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

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 stormpattern with release of 1,061 markers, together with a pattern suggestive of the massive consumptionof 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.

Automated summary

Trauma is a major cause of death and morbidity worldwide. The analysis of a longitudinal multi-omic dataset from severely injured humans revealed systemic stormpatterns and consumption patterns, as well as two human injury response endotypes. Prehospital thawed plasma is found to rescue traumatic brain injury patients of one endotype, with Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) identified as the most predictive circulating biomarker.