Genomic‐Based Epidemiological Analysis of the Post‐Pandemic <i>Mycoplasma pneumoniae</i> Resurgence

<i>Mycoplasma pneumoniae</i> infections resurged globally in 2023-2024 following a significant decline during the coronavirus disease 2019 (COVID-19) pandemic. To understand the genomic epidemiology of this resurgence in China, a nationwide 1-year genomic surveillance identified 9907 patients infected with <i>M. pneumoniae</i>, resulting in an overall positive rate of 10.05%. We developed a hybrid capture-based targeted next-generation sequencing (hc-tNGS) assay, obtaining 271 high-quality genomes directly from clinical samples. Phylogenetic analysis of a global collection of 562 <i>M. pneumoniae</i> genomes identified six distinct lineages, including three newly emerged main Chinese clades (MCCs) that co-circulated across various regions of China. Among these MCCs, one clade, comprising P1-1, ST17, and L4, was localized in Taiwan, while two others-P1-1, ST3, and L6 clade, and P1-2, ST14 and L2 clade-co-circulated in different regions of China during the 2023-2024 epidemic season. Notably, 96.31% of the isolates identified in this study exhibited a point mutation, primarily A2063G (95.94%). This study offers a comprehensive genomic characterization of the post-pandemic <i>M. pneumoniae</i> resurgence in China, highlighting the emergence and spread of resistant clades. These findings emphasize the importance of adopting a One Health approach to address the potential global public health threats posed by this resurgent pathogen.