BA.4 and BA.5, two new Omicron variants sweeping South Africa, detected in U.S.

“BA.4 sequences have been identified in samples from multiple U.S. states,” Andy Pekosz, virologist at the Johns Hopkins Bloomberg School of Public Health, told Fortune, adding that the variant is clearly circulating in the U.S., “it’s just not clear precisely how widely.”

Madison Stoddard, a COVID-19 researcher at drug development firm Fractal Therapeutics, confirmed Friday that there were 12 cases of U.S.-sequenced BA.4 in GISAID, an international research database that tracks changes in COVID and the flu virus, with the earliest collected on March 30. There were also five cases of BA.5 sequenced in the U.S. as of Friday, with the earliest collection date of March 29, they said.

The U.S. Centers for Disease Control did not immediately respond to a request for comment Friday. But the agency’s COVID Data Tracker states that cases of BA.4 and BA.5, in addition to BA.1, original strain of Omicron, and BA.3—as well as their sublineages, except for BA.1.1 and its sublineages—are all listed under the same variant, B.1.1.529. In sum, they total less than 1% of U.S. cases from April 17-23 but are labeled as variants of concern.

More infectious than ‘stealth Omicron’

BA.4 and BA.5 appear to be more infectious than BA.2, also known as “stealth Omicron,” which was more infectious than the original Omicron, BA.1, Bloomberg reported Thursday, citing South African COVID expert Tulio de Oliveira, the head of the institutes at the universities of KwaZulu-Natal and Stellenbosch.

The two new variants have “mutations in the lineages that allow the virus to evade immunity,” he told Bloomberg. “We expect that it can cause reinfections and it can break through some vaccines, because that’s the only way something can grow in South Africa, where we estimate that more than 90% of the population has a level of immune protection.”

Cases are surging in South Africa despite the fact that almost all South Africans have been vaccinated or had COVID, he said, signaling that these strains are more likely to be capable of evading the body’s defenses.

South African public health officials on Friday said that the country may be entering a fifth COVID wave, due to BA.4 and BA.5, as the number of positive tests rises. Hospitalizations are also rising, they said. Deaths have not yet, Bloomberg reported, though they’re considered a “lagging indicator” by public health officials.

A ‘fundamentally different’ subvariant

Significant mutations in BA.4 make it a new lineage distinct from stealth Omicron, Dr. Renee Wegrzyn, head of biotech firm Concentric’s innovation team, told Fortune. 

Concentric and XpresSpa Group’s XpresCheck have partnered with the CDC to track Omicron in travelers arriving from South Africa—including those that arrive via Europe—at John F. Kennedy International Airport and Newark-Liberty International Airport in New York, San Francisco International Airport in California, and Hartsfield-Jackson Atlanta International Airport in Georgia. Wegrzyn’s team identified the 11th reported case of BA.4 in the U.S.—in a passenger from South Africa arriving in Atlanta about a week ago, she told Fortune on Thursday.

A phenomenon called “S gene target failure” —a reference to some PCR tests’ initial inability to detect the variant due to a small deletion on the S gene, one of three genes the tests look for—was signature of the original Omicron, but not of BA.2 and BA.3.

But in BA.4, it’s back, Wegrzyn said. 

“Early indicators [were that] something was different, this looks different on that initial test. It looks positive, but not like other positives,” she said.

“Something is fundamentally different about this.”

South African scenario may not play out in U.S.

While it’s well established that BA.4 has “some kind of growth advantage, at least in South Africa,” the same scenario may not play out in the U.S., Stoddard said, pointing to Omicron variant Beta as an example.

“The Beta variant was very successful in the South African population and we didn’t see it spread very widely in the [United] States,” they said. “The contact patterns are different, the nature of immunity is different in different populations. There’s no guarantee we’ll have the same outcomes South Africa has seen with these particular variants.”

Pekosz said BA.4 and BA.5 are closely related and should act somewhat similarly to each other, and that immunity from previous Omicron strains should hold.

“Both have some mutations … that are of particular concern because they are linked to increased transmission, but immunity from BA.1 or BA.2 infection should still recognize these variants, so I would not expect a surge that rivaled what we saw with BA.1,” he said.

But de Oliveira disagrees, tweeting on Friday that “previous infections with Omicron BA.1 will not be sufficient to prevent a second infection with BA.4 and BA.5.”

“We are all tired of this virus, but he may not be tired of us,” he tweeted. “We need now to take seriously the decreasing immunity from previous infections and … show that vaccination is much more reliable to maintain immunity than only infection.”