Integrative vitamin D-inflammatory-coagulation biomarker index predicts COVID-19 severity : development and validation of the vitamin D inflammatory burden score (VDIBS)

Osredkar, Joško (avtor), Godnov, Uroš (avtor), Siuka, Darko (avtor)

Vitamin D deficiency is common in hospitalized COVID-19 patients and is associated 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. This is a prospective cohort study of 512 hospitalized COVID-19 patients (September 2022–December 2023) with serum 25(OH)D3 measurement at admission. The primary analysis (N = 301) included patients with complete data for VDIBS-Core components (CRP, ferritin, D-dimer, LDH). The Vitamin D Inflammatory Burden Score-Core (VDIBS-Core; range 0–7) integrated the following: (1) vitamin D tier (deficient < 30 nmol/L: 3 points; insufficient 30–50: 2; non-optimal 50–75: 1; sufficient > 75: 0), (2) inflammation score (CRP ≥ 100, ferritin ≥ 1000 each +1 point; 0–2 total), and (3) coagulation score (D-dimer ≥ 1000, LDH ≥ 3–6 or ≥ 6 each +0–2 points; 0–2 total). The IL-6 measurement (N = 48, 9.4%) was explored separately as VDIBS-Plus in the secondary analysis. The outcomes were severe COVID-19 (defined as the worst severity classification during hospitalization per WHO criteria), ICU admission, and mortality. The mean vitamin D was 63.4 ± 33.2 nmol/L (68.1% deficient). Among N = 301 with complete VDIBS-Core data, severe disease occurred in 221 (73.4%), ICU admission in 15 (5.0%), and mortality in 8 (2.7%). VDIBS-Core risk stratification showed the following: low-risk (VDIBS 0–2, n = 178) 8.4% severe; moderate-risk (VDIBS 3–5, n = 245) 45.7% severe; and high-risk (VDIBS 6–7, n = 89) 78.6% severe; χ2 = 142.3, p < 0.001. VDIBS-Core predicted severe disease with AUC 0.78 (95% CI 0.74–0.82), with excellent calibration (Hosmer–Lemeshow p = 0.40). When compared to complex multivariate models incorporating all seven individual biomarkers, VDIBS-Core demonstrated equivalent discrimination (AUC 0.82, Δ = 0.04, p = 0.08, not statistically significant) with superior clinical simplicity. Bootstrap internal validation confirmed modest optimism (optimism-corrected AUC 0.76). An incremental value analysis demonstrated that the vitamin D component contributes a significant additional predictive value compared to inflammation/coagulation biomarkers alone (LR test p = 0.004). VDIBS-Core provides bedside-implementable risk stratification using three simple components measurable in <5 min, integrating vitamin D-dependent immune regulation with systemic inflammation and coagulation activation. This composite approach offers a practical tool for treatment intensity escalation and monitoring frequency assignment in hospitalized COVID-19 patients. External validation in geographically diverse cohorts is required before widespread clinical implementation.

• Jezik: Angleški jezik
• Ključne besede: vitamin D deficiency, COVID-19 severity, biomarker integration, risk stratification, immunometabolism
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo ; MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2026
• Št. strani: 43 str.
• Številčenje: Vol. 27, iss. 4, art. 1770
• PID: 20.500.12556/RUL-179603
• UDK: 577.161.2:616.98:578.834
• ISSN pri članku: 1422-0067
• DOI: 10.3390/ijms27041770
• COBISS.SI-ID: 268282115
• Datum objave v RUL: 18.02.2026

Gradivo je del revije

• Naslov: International journal of molecular sciences
• Skrajšan naslov: Int. j. mol. sci.
• Založnik: MDPI
• ISSN: 1422-0067
• COBISS.SI-ID: 2779162

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: pomanjkanje vitamina D, resnost COVID-19, integracija biomarkerjev, stratifikacija tveganja, imunometabolizem, vitamin D, COVID-19

Projekti

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: P3-0124
• Naslov: Metabolni in prirojeni dejavniki reproduktivnega zdravja, porod III

• Financer: ARIS - Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije
• Številka projekta: J3-1756
• Naslov: Okoljski in genetski dejavniki pri motnjah avtističnega spektra