Multimorbidity Subphenotypes and Effects on Post-Intensive Care Physical Impairments

Post-Intensive Care Syndrome (PICS) affects up to half of ICU survivors, causing persistent physical and mental health impairments that reduce health-related quality of life (HRQoL) and increase healthcare utilization. Multimorbidity is common in this population yet is rarely modeled as an integrated risk profile that could explain heterogeneous recovery and inform tailored rehabilitation. Leveraging the Brown University Health Post-ICU Recovery Clinic (CALC-PIRC), we will deeply phenotype ICU survivors (n.40) to test the hypothesis that data-driven multimorbidity subphenotypes drive distinct trajectories of functional and mental health recovery after critical illness. Aim 1 will identify and validate multimorbidity subphenotypes and link them to standardized outcomes (e.g., EQ-5D-5L, 6-minute walk distance, spirometry) collected at 1, 3, 6, and 12 months post-discharge. Aim 2 will characterize physiologic impairments using submaximal exercise testing (SET), near-infrared spectroscopy (NIRS) to quantify muscle oxidative capacity, and 7-day research-grade wearable monitoring between visits to capture realworld activity, sleep, and vital-sign metrics. Aim 3 will integrate quantitative mental health measures (HADS, IES-R) with brief semi-structured interviews to elucidate how anxiety, depression, and posttraumatic stress intersect with dyspnea, fatigue, and functional recovery across subphenotypes. We will additionally pre-specify stratified analyses comparing trauma-related critical illness versus acute-on-chronic medical critical illness to strengthen Injury COBRE relevance. Deliverables include feasible assessment workflows, pilot effect-size estimates, and mechanism-informed targets to support a subsequent R01 testing precision rehabilitation strategies. Findings directly align with the Injury COBRE mission by advancing understanding of injury-related disability and recovery in an aging, multimorbid survivor population and will position the PI for a subsequent R01 to test tailored interventions that improve long-term outcomes after critical illness. Project Number: 5P20GM139664-05 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of General Medical Sciences (NIGMS) | Principal Investigator: Maya Cohen | Institution: RHODE ISLAND HOSPITAL, PROVIDENCE, RI | Award Amount: $275,460 | Activity Code: P20 | Study Section: ZGM1-RCB-2(C1) View on NIH RePORTER: https://reporter.nih.gov/project-details/11498899