The study program included a comprehensive analysis of 160 children in the main group who received inpatient treatment at the Municipal Non-Commercial Enterprises “Vinnytsia Regional Children’s Clinical Hospital of the Vinnytsia Regional Council” and “Vinnytsia Regional Children’s Clinical Infectious Diseases Hospital of the Vinnytsia Regional Council” during 2022–2023, aged 1 month to 18 years, diagnosed with SARS-CoV-2-associated pneumonia, and a control group (40 apparently healthy children). The study was conducted after prior informed consent had been obtained from parents/guardians, in accordance with the requirements of the UN Convention on the Rights of the Child, as well as the principles of bioethics and the provisions of the Declaration of Helsinki. All patients underwent general clinical examination, determination of CRP, procalcitonin, IL-1, IL-6, coagulation parameters, endothelin-1 and VEGF levels, Doppler assessment of FMD and CIMT, and determination of JAK2 V617F polymorphism by PCR. The study design included prospective observation and correlation-regression analysis of the obtained data.
Scientific Novelty.For the first time, a comprehensive assessment of endothelial dysfunction in children with SARS-CoV-2-associated pneumonia was performed with simultaneous evaluation of laboratory, instrumental, and genetic parameters. The prevalence and characteristics of endothelial dysfunction in this population were identified. significantly correlated with increased endothelin-1 and VEGF levels and instrumental signs of vascular injury. Severe disease was associated with significantly higher endothelin-1 (1.47-fold; p<0.05) and VEGF (1.62-fold; p<0.05) compared to non-severe cases, as well as increased IL-1 (1.54-fold) and IL-6 (1.69-fold). The pathogenetic role of endothelial dysfunction was confirmed by the association between high VEGF levels (IV quartile) and increased odds of bilateral lung involvement (OR=6.186; 95% CI 2.747–11.832), whereas low VEGF levels were associated with unilateral disease (OR=2.180; 95% CI 1.996–4.973). The impact of JAK2 V617F polymorphism on endothelial injury was demonstrated: mutation carriers showed increased endothelin-1 (1.54-fold), VEGF (1.57-fold), IMT (1.71-fold), and impaired FMD (1.03–1.35-fold; p<0.05), indicating genetically determined vascular reactivity. Age-related differences were identified: highest FMD values were observed in children aged 1–4 years (2.20±0.003%), while IMT was higher in those aged 5–18 years (4.20–16.96% higher). Instrumental vascular assessment showed high diagnostic value: FMD sensitivity 88.09%, specificity 85.69%, accuracy 90.22%; IMT sensitivity 71.05%, specificity 79.52%, accuracy 90.51%. Elevated CRP, procalcitonin, fibrinogen, and D-dimer significantly correlated with increased endothelin-1, VEGF, and instrumental signs of vascular injury, forming a set of key markers of severe SARS-CoV-2-associated pneumonia.
Practical Significance. The clinical value of systemic inflammatory markers in children with SARS-CoV-2-associated pneumonia was established. Elevated CRP was detected in 105 children (65.6%), and procalcitonin in 147 (91.9%), indicating a pronounced systemic inflammatory response in the majority of patients. Severe disease was associated with significant increases in IL-1 (1.54-fold) and IL-6 (1.69-fold) compared to non-severe cases (p<0.05), emphasizing the leading role of pro-inflammatory cytokines in the development of endothelial injury. These findings indicate that determination of CRP, procalcitonin, IL-1, and IL-6 levels may serve as accessible indicators of inflammatory progression risk and early endothelial dysfunction, as well as a basis for intensified management strategies in high-risk patients. The clinical informativeness of coagulation system parameters as early accessible indicators of hypercoagulation and risk of thrombotic complications in children was demonstrated. The inclusion of endothelin-1 and VEGF in the standard diagnostic algorithm for SARS-CoV-2-associated community-acquired pneumonia is justified, as their elevation reflects disease severity, extent of endothelial injury, and risk of complications, and may be used for risk stratification. The use of IMT and FMD as sensitive non-invasive markers of endothelial dysfunction is proposed for early detection of severe disease course, identification of high-risk groups, and therapy monitoring. The practical significance of JAK2V617F polymorphism as an additional genetic indicator of vascular reactivity was determined, enabling improved risk stratification and individualized patient management. The obtained results provide a foundation for the development of prognostic models incorporating laboratory, instrumental, and genetic markers to improve diagnostic accuracy, optimize management strategies, and reduce the risk of complications.
