Emergency-granulopoiesis trajectory, but not the CD4/NK lymphocyte trajectory, is directionally reproduced as a correlate of sepsis mortality: a cross-cohort transcriptomic study with external testing and clinical-analogue triangulation

The study investigated whether changes in blood immune cell gene programs in early sepsis can predict patient prognosis. Researchers analyzed five immune modules in three sepsis patient cohorts and developed a predictive model. Rising emergency-granulopoiesis trajectory was associated with higher mortality (odds ratio 1.65), while rising CD4/NK lymphocyte trajectory was associated with lower mortality. When tested on an independent group of 63 patients, only emergency-granulopoiesis consistently reproduced with similar effect size (odds ratio 1.72). The CD4/NK lymphocyte association did not confirm in independent testing. Results were supported by analysis of neutrophil-to-lymphocyte ratios in a database of 12,607 sepsis patients.