A newly published study from Ohio State University researchers found that the recently emerged SARS-CoV-2 BA.2.86 variant is more likely to infect certain lung cells than any previous Omicron variant. Research suggests that BA.2.86 has the potential to cause COVID-19 disease severity similar to the devastating 2021 Delta variant.
The SARS-CoV-2 variant BA.2.86 first appeared in August 2023. In a year dominated by recombinant XBBs and their extensive family trees, this new variant stands out. It is the first noteworthy viral lineage to emerge from the original BA.2Omicron family in nearly a year, and it appears to have emerged out of nowhere.
Regarding BA.2.86, most researchers hold a "wait-and-see" attitude. BA.2.86 appears to exhibit characteristics that enable it to produce more severe disease, but these characteristics come at the expense of reduced infectivity. BA.2.86 is simply not as immunologically aggressive as the XBB variant, so people who have previously acquired immunity are likely to be able to effectively fend off it.
But BA.2.86 only mutated once and turned into a virus called JN.1, which is incredibly immunoinvasive. Within months, JN.1 conquered the world, and now, as we enter 2024, it has become the most dominant SARS-CoV-2 variant, causing a massive wave of infections during the New Year.
Newly published cell culture research amplified BA.2.86 in an effort to better understand how this new coronavirus variant evades antibodies and enters human cells. This study first effectively confirmed the conclusion of previous epidemiological studies: BA.2.86 has weaker immune evasion ability than the XBB variant. So it's unlikely to become the dominant variant, at least until it moves to JN.1.
More worryingly, however, the findings showed BA.2.86's increased ability to infect lung cells called CaLu-3 cells. These cells, located in the lower part of the lung, are lined with a surface protein called TMPRSS2.
SARS-CoV-2 typically enters human cells via two different surface proteins: ACE2 and TMPRSS2. When the virus mutates into the Omicron form, it begins to preferentially select ACE2 for entry into cells. This makes the virus more transmissible and less severe, which is why Omicron's disease profile is milder.
Shan-Lu Liu, senior author of the latest study, noted that BA.2.86 enters CaLu-3 lung cells better than any COVID variant since Delta. This means that this subline of the virus may cause more severe disease than previous Omicron or XBB variants.
"...BA.2.86 appears to have increased infectivity to human lung epithelial cells compared to all Omicron variants, so that's a bit concerning," Liu said. "Consistent with infectivity, it also has enhanced fusion activity with human lung epithelial cells. This raises potential concerns about whether this virus is more pathogenic than recent omicron variants."
So far, according to the latest CDC report, there is no evidence that JN.1 causes more severe disease than other circulating variants. However, Liu took a slightly more cautious view, noting that BA.2.86's ability to infect certain lung cells was a distinguishing feature of early severe SARS-CoV-2 variants. And with infection levels so high in the world right now, it's likely the virus will continue to mutate in directions that could lead to more severe disease.
"The concern is whether this variant and its descendants, including JN.1, will have an increased propensity to infect human lung epithelial cells, like the parent virus that caused the pandemic in 2020," she explained. "We know that coronaviruses are prone to viral reassortment, which could lead to substantial mutations in new variants that would not only increase immune evasion but also increase disease severity. This is why surveillance of variants remains very important, even though we are entering the end of the fourth year of the pandemic."