1. A large transcriptomic analysis across 37 cohorts identified four consistent immune endotypes—inflammopathic, coagulopathic, adaptive, and neutrophil-associated—shared across bacterial sepsis, viral sepsis, COVID-19, and multiple noninfectious critical illnesses.
2. Higher inflammopathic expression and elevated myeloid dysregulation scores were strongly linked to increased illness severity and mortality.
3. Single-cell RNA sequencing showed detrimental signatures were driven by immature neutrophils, whereas protective signatures mapped to T and NK cells, with no harmful lymphoid signatures identified.
4. Researchers developed Hi-DEF scores that independently predicted mortality beyond the neutrophil-to-lymphocyte ratio and differentiated bacterial from viral immune patterns.
5. The framework is preliminary, with validation limited by early sampling and heterogeneous datasets, but it suggests a conserved immune architecture that could guide future precision endotyping in critical illness.

Source: Nature Medicine