Sepsis
Conditions
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, and subtype characteristics of multiple organ injury; (3) foster interdisciplinary collaboration between medical and engineering sciences to develop a series of precision diagnostic and therapeutic tools, including AI-assisted early infection warning systems, rapid immunotyping assays, multi-organ injury prediction models, and individualized prognostic calculators for real-time, accurate, and non-invasive bedside assessment; (4) establish a comprehensive precision management system for sepsis, forming an integrated "prevention-early warning-diagnosis-immunotyping-stratified treatment-prognostic evaluation-rehabilitation" care pathway; (5) drive clinical translation to improve patient outcomes, aiming to reduce ICU sepsis incidence, mortality, and healthcare costs, while improving long-term quality of life, cognitive function, and psychological status of survivors and reducing readmission rates; and (6) build a national-level sepsis research platform and cultivate talent by establishing a nationwide collaborative research network, and training professionals with integrated clinical-research-translational competencies.
Interventions
OTHERIndividualized anti-infective therapy
Antimicrobial agents (e.g., broad-spectrum or targeted antibiotics, antifungals) selected and adjusted by the attending physician based on suspected/confirmed infection source, culture and susceptibility results, and institutional antimicrobial stewardship protocols.
OTHERIndividualized immunomodulatory therapy
Immunomodulatory agents (e.g., corticosteroids, intravenous immunoglobulin) administered at the discretion of the attending physician according to the patient's immune/inflammatory status and relevant clinical guidelines.
OTHERIndividualized organ function support therapy
Organ support measures (e.g., mechanical ventilation, continuous renal replacement therapy, vasoactive agents) initiated and titrated by the treating team based on the patient's evolving organ function status.
OTHERStandardized ICU nursing care strategies
Nursing care measures (e.g., protocolized sedation/analgesia management, glycemic control, pressure injury prevention, early mobilization) delivered according to unit-based standardized nursing protocols.
Sponsors
Beijing Chao Yang Hospital
The People's Hospital of Hebei Province
Tianjin First Central Hospital
Second Hospital of Shanxi Medical University
Beijing Obstetrics and Gynecology Hospital
Affiliated Hospital of Hebei University
Hebei Provincial Hospital of Traditional Chinese Medicine
Hangzhou Hospital of Traditional Chinese Medicine
Baoding First Central Hospital
Beijing Shuyi Hospital
Cangzhou Central Hospital
Hengshui People's Hospital
General Hospital of Taiyuan Iron & Steel Company
Changzhi People's Hospital
Jincheng People's Hospital
Xinxiang Central Hospital
Luohe Central Hospital
Inner Mongolia Baogang Hospital
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * ICU stay ≥ 24 hours * Informed consent signed by the patient or their legal representative
Exclusion criteria
* ICU stay \< 24 hours * Refusal to provide informed consent * Pregnancy or lactation * Receiving palliative care or expected survival \< 24 hours * Previously enrolled in this study * Severe immunodeficiency (HIV infection, or long-term use of corticosteroids/immunosuppressants)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Source Control | 90 days after enrollment | Time, in hours, from infection recognition to definitive source-control intervention (drainage, debridement, catheter removal, or surgery). |
| Compliance Rate with SSC Bundle Elements | 90 days after enrollment | Percentage of eligible patients/bundle elements for which Surviving Sepsis Campaign bundle elements were completed within the recommended time window. |
| Total hospital length of stay | Through hospital discharge, up to 90 days | Number of days from hospital admission to hospital discharge. |
| In-hospital mortality | Through hospital discharge, up to 90 days | Percentage of patients who die prior to hospital discharge. |
| 28-day all-cause mortality | 28 days after enrollment | Percentage of patients who die from any cause within 28 days of enrollment. |
| 90-day all-cause mortality | 90 days after enrollment | Percentage of patients who die from any cause within 90 days of enrollment. |
