As the United States deals with its most recent set of coronavirus, new studies are finding that variants may keep the number of cases high, even in the future.
The next wave of Coronavirus infections will probably be caused by viruses from the new Omicron subvariant BA.4 and BA.5, two closely related viruses characterized in South Africa and that landed in the United States around late March, according to the gene sequence sharing site GISAID. These variants are gaining ground against BA.2, particularly in the central part of the country. Recent research suggests that they escape immunity created by vaccines and past infections.
According to the most recent updates from the US Centers for Disease Control and Prevention (CDC) and the genomics company Helix, two strains of gonorrhea—called BA.4 and BA.5—accounted for an estimated 6% to 7% of new infections in the US in late May. “It’s a serious threat,” said Dr. David Ho, a professor of microbiology and immunology at Columbia University in New York City. “Only a month ago, [the] numbers were .02 percent.”
According to the website Outbreak.info, which is maintained by the Scripps Research Institute, Bay Area 4 (BA.4) has been detected in at least 30 countries and Bay Area 5 (BA.5) has been sampled in 32 countries. Ho and his co-authors recently tested antibodies from the blood of vaccinated and boosted people, as well as the antibodies of people who’d recovered from breakthrough Covid-19 infections, against engineered BA.4 and BA.5 viruses in the lab. In each case, they found a drop in potency against BA.4 and BA.5.
In a study, researchers found that BA.4 and BA.5 viruses are four times as likely to escape antibodies in people who’ve been vaccinated and boosted compared with BA.2 viruses.
More breakthrough infections
All these findings mean that the BA.4 and BA.5 strains are more likely to lead to breakthrough infections in people who have had the Covid-19 vaccine, even if they have been vaccinated previously. Without upgraded vaccines or boosters, Ho expects that many Americans will become sick in the coming weeks or months. “I think we will see lots of infections but not necessarily more severe disease or deaths,” he said. Research posted by Ho as a preprint has not yet been scrutinized by outside experts or published in a medical journal.
The South African strain of influenza, which is ahead of the United States in its BA.4/BA.5 cycle, has seen infections rise but has not seen a corresponding increase in deaths, said Shishi Luo, associate director of bioinformatics and infectious disease at Helix. “So I think if we extrapolate from South Africa, what we’ll see in the United States is that BA.4 and BA.5 will increase, because it has some competitive advantages compared to existing strains,” Luo said.
Some researchers have wondered whether two variants of Omicron-type virus, BA.4 and BA.5, might outcompete the highly contagious strain that’s currently causing most Covid-19 infections in the US. These branches of the Omicron family tree rose to prominence around the same time; BA.2.12.1 quickly took over the US while BA.4 and BA.5 were establishing themselves in South Africa. They share some similarities, including changes at location 452 of their genome, a genetic address known for helping variants escape our immunity.
Viruses square off
Dr. Alex Greninger, assistant director of the University of Washington’s clinical virology laboratory, compared the fight between H5N1 and H7N9 to a boxing match wherein the South African champion is pitted against the U.S. champion. “You don’t know how to rank them if they haven’t ever fought,” he says.
In the UK, 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, indicating that those viruses are spreading faster than BA.2.12.1. The doubling times were included in a recent technical report from the UK Health Security Agency. The betting favorite now suggests that BA.4 and BA.5 would be able to take out BA.2.12.1 “The betting favorite now suggests that BA.4 and BA.5 would be able to take out BA.2.12.1,” Greninger said.”We may have figured out what’s giving BA4 and BA5 an extra edge.”
In addition to all the changes in other influenza viruses that help them avoid our immune systems, these viruses pulled off a mutation called F486V. It’s big change that helps disguise them from our immune system. In the past, it came with a downside: It made their spikes less likely to be able to bind to our cells, so they were less competitive. But BA.4 and BA.5 have an additional mutation, called R493Q, that restores their ability to bind to our cells—restoring their ability to infect us.
Although BA.4 and BA.5 are theoretically capable of overpowering BA.2.12.1, they have not squared off in the US, and the fitness of these strains depends on factors that are difficult to predict. The variants are not following a rulebook; however, experts say you can expect to see a lot of Covid-19 around you over the next few months because of its high transmission rate and ability to spread quickly among hosts. “For the summer, going into the winter, I expect these viruses to be out there at relatively high levels,” Greninger said. “Just the number of cases, the sheer disruptions of the work force — It’s just a very high, high burden of disease.”
