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Microbes & Immunity SARS-CoV-2 complementary classification

H1N1 and H3N2 being associated with near-complete evolving virus – despite genomic evidence indicating
immune escape and requiring substantial vaccine relatively slow evolutionary change – has led to widespread
reformulation with a long period of circulation. 152,153 misinformation, fostering public skepticism toward
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In contrast, no SARS-CoV-2 variant has maintained vaccination efforts and pandemic control measures. In
epidemiological dominance for over 12 months, a key addition, scientific resources have been misallocated, with
criterion for distinguishing transient genetic shifts from an excessive focus on sequencing minor genetic mutations
long-term evolutionary changes. For instance, while rather than investing in broadly protective vaccines, long-
Delta emerged as the dominant strain for several months, term antiviral solutions, and cross-reactive immunological
it was rapidly displaced by Omicron, which, in turn, has strategies. This relentless pursuit of tracking and naming
continued to generate multiple sub-lineages without a every emerging sub-lineage has diverted focus from more
single, stable successor. This pattern strongly suggests sustainable public health interventions, including endemic
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that SARS-CoV-2 evolution is characterized by alternating virus management and the development of durable,
variant prevalence rather than sustained antigenic pan-coronavirus strategies better suited for long-term
evolution, a hallmark of viruses undergoing immune- mitigation efforts.
driven lineage differentiation. On the other hand, HIV-1 Building on the findings of this study, several
subtypes/CRFs, HCV genotypes/subtypes, and influenza A areas for future research are warranted. Comparative
subtypes maintain long-term epidemiological dominance, genomic analyses should be expanded to include other
persisting for decades despite selective pressures from coronaviruses – such as SARS-CoV-1, Middle East
immune responses and antiviral therapies. 138,141 respiratory syndrome coronavirus (MERS-CoV), and
An important aspect that motivated this study can be endemic human coronaviruses – to establish divergence
presented as follows. By failing to incorporate both genetic thresholds that are biologically tailored to the coronavirus
divergence thresholds and functional impact assessments, family, rather than relying solely on benchmarks derived
the present WHO SARS-CoV-2 VOCs classification from HIV-1, HCV, and influenza A virus. Evolutionary
system may have resulted in unnecessary alarm and rate modeling should be extended to longer timeframes,
misdirected public health interventions. 155,156 The repeated incorporating host adaptation, immune-driven selection,
reclassification of variants might have eroded public trust and antiviral pressure, all of which may alter divergence
by creating the impression that SARS-CoV-2 is undergoing trajectories over time. Given the unique RNA proofreading
rapid, unpredictable evolutionary leaps, despite evidence mechanisms in coronaviruses, future work should also
indicating that it remains a genetically stable virus with a assess the role of recombination in shaping long-term
slow rate of change. This has also led to inefficient resource evolution. Studies should investigate whether observed
allocation, with disproportionate emphasis placed on genetic divergence corresponds to antigenic drift by
variant-specific vaccine formulations, booster campaigns, utilizing neutralization assays across multiple viral proteins
and travel restrictions, rather than investing in broad- beyond the spike. Moreover, large-scale meta-analyses are
spectrum immunological strategies that provide durable needed to clarify whether specific mutations consistently
protection against viral evolution. 47 associate with increased clinical severity. Variant-specific
The potential misclassification of SARS-CoV-2 variants models should be integrated into real-world vaccine
could have far-reaching consequences, influencing effectiveness studies to better quantify the impact of
public health policies, economic stability, and scientific mutations on breakthrough infections and the duration of
priorities, often in ways that lack a solid virological immunity. Finally, the framework proposed in this study
foundation. Reactive policy decisions, including travel could be integrated with existing nomenclature systems
bans, lockdowns, and stringent restrictions, were hastily such as Pango and the WHO variant classifications. By
implemented in response to the emergence of Beta, delineating transient, antigenically responsive sub-lineages
Gamma, and Omicron, despite these variants exhibiting from those exhibiting sustained phylogenetic divergence,
genetic distances well within the bounds of normal intra- this approach could provide a complementary strategy that
lineage variation. 157,158 Such responses were not only improves evolutionary resolution and may help prevent
scientifically unjustified but also economically disruptive, overinterpretation of SARS-CoV-2 genomic changes,
fueling cycles of uncertainty that undermined long-term thereby reducing unnecessary public health interventions.
pandemic planning. Compounding this issue, the frequent Finally, this study is subject to several limitations that
and often sensationalized designation of new variants has should be taken into account as follows. First, SARS-CoV-2
significantly eroded public trust in health authorities. The has circulated in humans for a relatively short period, and
portrayal of SARS-CoV-2 as an unpredictable, rapidly while evolutionary projections were made based on the

Volume 2 Issue 3 (2025) 99 doi: 10.36922/MI025190042