| Discriminative Performance of the Infection Risk-Prediction Model | 90 days after enrollment | Area under the receiver operating characteristic curve (AUC/C-statistic) of the multivariable model predicting infection occurrence, developed from patient, disease, and treatment-related candidate predictors using Cox regression, LASSO, and propensity score analysis. |
| Sensitivity and Specificity of the Infection Risk-Prediction Score | 90 days after enrollment | Sensitivity and specificity (%) of the infection risk-prediction score at its optimal cutoff value, determined by the Youden index. |
| Hand Hygiene Compliance Rate | 90 days after enrollment | Percentage of observed hand hygiene opportunities performed correctly, per WHO Five Moments guidance. |
| Catheter Care Bundle Compliance Rate | 90 days after enrollment | Percentage of eligible patient-days with full compliance to central line and urinary catheter care bundle elements. |
| Diagnostic Accuracy of Procalcitonin (PCT) | At enrollment (baseline), and at 72 hours after enrollment | Area under the receiver operating characteristic curve (AUC) of serum Procalcitonin (PCT) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value. |
| Diagnostic Accuracy of C-Reactive Protein (CRP) | At enrollment (baseline), and at 72 hours after enrollment | Area under the receiver operating characteristic curve (AUC) of serum C-Reactive Protein (CRP) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value. |
| Diagnostic Accuracy of Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) | At enrollment (baseline), and at 72 hours after enrollment | Area under the receiver operating characteristic curve (AUC) of serum Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value. |
| Diagnostic Accuracy of Presepsin | At enrollment (baseline), and at 72 hours after enrollment | Area under the receiver operating characteristic curve (AUC) of serum Presepsin concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value. |
| Diagnostic Accuracy of Soluble Urokinase Plasminogen Activator Receptor (suPAR) | At enrollment (baseline), and at 72 hours after enrollment | Area under the receiver operating characteristic curve (AUC) of serum Soluble Urokinase Plasminogen Activator Receptor (suPAR) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value. |
| Diagnostic Accuracy of Interleukin-6 (IL-6) | At enrollment (baseline), and at 72 hours after enrollment | Area under the receiver operating characteristic curve (AUC) of serum Interleukin-6 (IL-6) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value. |
| Diagnostic Accuracy of Interleukin-8 (IL-8) | At enrollment (baseline), and at 72 hours after enrollment | Area under the receiver operating characteristic curve (AUC) of serum Interleukin-8 (IL-8) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value. |
| Diagnostic Accuracy of Pro-Adrenomedullin (Pro-ADM) | At enrollment (baseline), and at 72 hours after enrollment | Area under the receiver operating characteristic curve (AUC) of serum Pro-Adrenomedullin (Pro-ADM) concentration for differentiating infection from non-infection and sepsis from non-sepsis, with corresponding sensitivity, specificity, and optimal cutoff value. |
| AUC of Combined Multi-Parameter Early-Warning Model | From 24 hours before to 72 hours after infection onset | Area under the receiver operating characteristic curve of a composite model integrating vital signs (temperature, heart rate, respiratory rate, blood pressure, SpO2), laboratory values, and the biomarkers listed above for early warning of infection. |
| Diagnostic Accuracy of AI-Based Automated Warning System | From 24 hours before to 72 hours after infection onset | Accuracy (%) of a machine-learning-based (random forest, XGBoost, deep learning) automated warning system using electronic medical record data to predict infection onset. |
| Lead Time of AI-Based Warning System | Up to 24 hours before clinical diagnosis | Time interval, in hours, between the AI system alert and the subsequent clinical diagnosis of infection. |
| Time to First Effective Antibiotic Administration | Within 6 hours of infection onset | Time, in hours, from infection recognition to administration of the first in vitro active antibiotic. |
| Rate of Appropriate Empirical Antibiotic Therapy | 90 days after enrollment | Percentage of patients receiving empirical antibiotic therapy subsequently confirmed to be active against the identified pathogen(s). |
| Rate of Antibiotic Coverage of Resistant Organisms | 90 days after enrollment | Percentage of patients with identified multidrug-resistant organisms whose empirical antibiotic regimen provided adequate in vitro coverage. |
