M. pneumoniae (MP) is a common cause of childhood pneumonia, but there is limited understanding of whether virus co-infections affect clinical severity of M. pneumoniae pneumonia (MPP). We conducted a retrospective cohort study of MPP at the Second Affiliated Hospital of Wenzhou Medical University in 2023 to compare clinical characteristics and outcomes between MP with and without viral co-infection in children, including length of stay, febrile/ cough /wheeze duration, treatment, severity of MPP, and serum biomarkers. We also collected MP targeted next generation sequencing (tNGS) data from the bronchoalveolar lavage fluid (BALF) samples and analyzed MP whole-genome sequencing (WGS) data from a public database to investigate MP genome, typing, and drug resistance. The annually seasonal analysis showed that a higher prevalence of MP occurred from summer to winter. Viral pathogens in our study were highly detected in either autumn or winter. Virus co-infection cases showed a peak in November. HRV was the most frequent detected virus in our study. There was no significant different of gender in all the MPP patients. Compared with single MP infection, children with virus co-infection were younger. They had a shorter febrile duration, longer cough duration, and less proportion of severe MPP cases. Laboratory biomarkers (e.g. CRP, WBC, D-D, PCT) were also significant different between MP mono and viral co-infection groups. 74.07% the samples from BALF performed an A2063G mutation with macrolide-resistant MP (MRMP). By the analysis of phylogenetic tree and the Multi-Locus Sequence Typing (MLST), we suggested that the predominant strains of MP in our study remains ST3 and MRMP strains were independently selected from various genetic backgrounds of MP due to macrolide usage. These findings illustrated that viral co-infection aggravated MP associated bronchi and bronchioles damage, but did not increased severity of MPP, suggesting a potential attenuation of disease severity. Medical Research Registration and Filing Information System. 2024-K-274-02.Registered 26 August 2024. https://www.medicalresearch.org.cn/clinicalResearch .
Chen et al. (2025) studied this question.