1556: Developing an Exposomic Medicine Program for Critical Care Using Precision Omics

Introduction: The first 48 hours of care for critically ill patients, called the “Golden Window,” are pivotal to determining outcomes. Our ability to reverse physiological deterioration and prevent secondary organ damage depends on our knowledge. However, ICU physicians lack comprehensive knowledge of exposures to infectious agents, diet, social interactions, and the endogenous biology for a given patient. Emerging omic platforms offer rapid insights into patient biology and exposomics. We present eight years of building omics capacity in critical care, from pilot testing to scalable bioinformatics and integration into clinical workflows. Methods: Corewell Health has developed cohorts integrating genomics, transcriptomics, and metabolomics to track exposure dynamics. These include: 55 NICU patients (genomes, blood/buccal transcriptomes), 27 PICU MODS (3 timepoints: blood transcriptome/metabolome), 20 NICU/PICU RSV (2 timepoints: blood transcriptome/metabolome, gut metagenome), 17 PICU TBI (3 timepoints: blood transcriptome/metabolome), 221 hospitalized adult COVID-19 (1–2 timepoints: blood transcriptome), and rapid Nanopore sequencing for PICU patients. Results: Initial workflows focused on rapid NICU genomics for rare disease diagnoses, returning results in 1–5 days. Genomics yielded diagnoses in 31%, while expanded transcriptomes uncovered microbial dynamics and immune dysregulation in ~20% of undiagnosed individuals. MODS and RSV studies revealed infection patterns (including secondary), antibody activation, and a case of EBV-induced genetically associated HLH. TBI studies showed associations between gut flora translocation during CPR and clonal anti-neural autoantibody expansions. Adult COVID-19 yielded robust exposomic signatures, including viral/bacterial diversity, vaccine breakthrough, antibody/ TCR dynamics, and interferon-driven pathology in specific subgroups. Conclusions: Omic tools have matured to enable rapid, nuanced insights into patient biology and exposures often missed by standard methods. As sequencing technologies (e.g., expandomer-based pore sequencing, Nanopore) continue to accelerate and decrease in cost, omics are becoming feasible for real-time clinical decision-making in critical care.