miRNA signatures for diagnosing sepsis and meningitis in children: a step towards reducing unnecessary procedures

Background: Invasive bacterial infections (IBIs) are initially challenging to diagnose in children. To receive effective care, IBIs require rapid and accurate testing. Current blood biomarkers are late-rising and non-specific, contributing to delays in treatment. Among potential novel biomarkers, miRNA are promising candidates. The project aims to discover miRNA signatures to rule out bacterial sepsis and reduce unnecessary lumbar punctures for children without meningitis. Methods: 85 paediatric plasma samples of bacterial, viral or healthy aetiology were extracted at 100µl with the miRNeasy serum/plasma kit (Qiagen). miRNA libraries were produced with the QIAseq miRNA Library Preparation kit (Qiagen). Sequencing analysis was conducted using the GeneGlobe software and the R coding language. P value <0.05 and a fold change ±2 was considered significant. Results: 84 miRNA were upregulated and 14 downregulated in clinically diagnosed sepsis patients vs healthy controls. To enhance sepsis diagnosis, patients with pSOFA scores >2 were compared to those with scores ≤2. This resulted in 41 upregulated and 10 downregulated miRNA. Six of the top 10 upregulated miRNAs overlap between clinically diagnosed sepsis and sepsis identified by pSOFA >2. 25 upregulated and 38 downregulated miRNA were discovered in bacterial and viral meningitis cases vs non-meningitis infections. Whereas 20 upregulated and 20 downregulated miRNA were identified for bacterial meningitis vs bacterial non-meningitis infections. Only one miRNA is shared among the top 10 upregulated miRNA between sepsis and bacterial meningitis, while two miRNAs overlap between all meningitis cases and bacterial meningitis. Conclusions/Learning Points: The miRNA profiles associated with meningitis and sepsis are relatively distinct, suggesting IBI miRNA testing needs to be specific. The results indicate that further biomarker selection and validation are required, and if successful, miRNA panels may offer diagnostic value for sepsis and meningitis.