Neutrophil-to-lymphocyte ratio for the clinical management of dengue: a systematic review and meta-analysis

Dengue fever (DF) remains a major global public health concern, especially in tropical and low-resource settings. The neutrophil-to-lymphocyte ratio (NLR) has been proposed as an accessible biomarker for diagnosis and severity assessment, but the existing evidence is heterogeneous. To summarize the current evidence on the behavior of the NLR in DF.

This study conducted a systematic search in five databases for observational studies published until April 2024. Inclusion and exclusion criteria were based on predefined eligibility criteria, and quality and methodological assessment were expressed using the Newcastle-Ottawa Scale. Data was pooled using a random-effects model and results generalized as applicable, when pooling could not be carried out. A summary receiver operating characteristic curve (sROC) was obtained to assess the diagnostic accuracy of NLR for distinguishing DF from COVID-19. The certainty of evidence was graded using the GRADE system.

A total of 6,166 participants from 15 observational studies were included, all with low risk of bias. A single study showed a higher NLR in dengue vs. healthy controls (Bhattarai, 2023; MD: 1.29; 95% CI: 0.87 to 1.71), with moderate certainty. The SROC curve for dengue vs. COVID-19 (2 studies, n = 226) showed sensitivity and specificity of 83.9% and an AUC of 0.907, indicating high diagnostic accuracy, with moderate certainty.

For prognosis, severe dengue showed a small, but significant NLR decrease compared with dengue with warning signs (MD: -0.54; 95% CI: -0.91 to -0.17, I2 = 0%), with very low certainty. NLR may serve as a supportive diagnostic biomarker for dengue. However, its prognostic value remains uncertain, highlighting the need for large, prospective studies to validate cutoff points and clinical utility.