New variants are poised to keep Covid-19 circulating at high levels throughout the summer

The next influx of infections is likely to come from the newer Omicron subvariants BA.4 and BA.5, two closely related viruses first characterized in South Africa that landed in the United States in late March, according to gene sequence sharing website GISAID .

These variants are gaining ground over BA.2, especially in the central part of the country. Recent research suggests they are escaping the immunity created by vaccines and past infections.

According to the latest updates from the US Centers for Disease Control and Prevention and genomics company Helix, BA.4 and BA.5 together accounted for an estimated 6% to 7% of new infections in the US at the end of May.

“It is a serious threat,” wrote Dr. David Ho, a professor of microbiology and immunology at Columbia University in New York City, in an email. “Just a month ago it was 0.02 percent.”

According to the website Outbreak.info, operated by the Scripps Research Institute, BA.4 has been detected in at least 30 countries and BA.5 has been tested in 32 countries.

Ho and his co-authors recently tested antibodies from the blood of vaccinated and boosted people, as well as those from people who had recovered from breakthrough Covid-19 infections, against man-made BA.4 and BA.5 viruses in the lab . They found a drop in potency compared to BA.4 and BA.5.

They found that BA.4 and BA.5 viruses were more than four times more likely to escape antibodies in vaccinated and boosted people compared to BA.2 viruses.

More breakthrough infections

All of this means that BA.4 and BA.5 are more likely to lead to breakthrough infections, even in people who have previously had Covid-19.

Without improved vaccines or boosters, Ho expects many Americans to get sick in the coming weeks to months. “I think we’re going to see a lot of infections, but not necessarily more serious illnesses or deaths,” he said.

Ho’s research is published as a preprint, meaning it has not been reviewed by outside experts or published in a medical journal.

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South Africa, which is ahead of the US in its BA.4/BA.5 cycle, saw an increase in infections but no corresponding increase in deaths, said Shishi Luo, deputy director of bioinformatics and infectious diseases at Helix.

“So I think if we extrapolate from South Africa, in the US we will see that BA.4 and BA.5 will increase because it has some competitive advantages compared to existing strains, but I have my fingers crossed that it doesn’t going to lead to more serious outcomes,” said Luo.

One question variant hunters have asked is whether BA.4 and BA.5 can outperform BA.2.12.1, the highly contagious strain that is currently the leading cause of Covid-19 infections in the US.

These branches of the Omicron family tree became known at about the same time; BA.2.12.1 quickly took over the US while BA.4 and BA.5 established themselves in South Africa.

They share some similarities, including changes at position 452 of their genome, a genetic address known for helping variants escape our immunity.

Viruses fight back

“It’s like boxing,” said Dr. Alex Greninger, Associate Director of the University of Washington Clinical Virology Laboratory. “It’s like the national champion from South Africa taking on the national champion from the United States.

“You don’t know how to classify them if they’ve never fought,” he says.

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But BA.4 and BA.5 have competed against BA.2.12.1 in other parts of the world, like the UK. There, scientists found that the time it took for the number of infections caused by a variant to double was about 5½ days for BA.2.12.1 and about a day less for BA.4 and BA.5, which suggesting that these viruses are spreading faster. The doubling times were included in a recent UK Health Security Agency technical report.

“The betting favorite now suggests that BA.4 and BA.5 would be able to knock out BA.2.12.1,” Greninger said.

Ho and his team believe they’ve figured out what gives BA.4 and BA.5 an extra edge.

In addition to all the changes in other Omicron variants that help them shrug off our vaccines, these viruses have spawned an F486V mutation. This is a big change that helps hide them from our immune system. In the past, this had a downside: it made the virus’ spike less likely to attach itself to our cells, making them less competitive. But BA.4 and BA.5 have an additional mutation called R493Q that restores their ability to attach to cells and restores their ability to infect us.

Although BA.4 and BA.5 appear capable of overpowering BA.2.12.1, they have not caught on in the US and the fitness of these strains is highly dependent on the playing field. The variants do not follow any set of rules.

But for the next few months, experts say, there’s just going to be a lot of Covid-19 around us.

“As summer transitions into winter, I expect these viruses to be out there in relatively high concentrations,” Greninger said. “Just the number of cases, the sheer disruption of the workforce — it’s just a very high disease burden.”