Inflammatory and Endothelial Dysfunction Biomarkers Predict Severe COVID-19 in Hospitalized Patients: Development of the CCBR Model

Background: Early identification of patients at risk of severe COVID-19 is critical for timely interventions. We evaluated a biomarker-based risk stratification model, the Composite COVID-19 Biomarker Risk (CCBR) score, integrating age and inflammatory biomarkers (IL-6, PAI-1, LDH, neutrophil-to-lymphocyte ratio [NLR], and ferritin) measured at hospital admission to support early clinical risk assessment. Methods: In this retrospective single-center study, 235 hospitalized COVID-19 patients were classified into non-severe (n = 106) and severe (n = 129) groups. Biomarkers were measured within 24 h of admission. The CCBR score (0–6 points) was constructed by assigning one point to each parameter exceeding predefined cut-off values derived from published clinical thresholds and confirmed using receiver operating characteristic (ROC) curve analysis (Youden’s index). Patients were stratified into three risk categories: low risk (0–1 points), moderate risk (2–3 points), and high risk (4–6 points). Associations between CCBR scores and clinical outcomes, including severe disease, acute respiratory failure, dyspnea, complications, and antibiotic use, were assessed using logistic regression and ROC analyses. Internal validation was performed using split-sample validation and bootstrap resampling. Results: CCBR scores were significantly higher among patients with severe disease (p > 0.001). Each 1-point increase in CCBR was associated with a 6.78-fold increase in the odds of severe disease (OR = 6.78, p < 0.001). ROC analysis demonstrated moderate to good discriminative performance for severe disease (AUC = 0.714) and acute respiratory failure (AUC = 0.751). Conclusions: The CCBR score represents a simple biomarker-based model integrating inflammatory and endothelial dysfunction markers for early stratification of COVID-19 severity. This approach may assist clinicians in identifying patients at higher risk of severe disease and acute respiratory failure early during hospitalization.