Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes

Background: Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of ten biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD). Methods: We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included. Results: On days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults. Conclusions: Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.

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Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes

10.1101/2021.03.13.21253501 ◽

2021 ◽

Author(s):

Nguyen Lam Vuong ◽

Phung Khanh Lam ◽

Damien Keng Yen Ming ◽

Huynh Thi Le Duyen ◽

Nguyet Minh Nguyen ◽

...

Keyword(s):

Early Identification ◽

Patient Management ◽

Case Control Study ◽

Case Control ◽

Severe Dengue ◽

Clinical Use ◽

Country Study ◽

Vascular Markers ◽

Nested Case Control ◽

Control Study

AbstractBackgroundEarly identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of ten biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).MethodsWe performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.ResultsOn days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.ConclusionsOur findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.Summary of the main pointHigher levels of any of VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, and CRP on illness days 1-3 increased the risk of developing severe/moderate dengue. The relationships differed between children and adults and some changed when assessed together.

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