New subvariants better evade immune defenses

A new version of omicron is dominant in the US

The coronavirus subvariant, known as BA.5, accounted for nearly 54 percent of the nation’s Covid cases as of Saturday, according to the Centers for Disease Control and Prevention. A similar sub-variant, the BA.4, makes 17% more.

“They’re taking over, so it’s clear that they’re more infectious than the earlier omicron variants,” said David Montefiori, a professor at Duke University Medical Center’s Human Vaccine Institute.

The two subvariants also seem to evade protection from vaccines and previous infections more easily than most of their predecessors.

Montefiori estimated that BA.4 and BA.5 are about three times less sensitive to neutralizing antibodies from existing Covid vaccines than the original version of the omicron variant, BA.1. Other research has shown that BA.4 and BA.5 are four times more resistant to vaccine antibodies than BA.2, which replaced the omicron variant as the dominant version of the coronavirus in the US in April.

Francois Ballou, director of University College London’s Institute of Genetics, said this was most likely another reason why the subvariants took over.

“At this stage now, I think all of these variants are actually about equally transmittable, so there’s not much difference,” he said. “It’s just that some are a little better at infecting people who have been vaccinated or infected by previous variants.”

Last week, the Food and Drug Administration recommended changing the upcoming booster shots from Pfizer and Moderna to target BA.4 and BA.5 directly.

Pfizer told NBC News that it may have an updated vaccine targeting BA.4 and BA.5 ready for distribution in October.

The most common symptoms of BA.4 and BA.5

In the UK, where BA.4 and BA.5 also account for the majority of new Covid cases, the most common Covid symptoms last week were runny nose, sore throat, headache, persistent cough and fatigue. Fewer than a third of people surveyed reported a fever, according to data from the Zoe COVID Symptom Study, which asks people to self-report their symptoms through smartphone apps.

This is consistent with symptoms reported in the UK in the spring when the BA.2 subvariant was dominant.

Balloux said that so far no difference has been observed between the symptoms of BA.4 or BA.5 and those of the previous subvariants. But people who were infected with the original version of the omicron variant during the winter may be susceptible to the newer sub-variants.

“BA.1 and BA.2 are quite different,” he said, so the cross-protection “isn’t that great.”

Ballou added, however, that “BA.2, BA.4 and B.5 from a neutralizing antibody perspective are essentially interchangeable.” This may mean that people infected with BA.2 have some protection now.

Montefiori said BA.4 and BA.5 have not been found to cause more severe disease.

“There’s really no clear evidence that they’re more or less likely to make people sick and cause severe illness and death,” he said.

Rather, the increase in cases and hospitalizations seen in some places is more likely due to waning vaccine protection.

“We now have waning immunity in people who were boosted half a year ago or more,” Montefiori said.

Will we need more booster shots and when?

The FDA estimates that omicron-specific boosters from Pfizer and Moderna will become available in early to mid-fall.

“Companies are now looking to make a vaccine containing BA.4/BA.5 and test it clinically,” Montefiori said.

However, experts stressed that there may not be a dramatic difference in protection between the extra boosts of current vaccines and the omicron-specific injections. Current vaccines still work well to prevent severe disease and death.

“The virus is moving in the direction of evading our vaccines more and more, but it hasn’t found a way to escape vaccines to a really significant degree,” Montefiori said.

For that reason, he added, people eligible for a second booster — those over 50 or the immunocompromised — may not want to wait.

“If your last boost was more than six months ago, you may want to consider reboosting now with the current vaccine to keep your protection strong while we’re still going through this pandemic,” Montefiori said.

Also, Balloux said, it’s hard to predict whether the BA.5 will still be dominant later this year.

“Given the uncertainty, there is no right or wrong,” he said. “There are only trade-offs.”

Europe and South Africa offer a preview of what’s to come

Reported cases of Covid have remained relatively flat in the US since May, but the number of cases is rising globally.

By the end of June, new weekly cases had increased by 32% in Southeast Asia, 33% in Europe and 47% in the region that includes the Middle East, Central Asia, North Africa and the Horn of Africa, the World Health Organization said. As of June 19, BA.5 accounted for 43% of omicron cases worldwide, while BA.4 accounted for 12%.

South Africa had a surge in cases caused by BA.4 and BA.5 this spring, and Covid hospitalizations are increasing in the UK. Experts said the trends likely show the virus is getting better at re-infecting people and evading vaccine protection.

Still, the future of the pandemic will depend not only on the properties of the variants, but also on human behavior and how much immunity is built up in the population.

“People tend to overestimate actually how much the virus has changed recently,” Balloux said. “There was a huge, huge change between delta and omicron, and then again there was a pretty huge change between BA.1 and BA.2.”

That’s not quite the case with BA.4 and BA.5, he said, although he noted that another major change in the evolution of the virus could still occur.

“I’m not saying it won’t happen,” he said.

CORRECTION (July 7, 2022, 7 a.m. ET): A previous version of this article incorrectly stated which group recommended boosters targeting BA.4 and BA.5. It was the FDA, not an FDA advisory committee.

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