OBJECTIVE: The purpose of this study was to identify a panel of biomarkers for distinguishing early stage sepsis patients from non-infected trauma patients. BACKGROUND: Accurate differentiation between trauma-induced sterile inflammation and real infective sepsis poses a complex life-threatening medical challenge because of their common symptoms albeit diverging clinical implications, namely different therapies. The timely and accurate identification of sepsis in trauma patients is therefore vital to ensure prompt and tailored medical interventions (provision of adequate antimicrobial agents and if possible eradication of infective foci) that can ultimately lead to improved therapeutic management and patient outcome. The adequate withholding of antimicrobials in trauma patients without sepsis is also important in aspects of both patient and environmental perspective. METHODS: In this proof-of-concept study, we employed advanced technologies, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and multiplex antibody arrays (MAA) to identify a panel of biomarkers distinguishing actual sepsis from trauma-induced sterile inflammation. RESULTS: By comparing patient groups (controls, infected and non-infected trauma and septic shock patients under mechanical ventilation) at different time points, we uncovered distinct protein patterns associated with early trauma-induced sterile inflammation on the one hand and sepsis on the other hand. SYT13 and IL1F10 emerged as potential early sepsis biomarkers, while reduced levels of A2M were indicative of both trauma-induced inflammation and sepsis conditions. Additionally, higher levels of TREM1 were associated at a later stage in trauma patients. Furthermore, enrichment analyses revealed differences in the inflammatory response between trauma-induced inflammation and sepsis, with proteins related to complement and coagulation cascades being elevated whereas proteins relevant to focal adhesion were diminished in sepsis. CONCLUSIONS: Our findings, therefore, suggest that a combination of biomarkers is needed for the development of novel diagnostic approaches deciphering trauma-induced sterile inflammation from actual infective sepsis.

Département d'Anesthésie Réanimation et Médecine Peri Operatoire Centre Hospitalier et Universitaire de Reims Université de Reims Champagne Ardenne Reims France

Department of Infectious Diseases 1st Faculty of Medicine Charles University and Military University Hospital Prague Prague Czechia

Division of Infection Medicine Department of Clinical Sciences Lund University Lund Sweden

Division of Infection Medicine Helsingborg Hospital and Department of Clinical Sciences Helsingborg Lund University Helsingborg Sweden

Genomics and Bioinformatics of Infectious Diseases Institute for Animal Genomics University of Veterinary Medicine Hannover Hannover Germany

Hôpitaux Universitaires de Strasbourg Service d'Anesthésie Réanimation and Médecine Péri opératoire Université de Strasbourg Fédération de Médecine Translationnelle de Strasbourg Strasbourg France

Réanimation Médico Chirurgicale Trauma Center Pôle Médecine Péri Opératoire Centre Hospitalier et Universitaire de Clermont Ferrand Clermont Ferrand France

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