FAQ: BA.4 and BA.5, potentially the most transmissible Omicron subvariants yet

While the CDC is not yet reporting BA.4 and BA.5 separately, the subvariants are included in B.1.1.529; this grouping is driving increased transmission in some Midwestern and Southern states. Chart via the CDC variant dashboard.

America’s current COVID-19 surge is being driven by BA.2 and its sublineage BA.2.12.1. But there are other versions of Omicron out there to which we need to pay attention—namely, BA.4 and BA.5. Here’s a brief FAQ on these two subvariants, including why scientists are concerned about them and where they’re spreading in the U.S.

What are BA.4 and BA.5?

Remember how, when South African scientists first sounded the alarm about Omicron in November, they identified three subvariants—BA.1, BA.2, and BA.3? BA.1 first spread rapidly around the world, followed by BA.2.

Then, in the winter, South African scientists again identified new Omicron subvariants, called BA.4 and BA.5. These two variations split from the original Omicron lineage, and tend to be discussed together because they have similar mutations. (Specifically, they have identical spike protein mutations; this article discusses the mutations in more detail).

It’s important to note that, while South African scientists characterized these subvariants, they likely didn’t originate in the country. South Africa has a better variant surveillance system than many other countries, particularly compared to its neighbors, allowing the country’s scientists to quickly identify variants of concern. BA.4 and BA.5 also caused a new surge in South Africa, allowing for study of the subvariants’ performance.

Why are scientists concerned about these subvariants?

Early studies of BA.4 and BA.5 indicate that not only are these subvariants more transmissible than other forms of Omicron, they’re also more capable of bypassing immunity from prior infection or vaccination.

Last week, I shared a new preprint from a Japanese research consortium that found BA.4 and BA.5 are more capable of resisting protection from a prior Omicron infection than BA.1. This study, while not yet peer-reviewed, followed similar research from a South African team that found antibodies from an Omicron BA.1 infection offered limited immunity against BA.4 and BA.5, compared to a new BA.1 or BA.2 infection.

Another study by researchers at Columbia University also follows this trend. These researchers tested antibodies from people who’d been vaccinated and boosted against BA.4 and BA.5; they found these two subvariants are “more than four times as likely to escape antibodies in people who’ve been vaccinated and boosted compared with BA.2 viruses,” CNN reports.

While the differences between BA.4/BA.5 and BA.1/BA.2 are less dramatic than the differences between the Omicron family and Delta, scientists hypothesize that there is still enough distinction between these two Omicron sub-groups that people who already had Omicron BA.1 or BA.2/BA.2.12.1 could potentially get reinfected by BA.4 or BA.5.

What are BA.4 and BA.5 doing in South Africa and other countries?

BA.4 and BA.5 have been detected in over 30 countries, according to CNN. But scientists have again focused on South Africa, as this country has better surveillance than many others—particularly as PCR testing declines around the world.

In South Africa, the BA.4/BA.5 wave that started in April has peaked and is now on the decline. Hospital admissions and deaths were lower in this recent wave than in the Omicron BA.1 wave in November and Decenter, largely thanks to high levels of immunity in the country. Still, the continued Omicron infections suggest that reinfection is a real concern for these subvariants.

South Africa never really had a BA.2 wave, so BA.4 and BA.5 mostly competed with other Omicron lineages in that country. But in the U.K., which did face BA.2, recent data suggest that BA.4 and BA.5 have a growth advantage over even BA.2.12.1. In other words, BA.4 and BA.5 could potentially outcompete BA.2.12.1 to become the most transmissible Omicron subvariants yet.

What are BA.4 and BA.5 doing in the U.S.?

The subvariants are definitely here and spreading, but we have limited visibility into where and how much thanks to declined testing and surveillance. The CDC has yet to separate out BA.4 and BA.5 on its variant dashboard; according to White House COVID-19 Data Director Cyrus Shahpar, this is because the CDC has yet to identify these subvariants as causing 1% or more of new national cases in a given week.

But the CDC does include BA.4 and BA.5 in its Omicron B.1.1.529 category, which has grown from causing 1% of new cases in the first week of May to causing 6% of new cases in the last week of the month. The number of cases sequenced in a week has dropped this spring compared to the first Omicron surge, leading me to wonder: are BA.4/BA.5 really causing fewer than 1% of new cases each, or do we just not have the data to detect them yet?

CDC data do show that the B.1.1.529 group (which includes BA.4/BA.5) is causing over 10% of new cases in the Plain States, Gulf Coast, and Mountain West—compared to under 5% in the Northeast, where BA.2.12.1 is more dominant. This data aligns with local reports of BA.4 and BA.5 spreading in wastewater in some Midwestern states that track variants in their sewage. For example, scientists at the Metropolitan Council in the Twin Cities recently said they expect BA.4 and BA.5 to “replace BA.2.12.1 as the dominant variants” in the next few weeks.

What could BA.4 and BA.5 mean for future COVID-19 trends in the U.S.?

As I noted above, data from the U.K. suggest that BA.4 and BA.5 could outcompete BA.2—and even BA.2.12.1—to become the dominant Omicron subvariants in the U.S. Early data from U.S. Omicron sequences are showing a similar pattern, reported variant expert Trevor Bedford in a recent Twitter thread.

“Focusing on the US, we see that BA.2.12.1 currently has a logistic growth rate of 0.05 per day, while BA.4 and BA.5 have logistic growth rates of 0.09 and 0.14 per day,” Bedford wrote. The country’s rising case counts can be mostly attributed to BA.2.12.1, he said, but BA.4 and BA.5 are clearly gaining ground. And, he noted, these two subvariants may be able to reinfect many people who already had BA.1 or BA.2.

In short: even more Omicron breakthrough infections and reinfections could be coming our way. Even if BA.2.12.1 transmission dips (as it seems to be doing in the Northeast), we could quickly see new outbreaks driven by BA.4 and BA.5—leading overall case numbers to plateau or rise again.

“For the summer, going into the winter, I expect these viruses to be out there at relatively high levels,” Dr. Alex Greninger from the University of Washington’s clinical virology lab told CNN. “Just the number of cases, the sheer disruptions of the workforce — It’s just a very high, high burden of disease.”

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