Abstract
The emergence and evolution of SARS-CoV-2 variants, such as Delta and Omicron, pose significant challenges to pandemic management. This study evaluated the effectiveness of reverse-transcription polymerase chain reaction (RT-PCR) and whole-genome sequencing (WGS) in detecting and characterizing SARS-CoV-2 variants using 624 samples collected in South Korea from mid-2021 to mid-2022. Two RT-PCR genotyping assays demonstrated a high concordance rate (90.4%) in identifying the Delta variant during its dominance. In contrast, WGS revealed extensive genetic diversity among Omicron sub-lineages, identifying 29 distinct sub-lineages, including two South Korea-specific variants (BA.1.1.5 and BA.2.3.8). Clustering analysis of WGS data highlighted distinct groupings of BA.1, BA.2, and BA.5 sub-lineages, with overlap in shared mutations suggesting evolutionary convergence. Sub-lineage diversity expanded during rapid transmission phases and subsequently consolidated as dominant lineages emerged. These findings highlight the complementary strengths of RT-PCR and WGS and underscore the importance of integrating these methodologies for effective variant monitoring and public health response.