Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to an infection. In 2020, 49 million sepsis cases were estimated globally, resulting in 13.7 million deaths, meaning that sepsis accounts for approximately 20% of all global deaths. By studying different cohorts of septic patients, we found how the dynamics of the inflammatory response from pro-inflammatory state to an immunosuppressive state are reflected in the formation of ASC specks in response to the activation of the NLRP3 inflammasome in monocytes. Using our patented method to stimulate blood cells to activate the NLRP3 inflammasome, we identified that an early defective activation of NLRP3 is an immunological feature of some septic patients, even when high pro-inflammatory markers are found in their plasma. Those with reduced NLRP3 activation experienced more complications and higher mortality. Importantly, these at-risk patients could not be identified by conventional plasma markers or clinical scores. This method was tested in clinical samples with remarkable results, validating ASC specks quantification as a readout of NLRP3 impairment and establishing it as a potential biomarker for predicting
complications in immunocompromised septic patients.
Our overall objective is to develop an easy-to-use immunoassay that can be seamlessly implemented into hospitals and clinics. Our approach involves the development of a highly sensitive immunoassay, designed as a classic quantitative sandwich ELISA, that requires only a small blood sample to induce and measure ex vivo NLRP3 activation.
This objective is divided into the following specific objectives:
O1: To complete the adaptation of the in vitro method developed in the ERC SPEDI-TEST into a fully scalable clinical test system
O2: To develop an Optimized ELISA to be introduced in clinical practice.
O3: To carry out the analytical and clinical validation of the system
O4: To complete the process for the regulatory approval
O5: To design measures for market deployment and future exploitation of the project results
The solution has undergone extensive validation and will continue to address unmet needs in sepsis diagnostics. Clinical validations have already confirmed NLRP3's importance as a biomarker for prognosis and patient stratification, and we will further validate the biomarker and assay through analytical performance tests to confirm repeatability and reproducibility, with multicenter clinical studies to demonstrate its clinical value across hospitals in the EU and US, showing its importance across any ethnicity. In addition to CE and FDA approvals, economic impact assessments will show benefits for hospitals and patients. Post-market surveillance will ensure long-term efficacy and regulatory compliance.
VIVA-ELISA’s clinical impact goals are, based upon the preliminary data from our last clinical cohort:
i. To reduce in-hospital sepsis-related deaths.
ii. To reduce average stay of sepsis patients, reducing the pressure of ICUs and diminishing sanitary costs.
iii. To promote better recovery from sepsis and decrease long-lasting effects of sepsis.
In terms of economic impact, sepsis imposes a substantial economic burden on the sustainability of health systems in the EU and the US, mainly due to its impact on ICU bed occupancy.
-In the EU, the total healthcare expenditure related to sepsis represents approximately 2.65% of the healthcare budget, which amounts to 0.33% of the gross national income (GNI). The total healthcare expenditure in 2020 in the EU was €1.073T while sepsis expenditure amounted to €28.4B.
-In the US, at least 1.7 million adults suffer from sepsis every year, and about 350,000 pass away in the hospital or are moved to a palliative care facility. The average cost per patient is about €34,000, higher than in European countries, leading to a yearly expenditure of €57.8B.
The development of a predictive prognostic system to assess the risk of sepsis complicationscould play a crucial role in reducing associated expenses for these patients.
