Genetic factors driving the Mycoplasma pneumoniae outbreak among children post-COVID-19 in China: a whole genome analysis
Weiwei Jiao, Jie Wang, Cuidan Li, Peihan Wang, Sihong Xu, Jing Bi, Liya Yue, Fang Liu, Lin Sun, Hui Qi, Tingting Jiang, Xue Tian, He Tang, Xu Li, Man Li, Xuemei Yang, Xiaoxuan Yang, Yuting Sun, Haitao Niu, Wenbao Zhang, Adong Shen, Fei Chen
Abstract
Background Mycoplasma pneumoniae (M. pneumoniae) is a leading cause of community-acquired pneumonia in children. Post-COVID-19, a significant resurgence of M. pneumoniae infections has been observed in China, but whole-genome analyses on the genetic mechanisms driving this resurgence remain limited. Methods We performed whole-genome sequencing on 169 M. pneumoniae isolates from Beijing and Baoding, collected before and after COVID-19. All M. pneumoniae genomes from GenBank were included for analysis. Genotypes were identified using multilocus variable-number tandem-repeat analysis (MLVA), multilocus sequence typing (MLST), phylogenetic analysis. Genomic conservation and transmission patterns were assessed via SNP distance. Findings We identified a post-COVID-19 resurgence of M. pneumoniae infections among children, with infection rates peaking at 60%–70% in late 2023, higher than during the pandemic (10%–20%) and pre-pandemic (∼30%). Genomic analysis revealed distinct genotypes, with T1-2 (4-5-7-2) dominating in Beijing, and both T1-2 and T2-2 (3-5-6-2) prevalent in Baoding. Minimal SNP distances and genomic conservation indicated rapid spread of M. pneumoniae . Genomic analysis uncovered key genetic factors driving the outbreak: near-100% macrolide resistance and increased prevalence of the 4-5-7-2 genotype (enriched in virulence and metabolism-related genes). Interpretation This study provides a comprehensive genomic analysis of genetic factors driving the outbreak. With near-100% macrolide resistance in China, urgent changes in treatment policies are needed. The rising prevalence of 4-5-7-2 and its functional advantages warrant close monitoring. Our findings offer insights into the outbreak causes and guide future prevention and control strategies. Funding National Key R&D Program of China; Training Plan for High level Public Health Technical Talents.