Pediatric sepsis inflammatory blood biomarkers that correlate with clinical variables and severity of illness scores

Sean Leonard; Hailey Guertin; Natalya Odoardi; Michael R Miller; Maitray A Patel; Mark Daley; Gediminas Cepinskas; Douglas D Fraser

doi:10.1186/s12950-024-00379-w

Pediatric sepsis inflammatory blood biomarkers that correlate with clinical variables and severity of illness scores

J Inflamm (Lond). 2024 Mar 7;21(1):7. doi: 10.1186/s12950-024-00379-w.

Authors

Sean Leonard¹, Hailey Guertin¹, Natalya Odoardi², Michael R Miller¹, Maitray A Patel³, Mark Daley^{3

4}, Gediminas Cepinskas^{5

6}, Douglas D Fraser^{7

8

9

10

11}

Affiliations

¹ Pediatrics, Western University, London, ON, Canada.
² Emergency Medicine, Lakeridge Health, Ajax/Oshawa, ON, Canada.
³ Epidemiology and Biostatistics, Western University, London, ON, Canada.
⁴ Computer Science, Western University, London, ON, Canada.
⁵ Medical Biophysics, Western University, London, ON, Canada.
⁶ Lawson Health Research Institute, London, ON, Canada.
⁷ Pediatrics, Western University, London, ON, Canada. douglas.fraser@lhsc.on.ca.
⁸ Lawson Health Research Institute, London, ON, Canada. douglas.fraser@lhsc.on.ca.
⁹ Clinical Neurological Sciences, Western University, London, ON, Canada. douglas.fraser@lhsc.on.ca.
¹⁰ Physiology & Pharmacology, Western University, London, ON, Canada. douglas.fraser@lhsc.on.ca.
¹¹ Room C2-C82, London Health Sciences Centre, 800 Commissioners Road East, London, ON, N6A 5W9, Canada. douglas.fraser@lhsc.on.ca.

Abstract

Background: Sepsis is a dysregulated systemic inflammatory response triggered by infection, resulting in organ dysfunction. A major challenge in clinical pediatrics is to identify sepsis early and then quickly intervene to reduce morbidity and mortality. As blood biomarkers hold promise as early sepsis diagnostic tools, we aimed to measure a large number of blood inflammatory biomarkers from pediatric sepsis patients to determine their predictive ability, as well as their correlations with clinical variables and illness severity scores.

Methods: Pediatric patients that met sepsis criteria were enrolled, and clinical data and blood samples were collected. Fifty-eight inflammatory plasma biomarker concentrations were determined using immunoassays. The data were analyzed with both conventional statistics and machine learning.

Results: Twenty sepsis patients were enrolled (median age 13 years), with infectious pathogens identified in 75%. Vasopressors were administered to 85% of patients, while 55% received invasive ventilation and 20% were ventilated non-invasively. A total of 24 inflammatory biomarkers were significantly different between sepsis patients and age/sex-matched healthy controls. Nine biomarkers (IL-6, IL-8, MCP-1, M-CSF, IL-1RA, hyaluronan, HSP70, MMP3, and MMP10) yielded AUC parameters > 0.9 (95% CIs: 0.837-1.000; p < 0.001). Boruta feature reduction yielded 6 critical biomarkers with their relative importance: IL-8 (12.2%), MCP-1 (11.6%), HSP70 (11.6%), hyaluronan (11.5%), M-CSF (11.5%), and IL-6 (11.5%); combinations of 2 biomarkers yielded AUC values of 1.00 (95% CI: 1.00-1.00; p < 0.001). Specific biomarkers strongly correlated with illness severity scoring, as well as other clinical variables. IL-3 specifically distinguished bacterial versus viral infection (p < 0.005).

Conclusions: Specific inflammatory biomarkers were identified as markers of pediatric sepsis and strongly correlated to both clinical variables and sepsis severity.

Keywords: Biomarkers; PICU; Pediatrics; Plasma proteins; Sepsis; Severity.