(CNN) — There’s no denying the numbers: Even with spotty reporting, Covid-19 cases and hospitalizations are rising again in the United States.

Cases are trending up in most states and have increased by more than 50% compared with the previous week in Washington, Mississippi, Georgia, Maine, Hawaii, South Dakota, Nevada and Montana. In New York, more than a quarter of the state’s population is in a county with a “high” Covid-19 community level, where the US Centers for Disease Control and Prevention recommends indoor masking.

Average daily hospitalizations are up about 10% since last week, according to data collected by the US Department of Health and Human Services.

The culprit this time appears to be a spinoff of Omicron’s BA.2 subvariant called BA.2.12.1, which was first flagged by New York state health officials in April.

BA.2.12.1, which is growing about 25% faster than its parent virus, BA.2, accounts for nearly 37% all Covid-19 cases across the US, according to new estimates from the CDC.

BA.2 caused an estimated 62% of all Covid-19 cases last week, down from 70% the week before.

US, South Africa contend with faster new variants
BA.2.12.1 isn’t the only Omicron offshoot that scientists are watching.

After weeks of declines, South Africa saw its Covid-19 cases rise steeply in the past two weeks. Test positivity and hospitalizations have also popped up as scientists have watched two relatively new subvariants, BA.4 and BA.5, dominate transmission in that country. Taken together, they accounted for almost 60% of all new Covid-19 cases by the end of April, according to South Africa’s National Institute of Communicable Diseases.

These new Omicron subvariants are spreading around the globe. BA.4 sequences have been reported in 15 countries and 10 US states, while BA.5 has been picked up in 13 countries and five US states, according to the website Outbreak.info, which maintained by a coalition of academic research centers and is supported by funding from the National Institutes of Health.

Like BA.2.12.1, BA.4 and BA.5 have a growth advantage over BA.2.

Omicron subvariants escape immunity
A new preprint study, published ahead of peer review, is pointing to why BA.4 and BA.5 are gaining ground: They can escape antibodies generated by previous infections caused by the first Omicron virus, BA.1, the variant responsible for the huge wave of infections that hit many countries in December and January. They can also escape antibodies in people who’ve been vaccinated and had breakthrough BA.1 infections, though this happened to a lesser degree than seen in people who’ve only been infected.

Researchers in South Africa tested the ability of antibodies in blood to disable BA.4 and BA.5 viruses in a lab. In people who were unvaccinated but recently recovered from a BA.1 infection, they saw a more than seven-fold drop in the ability of their antibodies to neutralize BA.4 and BA.5 viruses. In people who’d been vaccinated but recently had a breakthrough infection caused by BA.1, the drops were smaller, about three-fold lower.

By way of comparison, the World Health Organization uses an eight-fold drop in neutralization as the threshold for the loss of protection that requires an update to seasonal influenza vaccines.

The study results led the researchers to write that “BA.4 and BA.5 have potential to result in a new infection wave,” making Covid-19 vaccinations and booster shots crucial to stopping the next wave.

“Our conclusions from this are, first, that Omicron by itself is not a great vaccine, right?” said Alex Sigal, a virologist at the Africa Health Research Institute who led the study. “Just because you were infected does not mean you have a lot of protection from what’s coming next.”

Dr. Eric Topol, a cardiologist who is the founder and director of the Scripps Research Translational Institute, praised the research, pointing out that this lab was also the first to characterize the first Omicron variant: “They’ve been first-rate all the way through the pandemic.”

He said that overall, the finding was not good news. Even people who recovered from a Covid-19 infection as recently as December or January can be reinfected by these new subvariants.

“That dropoff of immune escape or immune evasion was pronounced in people who were unvaccinated,” Topol said, pointing out that only about 1 in 3 people in South Africa have been vaccinated against Covid-19.

For those who are vaccinated, “those people are also not as bad, but they also have to face BA.4 and BA.5 with less solid neutralizing antibody response,” he said. “The mutations in BA.4 and BA.5 are playing out to be a challenge to our immune response.”

Only a few dozen sequences of these viruses have been reported in the US and Canada. Researchers say it’s just too early to know whether BA.4 or BA.5 will take off in the United States.

It wouldn’t be surprising if they do, said Andy Pekosz, a virologist and professor of molecular microbiology and immunology at Johns Hopkins University.

“We’ve seen this over and over again. As a variant becomes dominant in another country eventually ends up here in the US and spreading globally,” Pekosz said.

In the meantime, Topol said, we have our own sublineage to deal with: BA.2.12.1.

“It may simulate the problems of BA.4 and BA.5,” Topol said. “We don’t know yet because there’s no study like this one from the Sigal lab.”

Shared mutation
The BA.4 and BA.5 viruses and BA.2.12.1 have mutations at location 452 of their genomes. This region codes for a part of the viruses receptor binding domain — the part of the virus that docks onto a door on the outside of our cells. The Delta variant and some others have picked up mutations in this location. Researchers believe that changes there help the virus bind more tightly to our cells and hide from frontline immune defenders called antibodies that try to block the virus from invading our cells.

“That may make it transmit better perhaps between our cells as well,” Sigal said.

BA.4 and BA.5 also have changes at location 486, which is a bit of a head-scratcher because previous viruses that changed in this location didn’t do well. They fizzled out.

“Suddenly, this guy manages it. So we don’t know what that does,” Sigal said. “My suspicion is that’s a heavy escape mutation,” meaning it helps the virus hide from our immune system.

Scientists have begun work to try to better understand BA.2.12.1, which has been detected in 22 countries, though most of the sequences have come from the United States.

Pekosz said he has been growing copies of BA.2.12.1 in his lab and has recently shipped samples of the virus to other research groups for study. He said scientists have just started talking about experiments they want to do to try to answer two key questions: How quickly is it copying itself, and how well does it escape our immunity?

Before the SARS-CoV-2 virus, scientists thought coronaviruses didn’t change much. Pekosz said that, looking back, we didn’t know what we didn’t know.

As long as the virus continues to find hosts to infect, it will continue to evolve.

“This virus has shown that it mutated slowly, but when it started to pick up good mutations, they just kept coming and coming and coming,” he said.

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