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Microbes & Immunity SARS-CoV-2 complementary classification

Certain SARS-CoV-2 variants are classified as VOCs implications. Other public health agencies, such as the
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due to their ability to maintain or enhance replication United States Centers for Disease Control and Prevention
fitness despite increasing levels of population immunity – (CDC), maintain independent classification criteria,
either through natural infection or vaccination. 43,45 These which can lead to differences in the timing of variant
variants often exhibit mutations that provide a selective de-escalation. 62,63 For example, the CDC, the European
advantage, allowing them to spread more efficiently in Centre for Disease Prevention and Control (ECDC), and
partially immune populations. A defining feature of the WHO de-escalated SARS-CoV-2 variants at different
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many VOCs is the presence of mutations in the RBD of times, reflecting regional epidemiological assessments and
the S protein, which plays a critical role in host cell entry risk evaluations. 35,64,65
through the human ACE2 receptor. Thus, the designation At this point, it is important to consider the foundational
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VOC is reserved for SARS-CoV-2 lineages in which specific pillars in the field of virus evolution. It is well established
genetic changes significantly enhance RBD binding affinity that the accumulation of sufficient genetic divergence to
– as seen with substitutions such as N501Y – while also produce a biologically distinct virus lineage – one with
demonstrating epidemiological evidence of increased unique properties affecting transmission dynamics,
transmissibility. 57,58 pathogenicity, or immune interactions – typically requires
Before being categorized as a VOC, an emerging several years of sustained evolutionary pressure. 66-70 The
SARS-CoV-2 lineage is often first labeled as a VOI or, in present classification framework for SARS-CoV-2, which
some national surveillance frameworks, a variant under designates new variants based on short-term genetic
investigation. If subsequent data confirm enhanced fluctuations, contradicts this fundamental understanding
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transmissibility, immune escape potential, or increased of viral evolution. The issue is particularly pronounced in
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disease severity, the variant is formally designated SARS-CoV-2 due to its genomic stability relative to other
as a VOC. Once a variant reaches VOC status, it is RNA viruses, such as human immunodeficiency virus type 1
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systematically classified within the Pango nomenclature (HIV-1), hepatitis C virus (HCV), and influenza A virus,
system, which provides detailed lineage assignments based all of which evolve under stronger selection pressures and
on phylogenetic relationships. In addition, the variant is exhibit markedly higher mutation rates. 72-75 Unlike HIV-
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assigned to specific clades within Nextstrain and Global 1, HCV, and influenza A virus, SARS-CoV-2 possesses a
Initiative on Sharing All Influenza Data (GISAID), two proofreading exonuclease (nsp14-ExoN), a unique feature
global platforms used for genomic epidemiology and among the majority of RNA viruses that reduces the
viral evolution tracking. 59,60 These classification systems accumulation of replication errors. 76,77 This proofreading
facilitate real-time monitoring of SARS-CoV-2 evolution, mechanism results in a significantly slower evolutionary
aiding in public health responses and vaccine adaptation rate for SARS-CoV-2, estimated between 0.0004 and
strategies. 0.002 substitutions per site per year (s/s/y). 49,73,78 This
evolutionary rate allows for gradual adaptation; however,
The WHO played a central role in the classification and
monitoring of SARS-CoV-2 variants, regularly updating its it does not support the level of rapid divergence seen
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framework to reflect emerging evidence on viral evolution, among other RNA viruses. Consequently, it is plausible
transmissibility, and immune escape potential. 35,47 Thus, to assume that the frequent designation of SARS-CoV-2
the identification and designation of SARS-CoV-2 variants variants as distinct entities, based on transient mutational
rely on genomic surveillance efforts, with submissions changes rather than sustained functional divergence,
from member states analyzed through global platforms represents a departure from well-established evolutionary
such as GISAID. This is followed by field investigations to virology principles.
assess the public health impact of SARS-CoV-2 variants. Thus, the present study argues that the currently adopted
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Over time, the WHO expanded its classification system classification of SARS-CoV-2 lineages has introduced
to include additional categories beyond VOCs. The significant challenges in COVID-19 risk communication.
updated framework now includes VOIs and variants under The existing SARS-CoV-2 classification systems are often
monitoring. A VOI is defined as a variant possessing the source of unnecessarily amplified public concern and
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genetic changes that are predicted or known to affect viral inconsistent scientific justification that influences policy
characteristics, such as transmissibility, virulence, antibody decisions, leading to a cycle of reactionary responses
evasion, therapeutic susceptibility, or detectability. 35,47 In rather than well-balanced epidemiological measures.
addition, to be classified as a VOI, a variant must exhibit Accordingly, the present study aimed to: (1) Assess the
increasing circulation in at least one WHO region, genetic divergence of SARS-CoV-2 variants in comparison
raising concerns about potential global public health to established RNA virus speciation models (e.g., HIV-1,

Volume 2 Issue 3 (2025) 89 doi: 10.36922/MI025190042