Despite Debut of New SAR-CoV-2 BA.3.2 Variant With 50 Plus Mutations, NB.1.8.1 and XFG Will Prevail in Weeks Ahead
Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 10, 2025 6 hours, 41 minutes ago
Medical News: A New Variant Emerges, But Others Are Gaining Ground Faster
Just when the world was beginning to breathe easier, the COVID-19 virus has unveiled another surprise—a new variant labeled BA.3.2, which carries over 50 genetic mutations. First detected in the Netherlands on April 2, 2025, this sub-lineage of Omicron has alarmed many due to its heavily mutated spike protein, which often determines how easily the virus infects human cells and evades immune detection.
Despite Debut of New SAR-CoV-2 BA.3.2 Variant With 50 Plus Mutations, NB.1.8.1 and XFG Will Prevail in
Weeks Ahead
However, despite its fearsome mutation profile, BA.3.2 may not be the next global threat. A new study conducted by researchers from several top institutions in China—including the Biomedical Pioneering Innovation Center (BIOPIC) at Peking University, the Changping Laboratory, and the Peking-Tsinghua Center for Life Sciences—has painted a more nuanced picture. According to this
Medical News report, the BA.3.2 variant, though notable for its immune evasion capabilities, appears to lack the infectivity and growth dynamics necessary to dominate.
The Competitors: NB.1.81 and XFG
As BA.3.2 makes headlines, other variants are quietly spreading—and gaining a strong foothold. NB.1.8.1 (commonly abbreviated NB.1.81) and XFG are two such variants that the new study highlights as more viable threats in the immediate future. These variants show stronger infectivity and better balance between immune evasion and ACE2 receptor binding, key characteristics for efficient transmission and survival.
NB.1.81 and XFG have already shown signs of replacing the current dominant variant LP.8.1.1, according to global sequencing data collected through GISAID (Global Initiative on Sharing All Influenza Data) from April 2024 to April 2025.
Breaking Down BA.3.2’s Genetic Arsenal
BA.3.2 is a descendent of the BA.3 lineage and has accumulated more than 50 mutations, with 44 of them not found in LP.8.1.1. This has sparked concerns that it could trigger a new wave of infections similar to what was seen with variants like BA.2.86 and JN.1. But appearances can be deceptive.
The study used laboratory-engineered pseudoviruses mimicking the spike protein of BA.3.2 to assess how efficiently it could bind to the human ACE2 receptor—a critical step for infecting cells. Surprisingly, BA.3.2 showed the lowest ACE2 engagement efficiency among all tested variants, even lower than its predecessor BA.3. Although its receptor-binding domain (RBD) had a similar ACE2-binding affinity to LP.8.1.1, the structural conformation of the spike protein likely prevents efficient binding.
This means that despite being a “mutation-rich” variant, BA.3.2 might be too biologically impaired to spread widely—unless it undergoes further evolutionary changes.
NB.1.81 and XFG: Built for Spread
In contrast, NB.1.8
1, a descendent of the XDV.1.5.1 sublineage, has become increasingly common in regions such as China and Hong Kong. Its mutations, especially Ala435Ser and Lys478Ile, provide it with a strong balance of immune evasion and high infectivity. According to the study, NB.1.81 exhibited the highest RBD–ACE2 binding affinity of all tested variants.
XFG, which originates from LF.7 and LP.8.1.2, carries His445Arg, Asn487Asp, Gln493Glu, and Thr572Ile mutations. These genetic changes allow it to evade antibodies while maintaining moderate infectivity. While its ACE2 engagement is slightly lower than NB.1.81, it is still significantly better than that of BA.3.2.
Immune Evasion: Who Slips Through the Cracks?
The researchers also tested how well these variants could escape immune detection using convalescent plasma from individuals with past breakthrough infections. The BA.3.2 variant stood out for its ability to evade neutralizing antibodies—it showed an 11-fold reduction in neutralization compared to BA.3 and a 3–4-fold reduction relative to LP.8.1.1. However, this immune escape is nullified by its weak infectivity.
On the other hand, NB.1.81 and XFG demonstrated a well-rounded immune evasion profile. NB.1.81 showed a 1.5 to 1.6-fold reduction in neutralizing antibodies, while XFG exhibited close to a 2-fold reduction. These values, while not as extreme as BA.3.2’s, suggest a strong ability to dodge immune defenses without compromising transmissibility.
Why Antibody Classes Matter
To better understand these evasion strategies, scientists examined how well each variant resisted different classes of neutralizing monoclonal antibodies. BA.3.2 managed to escape multiple antibody classes—including the potent Class 1/4 antibodies. These are particularly important because they are common in people immunized with inactivated vaccines, such as those used in China.
NB.1.81’s key mutation Ala435Ser, and XFG’s Asn487Asp and Gln493Glu, also provided significant antibody resistance. Notably, NB.1.81 retained sensitivity to some monoclonal antibodies, hinting at a “Goldilocks” zone of mutations—not too many to impair function, but enough to escape detection.
Infection Potential in the Lab
To test how efficiently the variants could infect cells, researchers used pseudovirus infectivity assays in Vero cells. BA.3.2 demonstrated disastrously low fitness, showing it’s unlikely to spread in real-world conditions. Conversely, NB.1.81 maintained good infectivity, while XFG had moderate levels.
In another test using antigenic mapping, which charts how similar or different viruses are to known immune responses, BA.3.2 appeared antigenically distinct from JN.1 and XBB.1.5. Meanwhile, NB.1.81 and XFG clustered closely with the JN.1 lineage—suggesting these newer variants might still trigger partial immune recognition in vaccinated or previously infected individuals.
Conclusion: Don’t Panic, But Don’t Relax Either
The debut of BA.3.2 with its 50-plus mutations may appear alarming at first glance. But science paints a more complex picture. Despite its immune evasion capabilities, BA.3.2's poor ACE2 binding and low infectivity essentially sideline it in the evolutionary race—unless it evolves further.
In contrast, NB.1.81 and XFG are better poised to dominate the next wave of COVID-19 cases. They combine immune evasion with efficient cell entry mechanisms, making them formidable candidates for community spread. NB.1.81 in particular has shown the highest RBD–ACE2 binding affinity and a solid resistance to neutralizing antibodies, placing it at the forefront of potential dominant strains in the coming weeks. While XFG doesn’t bind as efficiently as NB.1.81, its balanced profile makes it a close contender. As we’ve learned throughout the pandemic, viral evolution favors balance. Variants that are too stealthy but weak can fade out, while those that balance stealth and spread—like NB.1.81—tend to rise. Vigilant monitoring and real-time genomic surveillance remain essential tools in containing the virus’s ever-changing face.
The study findings were published in the peer reviewed journal: The Lancet Infectious Diseases
https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00308-1/fulltext
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