Enhancing Sepsis Recognition and Treatment: A Multifaceted Personalized Approach

Abstract: Sepsis affects 50 million cases per year globally and is among the major causes of death worldwide. Early recognition of infections and accurate discrimination between viral and bacterial etiology is imperative to allow the timely initiation of effective therapy. Current sepsis treatment is limited to source control (i.e., antibiotics in the case of bacterial infections) and supportive care due to incomplete knowledge of the mechanisms leading to organ failure, which hinders the development of more effective targeted therapies. The absence of typical infection signs like fever can complicate early recognition of sepsis. As the clinical presentation varies widely between individuals, the timely identification of sepsis remains a challenge, while the selection of treatments progresses towards a more personalized approach. In response to this challenge, our team has initiated the Acutelines data-biobank (www.acutelines.nl) at the emergency department of our tertiary care hospital. This data-biobank combines electronic health record information with cardiorespiratory waveforms (such as ECG and PPG from monitors and wearables), photographs, and extensive molecular analyses from blood (including RNAseq and proteomics). Hereby, we aim to identify risk markers predictive of clinical progression and response to treatment, such as (narrow spectrum) antibiotics, supportive care and novel, targeted treatments. In collaboration with Inflammatix Inc., we are developing a smart tool to facilitate the early recognition of sepsis and support clinical decisions in the early phase of the disease. Blood samples will be collected, and the expressions of genes associated with the immune response to infection will be measured. These biological signals, along with clinical record data collected during the patient encounter, will be used to derive diagnostic algorithms that can better inform on the presence, type, and severity of infection. Next, the molecular mechanisms associated with organ failure and death in patients with sepsis are used to discover novel therapeutic targets by unraveling the mechanisms leading to organ failure using pre-clinical models of sepsis. Inspired by the cytoprotective effects of hibernating animals, in collaboration with Sulfateq BV, we have developed SUL-compounds. These molecules preserve mitochondrial function, reduce inflammation, and prevent acute kidney injury in septic mice. In conclusion, advancing personalized medicine to enhance early sepsis recognition and develop targeted therapies is imperative in reducing the morbidity and mortality associated with this common and potentially lethal condition.