Distinct immunological signatures define three sepsis recovery trajectories: a multi-cohort machine learning study.

Importance: Understanding heterogeneous recovery patterns in sepsis is crucial for personalizing treatment strategies and improving outcomes. Objective: To identify distinct recovery trajectories in sepsis and develop a prediction model using early clinical and immunological markers. Design setting and participants: Retrospective cohort study using data from 28,745 adult patients admitted to 12 intensive care units (ICUs) with sepsis between January 2014 and December 2024. Main outcomes and measures: Primary outcome was the 28-day trajectory of Sequential Organ Failure Assessment (SOFA) scores. Secondary outcomes included 90-day mortality and hospital length of stay. Results: Among 24,450 eligible patients (mean [SD] age, 64.5 [15.3] years; 54.2% male), three distinct recovery trajectories were identified: rapid recovery (42.3%), slow recovery (35.8%), and deterioration (21.9%). The machine learning model achieved an AUROC of 0.85 (95% CI, 0.83-0.87) for trajectory prediction. Key predictors included initial SOFA score, lactate levels, and inflammatory markers. Mortality rates were 12.3, 28.7, and 45.6% for rapid, slow, and deterioration groups, respectively. Conclusions and relevance: Early prediction of sepsis recovery trajectories is feasible and may facilitate personalized treatment strategies. The developed model could assist clinical decision-making and resource allocation in critical care settings.