Multi-omic analysis in injured humans: Patterns align with outcomes and treatment responses

Summary Trauma is a leading cause of death and morbidity worldwide. Here, we present the analysis of a longitudinal multi-omic dataset comprising clinical, cytokine, endotheliopathy biomarker, lipidome, metabolome, and proteome data from severely injured humans. A “systemic storm” pattern with release of 1,061 markers, together with a pattern suggestive of the “massive consumption” of 892 constitutive circulating markers, is identified in the acute phase post-trauma. Data integration reveals two human injury response endotypes, which align with clinical trajectory. Prehospital thawed plasma rescues only endotype 2 patients with traumatic brain injury (30-day mortality: 30.3 versus 75.0%; p = 0.0015). Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) was identified as the most predictive circulating biomarker to identify endotype 2-traumatic brain injury (TBI) patients. These response patterns refine the paradigm for human injury, while the datasets provide a resource for the study of critical illness, trauma, and human stress responses.
Graphical abstract
Highlights An integrated longitudinal multi-omic analysis of the human response to trauma Systemic storm and massive consumption patterns are related to early mortality Unique resolution and non-resolution signatures across multiple “omics” platforms Only endotype 2-TBI patients with high UCHL1 levels benefit from early plasma
Wu et al. report a longitudinal multi-omic analysis of the circulation in trauma patients. Cross-platform data integration reveals a massive systemic release of cellular contents (“systemic storm”) and simultaneous consumption of blood constituents. Also defined are patient endotypes that differ in outcomes and responses to early plasma administration.