A large multi-cohort transcriptomic analysis across more than 7,000 blood samples identified four reproducible immune endotypes—inflammopathic, coagulopathic, adaptive, and neutrophil-associated—shared across bacterial sepsis, viral sepsis, COVID-19, and noninfectious critical illnesses such as acute respiratory distress syndrome, trauma, and burns. Higher expression of the inflammopathic signature and elevated myeloid dysregulation scores were strongly associated with greater illness severity and mortality, while lymphoid-driven signatures were protective. Single-cell RNA sequencing of more than 600,000 cells revealed that detrimental profiles were dominated by immature neutrophils, whereas beneficial signatures mapped to T and NK cells. Using these insights, researchers developed continuous human immune dysregulation evaluation framework scores that independently predicted mortality beyond the neutrophil-to-lymphocyte ratio and distinguished bacterial from viral immune phenotypes.

Source: Nature Medicine