Early and late biomarkers as predictors of severe dengue: a comprehensive umbrella review protocol

Predicting the progression to severe dengue remains a critical yet challenging aspect of patient management. This umbrella review aims to identify biomarkers associated with the development of severe dengue. The primary objective is to determine which biomarkers can predict progression to severe disease in dengue-infected patients. Secondary objectives include identifying (a) early biomarkers (detected on days 1-3 of illness), (b) late biomarkers (detected after day 3), (c) biomarkers requiring further investigation and (d) differences in predictive biomarkers between patients aged <15 years and those ≥15 years.

The review questions were formulated based on the Population, Concept and Context (PCC) framework. This review will follow the Joanna Briggs Institute methodology for umbrella reviews and be reported in accordance with the Preferred Reporting Items for Overviews of Systematic Reviews guidelines. The protocol has been registered in PROSPERO (CRD420251058284). MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, JBI Evidence Synthesis and DARE databases will be searched from 1/1/1990 to 1/6/2025. The findings are expected to support early risk stratification and guide future biomarker research in dengue infection. The systematic reviews included in this umbrella review may define severe dengue according to either the WHO 1997 or 2009 guidelines.

Ethical approval is not required since the work involves published documents. The review findings will be communicated to relevant stakeholders through conference presentations and publication in an open-access journal.

PROSPERO 2025 CRD420251058284. Available from: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251058284.