A paradigm shift in DENV-4 clinical presentation: A viewpoint on pulmonary inflammatory symptoms from the 2023 Lincang outbreak

TL;DR

A 2023 DENV-4 outbreak in China revealed common lower-respiratory symptoms in dengue patients, suggesting a need for updated clinical guidelines.

Contribution

Identified a new clinical pattern of lower-respiratory symptoms in DENV-4 infections and their association with disease severity.

Findings

31.3% of DENV-4 patients exhibited pulmonary symptoms, including lower respiratory infection and chest distress.

Thrombocytopenia and hepatic hypofunction were independently linked to severe dengue.

Pulmonary symptoms resolved within a median of 7 days with no long-term effects.

Abstract

During the 2023 outbreak of dengue virus serotype 4 (DENV-4) in Lincang, China, we noted prominent lower-respiratory involvement not typically emphasized in dengue descriptions.

We retrospectively analyzed 147 hospitalized, RT-PCR-confirmed DENV-4 cases. Respiratory assessment followed a tiered protocol: daily symptom screening and pulse oximetry for all patients; chest radiography and point-of-care lung ultrasound as indicated; and chest CT for severe or atypical presentations. Symptom structure was evaluated using EBICglasso network analysis. Predictors of severe dengue were examined with logistic regression.

Pulmonary symptoms occurred in 31.3% (46/147), most frequently lower respiratory infection (28.6%), cough (25.9%), and chest distress (15.0%). Symptoms resolved quickly with supportive care (median 7 days, IQR 6–9), with no residual pulmonary sequelae at discharge. Network analysis identified a cohesive respiratory cluster with regularized partial correlations of 0.19–0.23, indicating robust conditional associations among pulmonary symptoms within the overall clinical spectrum. In regression models, thrombocytopenia (Adjusted Odds Ratio, AOR 3.06, 95% CI 1.05–9.03) and hepatic hypofunction (AOR 3.82, 95% CI 1.00–13.61) were independently associated with severe dengue; coexisting lower respiratory infection was associated with severity in univariate analysis (Odds Ratio, OR 2.91, 95% CI 1.05–8.07). Sex-specific patterns emerged: females more often had weakness, leukopenia, headache, and hypokalemia, whereas males had higher rates of hyperuricemia.

In this genotype I DENV-4 cohort, lower-respiratory manifestations were common, formed a coherent symptom network, and showed signals of association with severity. These findings support routine respiratory screening, pulse oximetry, and stepwise imaging in dengue care pathways, with validation needed in multicenter studies.

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