# Characterization of dengue patients in Vietnam: Clinical, virological, and IL-10 profiles during 2021– 2022 outbreaks

## TL;DR

This study analyzed dengue patients in Vietnam during 2021–2022 outbreaks, finding that IL-10 levels and genetic variants are linked to disease severity and that DENV-1 and DENV-2 were the main circulating serotypes.

## Contribution

The study identifies specific IL-10 promoter variants and elevated IL-10 levels as factors associated with dengue severity in Vietnamese patients.

## Key findings

- DENV-1 and DENV-2 were the predominant serotypes in 2021–2022 outbreaks in Vietnam.
- Plasma IL-10 levels were significantly higher in more severe dengue cases.
- Certain IL-10 promoter variants were associated with increased or decreased risk of dengue and its severity.

## Abstract

The pathogenesis of dengue is attributed to a complex interaction between the dengue virus (DENV) and the host immune system. The aim of this study is to investigate the clinical, virological, and Interleukin-10 (IL-10) profiles of dengue patients in Vietnam from two consecutive outbreaks in 2021 and 2022.

A total of n=306 dengue patients were examined, who were clinically stratified according to dengue without warning signs (DF; n=178), dengue with warning signs (DWS; n=115) and severe dengue (SD; n=13). Patients were screened for dengue, Zika and chikungunya viruses. DENV were subjected to serotype specific real-time RT-PCR. Interleukin-10 (IL-10) levels were measured by ELISA, and IL-10 promoter variants (-1082G/A; -819C/T; -592C/A) were genotyped by direct Sanger sequencing to determine a possible association with susceptibility to dengue and disease severity.

No chikungunya or Zika viruses were detected. Patients were infected by one of the three different DENV serotypes (DENV-1, -2, -4). Plasma IL-10 levels were significantly elevated in patients (DF vs. DWS, p=0.004; DF vs. SD, p=0.001; DWS vs. SD, p=0.015). While the IL-10 allele -819C contributed to an increased risk of dengue (OR = 1.5, 95% CI = 1.1-2.0, p=0.04), genotype -1082GA showed a protective role against the disease (OR = 0.45, 95% CI = 0.27-0.72, p=0.009), and allele -1082G showed a protective role against DWS (OR = 0.44, 95% CI = 0.22-0.81, p=0.049). Also, the IL-10 GTA (-1082G/-819T/-592A) haplotype was observed to confer protection (OR = 0.31, 95% CI = 0.14-0.67, p< 0.003).

While DENV-1 and DENV-2 were the predominant serotypes in circulation, plasma IL-10 levels and IL-10 promoter variants were also significantly associated with dengue and its severity.

Dengue places a significant burden especially in low- and middle-income countries, including Vietnam. The pathogenesis of dengue is attributed to a complex interaction between the dengue virus and the host immune system. We explicitly investigated on the occurrence of arboviruses (CHIKV, DENV and ZIKA) during two consecutive outbreaks in 2021 and 2022 from Northern Vietnam and compared the results with those of previous outbreaks. From the study cohort of cases of dengue without warning signs, dengue with warning signs and severe dengue, we investigated whether levels of the human cytokine IL-10 and IL-10 promoter variants were associated with susceptibility and with their clinical course. The results show that DENV-1, DENV-2 and DENV-4 were the circulating serotypes in 2021-2022. Serotypes DENV-1 and DENV-2 were more frequently observed in dengue cases with warning signs and in severe dengue, while no cases of chikungunya or Zika viruses were detected in the studied period. Plasma IL-10 levels and IL-10 promoter variants were significantly modulated in patients with varying degrees of severity.