Biomarkers established to stratify sepsis long-term adverse effects to improve patients’ health and quality of life

Informazioni relative al progetto

BEATsep

ID dell’accordo di sovvenzione: 101137484

DOI

10.3030/101137484

Data della firma CE 11 Dicembre 2023

Data di avvio 1 Gennaio 2024

Data di completamento 31 Dicembre 2028

Finanziato da

• Health

Costo totale

€ 6 912 872,50

Contributo UE

€ 6 912 872,00

Coordinato da

FAKULTNI NEMOCNICE U SV ANNY V BRNE
Czechia

Periodic Reporting for period 1 - BEATsep (Biomarkers established to stratify sepsis long-term adverse effects to improve patients’ health and quality of life)

Periodo di rendicontazione: 2024-01-01 al 2025-06-30

Sintesi del contesto e degli obiettivi generali del progetto

Sepsis is a life-threatening condition and one of the leading causes of death worldwide, with survivors often facing long-term consequences such as immunologic, cognitive, neurological, and psychological impairments collectively referred to as post-intensive care syndrome (PICS), a long-lasting state of immune dysfunction predisposing them to the development of infections, autoimmune and non-communicable diseases (NCDs), and overall long-term reduced fitness. Despite its global burden, systematic follow-up and monitoring of sepsis survivors remain limited, creating an urgent need for better diagnostic tools, predictive models, and patient-centered care strategies. The BEATsep project addresses this gap by integrating clinical research, immunological research, advanced data science, and social sciences to capture the multifaceted impact of sepsis and improve long-term outcomes. Through the establishment of a unique novel set of biomarkers and innovative patients assessment protocols, the project lays the foundation for machine learning models that can predict complications and guide personalized interventions. By combining biomedical sciences with patient-reported outcomes and ethical, legal, and social perspectives, BEATsep not only advances the scientific state of the art but also contributes to European and global health priorities. Ultimately, the project’s pathway to impact lies in reducing the personal, societal, and healthcare burdens of sepsis, improving the quality of life of survivors, and informing future clinical guidelines and policy at scale.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

During the reporting period, the BEATsep project progressed in coordination, project management, and data governance, including a robust internal monitoring framework, including semi-annual internal reporting and regular consortium meetings, ensuring effective oversight of scientific activities and timely identification of risks. Governance structures, such as the Project Management Board (PMB), Internal Ethical Coordination Board (IECB), Technology Transfer Advisory Committee (TTAC), and External Project Advisory Committee (ePAC), were implemented including clear rules of procedure. A Data Management Plan (DMP) was developed and approved by all partners, providing clear guidelines for handling, sharing, and protecting data in compliance with FAIR principles. Most of the legal framework documents were established to enable secure data and sample sharing among partners. The BEATsep team finalised the hiring process actress all the partners’ sites assuring full scientific performance. The methodology for the project was fully established, including validations and several SOPs.
The first reporting period served mainly to establish the cornerstones of the project in terms of data collections and standardising the procedures. This resulted ‘into establishment of a unique REDcap database allowing the reporting of all the data of the BEATsep multicentric study through Electronic Case Report Form (eCRF). Furthermore the accessibility of REDcap data for future machine-learning readiness from the outset has been validated in order to ensure elimination of the need for later data rectification. The BEATsep aims for outstanding standardization of patients data evaluation, therefore a two-tier access and training system was introduced to guarantee both security and data quality: users first complete structured training with trial databases (supported by custom text and video manuals) before gaining access to the live BEATsep database. This structured onboarding ensures standardized, error-minimized data entry across sites, a critical advancement for multi-center clinical research. All necessary assays were validated using samples prepared according to BEATsep SOPs. The BEATsep collected preliminary data suggesting changes in flow cytometry phenotyping (surface, metabolic, functional marker) spectra of plasma markers including cytokines, NETs, extracellular ASC specks. A rodent model assessing the PICS has been set.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

The BEATSep has established a clinically relevant murine model of post-intensive care syndrome (PICS), allowing investigation of long-term immune, metabolic, and cognitive consequences. The model is novel in demonstrating sex-dependent differences in survival, hematological alterations, and behavioral deficits, closely reflecting patterns seen in human sepsis survivors. Comprehensive behavioral testing (Morris Water Maze, Novel Object Recognition, Open Field) alongside hematological and tissue analyses provides a multidimensional readout of post-sepsis sequelae. Beyond the current state of the art, this platform enables mechanistic studies on the role of metabolic alterations, NETs, autoantibodies, and ASC specks in chronic post-sepsis impairments, thereby offering a powerful translational bridge between experimental findings and clinical observations.
BEATsep developed a novel strategy to assess neurological and psychological sequelae in sepsis survivors, exceeding standard clinical follow-up. It integrates validated psychological screening (PHQ-9) with rarely combined advanced methods: i) a comprehensive neuropsychological battery, ii) non-invasive EEG, iii) actigraphy via smart wristbands, iv) MRI neuroimaging, and v) a digital handwriting test for fine-motor deficits. Structured six-month post-sepsis recalls allow high-resolution detection of cognitive, emotional, and neurological perturbations. This multidimensional approach, combining digital and clinical biomarkers, advances monitoring of post-sepsis syndrome and supports personalized rehabilitation and long-term care.