The coronavirus could mutate to cause more severe disease, according to experts

JN.1's parent can infect lung cells more efficiently, a mutation that's different from the "milder" Omicron

By Nicole Karlis

Senior Writer

Published January 12, 2024 7:30AM (EST)

Woman Suffering From A Cold Lying In Bed (Getty Images/Obradovic)
Woman Suffering From A Cold Lying In Bed (Getty Images/Obradovic)

The coronavirus subvariant JN.1 continues to retain its status as the most dominant strain in the United States this year.

According to CDC estimates, nearly 61 percent of COVID-19 cases are infections with the JN.1 strain. Over the course of one month, JN.1 went from being the third most prevalent strain in the U.S., after EG.5 and HV.1., to No. 1. Experts have previously said that JN.1 is largely contributing to this year’s surge of winter illnesses as COVID-19 hospitalizations and deaths are on the rise in some parts of the country.

But as previously reported, JN.1 didn't come out of nowhere. In August 2023, virus trackers first discovered its parent, BA.2.86, and noted that it was significantly different from Omicron. With nearly double the number of mutations on the spike protein than previous strains, experts warned BA.2.86 likely had a stronger ability to bind to cells, making it more infectious. It also had a mutation in the virus’s spike protein, which experts said increased the chances of immune evasion to the disease. Until recently, BA.2.86  and JN.1 were grouped together as experts referred to them as the so-called "Pirola clan.” In December, the World Health Organization announced that it was classifying JN.1 as a separate variant of interest. This week, two new studies reveal not so great news about what has been dubbed the Pirola clan, perhaps revealing more clues as to why JN.1 is behind a coronavirus surge this winter.

In the first study published in the journal Cell, researchers found that BA.2.86, the parent of JN.1, can infect lung cells more efficiently. Specifically, the researchers found that it can infect lung cells more easily with the help of a cellular enzyme called TMPRSS2, suggesting that two mutations in the spike protein are responsible for making it easier for the virus to enter the lung cells. Researchers said this is significant because previously circulating Omicron sub-variants did not have this mutation, hence contributing to it being a "more mild" form of COVID-19. But the variants Alpha, Beta, Gamma and Delta, which circulated during the first years of the pandemic, did have mutations that made it easier for the virus to enter into lung cells.

“It is noteworthy that two years after the global dominance of the Omicron variant, which fails to robustly enter lung cells, now a quite different virus is spreading,”  said Stefan Pöhlmann, co-author of the study and head of the Infection Biology Unity of the German Primate Center, said in a media release. “And that this virus is able to again enter lung cells with high efficiency.”

The good news is that once the lung cells were infected, according to the study, they weren’t able to replicate as effectively as the pre-Omicron variants. 

“No matter how virulent a variant is, it won’t cause much damage overall if it can’t successfully infect new hosts.”

A second study published in Cell this week by researchers at Ohio State University also found that BA.2.86 can merge with cells more efficiently and that they can easily infect cells in the lower lung. Both studies show that instead of the virus evolving to be more “mild” it could be evolving in a more disconcerting direction. What does this all mean for JN.1, which is dominating U.S. infections?

Technically, the jury is still out regarding whether or not JN.1. leads to more severe disease or not. These studies focused on BA.2.86. But as Ryan Gregory, an evolutionary and genome biologist at the University of Guelph in Canada, told Salon there are very few genetic differences between JN.1 and BA.2.86.

“It seems likely that the same lung infecting properties are found in JN.1, along with the significantly increased ability to infect new hosts versus BA.2.86,” he told Salon via email, adding that there is good news in terms of how it weakly replicates. “No matter how virulent a variant is, it won’t cause much damage overall if it can’t successfully infect new hosts.”

As the first study noted, BA.2.86 has not been especially successful in that regard. Gregory said it’s concerning to see variants succeeding in terms of immune escape, transmissibility and its ability to infect the lungs. At the same time, he noted, the level of immunity in the world’s population is much higher compared to pre-pandemic times. Just because JN.1 could be better at infecting lungs, and maybe even better at infecting more hosts, that doesn’t necessarily mean JN.1 will “cause a huge wave of severe respiratory infections,” he said.

“It will add to pressure on healthcare systems, though, and of course there is the ever-present issue of long COVID,” he said, adding that future generations of JN.1 could pick up “additional mutations” that make it even more concerning. Indeed, this appears to be the crux of the concern. 

Dr. Rajendram Rajnarayanan, of the New York Institute of Technology campus in Jonesboro, Arkansas, told Salon he is also concerned about what this means for future generations of the coronavirus.

“Concerns arise with JN.1 and its sublineages, as new mutations could potentially push boundaries,” he said via email. “The lack of efficient lung tropism in previous Omicron lineages contributed to their mild presentation without immediate hospitalization requirements.”

The idea that viruses evolve to become benign . . . is a “myth” and was never guaranteed.

He added that he believes it’s urgent for the next round of vaccines to be utilizing “a JN.1 spike backbone” and anticipate further mutations as the variant continues to spread. 

In terms of how the coronavirus will evolve from here, Gregory emphasized that the idea that viruses evolve to become benign — like the coronavirus evolving into the “common cold” — is a “myth” and was never guaranteed. “That’s not how evolution works,” he said, adding that it’s important to recognize that the current situation is “unprecedented.” 

“We’ve had pandemics before, but never one with 8 billion potential hosts, massive global travel, a virus that can infect and reinfect year-round, and a population living to older age as we have now,” he said.

By Nicole Karlis

Nicole Karlis is a senior writer at Salon, specializing in health and science. Tweet her @nicolekarlis.

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