February 23, 2023

Rapid Personalized Diagnosis of Sepsis in Children (RAPIDS)

7th Call, PM / PH Research

Short Summary

Sepsis is a leading cause of death of children worldwide. A major limitation in the management of sepsis in children is the delay in obtaining accurate diagnosis, because children with sepsis initially often have symptoms akin to common and mild viral illnesses. Rapid and reliable diagnosis of sepsis is a major unmet clinical need, which will be addressed in this project. We will perform a large study to discover and validate cutting-edge biomarkers to improve detection and management of sepsis in children. The study cohort will include at least 1750 children with various types of infection and inflammation, ranging from low severity to high severity with organ dysfunction. The findings from this study will yield comprehensive information on the biological mechanisms underlying sepsis in children with the ultimate goal to decipher the heterogeneity of the disease. The identification of key pathways involved may open new avenues for personalized interventions.

Goals

The goal of this large and innovative study is to improve the diagnosis of sepsis in children through assessing the response of the body to infection and inflammation so called “muli-omics” blood analyses. Specifically, these analyses will allow us to understand the biological mechanisms that occur in response sepsis, such as changes in proteins (proteomics) and chemical processes (metabolomics), in addition to the gene expression (transcriptomics). We will identify novel markers which can improve diagnosis and management of sepsis in children. Using machine learning on this unique dataset, we aim characterize the individual response to sepsis. Thereby, we hope to identify new avenues for better, more personalized sepsis management.

Significance

The proposed research overcomes the limitations of traditional one-dimensional diagnostic approaches, which rely on time-consuming isolation, growth, and identification of a causative pathogen. The use of multi-omics has huge potential to profoundly improve our understanding of sepsis. Specifically, the project seeks to identify phenotypes (“patterns”) in children with sepsis, and to unravel key biological mechanisms underlying these. We thereby aim to gain insight into the progression from infection without organ dysfunction to life-threatening sepsis. Ultimately, this approach is expected to provide the urgently needed understanding on the individual susceptibility to sepsis and to contribute to the identification of novel targets for personalized medicine.

Background

Sepsis is defined as the body’s dysregulated response to infection leading to life-threatening organ dysfunction. It remains a leading cause of death in children worldwide. Up to 50% of deaths from sepsis in children occur within 24 hours of presentation to paediatric intensive care units (PICUs), implying an urgent need for rapid diagnostics. Yet, current diagnostic tools remain insufficient to recognize sepsis early. In addition, difficulties in distinguishing bacterial from viral infection risks to lead to unnecessary (or delayed) antibiotic treatment. Furthermore, current laboratory tests do not allow to predict which children will develop organ failure. Finally, at present despite modern medicine we lack personalized approaches to improve outcomes for children with sepsis. Thus, there is an urgent need for innovative strategies to facilitate the accurate and rapid diagnosis of sepsis in critically ill children.