Severe acUte Respiratory Viral Infections in Intensive care units: Integrative translational approaches for future emerging and re-merging diseases

"Acute hypoxemic respiratory failure (AHRF) is the leading cause of intensive care unit (ICU) admissions worldwide. Over the past decades, increases in AHRF incidence and ICU bed utilization have been associated with emerging respiratory diseases. Unfortunately, one size does not fit all and there is an urgent need to develop precision medicine tools to provide these patients with the most appropriate therapeutic intervention. In this context, precise characterization of AHRF endotypes is a necessary first step. In the next 2 to 5 years, The following scenarios of exceptional public health situations can be expected: i) human emergence and spread of pathogens with a high pandemic potential and high case fatality rate; ii) human emergence and spread of pathogens with a pandemic potential but a lower CFR; and/or iii) an interpandemic period with respiratory virus epidemics (seasonal influenza A/B, RSV, hMPV, PIV, SARS CoV-2). Primary objective: The SURVI3 project aims to address the biological basis of critical respiratory viral disease subclasses by identifying subsets of critically ill patients based on shared characteristics, including clinical and biological biomarkers. We will identify endotypes based on clinical, virological, immunological pathways, and/or multi-omic markers in adults hospitalized in ICUs using integrative and translational approaches. We will rely on the SEVARVIR research group, which includes a nationwide network of 55 ICUs and microbiology/virology laboratories in France, both in metropolitan areas and overseas territories. Our ambition is to structure a very large multidisciplinary and translational study involving adult patients with severe viral respiratory infections on a sustainable basis, relying on an already established large multicenter network research group We have assembled a high quality Consortium and a strong interdisciplinary partnership within the SURVI3 organization, bringing together 2 clinical networks (the SEVARVIR ICU cohort and a cohort of less severe patients hospitalized in conventional medical wards) and 9 research groups. The planned duration of the project is 36 months and the total number of patients to be included is 1500 (1000 ICU patients and 500 medical ward patients). The project consists of the following work-packages (WP): WP0: Project coordination (ethical and regulatory aspects, biocollection and banking); WP1: SEVARVIR research network (clinical characterization of patients admitted to ICU or conventional wards for acute respiratory failure related to respiratory virus infection; WP2: Multi-omics platforms (diagnostic metagenomics, respiratory microbiota / bacterial coinfections, transcriptomics and proteomics, metabolomics); WP3: Immune response to infection (innate immunity, inborn errors of immunity, adaptive immunity); WP4: Pathogen characterization (viral genetics and functional characterization); WP5: Biostatistical and machine learning analyses (identification of patient subphenotypes, immunological and viral kinetic modeling). Expected scientific outcomes and potential impacts: The project is expected to provide a comprehensive characterization of the mechanisms underlying subclasses of severe acute viral respiratory infections in the ICU using integrative and translational approaches. The methodology used will enable the identification of endotypes and/or clinical biomarker-based phenotypes in critically ill patients that are associated with differential outcomes, to enable the future design of precision critical care medicine. The project will actively contribute to the overall objectives of the PEPR and the National Acceleration Strategy by addressing the need for interdisciplinary and multi-institutional research on emerging infectious diseases and pandemic preparedness."