Age-Specific Cytokine Profiling in Children with Mycoplasma Pneumoniae Infections in Post-COVID-19 Era: A Retrospective Study

Ying Sun,1,* Lin Tong,1,* Ming Lin,1 Zuowei Huang,1 Jing He,1 Lin Su,1 Songmin Ying,2,3 Zhimin Chen1 1Department of Pulmonology, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, 310000, People’s Republic of China; 2Department of Pharmacy, Center for Regeneration and Aging Medicine, the Fourth Affiliated Hospital of School of Medicine, Yiwu, 322000, People’s Republic of China; 3Zhejiang-Denmark Joint Laboratory of Regeneration and Aging Medicine, Yiwu, 322000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Songmin Ying, Email [email protected] Zhimin Chen, Email [email protected]: In the wake of COVID-19, a resurgence of Mycoplasma pneumoniae pneumonia (MPP) has emerged globally since mid-2023. However, the clinical manifestations and immune responses following infection vary across different age groups of pediatric patients (infants, preschoolers and school-aged children), increasing the complexity of diagnosis and treatment.Methods: This study retrospectively analyzed serum cytokine levels in 40 healthy children and 87 MPP patients, with additional cytokine profiling of bronchoalveolar lavage fluid (BALF) in severe cases, combining KEGG pathway analysis to investigate age-related immune patterns. SARS-CoV-2 antibody levels were further detected in these MPP patients, followed by Spearman correlation analysis to assess their correlation with cytokines in MPP children.Results: Age-specific cytokine patterns emerged in MPP children. In 0– 2 years, cytokines enriched in IL-17, TLR, and TNF pathways were upregulated in MPP groups compared to controls, while in 6– 12 years, cytokines enriched in TLR, RLR, and JAK-STAT pathways were downregulated in MPP groups. Serum patterns in 3– 5 years resembled those in 0– 2 years, but BALF aligned with 6– 12 years. SARS-CoV-2 IgG positively correlated with TWEAK, IL-22, IL-16, IL-12p40, CCL7, and CD152 in 0– 2 years (P < 0.05), but negatively with CCL13 in 6– 12 years (P < 0.01).Conclusion: Overall, the immune pattern in children with MPP is age-specific and severity-dependent. Higher levels of SARS-CoV-2 IgG are associated with a more robust and mature anti-infective immune response in younger MPP patients, while in older children, besides providing immune memory against pathogens, SARS-CoV-2 IgG also appears to plant a landmine of immune exhaustion.Keywords: age-specific, children, cytokines, immune patterns, Mycoplasma pneumoniae, SARS-CoV-2 antibody