Twin Omicron subvariants have taken over the U.S., but they’re not quite identical. One is ‘the worst version of the virus we’ve seen’

BA.4 and BA.5, which swept South Africa this spring thanks to their ability to evade immunity, were estimated to have caused slightly more than half (52%) of COVID infections in the U.S. last week, according to new data from the U.S. Centers for Disease Control and Prevention.

“The Omicron subvariant BA.5 is the worst version of the virus that we’ve seen,” Dr. Eric Topol, a professor of molecular medicine at Scripps Research and founder and director of the Scripps Research Translational Institute, wrote Monday in anticipation of the viral coup.

“It takes immune escape, already extensive, to the next level, and, as a function of that, enhanced transmissibility,” well beyond what has been seen before, he wrote. “You could say it’s not so bad because there hasn’t been a marked rise in hospitalizations and deaths as we saw with Omicron, but that’s only because we had such a striking adverse impact from Omicron, for which there is at least some cross-immunity.”

BA.2.12.1, another Omicron subvariant dominant before the advent of BA.4 and BA.5, was responsible for 42% of cases. So-called stealth Omicron, BA.2, nicknamed for its ability to evade detection on PCR tests, came in third, comprising nearly 6% of cases. It had been dominant in the U.S. until BA.2.12.1 overtook it last month.

The jury is still out on whether current vaccines hold up against BA.5. But given that vaccines experienced an approximate 15% drop in protection against severe disease from Delta to Omicron, “it would not be at all surprising to me to see further decline of protection against hospitalizations and deaths,” Topol wrote.

BA.4 and BA.5 were first detected in the U.S. in late March, as Fortune previously reported. The variants, discovered in South Africa, quickly took hold in the country in April and May despite the fact that almost all South Africans had been vaccinated or previously had COVID by that point.

The pair of variants are quickly taking hold globally. But their rise is often masked because in many countries, it’s occurring at the same time as a decline in BA.2 infections, Topol wrote. This can lead to the appearance of a sustained wave when, in reality, dual waves are present—the first from an older version of Omicron, and the second from BA.4/BA.5.

A recent study out of South Africa found that those who had been previously infected with Omicron but not vaccinated experienced a nearly eightfold drop in neutralizing antibodies when exposed to BA.4 and BA.5. Those who had been vaccinated and previously infected with Omicron saw a milder threefold decrease. 

Alex Sigal, a professor at the Africa Health Research Institute in South Africa, told Fortune in May that symptoms of the new subvariants are similar to typical Omicron symptoms, which include fever, loss of smell, and malaise. 

“I haven’t seen early symptoms of respiratory distress, the major COVID-specific symptom that makes this disease so dangerous,” he said. “It doesn’t feel nice, but there’s less chance of dying.”