that BA.4, BA.5, and BA.2.12.1 are more contagious than past versions of Omicron, which is allowing them to spread even faster. According to estimates from the CDC, BA.4 and BA.5 grew from causing about 1% of new COVID-19 cases nationwide in the first week of May to causing 22% of new cases in the week ending June 11. BA.2.12.1 has similarly exploded: it’s now causing an estimated 64% of new infections in the U.S. and has caused the majority of new cases nationwide since mid-May.

Data from Helix, a genomics and viral surveillance company, also show BA.4, BA.5, and BA.2.12.1 gaining ground while older versions of Omicron decline. The U.S. already had a BA.1 wave and is now in the middle of a BA.2 wave, says Shishi Luo, associate director of bioinformatics and infectious diseases at Helix. BA.4 and BA.5 could cause a new wave on top of this BA.2 surge, she says.

It’s unclear which strain will dominate the U.S. next

Luo and other experts are watching to identify whether one or two of these concerning Omicron subvariants will outcompete the others. While BA.4 and BA.5 have driven new COVID-19 surges in other countries, these subvariants have yet to compete directly with BA.2.12.1. Early data from the U.K. suggest BA.4 and BA.5 may spread slightly faster than BA.2.12.1, but the landscape is unclear.

BA.4, BA.5, and BA.2.12.1 are all “competing for the same people, because they kind of have the same advantage,” Johnson says. His team’s Missouri wastewater surveillance network is showing that BA.4 and BA.5 are causing more cases in some places, while BA.2.12.1 is causing more cases in others. However, the regions dominated by BA.2.12.1 are showing more of an increase in cases, he says. This pattern contradicts other reports of BA.4 and BA.5 taking over from BA.2.12.1.

Different versions of Omicron could become the dominant strains in different parts of the country, Bieniasz says. For example, in the Northeast, where a BA.2.12.1-driven surge appears to have already reached its peak, BA.4 and BA.5 may gain less of a foothold, while they become more prevalent in the South and West. People’s behavior, such as the choices to hold large gatherings or travel, can also play a role in which variant comes out on top when different strains are “closely matched in their fitness,” he says.

One thing is clear, though: a lot of Americans are susceptible to reinfection from these subvariants. “We can expect to be reinfected,” Luo says. “And every time we’re infected, it’s at best a hassle. And at worst, it can lead to debilitating symptoms,” she adds, pointing to the risk of Long COVID—which, recent studies suggest, is common even among people who have been vaccinated.

“We didn’t really appreciate how slippery this virus would be,” Bieniasz says. He expects the coronavirus to continue evolving around the immune system’s defenses. New vaccine candidates, like the Omicron-specific booster developed by Moderna, may be needed to increase protection against further reinfections.