New, highly mutated COVID variants ‘Pirola’ BA.2.86 and JN.1 may cause more severe disease, new studies suggest

In one study, researchers from Ohio State University performed a variety of experiments using a BA.2.86 pseudovirus—a lab-created version that isn’t infectious. They found that BA.2.86 can fuse to human cells more efficiently and infect cells that line the lower lung—traits that may make it more similar to initial, pre-Omicron strains that were more deadly.

In the other study, researchers in Germany and France came to the same conclusion. “BA.2.86 has regained a trait characteristic of early SARS-CoV-2 lineages: robust lung cell entry,” the authors wrote. The variant “might constitute an elevated health threat as compared to previous Omicron sublineages,” they added.

While illness caused by the initial Omicron strain was typically considered more mild than that caused by earlier variants, it’s impossible to say definitively, experts say. That’s because those sickened by Omicron had generally already been infected with an earlier version of the virus, likely softening the blow. Additionally, many had been vaccinated, to the same effect.

Still, Omicron had a penchant for infecting the upper airway versus the lower airway, where prior versions of the virus tended to accumulate, causing more severe disease. The new studies offer proof that this trend may very well be reversing, the authors contend. If true, it’s bad news for those who hoped the virus was slowly attenuating to the equivalent of a common cold.

“We cannot ignore the evidence” that Omicron may be evolving into a more severe form of itself, Dr. Shan-Lu Liu—professor and co-director of the Viruses and Emerging Pathogens Program at Ohio State University, and lead author on the first study—told Fortune.

Increasing COVID hospitalizations in the U.S. and around the globe potentially bolster the argument, he added.

It’s tough to tell if disease caused by COVID is again becoming more severe because waning immunity muddles matters, experts say. Antibody immunity to COVID from vaccination or prior infection—which can reduce the severity of the disease or prevent infection altogether—declines after three to six months. Globally, uptake of the latest COVID booster, released this past fall, leaves much to be desired. In the U.S., it sits under 20%, according to the Centers for Disease Control and Prevention. In theory, the longer it’s been since someone was infected with COVID or received a booster, the greater their risk for severe outcomes like hospitalization and death.

Is JN.1 more severe than Omicron?

As for what the studies might mean regarding the severity of JN.1 infection, the jury is still out. But the new findings—combined with expert speculation that JN.1 may be showing a preference for infecting the GI tract—warrant more study into the evolving nature of the virus, according to Liu.

Another concern of his: the possibility of COVID recombining with another coronavirus in animals, then transitioning back over to humans—throwing another viral plot twist into the pandemic’s narrative.

Some experts contend that Omicron—highly mutated compared to previous strains—originated in animals, then spilled back over into humans (as opposed to developing in a human with a long-term infection, as others contend). Regardless, animals serve as an underappreciated wild card, Liu contends. Case in point: Nearly every white-tailed deer in Ohio has tested positive for COVID, affording the virus an entire additional population in which to mutate.

Another, perhaps larger concern of Liu: the possibility that COVID recombines with another, more deadly coronavirus like SARS or MERS, which had case fatality rates around 10% and 34%, respectively. In contrast, COVID’s case fatality rate, among unvaccinated Americans, sat around 1% prior to Omicron, and around 0.11% after.

“Anything can happen,” Liu said. “It’s really hard to predict what’s going to come next, but nature can do amazing things.”

The bottom line when it comes to the power of animals to further evolve the virus and send another curveball flying humanity’s way: “Humans, watch out.”