| Antibiotic De-escalation Rate | 90 days after enrollment | Percentage of patients whose antibiotic regimen was narrowed (de-escalated) based on culture and susceptibility results. |
| Duration of Antibiotic Therapy | 90 days after enrollment | Number of days of antibiotic treatment administered for the index infection. |
| Total hospitalization cost | Through hospital discharge, up to 90 days | Total direct cost of hospital care per patient, in Chinese Yuan (CNY), from hospital admission to discharge. |
| ICU length of stay | Through ICU discharge, up to 90 days | Number of days from ICU admission to ICU discharge. |
| Duration of mechanical ventilation | Through 90 days | Number of days on invasive mechanical ventilation. |
| ICU mortality | Through ICU discharge, an average of 28 days | Percentage of patients who die prior to ICU discharge. |
| Duration of vasoactive agent use | Through 90 days | Number of days on any vasoactive agent (e.g., norepinephrine, vasopressin, dobutamine, epinephrine). |
| Duration of renal replacement therapy | Through 90 days | Number of days receiving renal replacement therapy (continuous or intermittent). |
| Daily ICU cost | Through ICU discharge, up to 90 days | Average direct cost of ICU care per patient per day, in Chinese Yuan (CNY). |
| Annual incidence of sepsis in ICU | 90 days after enrollment. | Number of new sepsis cases (diagnosed by Sepsis-3 criteria) per 1,000 ICU admissions (or per 1,000 patient-days). |
| Prevalence of sepsis in ICU | 90 days after enrollment | Percentage of ICU admissions meeting Sepsis-3 criteria for sepsis during the study period. |
| Distribution of infection site (lung/abdominal/bloodstream/urinary tract) | 90 days after enrollment | Percentage of patients with infection originating from the lung, abdomen, bloodstream, or urinary tract, respectively. |
| Distribution of infection type (community-acquired/hospital-acquired/secondary) | 90 days after enrollment | Percentage of patients with community-acquired, hospital-acquired, or secondary infection, respectively. |
| Pathogen distribution (Gram-negative/Gram-positive/fungal) | 90 days after enrollment | Percentage of microbiological isolates classified as Gram-negative bacteria, Gram-positive bacteria, or fungi. |
| Antimicrobial resistance rate (CRE/CRAB/MRSA) | 90 days after enrollment | Percentage of isolates identified as carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), or methicillin-resistant Staphylococcus aureus (MRSA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Endothelin-1 Concentration | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Plasma endothelin-1 concentration, in pg/mL, measured by immunoassay. |
| DPP3 Concentration | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Plasma dipeptidyl peptidase 3 concentration, in ng/mL, measured by immunoassay. |
| Fibrinogen Concentration | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Plasma fibrinogen concentration, in g/L, measured by standard coagulation assay. |
| Platelet Count | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Platelet count, in ×10⁹/L, measured by complete blood count. |
| Thrombin Time | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Thrombin time, in seconds, measured by standard coagulation assay. |
| Concentration of D-dimer | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Plasma D-dimer concentration measured at each specified timepoint, reported in μg/mL (or ng/mL FEU). |
| Discriminative Performance of Multi-Organ Injury Risk-Prediction Model | 90 days after enrollment | Area under the receiver operating characteristic curve (AUC/C-statistic) of the multivariable model predicting multi-organ injury, developed from infection, immune, endothelial, coagulation, and patient/treatment-related candidate predictors using Cox regression, LASSO, and machine learning methods. |
| Sensitivity and Specificity of Multi-Organ Injury Risk Score | 90 days after enrollment | Sensitivity and specificity (%) of the multi-organ injury risk score at its optimal cutoff value. |
| Composite Multi-Organ Dysfunction Score (MODS-score) | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, at 5 days after diagnosis and 90 days after diagnosis | Multi-organ dysfunction assessed by the Marshall Multiple Organ Dysfunction Score (MODS), which evaluates six organ systems (respiratory, renal, hepatic, cardiovascular, hematologic, and neurologic), each scored 0-4, for a total score ranging from 0 (no dysfunction) to 24 (maximum dysfunction). Higher scores indicate more severe multi-organ dysfunction. |
