The pandemic might be over in the minds of some. But like it or not, COVID is ramping up for a fall wave-one likely to be fueled by multiple variants, experts say, as the virus mutates and spreads exponentially.
The Institute for Health Metrics and Evaluation at the University of Washington and other experts, including Dr. Anthony Fauci, the nation's top infectious disease expert, foresee a wave beginning to swell in late October, and peaking in late December or January.
It could kill another 20,500 Americans, according to the IHME.
While the coming wave may be caused by multiple variants, they may start to look increasingly similar as they mutate to become more efficient-and take the same path to achieve it.
The wave may be carried by one variant, Dr. Raj Rajnarayanan, assistant dean of research and associate professor at the New York Institute of Technology campus in Jonesboro, Ark., told Fortune this week.
"But if you look closer, they may all have the same set of mutations."
And they may all end up with the same disastrous effect: rendering current COVID countermeasures like drugs and vaccines powerless.
The spawn of Centaurus
Omicron spawn BA.2.75, dubbed "Centaurus," seemed like the COVID variant to watch this summer-one with the potential to wreak havoc later in the year.
But Centaurus is no longer a worry, according to Rajnarayanan. Instead, one of its children, BA.2.75.2, has outcompeted it, eliminating it as a threat-but replacing it with a more formidable one.
Fauci this week called the BA.2.75.2 variant "suspicious," in that it has the potential to develop into a variant of concern for the fall.
In Rajnarayanan's book, it's the most formidable of up-and-coming strains because of its spike protein-a feature that allows it to enter cells-binds more tightly to human cells than that of any other variant. By doing so, it makes it more difficult for antibodies to successfully attack.
The variant is picking up mutations that make it more similar to globally dominant BA.5 and the deadly Delta variant of late 2021. And it's just "a couple of mutations away from picking up increased transmission speed," Rajnarayanan said.
To make matters worse, the new variant shows "extensive escape" ability, according to a new preprint paper released this week by researchers at the Imperial College in London and the Karolinska Institute in Sweden.
The paper, which is not yet peer reviewed but has been widely cited by experts, called the variant "the most neutralization-resistant variant evaluated to date," and said it may effectively evade antibody immunity, built by vaccination and prior infection.
A spin-off of a heavyweight champ
Another major contender: Omicron spawn BF.7. It's a spin-off of globally dominant strain BA.5, three generations removed.
The new subvariant has a change in the spike protein seen in other Omicron strains making headway. It also has a change in the nucleotide sequence-sometimes referred to as the blueprint of an organism-that could cause it to behave differently than other subvariants, Dr. Stuart Ray, vice chair of medicine for data integrity and analytics at Johns Hopkins Department of Medicine, told Fortune this week.
Scientists are taking note of BF.7 because it's making headway in an increasingly crowded field of Omicron subvariants.
"The same growth advantage in multiple countries makes it reasonable to think that BF.7 is gaining a foothold," and that it's potentially more transmissible than parent BA.5, Ray said.
Convergent evolution & 'frankenviruses'
There are more contenders, including BQ.1.1. The variant is jockeying with BA.2.75.2 to lead the wave this fall, Rajnarayanan said.
Major players are beginning to pick up identical advantageous mutations as they try to gain supremacy over their rivals, according to Rajnarayanan. Some mutations offer advantages like increased transmissibility, while others make it more difficult for the human immune system-as well as treatments and vaccines-to fight them off.
It's common for variants to garner multiple mutations-and increasingly, variants of potential concern are acquiring many of the same ones.
"Eventually all variants may look the same at the spike level," Rajnarayana said.
Variant hunters are also keeping their eye on recombinants-combinations of multiple variants that form "frankenviruses" of sorts.
One Rajnarayanan and others are watching: XBB, a combination of two different Omicron spawns. It's not currently a concern in terms of spread, but "it's probably the most immune evasive yet"-even more so than the rising BA.2.75.2, which is more immune evasive than globally dominant BA.5, the most immune evasive until recently.
It's a concerning pattern that has the ability to reduce the effectiveness of COVID treatments, as acknowledged by World Health Organization officials this week-and perhaps even vaccines. In a worst-case scenario, increasingly immune-evasive variants could render them ineffective entirely.
BA.2.75.2 is being watched for its potential to escape the immunity provided by the last antibody drug that is effective on all variants: Bebtelovimab. It's administered to those at high risk of serious outcomes from COVID.
According to a preprint updated Friday by Yulong Richard Cao, an assistant Professor at Peking University's Biomedical Pioneering Innovation Center in China, and others, BQ.1.1 beat it to the punch. The variant escapes immunity from Bebtelovimab, as well as another antibody drug that only works against some variants.
"Such rapid and simultaneous emergence of variants with enormous advantages is unprecedented," Cao and others wrote in the paper.
It's unknown how well new Omicron boosters will hold up against coming variants. But Cao's paper notes that herd immunity and boosters may not protect against new strains. It urges the rapid development of broader COVID vaccines and new antibody drugs, and encourages researchers to test them against recombinants they construct in the lab, in an effort to gauge their effectiveness ahead of time.
Rajnarayanan worries for the future of COVID countermeasures and, like WHO officials, calls on countries to keep up testing and the genetic sequencing of samples. It's the only way to know what's coming, they contend. Ideally, such knowledge will allow researchers to scramble to create new countermeasures, or update old ones, as necessary.
"We used to say we have the tools," he said. "The tools are getting picked off."
This story was originally featured on Fortune.com