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Microbes & Immunity

ORIGINAL RESEARCH ARTICLE
A proposal for biologically relevant classification

of SARS-CoV-2 variants

1
1
1
Saja Al-Baidhani , Tarneem Sabra , Aslam Al-Baidhani , Mohammed Sallam 2,3,4 ,
and Malik Sallam 1,5*
1 Department of Pathology, Microbiology and Forensic Medicine, School of Medicine,
The University of Jordan, Amman, Jordan
2 Department of Pharmacy, Mediclinic Parkview Hospital, Mediclinic Middle East, Dubai,
United Arab Emirates
3 Department of Management, Mediclinic Parkview Hospital, Mediclinic Middle East, Dubai,
United Arab Emirates
4 College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai,
United Arab Emirates
5 Department of Clinical Laboratories and Forensic Medicine, Jordan University Hospital,
Amman, Jordan

Abstract

The present classification of severe acute respiratory syndrome coronavirus 2
(SARS-CoV-2) variants plays a central role in shaping public health policies, vaccine
strategies, and global risk communication. However, existing designations of
*Corresponding author: variants of concern (VOCs) rely on evolving epidemiological and phenotypic criteria
Malik Sallam
(malik.sallam@ju.edu.jo) rather than quantitative genetic divergence thresholds. In this study, we evaluated
the genetic divergence of SARS-CoV-2 variants relative to human immunodeficiency
Citation: Al-Baidhani S, Sabra T, virus type 1 (HIV-1), hepatitis C virus (HCV), and influenza A virus, and proposed a
Al-Baidhani A, Sallam M, Sallam M.
A proposal for biologically relevant framework integrating genetic, functional, and epidemiological criteria for variant
classification of SARS-CoV-2 classification. Comparative phylogenetic analysis assessed the divergence of
variants. Microbes & Immunity. SARS-CoV-2 (S) relative to HIV-1 (env), HCV (E1), and influenza A virus (HA). Maximum
2025;2(3):87-107.
doi: 10.36922/MI025190042 likelihood phylogenies with bootstrap support were constructed using MEGA6,
and pairwise genetic distances were calculated through the maximum composite
Received: May 10, 2025
likelihood model. Monte Carlo simulations (n = 1,000) using adjusted SARS-CoV-2
1st revised: May 30, 2025 evolutionary rates (0.0006 – 0.003 substitutions/site/year) estimated time to reach
2nd revised: June 3, 2025 divergence thresholds defined by other viruses. SARS-CoV-2 variants showed
a maximum divergence of 0.006 substitutions/site – far below thresholds for
Accepted: June 4, 2025
HIV-1 (0.157), HCV (0.371), and influenza A (1.956). Projections estimate HIV-1-like
Published online: June 17, 2025 divergence in 53.7 years, HCV-like in 126.8 years, and influenza A-like in 668.6 years.
Copyright: © 2025 Author(s). No present VOC met all proposed functional criteria: transmissibility, immune escape,
This is an Open-Access article disease severity, and global dominance. Omicron exhibited partial immune escape
distributed under the terms of the but insufficient divergence for lineage reclassification. While present classification
Creative Commons Attribution
License, permitting distribution, supports short-term response, integrating evolutionary benchmarks would enhance
and reproduction in any medium, their biological relevance as the virus continues to diversify. A new evidence-based
provided the original work is framework is needed to reduce public alarm, guide rational policymaking, and
properly cited.
prioritize durable countermeasures over variant-specific responses.
Publisher’s Note: AccScience
Publishing remains neutral with
regard to jurisdictional claims in Keywords: Phylogeny; Classification; COVID-19; Lineage; Variant
published maps and institutional
affiliations.

Volume 2 Issue 3 (2025) 87 doi: 10.36922/MI025190042