key: cord-0957751-hyeshh63
authors: Kong, Yaxian; Han, Junyan; Wu, Xueying; Zeng, Hui; Liu, Jingyuan; Zhang, Henghui
title: VEGF-D: a novel biomarker for detection of COVID-19 progression
date: 2020-06-23
journal: Crit Care
DOI: 10.1186/s13054-020-03079-y
sha: 2a82a34bf08c4f627f6315bdd9451c3130d0a9bb
doc_id: 957751
cord_uid: hyeshh63

nan

variable importance of the feature rankings. A receiver operating characteristic (ROC) curve was generated to evaluate the diagnostic accuracy of a protein.

A total of 24 COVID-19 patients were enrolled in this study, including 14 (58.3%) severe patients and 10 (41.7%) critical patients (Table 1 ). Compared to the severe group, critical cases were of significantly older ages and showed higher white blood cell counts and neutrophil counts. Levels of VEGF-D, TNF-α, SCF, LIF, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IL-17A, IL-18, IL-1β, and IFN-γ were significantly higher in the critical group than in the severe group (Table 1) . Additionally, lymphocyte count, CRP, LDH, and coagulation indicators (D-dimer, platelet count, PT, and APTT), which were reported to associate with clinical outcome [4, 5] , were also included in the random forests model. Strikingly, VEGF-D was identified as the most important indicator related to the severity of COVID-19 (ranked as 1, Fig. 1a ). As expected, D-dimer, age, IL-6, and lymphocyte count associated with clinical outcomes of COVID-19 patients reported previously were also highly ranked. VEGF-D had a higher area under the curve (AUC) (0.836 (95% CI 0.648-1); Fig. 1b ) than Ddimer (0.755 (95% CI 0.527-0.982); Fig. 1c ). Consistently, VEGF-D levels were positively correlated with sequential organ failure assessment (SOFA) scores (Fig. 1d ). As shown in Fig. 1e , critical patients had higher levels of VEGF-D than the severe cases during the whole course of hospitalization.

To our knowledge, this is the first report of VEGF-D as a potential biomarker for detecting the progression of COVID-19. Despite limited evidence in COVID-19, previous studies demonstrated an important role of VEGF in the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) by its properties to increase vascular permeability. Furthermore, VEGF is regarded as an indirect procoagulant for altering the WBC white blood cells, CRP C-reactive protein, LDH lactate dehydrogenase, PT prothrombin time, APTT activated partial thromboplastin time, ALT alanine aminotransferase, VEGF vascular endothelial growth factor; TNF-α tumor necrosis factor-alpha, SCF stem cell factor; LIF leukemia inhibitory factor, IL interleukin, IFN interferon hemostatic features of endothelial cells [6] . We hypothesized that elevated VEGF-D level might potentially relate to the storm of blood clots occurring in COVID-19 patients. Notably, it is of great interest to investigate the therapeutic effects of VEGF inhibitor in COVID-19 patients. This study has limitations, including the small sample size, a single-center experience, and a variable time interval of each patient from admission to symptoms onset. Studies based on a larger cohort in additional sites are needed to verify our findings. 

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Publisher's Note

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We thank all patients included in this study. We appreciate the works from Dr. 

Authors' contributions YK and H. Zhang designed the study and wrote the manuscript. JL conducted the study and recruited the patients. YK and JH collected the samples, performed the experiments, and analyzed the data. XW analyzed the data and performed the statistical analysis. H. Zeng participated in the critical review of the manuscript. All authors read and approved the final manuscript. 

All data generated or analyzed during this study are included in this published article.

This study was approved by the Committee of Ethics at Beijing Ditan Hospital, Capital Medical University, Beijing, China, and each patient gave written informed consent.

Not applicable.

The authors declare that they have no competing interests.