| Serum Creatinine Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum creatinine concentration, in μmol/L (or mg/dL), measured by standard laboratory assay, reflecting renal function. |
| Serum Total Bilirubin Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum total bilirubin concentration, in μmol/L (or mg/dL), measured by standard laboratory assay, reflecting hepatic function. |
| Serum Troponin Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of high-sensitivity cardiac troponin T (hs-cTnT) or troponin I (hs-cTnI), measured by standard immunoassay, reported in ng/L (or ng/mL), reflecting myocardial injury. |
| Serum Lactate Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum lactate concentration, in mmol/L, measured by standard laboratory assay. |
| Serum Syndecan-1 Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum syndecan-1 concentration, in ng/mL, measured by immunoassay, reflecting glycocalyx/endothelial injury. |
| Proportion of Patients per Organ-Injury Subtype | Within 5 days after enrollment | Percentage of patients classified as lung-predominant, kidney-predominant, heart-predominant, coagulation-predominant, or mixed subtype, based on the pattern, mechanism, and severity of organ injury. |
| Rate of Multi-Organ Injury Progression | From baseline (at infection diagnosis) to 72 hours after diagnosis | Percentage of patients demonstrating worsening of organ-specific SOFA sub-score between baseline and 72 hours. |
| Rate of Multi-Organ Injury Reversibility | From 72 hours after diagnosis to 5 days after diagnosis | Percentage of patients demonstrating recovery of organ-specific SOFA sub-score between 72 hours and day 5. |
| Compliance Rate with Lung-Protective Ventilation Strategy | 90 days after enrollment | Percentage of mechanically ventilated patients receiving tidal volume ≤8 mL/kg predicted body weight. |
| Time from AKI Diagnosis to RRT Initiation | 90 days after enrollment | Time, in hours, from acute kidney injury diagnosis to initiation of renal replacement therapy. |
| Lactate Clearance Rate | From baseline (at infection diagnosis) to 72 hours after diagnosis | Percentage change in serum lactate concentration from baseline to 72 hours after diagnosis, calculated as (baseline lactate - 72-hour lactate) / baseline lactate × 100%. |
| Discriminative Performance of Prognostic Model for 28-Day Mortality | 28 days after enrollment | Area under the receiver operating characteristic curve (AUC/C-statistic) of a prognostic model integrating infection, immune, and organ-injury indicators to predict 28-day all-cause mortality. |
| Discriminative Performance of Prognostic Model for 90-Day Mortality | 90 days after enrollment | Area under the receiver operating characteristic curve (AUC/C-statistic) of the same prognostic model to predict 90-day all-cause mortality. |
| 1-Year All-Cause Survival Rate | 1 year after enrollment | Percentage of enrolled patients alive at 1 year after enrollment. |
| Hospital Readmission Rate | 1 year after enrollment | Percentage of patients readmitted to the hospital for any cause within 1 year after enrollment. |
| Cognitive Function (MoCA) | 1 year after enrollment | Cognitive function assessed by the Montreal Cognitive Assessment (MoCA), scored 0-30 (higher scores indicate better cognitive function). |
| Cognitive Function (TICS) | 1 year after enrollment | Cognitive function assessed by the Telephone Interview for Cognitive Status (TICS), scored 0-41, with higher scores indicating better cognitive function. |
| Anxiety Symptoms (HADS-Anxiety subscale) | 1 year after enrollment | Anxiety symptoms assessed by the Hospital Anxiety and Depression Scale, Anxiety subscale (HADS-A), scored 0-21 (higher scores indicate more severe anxiety). |
| Depressive Symptoms (HADS-Depression subscale) | 1 year after enrollment | Depressive symptoms assessed by the Hospital Anxiety and Depression Scale, Depression subscale (HADS-D), scored 0-21 (higher scores indicate more severe depression). |
| Post-Traumatic Stress Symptoms | 1 year after enrollment | Post-traumatic stress symptoms assessed by the PTSD Checklist for DSM-5 (PCL-5), a 20-item self-report measure scored 0-80, with higher scores indicating more severe post-traumatic stress symptoms. |
| Functional Disability (mRS) | 1 year after enrollment | Functional disability assessed by the modified Rankin Scale (mRS), scored 0-6 (higher scores indicate greater disability). |
