A Systemic Storm in Critically Injured Humans Revealed by Longitudinal Multi-Omics

Trauma is a leading cause of death and morbidity worldwide. The lack of a comprehensive characterization of the human response to severe injury limits progress in this field. Here, we analyzed a longitudinal, multi-omic dataset comprised of clinical, cytokine, endotheliopathy biomarker, lipidome, metabolome and proteome data from severely injured humans. A “Systemic Storm” pattern with release of 1061 markers together with a pattern suggestive of the “Massive Consumption” of 892 circulating markers were identified in the hyper-acute phase post-trauma. This was followed by resolution and non-resolution signatures represented by 56 and 172 biomarkers, respectively. Data integration yielded two human injury response endotypes, which aligned with clinical trajectory. Prehospital allogeneic thawed plasma rescued only endotype 2 patients with traumatic brain injury (30d mortality: 30.3% vs. 75%, p=0.0015). These novel response patterns re-define the paradigm and the datasets provide a resource for the study of critical illness, trauma and human stress response.