The Virus Has No Big Hands Left to Play, But Could Still Drive Meaningful Waves?

Author: G. Vanden Bossche                                                                                               April 5th, 2026

The Virus Has No Big Hands Left to Play, But Could Still Drive Meaningful Waves? Hmmm...

The title captures how some folks interpret the current SARS-CoV-2 evolutionary dynamics - especially those of BA.3.2. There is a peculiar contradiction emerging in current discussions on viral evolution. On the one hand, some argue that SC-2 has essentially exhausted its repertoire of impactful evolutionary moves–that the virus has ‘no big hands left to play.’ On the other hand, those same voices concede that ongoing antigenic changes can still accumulate and generate what they call ‘meaningful waves’ (https://x.com/mrmickme2/status/2040262345520562204?s=46; https://x.com/mrmickme2/status/2040339701291463032?s=12).

Both statements cannot be true at the same time!

If viral evolution were truly reduced to small, incremental antigenic adjustments with limited individual impact, then the epidemiological consequences should likewise be modest. Minor changes yield minor effects. That is the very definition of incrementalism. Yet, the notion of ‘meaningful waves’ implies something entirely different. At the population level, a wave becomes ‘meaningful’ only when there is a substantial increase in viral fitness, whether through enhanced intrinsic transmissibility, immune evasion or pathogenic interaction with the host (virulence). Such outcomes are not the linear sum of trivial changes; they reflect non-linear dynamics within the evolutionary landscape.

This brings us to a fundamental principle of evolutionary biology:

When a system operates under increasing constraint, adaptive progress through small, independent steps becomes progressively inefficient. The marginal fitness gain of individual mutations diminishes, especially in a highly COVID-19-vaccinated host population shaped by widespread prior exposure and converging immune pressure.

So how, then, can the virus continue to produce ‘meaningful waves’?

There are only two logically consistent answers.

Either these waves are not truly meaningful–mere statistical noise dressed up as significance–or they arise from cooperative interactions between Spike (S)-associated mutations, where combinations of changes produce effects that far exceed the sum of their parts. The latter is not speculation. It is a well-established evolutionary mechanism known as epistasis. As previously explained, the phenotypic effect of currently observed S-associated mutations likely arises from sterically mediated interactions among them (https://www.trialsitenews.com/a/plausibility-of-more-extended-o-glycosylation-as-last-resort-for-sars-cov-2-immune-escape-e1a08faf). I call it ‘steric epistasis.’

And here lies the key of all misinterpretation related to the ongoing evolutionary dynamics of SC-2 in highly COVID-19-vaccinated populations. Such sterically mediated interactions are precisely what enables qualitative shifts in phenotype (https://voiceforscienceandsolidarity.substack.com/p/everyone-knows-a-pus-filled-abscess). Epistasis largely explains how evolution crosses fitness valleys and reaches new adaptive peaks. It is how systems transition, not gradually, but abruptly, into new regimes of behavior.
In other words, what is being described as ‘stacking over time’ is, in reality, the precondition for a functional jump. Calling it incremental does not make it so.

Moreover, the discussion is often artificially narrowed to amino acid substitutions, as if changes in amino acid sequences alone define the virus’s adaptive potential. This overlooks a critical and far more flexible layer of viral evolution: the glycosylation landscape of the S protein.

Glycosylation is not merely decorative. It is functionally decisive. Changes in glycan shielding can alter antigenicity, modulate receptor accessibility, and reshape interactions with the host immune system–all without requiring extensive sequence divergence. These modifications provide the virus with a powerful means of reconfiguring its phenotype under immune pressure (https://voiceforscienceandsolidarity.substack.com/p/scientific-summary-4-pp-on-plausibility?r=y46t6)..

Importantly, such changes are inherently non-linear in their effects. A shift in glycosylation pattern can abruptly transform how the immune system perceives and handles the virus or....how the virus gets a handle on the host immune system! This is not gradual drift; it is reorganization at the interface between virus and host.

So the idea that the virus can indefinitely ‘struggle’ against widespread immunity through marginal gains is not biologically plausible.

Evolution under constraint does not proceed through endless fine-tuning. When incremental pathways lose efficiency, systems tend to reorganize–sometimes suddenly. This is not an exception to evolutionary rules. It is a consequence of them.

Which brings us back to the original claim. To assert that the virus has ‘no big hands left to play,’ while simultaneously acknowledging the emergence of ‘meaningful waves,’ is not a nuanced position. It is an internally inconsistent one. If the waves are real, then so is the mechanism behind them. And that mechanism, by definition, involves the potential for non-linear, qualitative change.

In evolutionary terms, the pandemic game is not over. It is, in fact, highly likely of approaching a turning point.

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