Sepsis is a major cause of organ failure and death in both children and adults around the world for which there
are no specific therapies other than antibiotics and supportive care. A major reason for the lack of targeted
therapies is our incomplete understanding of the genetic, environmental, microbial, socioeconomic and biologic
factors that underly risk of and outcomes from human sepsis and that drive heterogeneity within this clinical
syndrome. We propose to create a unique resource, the Sepsis ClinicAl Resource And Biorepository
(SCARAB), a two center prospective study in adults and children with sepsis and critically ill controls that is
designed to be both comprehensive and scalable to large multicenter implementation. To create this resource,
we will leverage our experience with large scale prospective observational studies in the ICU, our novel
method of non-invasively sampling the distal airspace in mechanically ventilated patients, our world class
bioinformatics expertise, state-of-the-art phenotyping methodologies, and unique institutional resources.
SCARAB will prospectively enroll subjects from pediatric and adult ICUs at VUMC and Meharry Medical
College, an institution that cares for a primarily minority population. Subjects will be enrolled early in their
illness and serial biologic specimens of blood, DNA, respiratory micro-droplets (from Heat Moisture Exchange
(HME) filters), tracheal aspirates and urine will be collected. To study the end organ most commonly injured in
sepsis, we will establish best practices for collection, processing and storage of lung fluid collected from HME
filters, a novel method for sampling the distal airspace in ventilated patients. Working with our collaborators in
Biomedical Informatics, we will develop automated phenotyping algorithms to identify patients with sepsis and
organ failures including ARDS, AKI and delirium. We will use cutting edge natural language processing
methods such as concept mapping to conduct detailed sub-phenotyping for clinically important variables that
are challenging to phenotype on a large scale, such as hyper- and hypoactive forms of delirium. SCARAB will
also be linked to unique VUMC resources such as MicroVU which retains clinical isolates of all microbial
specimens at VUMC allowing large studies of host-pathogen interactions using contemporary multi-omics
approaches. SCARAB clinical data and biospecimens will be accessible to the broader research community
through an application on our web based study portal. Proposals will be reviewed by a Resource Utilization
Committee comprising study investigators and national experts in sepsis and organ dysfunction. Data will be
de-identified using the most rigorous security standards. SCARAB is also designed to be readily accessible to
early career investigators by providing statistical support, customized phenotyping and access to Studios for
expert engagement for study design. Bringing together all of these innovative elements will allow for
mechanistic studies, development of predictive biomarkers, understanding of pre-hospital factors and clinical
outcome studies in patients with sepsis and appropriate controls at a scale not previously possible.