| Activities of Daily Living (Barthel Index) | 1 year after enrollment | Activities of daily living assessed by the Barthel Index, scored 0-100 (higher scores indicate greater independence). |
| Health-Related Quality of Life (EQ-5D-5L Utility Index) | 1 year after enrollment | Health-related quality of life assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) descriptive system, reported as a utility index value derived using the Chinese value set. The utility index ranges from -0.391 (worst health state) to 1.0 (full health), with higher scores indicating better health-related quality of life. A score of 0 represents a health state equivalent to death, and negative scores represent health states considered worse than death. |
| Health-Related Quality of Life (EQ-VAS) | 1 year after enrollment | Health-related quality of life assessed by the EQ-5D-5L Visual Analogue Scale, scored 0-100 (higher scores indicate better self-rated health). |
| Concentration of Plasmin-Antiplasmin Complex (PAP) | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Plasma PAP complex concentration measured at each specified timepoint, reported in ng/mL. |
| Concentration of Tissue Plasminogen Activator (tPA) | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Plasma tPA concentration measured at each specified timepoint, reported in ng/mL |
| Muscle Function | 1 year after enrollment | Muscle function assessed by the Medical Research Council (MRC) sum score, which evaluates strength in six muscle groups bilaterally (shoulder abductors, elbow flexors, wrist extensors, hip flexors, knee extensors, and ankle dorsiflexors), each scored 0-5, for a total score ranging from 0 (complete paralysis) to 60 (normal strength). Lower scores indicate greater muscle weakness; an MRC sum score \<48 is commonly used to define ICU-acquired weakness. |
| Concentration of Fibrin/Fibrinogen Degradation Products (FDP) | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Plasma FDP concentration measured at each specified timepoint, reported in μg/mL. |
| Concentration of Plasminogen Activator Inhibitor-1 (PAI-1) | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Plasma PAI-1 concentration measured at each specified timepoint, reported in ng/mL |
| CD3+ T Lymphocyte Count/Percentage | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Absolute count (cells/μL) and/or percentage of CD3+ T lymphocytes, measured by flow cytometry. |
| CD4+ T Lymphocyte Count/Percentage | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Absolute count (cells/μL) and/or percentage of CD4+ T lymphocytes, measured by flow cytometry. |
| CD8+ T Lymphocyte Count/Percentage | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Absolute count (cells/μL) and/or percentage of CD8+ T lymphocytes, measured by flow cytometry. |
| CD4+/CD8+ Ratio | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Ratio of CD4+ to CD8+ T lymphocyte counts, calculated from flow cytometry measurements |
| Regulatory T Cell (Treg) Percentage | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Percentage of CD4+CD25+FoxP3+ regulatory T cells among total CD4+ T cells, measured by flow cytometry. |
| Th1/Th2 Ratio | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Ratio of Th1 to Th2 helper T cell subsets, measured by flow cytometry. |
| Monocyte HLA-DR (mHLA-DR) Expression | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Monocyte human leukocyte antigen-DR expression, measured by flow cytometry and reported as mean fluorescence intensity or percentage of HLA-DR-positive monocytes. |
| Natural Killer (NK) Cell Count/Percentage | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Absolute count (cells/μL) and/or percentage of NK cells, measured by flow cytometry. |
| Absolute Lymphocyte Count | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Total lymphocyte count, in cells/μL, measured by complete blood count with differential. |
| Lymphocyte Apoptosis Rate | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Percentage of lymphocytes undergoing apoptosis, measured by flow cytometry (e.g., Annexin V/propidium iodide staining). |
| Monocyte Phagocytic Index | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Percentage of monocytes demonstrating phagocytic activity, measured by flow cytometry-based phagocytosis assay, reported as percentage of phagocytic monocytes (%). |
| Serum Ferritin Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum ferritin concentration, in ng/mL, measured by immunoassay. |
