High-Risk CCL14 lineage drives severe Mycoplasma pneumoniae pneumonia in children: a study in central China

Background: The post-coronavirus disease 2019 (COVID-19) pandemic resurgence of Mycoplasma pneumoniae (MP) infections, particularly in China, underscores the need to understand the drivers of disease severity. Purpose: This study aimed to evaluate the association between predominantly circulating MP strains and disease severity in Henan Province, central China. Methods: We integrated the clinical data of 3,060 pediatric patients and analyzed the epidemiological characteristics of MP pneumonia (MPP) in the Henan region in 2020-2024. Bronchoalveolar lavage fluid collected from 137 patients was analyzed using multilocus sequence typing and multilocus variable number tandem-repeat analysis to investigate the correlation between genotype and clinical outcome. Results: A significant post-COVID MPP outbreak was predicted in 2023. Genotyping revealed the cocirculation of 2 major genotypes: the prevalent ST3 (57.7%, severe ratio [31.6%]) and the less common but highly virulent ST14 (26.3%, severe ratio [72.2%]). Phylogenetic clustering confirmed ST14/3-5-6-2 as part of a broader hypervirulent lineage, common cluster label 14 (CCL14), which was significantly associated with disease severity (χ2=19.39; P<0.001). Patients infected with CCL14 strains exhibited a distinct hyperinflammatory profile marked by elevated D-dimer levels, complement C4 levels, and platelet count. The mutation ratio of macrolide resistance sites in the MP strains from Henan Province was approximately 75%. Conclusion: Our findings identified the CCL14 lineage as a key driver of disease severity in macrolide-resistant pediatric MPP in Henan Province, China. This under scores the importance of integrating molecular surveillance with clinical monitoring to mitigate disease burden.