# Screening of early predictive serum biomarkers and construction of a combined predictive model for refractory Mycoplasma pneumoniae infection in children

**Authors:** Ling Zhu, Jinsheng Xu, Tailei Yuan, Haoyue Li, Jun Li

PMC · DOI: 10.3389/fped.2026.1680913 · 2026-02-19

## TL;DR

This study identifies serum biomarkers and builds a predictive model to distinguish severe Mycoplasma pneumoniae infections in children early on.

## Contribution

A novel multi-marker random forest model is developed for early prediction of refractory Mycoplasma pneumoniae infection in children.

## Key findings

- RMPP patients showed higher rates of severe symptoms and longer hospital stays compared to GMPP.
- Elevated CRP, LDH, IgA, IL-6, IL-10, and IFN-γ were identified as significant serum biomarkers for RMPP.
- The random forest model achieved high accuracy (AUC = 0.978) in distinguishing RMPP from GMPP.

## Abstract

Mycoplasma pneumoniae pneumonia (MPP) is a prevalent respiratory infection. Refractory MPP (RMPP) presents more severe symptoms and requires more intensive treatment compared to general MPP (GMPP). This study aimed to identify distinguishing clinical, laboratory, and radiological characteristics between RMPP and GMPP and develop an early predictive model for RMPP risk stratification.

A total of 568 patients, including 130 RMPP cases and 438 GMPP cases, were enrolled. Clinical information, laboratory tests, and radiological features were compared. Univariate and multivariate logistic regression analyses identified serum biomarkers associated with RMPP. A combined predictive model using random forest approach was developed and externally validated.

RMPP patients showed significantly higher rates of older age, fever, tachypnea, chest tightness, wheezing, chills, extrapulmonary complications, decreased unilateral lung sounds, longer fever duration, hospital stay, antibiotic therapy, oxygenotherapy use, and Intensive Care Unit (ICU) admission (all P < 0.05). Laboratory findings revealed elevated neutrophil percentage, C-reactive protein (CRP), lactate dehydrogenase (LDH), immunoglobulin A (IgA), interleukin (IL)-6, IL-10, and interferon-gamma (IFN-γ), but lower prealbumin (PAB) concentrations in RMPP. Radiologically, RMPP exhibited more severe manifestations such as large lesions, pleural effusion, lobar atelectasis, pulmonary consolidation, and pleural thickening. Using the eight independently associated serum biomarkers, we developed a multi-factor random forest model that showed excellent discrimination between RMPP and GMPP (AUC = 0.978 in the development cohort), which was confirmed in an external validation cohort (AUC = 0.957).

Significant differences in clinical, laboratory, and radiological characteristics were observed between RMPP and GMPP. The combined multi-marker model shows strong potential for early risk identification of RMPP and may support timely clinical decision-making; however, prospective validation is needed before routine implementation.

## Linked entities

- **Proteins:** IL6 (interleukin 6), IL10 (interleukin 10)
- **Diseases:** Mycoplasma pneumoniae pneumonia (MONDO:0005867)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IL2 (interleukin 2) [NCBI Gene 3558] {aka IL-2, TCGF, lymphokine}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IGHE (immunoglobulin heavy constant epsilon) [NCBI Gene 3497] {aka IgE}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** septic shock (MESH:D012772), immune dysregulation (OMIM:614878), primary or secondary immunodeficiency (MESH:D000081207), pulmonary embolism (MESH:D011655), Fever (MESH:D005334), respiratory distress (MESH:D012128), acute (MESH:D000208), CAP (MESH:D003147), tissue damage (MESH:D017695), hypoxia (MESH:D000860), pleural effusion (MESH:D010996), bacterial (MESH:D001424), pulmonary infiltrates (MESH:D017254), wheezing (MESH:D012135), interstitial lung disease (MESH:D017563), chronic lung disease (MESH:D029424), allergic disease (MESH:D004342), GMPP (MESH:D011014), liver dysfunction (MESH:D017093), bacterial pneumonia (MESH:D018410), necrotizing pneumonia (MESH:D000071067), infection (MESH:D007239), Mycoplasma encephalitis (MESH:D004660), pleural thickening (MESH:D010995), chill (MESH:D023341), Pulmonary complications (MESH:D008171), LDH (MESH:C538133), bronchopulmonary dysplasia (MESH:D001997), cough (MESH:D003371), lung injury (MESH:D055370), bronchiolitis obliterans (MESH:D001989), MP (MESH:D011019), Tachypnea (MESH:D059246), rheumatic or autoimmune disease (MESH:D012216), chronic liver or kidney disease (MESH:D051436), viral bronchiolitis (MESH:D001990), congenital heart disease (MESH:D006330), atelectasis (MESH:D001261), inflammation (MESH:D007249), bacterial co-infection (MESH:D060085), respiratory infection (MESH:D012141), HL (MESH:C538324), radiologic abnormalities (MESH:D000014), neutrophil-mediated (MESH:C564275), bronchiectasis (MESH:D001987), mycoplasma infections (MESH:D009175)
- **Chemicals:** beta-lactam (MESH:D047090), erythromycin (MESH:D004917), cephalosporins (MESH:D002511), Macrolide (MESH:D018942), GMPP (-), azithromycin (MESH:D017963), oxygen (MESH:D010100)
- **Species:** Mycoplasmoides pneumoniae (Filterable agent of primary atypical pneumonia, species) [taxon 2104], Adenoviridae (family) [taxon 10508], Homo sapiens (human, species) [taxon 9606], Respiratory syncytial virus (no rank) [taxon 12814]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12961581/full.md

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Source: https://tomesphere.com/paper/PMC12961581