| Serum IgG Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IgG, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum IgA Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IgA, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum IgM Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IgM, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Complement C3 Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of C3, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Complement C4 Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of C4, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Complement C5a Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of C5a, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum IL-1β Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IL-1β, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum IL-2 Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IL-2, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum IL-4 Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IL-4, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum IL-6 Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IL-6, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum IL-8 Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IL-8, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum IL-10 Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IL-10, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum TNF-α Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of TNF-α, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Serum IFN-γ Concentration | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Serum concentration of IFN-γ, measured by immunoassay (e.g., ELISA or multiplex bead-based assay). |
| Pro-/Anti-Inflammatory Cytokine Ratio | At ICU admission (baseline), at the time of infection diagnosis, at 72 hours after diagnosis, and at 5 days after diagnosis | Ratio of serum IL-6 to IL-10 concentration, calculated as a composite index of pro- versus anti-inflammatory balance. |
| Incidence of Immunoparalysis | Through 5 days after enrollment | Percentage of patients with monocyte HLA-DR (mHLA-DR) expression below 8,000 antibodies/cell (measured by quantitative flow cytometry, QuantiBRITE method), indicating immunoparalysis. |
| Duration of Immunoparalysis | Through day 5 after enrollment | Number of days during which mHLA-DR expression remains below the pre-specified immunoparalysis threshold. |
| Time to Onset of Immunoparalysis | Within 24 hours after infection onset | Time, in hours, from infection recognition to the first mHLA-DR measurement below the pre-specified immunoparalysis threshold. |
| Proportion of Patients with Hyperinflammatory Immune Phenotype | Within 5 days after enrollment | Percentage of patients classified as hyperinflammatory phenotype (high IL-6/TNF-α/ferritin, low IL-10, normal CD4+/mHLA-DR) by unsupervised clustering (K-means/latent class analysis/PCA) of the immune parameters listed above. |
| Proportion of Patients with Immunosuppressive Immune Phenotype | Within 5 days after enrollment | Percentage of patients classified as immunosuppressive phenotype (normal IL-6/TNF-α/ferritin, high IL-10, low CD4+, high Treg, low mHLA-DR) by the same clustering method. |
| Proportion of Patients with Mixed Immune Phenotype | Within 5 days after enrollment | Percentage of patients classified as mixed phenotype (concurrently elevated pro- and anti-inflammatory markers) by the same clustering method. |
| Sensitivity and Specificity of Bedside Rapid Immunophenotyping Test | Within 5 days after enrollment | Sensitivity and specificity (%) of a bedside rapid test/scoring tool for immune phenotype classification, benchmarked against the reference clustering-based classification. |
| Time to Complete Bedside Immunophenotyping Test | Within 5 days after enrollment | Time, in minutes, required to obtain a result from the bedside rapid immunophenotyping test. |
| Plasma Angiopoietin-2 (Ang-2) Concentration | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Plasma Ang-2 concentration, in pg/mL, measured by immunoassay. |
| Soluble VCAM-1 Concentration | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Serum/plasma soluble vascular cell adhesion molecule-1 concentration, in ng/mL, measured by immunoassay. |
| VEGF Concentration | At ICU admission (baseline), at the time of sepsis diagnosis, and at 72 hours after sepsis diagnosis | Vascular endothelial growth factor concentration, in pg/mL, measured by immunoassay. |
Countries
China
Outcome results
None listed