Temporal Dynamics and Genomic Landscape of SARS-CoV-2 After Four Years of Evolution.

Introduction Since its emergence, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone extensive genomic evolution, impacting public health policies, diagnosis, medication, and vaccine development. This study leverages advanced bioinformatics to assess the virus's temporal and regional genomic evolution from December 2019 to October 2023. Methods Our analysis incorporates 16,575 complete SARS-CoV-2 sequences collected from 214 countries. These samples were comparatively analyzed, with a detailed characterization of nucleic mutations, lineages, distribution, and evolutionary patterns during each year, using the Wuhan-Hu-1 strain as the reference. Results Our analysis has identified a total of 21,580 mutations that we classified into transient mutations, which diminished over time, and persistent mutations with steadily increasing frequencies. This mutation landscape led to a notable surge in the evolutionary rate, rising from 13 mutations per sample in 2020 to 96 by 2023, with minor geographic variations. The phylogenetic analysis unveiled three distinct evolutionary branches, each representing unique viral evolution pathways. These lineages exhibited a tendency for a reduced duration of dominance with a shortening prevalence period over time, as dominant strains were consistently replaced by more fit variants. Notably, the emergence of the Alpha and Delta variants in 2021 was followed by the subsequent dominance of Omicron clade variants that have branched into several recombinant variants in 2022, marking a significant shift in the viral landscape. Conclusion This study sheds light on the dynamic nature of SARS-CoV-2 evolution, emphasizing the importance of continuous and vigilant genomic surveillance. The dominance of recombinant lineages, coupled with the disappearance of local variants, underscores the virus's adaptability.