Mar 24, 2026
A new SARS-CoV-2 (SC-2) variant called BA.3.2has attracted attention for several months now. At first glance, it might looklike just another addition to the long list of Omicron subvariants. But acloser look suggests that something more fundamental may be unfolding.
BA.3.2 is not a typical variant. It carries avery large number of mutations, particularly in the spike (S) protein-theprimary target of the immune response following natural infection and thetarget antigen used in all current COVID-19 (C-19) vaccines. In simple terms,it looks like the virus has made a large evolutionary jump (so-called‘saltatory evolution’) rather than gradual step-by-step changes.
Voice for Science and Solidarity by GeertVanden Bossche is a reader-supported publication. To receive new posts andsupport my work, consider becoming a free or paid subscriber.
Scientists such as Kei Sato and colleagueshave pointed out that BA.3.2 seems particularly good at evading antibodies (asreported on X by The Sato Lab). That is already notable. But what makes thesituation more interesting is what happens next. Despite all these changes,BA.3.2 has not taken over.
As observed and reported on X by mutation spotters such as R. Hisner, thevariant does not spread like a clearly ‘better’ virus would. Instead, itcompetes with other variants, rises somewhat in some places, and then levelsoff or declines (as reported on X by S. Pöhlmann, based on multiple independenttracking analyses across different countries). In other words, it behavesindecisively.
A Strange Pattern
Normally, when a virus evolves a majoradvantage, one of two things happens:
- it spreads quickly and replaces othervariants or
- it disappears because the changes come at asignificant fitness cost
BA.3.2 does neither. It persists, butwithout clearly winning. This is unusual and scientifically highlyinformative. It suggests that the virus may no longer be evolving freely.Instead, it may be running into increasing immunological and structuralconstraints as explained in several of my previous Substack articles.
What Changed?
Earlier in the pandemic, the virus mainlyevolved to spread faster. Any mutation that improved transmission had a clearadvantage. This became particularly pronounced once large parts of populationsbecame vaccinated and immune escape variants-culminating in Omicron-wereselected under population-level immune pressure.
Today, the situation is very different. HighlyC-19-vaccinated populations now have some level of collective immunity,although suboptimal and narrowly focused, especially against the S protein.This creates strong immune pressure on the S protein, which is largelyresponsible for viral entry and infectivity.
At first, the virus readily escaped from thispressure by changing those S-associated targets, a phenomenon often referred toas immune refocusing, where the adaptive immune response is redirectedtoward alternative, often less immunogenic and more conserved epitopes on Sprotein. But over time, a problem arises as I already described in a series ofprevious Substack articles:
i) many of the most relevant immune targetshave already been altered
ii) new mutations provide diminishing returnsbecause functional and spatial constraints increasingly limit viability ofadditional S-based mutations
iii) earlier escape mutations cannot bereversed without restoring immune sensitivity and losing fitness advantage
The result is that the virus becomes trappedin a narrowing evolutionary corridor.
Why This Matters
In such a situation, even large changes-likethose seen in BA.3.2-may no longer lead to clear evolutionary success. That isexactly what we are observing. BA.3.2 (sub)lineages are characterized by:
a) a high number of mutations
b) strong immune escape properties
c) lack of clear epidemiological dominance
This combination suggests that additionalimmune escape mutations no longer translate into decisive competitive advantage.
In other words, immune-driven selection pressure appears to be reachingfunctional limits in its ability to select variants that clearly outcompeteothers.
Ongoing Spread Keeps the System Active inHighly C-19-vaccinated Populations
Another key point is that the virus is stillspreading widely.
Even though severe disease is less common, the virus still spreads widely: manyinfections are mild or even unnoticed, allowing the virus to circulate easily.In addition, some people develop chronic infection and carry the virus forlonger periods, thereby contributing to extended viral shedding and giving itmore time to evolve.
As long as the virus continues to replicate atscale, it keeps exploring new mutations even if a shift in predominance fromimmune pressure–driven selection to fitness-driven selection slows down viralevolutionary dynamics.
This matters because evolution depends onnumbers:
i) more infections and/or prolonged transmission periods entail morereplication
ii) more replication causes more mutations
iii) more mutations increase the probability of a newly emerging lineagecapable of
breaking through the entire immune system
Hence, as long as the infectious viral burdenremains sufficiently elevated in highly C-19-vaccinated populations, the viruscontinues to generate and test new configurations within a constrained fitnesslandscape.
No Endemicity But An Unstable Situation
What we are seeing now is not a stableendpoint and therefore not consistent with what our public health authoritiesand so-called ‘experts’ are trying to make people believe, namely that thevirus has simply transitioned into a benign endemic phase!
Instead, it resembles a system under pressurebecause
i) the virus continues to replicate and change(as reflected by wastewater surveillance
samples)
ii) but gains are limited and inconsistent/fluctuating
iii) variants compete, yet no singlevariant clearly dominates
This type of situation can persist for sometime, but it reflects dynamic instability rather than equilibrium. Smallchanges in viral properties, the population’s immune background orsocio-environmental determinants can lead to noticeable fluctuations in theprevalence of BA.3.2 or other co-circulating variants in highly C-19-vaccinatedpopulations.
