Genomic surveillance and evolutionary dynamics of SARS-CoV-2 variants in Yunnan, China, 2022–2025

Monitoring viral evolutionary dynamics in regions with complex demographics is essential for understanding the adaptation and transmission patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Yunnan Province, situated in Southwest China and characterized by significant cross-border population movement, offers a unique context for regional surveillance. A total of 1,011 respiratory samples collected between 2023 and 2025 were screened for SARS-CoV-2. Among these, 212 samples exhibiting a cycle threshold (C_t) value of less than 32 underwent whole-genome sequencing. Additionally, 47 publicly available genomes from the Global Initiative on Sharing All Influenza Data (GISAID) were incorporated into the phylogenetic analysis. Viral evolution, lineage dynamics, and mutational patterns were assessed using Nextstrain (v2.4.1). The potential immune escape characteristics of receptor-binding domain (RBD) mutations were examined using previously published deep mutational scanning datasets. The predominant circulating variants transitioned from clade 22D to clade 25B, primarily represented by the NB.1.8.1 lineage. Several recurrent spike mutations, including E484K, Y505H, and F456L, were detected in the dominant clades; these mutations have been associated with immune escape-related phenotypes. Phenotypic modeling indicated that these mutations may lead to increased immune escape scores, potentially compromising the efficacy of antibody-based interventions. Phylogenetic analysis revealed distinct lineage replacement patterns throughout the study period. The unique regional context may contribute to the complexity of SARS-CoV-2 circulation dynamics and lineage diversity within the region. Ongoing regional genomic surveillance, alongside phylogenetic and phenotypic analyses, is essential for identifying emerging variants with potential immune-evasion characteristics.