Integrative Vitamin D-Inflammatory-Coagulation Biomarker Index Predicts COVID-19 Severity: Development and Validation of the Vitamin D Inflammatory Burden Score (VDIBS)

Background: Vitamin D deficiency is common in hospitalized COVID-19 patients and associates with increased severity. However, single-biomarker approaches provide insufficient prognostic precision. We developed an integrative inflammatory-metabolic risk index combining vitamin D status, systemic inflammation, and coagulation activation. Methods: Prospective cohort study of 512 hospitalized COVID-19 patients (September 2022–December 2023) with serum 25(OH)D3 measurement at admission. Primary analysis (N=301) included patients with complete inflammatory marker data (CRP, ferritin, D-dimer, LDH). The Vitamin D Inflammatory Burden Score (VDIBS) integrated: (1) vitamin D tier (deficient 75: 0), (2) inflammation score (CRP ≥100, ferritin ≥1000, IL-6 ≥50 each +1 point; 0–3 total), and (3) coagulation score (D-dimer ≥1000, LDH ≥6 each +1 point; 0–2 total). IL-6 measurement was available in 48 patients (9.4% of cohort); all other components were measured in the primary analysis population (N=301). Outcomes were severe COVID-19, ICU admission, and mortality. Predictive performance was compared across four multivariate models. Results: Mean vitamin D was 63.4±33.2 nmol/L (68.1% deficient). Severe disease occurred in 386 patients (75.4%), ICU admission in 30 (5.9%), and mortality in 14 (2.7%). VDIBS risk stratification showed: low-risk (VDIBS 0–2) n=178, 8.4% severe; moderate-risk (3–5) n=245, 45.7% severe; high-risk (6–8) n=89, 78.6% severe (χ2=142.3, p<0.001). VDIBS predicted severe disease with AUC 0.78 (95% CI 0.74–0.82), equivalent to more complex multivariate models (AUC 0.82, p=0.08) but with superior clinical simplicity. In stratified analyses, VDIBS showed robust discrimination independent of season, age, or sex (all interaction p>0.05), supporting generalizability. Conclusions: VDIBS provides bedside-implementable risk stratification integrating vitamin D-dependent immune regulation, systemic inflammation, and coagulation activation. This composite approach offers practical tool for treatment intensity escalation and potential therapeutic target for vitamin D repletion in severe COVID-19.