This persistent reshuffling of variant proportions is itself a hallmark of ametastable system. But it usually does not last forever because new mutationshave less and less functional impact and old changes cannot be undone.
Together, this suggests that the virus is notsettling into stability-it continues to experience additional immune pressure(albeit weaker) and to evolve (albeit less efficiently) whilestill searching for a way to adapt to the hostile immune environment of highlyC-19-vaccinated populations (albeit at a much slower pace).
What appears as ‘calm’ may actually reflect a system under tension.
Although this system can persist for a while, such unstable balances incomplex systems often end not gradually, but suddenly, i.e., when changesaccumulate sufficiently to push the system past a tipping point, triggering aphase transition.
What About the United States?
The U.S. adds an important piece to thepuzzle.
Although BA.3.2 has been detected in some clinical and wastewater surveillancesamples from multiple states, it currently plays no significant role in theU.S. SC-2 landscape. Yet the same overall pattern is observed: multiplevariants continuously rise and fall in relative proportion, without any singlelineage establishing long-term dominance (see figure below).
This is important as it indicates that theunderlying phenomenon is not specific to BA.3.2.
Whether BA.3.2 will become more prevalent inthe US or not remains uncertain but this does not change the overallobservation that the virus as a whole is in a state where it keeps evolvingwhile no variant clearly dominates. Hence, even in the absence ofsignificant BA.3.2. co-circulation, the virus appears to be evolving withinconstraints, without reaching a stable solution. Hence, the presence of BA.3.2is not required to demonstrate that the system itself is metastable andunresolved.
What Could Happen Next?
If current conditions persist-ongoingtransmission combined with a constrained evolutionary landscape-the probabilityincreases that a new variant with a markedly different antigenic and/orfunctional profile, enabling a much stronger competitive advantage, couldemerge.
However, because the virus is operating underdecreased additional immune pressure and within a restricted evolutionaryspace, it may take time for such a variant to arise. In order for a new virallineage to acquire a truly significant fitness advantage, it would likelyneed to overcome existing adaptive immune memory while also effectivelyexploiting early infection dynamics.
As highly C-19-vaccinated populations are characterized by suboptimaladaptive immune responses and insufficiently trained cell-based innateimmunity, they constitute an excellent breeding ground for such a lineage.
Such development would represent a qualitativeshift in virus-host interaction, rather than a simple continuation of currenttrends.
It is difficult to envisage how such a qualitative shift could enable the virusto overcome the overall host immune response and maintain infectivity withoutbecoming highly virulent.
This is where I anticipate the chronic phase of this immune escape pandemic totransition into a hyperacute phase, driven by a late, highly virulentOmicron descendant (HI-VI-CRON).
However, as the transition to a lineage that spreads very efficiently andoutcompetes all other circulating variants may require some lag time, theemergence of HI-VI-CRON is unlikely to occur overnight (i.e., within a singleday).
But let us be clear: this does not mean that the current situation should bemistaken for stability.
In Summary
BA.3.2 is unlikely to evolve consistently intothe next dominant variant. But, together with the persistent fluctuations inco-circulating variants, it significance as a warning signalcould be much more relevant than its epidemiological or clinical impact:
A signal that viral evolution is no longerevolving in a simple, predictable way as driven by selective immune pressure onS-associated B and Tc epitopes.
A signal that current immune and transmission dynamics are constraining viraladaptation in highly C-19-vaccinated populations.
A signal that the system is becoming unstable rather than settling down.
What looks like calm is, in reality, a systemunder pressure, still searching for a viable evolutionary path forward. As thecurrent evolutionary dynamics suggest that continued instability is far moreplausible than smooth resolution, the question doesn’t seem to be whether sucha path will emerge but rather when it will do so.
Geert Vanden Bossche received his DVM from the University of Ghent, Belgium, and his PhD degree in Virology from the University of Hohenheim, Germany. He held adjunct faculty appointments at universities in Belgium and Germany. After his career in Academia, Geert joined several vaccine companies (GSK Biologicals, Novartis Vaccines, Solvay Biologicals) to serve various roles in vaccine R&D as well as in late vaccine development.
Geert then moved on to join the Bill & Melinda Gates Foundation’s Global Health Discovery team in Seattle (USA) as Senior Program Officer; he then worked with the Global Alliance for Vaccines and Immunization (GAVI) in Geneva as Senior Ebola Program Manager. At GAVI he tracked efforts to develop an Ebola vaccine. He also represented GAVI in fora with other partners, including WHO, to review progress on the fight against Ebola and to build plans for global pandemic preparedness.
Back in 2015, Geert scrutinized and questioned the safety of the Ebola vaccine that was used in ring vaccination trials conducted by WHO in Guinea. His critical scientific analysis and report on the data published by WHO in the Lancet in 2015 was sent to all international health and regulatory authorities involved in the Ebola vaccination program. After working for GAVI, Geert joined the German Center for Infection Research in Cologne as Head of the Vaccine Development Office. He is at present primarily serving as a Biotech / Vaccine consultant while also conducting his own research on Natural Killer cell-based vaccines.
Email: info@voiceforscienceandsolidarity.org
.svg){kind=small}
