{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:15:58Z","timestamp":1783487758382,"version":"3.55.0"},"reference-count":63,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>In recent years, vascular endothelial growth factor D (VEGF-D) has been recognized as a promising biomarker for disease severity stratification in coronavirus disease, as well as an indicator of endothelial dysfunction, hypoxia, and pathological angiogenesis \u2212 all of which are hallmarks of severe COVID-19. However, there is limited evidence on the specific role of VEGF-D in children with COVID-19, and its relevance in multisystem inflammatory syndrome in children (MIS-C) has not been thoroughly explored.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study included 200 children with confirmed COVID-19 (through PCR or rapid antigen test), 40 children with MIS-C, and 24 healthy children without SARS-CoV-2 infection. Serum VEGF-D concentrations, acute-phase markers (C-reactive protein, procalcitonin, ferritin), and interleukin levels (IL-1\u03b2, IL-6, TNF-\u03b1) were measured using enzyme-linked immunosorbent assay (ELISA) with commercial kits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results showed that VEGF-D levels were significantly higher in children with COVID-19 (325.61 (189.93; 535.85) pg\/ml) and MIS-C (920.92 (473.45; 1157.70) pg\/ml) compared with the control group (195.88 (115.58; 256.70) pg\/ml), with the highest levels observed in patients with MIS-C and severe COVID-19. The increase in VEGF-D was more prominent in boys infected by SARS-CoV-2, but there were no significant differences based on age within the groups. Multivariable logistic regression analysis showed that VEGF-D was independently associated with severe COVID-19 and MIS-C in children. Receiver operating characteristic (ROC) analysis established clinically relevant cut-off values for VEGF-D: 387.87 pg\/mL for identifying severe COVID-19 and 461.96 pg\/mL for differentiating MIS-C from acute COVID-19. In children with COVID-19, exceeding the VEGF-D cut-off was associated with more severe hypoxia and higher levels of C-reactive protein and ferritin, while in MIS-C it was associated with elevated CRP and IL-6. Principal component analysis showed that VEGF-D, along with acute-phase markers and pro-inflammatory cytokines, contributes to an integrated inflammatory-endothelial profile in both COVID-19 and MIS-C.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>VEGF-D is an independent marker associated with disease severity in pediatric COVID-19 and MIS-C and may be useful for severity stratification, differentiating clinical phenotypes, and informing patient management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1799910","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T04:36:52Z","timestamp":1783485412000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic performance of vascular endothelial growth factor D in severity stratification of pediatric COVID-19 and multisystem inflammatory syndrome in children"],"prefix":"10.3389","volume":"17","author":[{"given":"Kateryna","family":"Kozak","sequence":"first","affiliation":[{"name":"Department of Pediatrics No. 2, I. Horbachevsky Ternopil National Medical University","place":["Ternopil, Ukraine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halyna","family":"Pavlyshyn","sequence":"additional","affiliation":[{"name":"Department of Pediatrics No. 2, I. 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