Why new COVID variants surge
In its evolutionary fight for survival, the COVID virus is switching strategies: It's becoming a master at slipping past our immune systems. And that, say experts, is largely why we're dealing with an unexpected surge.
Powered by two mutations, new lineages of the omicron variant — BA.2 and its more recent descendants BA.2.12.1, BA.4 and BA.5 — are increasing rates of vaccine breakthrough and reinfection, according to an analysis published Saturday by Trevor Bedford, a virologist at the Fred Hutchinson Cancer Research Center in Seattle, who studies the evolution of viruses.
These latest strains are succeeding “not because they're more contagious as much as they are more immune evasive,” Dr. Paul Offit, an FDA adviser and director of the Vaccine Education Center at Children's Hospital of Philadelphia, said at a recent presentation at UC San Francisco. “This is something that surprises virologists.”
They're driving up case counts, even among those who are fully vaccinated or previously infected.
The United States is averaging about 110,000 new cases each day, a roughly 30% increase over the last two weeks. California's seven-day average case rate has more than doubled since the beginning of May to 34 cases for every 100,000 residents as of Friday. Because many cases go uncounted in official reports as people increasingly test at home, the true toll is higher than these figures show.
At the beginning of the pandemic, the virus grew more contagious, Offit said. The original virus first detected in Wuhan, China, was replaced by the alpha variant, which was replaced by the delta variant, which was replaced by the omicron variant.
Now its descendants are also getting better at dodging our immune system.
“They're different genetically — they have a different pattern of mutations in the genome,” said UC San Francisco virologist Dr. Charles Chiu.
This genetic change doesn't make the COVID virus deadlier, however. Even though immunity from vaccination and prior infections doesn't block infection, it blunts its impact.
But as COVID-19 case numbers increase, hospital and ICU admissions are starting to creep up, too, say experts. In California, the number of COVID patients topped 2,000 this past week, more than doubling from a lull in mid-April after this winter's original omicron surge.
“These viruses should not be underestimated. For every person infected with the Wuhan strain, these (new subvariant) viruses may infect roughly 12,” wrote Dr. William Haseltine, former professor at Harvard Medical School and Harvard School of Public Health.
That is especially troubling, experts say, with COVID mandates a thing of the past, even though masks remain important protection.
Early in the pandemic, few people had been exposed to SARS-CoV-2. There was no evolutionary advantage to skirting the immune system. Rather, all the virus had to do was transmit better.
Now, with an estimated 90% of Americans with antibodies from vaccination or prior infection, immuneevading variants have an increasing advantage — especially if our antibodies have waned over time.
In lab tests by Qian Wang and David Ho and colleagues at Columbia University, antibodies from people “boosted” by vaccines or breakthrough infections were less successful at fending off the BA.4 and BA.5 subtypes of the virus.
Fortunately, the virus isn't changing in a way that will profoundly alter the pandemic — turning it into something deadlier, such as Ebola.
But it is drifting in smaller ways that have long-term consequences. Initially, a subvariant called BA.1 was the most common circulating version of omicron. Then BA.2 became the dominant variant around the world.
Why are the names of mutations so complicated? Proteins are made up of building blocks called amino acids. When a mutation causes a change in an amino acid, the letter changes.
A newer subvariant, BA.2.12.1, now represents 47% of California cases and is on the climb. It has a mutation called L452Q. The lineages of BA.4 and BA.5 represent less than 1% of all cases in California. First described in South Africa in January and February, the two carry mutations called L452R and F486V. In Portugal, where BA.5 got an early start, it has pushed cases past BA.2 levels.
The L452R mutation helps the virus more firmly attach to the cell, as well as escape death by antibodies.
These mutations suggest that BA.4 and BA.5 are “fitter” than BA.2.12.1 and are expected to increase in frequency in the United States, according to Bedford. Compared to BA.2.12.1, BA.4 is expected to cause 1.2 more infections; BA.5 could cause 1.5 more infections.
Multiple infections in the same person may be expected. Both BA.4 and BA.5 are capable of escaping immune protection induced by infection with the original omicron variant, BA.1, Bedford said.
These changes are setting the stage for an endless evolutionary arms race — because the immune system can always make new antibodies, and the virus has a vast set of mutations to explore in response. In contrast, transmissibility of viruses tends to plateau over time.
“As weeks go by, it is evident that the omicron family of viruses continue to grow in complexity,” according to Haseltine. “The story of the omicron family of variants is still emerging and one that the world is watching closely.”