Immunity in Critical Sepsis

Registry record from ClinicalTrials.gov (NCT07770347). This is a study registration, not published results. Lead sponsor: Beijing Chao Yang Hospital. Recruitment status: ENROLLING_BY_INVITATION. Phase: NA. Study type: INTERVENTIONAL. Enrollment: 2400 participants (ESTIMATED). Conditions: Sepsis. Interventions: OTHER: Individualized anti-infective therapy; OTHER: Individualized immunomodulatory therapy; OTHER: Individualized organ function support therapy; OTHER: Standardized ICU nursing care strategies. Primary outcome measures: Annual incidence of sepsis in ICU , 90 days after enrollment.; Prevalence of sepsis in ICU , 90 days after enrollment; Distribution of infection site (lung/abdominal/bloodstream/urinary tract) , 90 days after enrollment; Distribution of infection type (community-acquired/hospital-acquired/secondary) , 90 days after enrollment; Pathogen distribution (Gram-negative/Gram-positive/fungal) , 90 days after enrollment; Antimicrobial resistance rate (CRE/CRAB/MRSA) , 90 days after enrollment; ICU length of stay , Through ICU discharge, up to 90 days; Duration of mechanical ventilation , Through 90 days; Duration of vasoactive agent use , Through 90 days; Duration of renal replacement therapy , Through 90 days; Daily ICU cost , Through ICU discharge, up to 90 days; Total hospitalization cost , Through hospital discharge, up to 90 days; ICU mortality , Through ICU discharge, an average of 28 days; In-hospital mortality , Through hospital discharge, up to 90 days; 28-day all-cause mortality , 28 days after enrollment; 90-day all-cause mortality , 90 days after enrollment; Discriminative Performance of the Infection Risk-Prediction Model , 90 days after enrollment; Sensitivity and Specificity of the Infection Risk-Prediction Score , 90 days after enrollment; Hand Hygiene Compliance Rate , 90 days after enrollment; Catheter Care Bundle Compliance Rate , 90 days after enrollment; Diagnostic Accuracy of Procalcitonin (PCT) , At enrollment (baseline), and at 72 hours after enrollment; Diagnostic Accuracy of C-Reactive Protein (CRP) , At enrollment (baseline), and at 72 hours after enrollment; Diagnostic Accuracy of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) , At enrollment (baseline), and at 72 hours after enrollment; Diagnostic Accuracy of Presepsin , At enrollment (baseline), and at 72 hours after enrollment; Diagnostic Accuracy of Soluble Urokinase Plasminogen Activator Receptor (suPAR) , At enrollment (baseline), and at 72 hours after enrollment; Diagnostic Accuracy of Interleukin-6 (IL-6) , At enrollment (baseline), and at 72 hours after enrollment; Diagnostic Accuracy of Interleukin-8 (IL-8) , At enrollment (baseline), and at 72 hours after enrollment; Diagnostic Accuracy of Pro-Adrenomedullin (Pro-ADM) , At enrollment (baseline), and at 72 hours after enrollment; AUC of Combined Multi-Parameter Early-Warning Model , From 24 hours before to 72 hours after infection onset; Diagnostic Accuracy of AI-Based Automated Warning System , From 24 hours before to 72 hours after infection onset; Lead Time of AI-Based Warning System , Up to 24 hours before clinical diagnosis; Time to First Effective Antibiotic Administration , Within 6 hours of infection onset; Rate of Appropriate Empirical Antibiotic Therapy , 90 days after enrollment; Rate of Antibiotic Coverage of Resistant Organisms , 90 days after enrollment; Antibiotic De-escalation Rate , 90 days after enrollment; Duration of Antibiotic Therapy , 90 days after enrollment; Time to Source Control , 90 days after enrollment; Compliance Rate with SSC Bundle Elements , 90 days after enrollment; Total hospital length of stay , Through hospital discharge, up to 90 days. Brief summary: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host immune response to infection, and remains the leading cause of death in critical care medicine worldwide. According to the 2024 Global Burden of Disease data, there are 48.9 million new cases and 11 million deaths annually worldwide, with 11 million deaths accounting for 19.7% of all global deaths. In China, the incidence of sepsis continues to rise due to population aging, increased invasive procedures, overuse of antimicrobials, the prevalence of multidrug-resistant organisms, and a growing number of patients with chronic diseases. Regional studies indicate that the incidence of sepsis in Chinese ICUs ranges from 15% to 30%, with mortality rates as high as 40% to 60%-far exceeding those in developed countries. Among critically ill patients admitted to the ICU-such as those with severe trauma, major surgery, acute respiratory distress syndrome, severe pancreatitis, and advanced malignancies-hospital-acquired infections leading to secondary sepsis represent the most critical trigger for clinical deterioration, multiple organ dysfunction syndrome (MODS), and death. This creates a vicious cascade of "primary disease exacerbation → nosocomial infection → sepsis → MODS → death", resulting in skyrocketing costs, prolonged hospital stays, and heavy burdens on families and society.To address this challenge, this project aims to: (1) establish the largest and internationally leading multimodal dataset for severe sepsis in China, covering 19 tertiary ICUs nationwide over a 5-year period, with 5,300 critically ill patients including 800 sepsis cases, integrating clinical data, immunological indicators, biomarkers, microbiological data, imaging, longitudinal biospecimens, and long-term follow-up information into a standardized, shareable, and sustainable national sepsis database; (2) systematically elucidate the three core pathophysiological mechanisms of severe sepsis-identifying risk factors, pathogen profiles, antimicrobial resistance patterns, and early warning indicators; revealing the dynamic dysregulation patterns of cellular immunity, humoral immunity, and innate immunity to establish immunophenotyping standards; and clarifying the risk factors, mechanisms,