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Background: Dengue is a major public health issue worldwide and severe dengue (SD) is life threatening. It is critical to triage patients with dengue infection in the early stage. However, there is limited knowledge on early indicators of SD. The objective of this study is to identify risk factors for the prognosis of SD and try to find out some potential predictive factors for SD from dengue fever (DF) in the early of infection., Methods: The PubMed, Cochrane Library and Web of Science databases were searched for relevant studies from June 1999 to December 2020. The pooled odds ratio (OR) or standardized mean difference (SMD) with 95% confidence intervals (CI) of identified factors was calculated using a fixed or random effect model in the meta-analysis. Tests for heterogeneity, publication bias, subgroup analyses, meta-regression, and a sensitivity analysis were further performed., Findings: A total of 6,848 candidate articles were retrieved, 87 studies with 35,184 DF and 8,173 SD cases met the eligibility criteria. A total of 64 factors were identified, including population and virus characteristics, clinical symptoms and signs, laboratory biomarkers, cytokines, and chemokines; of these factors, 34 were found to be significantly different between DF and SD, while the other 30 factors were not significantly different between the two groups after pooling the data from the relevant studies. Additionally, 9 factors were positive associated with SD within 7 days after illness when the timing subgroup analysis were performed., Conclusions: Practical factors and biomarkers for the identification of SD were established, which will be helpful for a prompt diagnosis and early effective treatment for those at greatest risk. These outcomes also enhance our knowledge of the clinical manifestations and pathogenesis of SD., Competing Interests: The authors have declared that no competing interests exist.

Guangdong is a main dengue epidemic area in China and undergoes dengue outbreaks frequently. In 2014, Guangdong experienced a serious dengue outbreak with 45,224 confirmed cases and six deaths, which might affect the seroprevalence among the local population. There is evidence that dengue virus (DENV) infection during pregnancy may cause adverse outcomes. Therefore, it is important to assess the seroprevalence of DENV among Guangdong pregnant women. We aimed to survey the seroprevalence of anti-DENV antibodies among pregnant women in Guangdong and to analyze the features of different seroprofiles. We collected a total 951 samples from pregnant women living in Guangdong in 2016. All serum samples were screened for DENV-specific antibodies (IgG and IgM) by indirect enzyme-linked immunosorbent assay (ELISA) and confirmed using capture ELISA. In IgM-positive samples, we performed DENV RNA detection using reverse transcriptase polymerase chain reaction. We collected information of delivery outcomes, neonate features, and clinical laboratory variables of parturients and newborns following delivery. Seroprevalence of DENV among the women in our sample was 4.31%. A total 1.26% and 3.15% of samples were IgM and IgG positive, respectively. In addition, 22.22% of IgM-positive and 9.09% of IgG-positive participants had adverse outcomes. There was no difference with respect to adverse outcomes compared with controls (8.80%) who were IgG and IgM negative. There was no difference in clinical laboratory variables among the different seroprofiles. We found a high seroprevalence of DENV among pregnant women in Guangdong comparing with the overall seroprevalence of local population before 2014. Asymptomatic DENV infection during pregnancy was not found to contribute to adverse outcomes.

Dengue virus infection (DEN) is one of the most prevalent arbovirus diseases in the tropical and subtropical areas. Some human leukocyte antigen (HLA) alleles have been reported to be a protective or risk factor to DEN. Due to the limited sample sizes and regional limitations, the results of individual studies were various. This meta-analysis aimed at investigating the relationship between HLA alleles and dengue disease. Relevant studies of the relationship between HLA and dengue disease were searched through PubMed, Embase, Web of science, and Cochrane databases. Subgroups according to ethnicity or sub-alleles and sensitivity analysis were used to explore the potential source of heterogeneity, which was performed to confirm the findings. The relationships between HLA and dengue disease were defined by odds ratios (ORs) with a 95% confidence interval (CI). Fourteen studies were finally confirmed. Results indicated that A*0203 (OR = 2.19, 95% CI = 1.30-3.69) and A*24 in the Asian group (OR = 1.44, 95% CI = 1.21-1.71) were positively associated with an increased risk of DEN when compared with normal controls. A*33 (OR = 0.49, 95% CI = 0.34-0.69) in Southeast Asia was negatively associated with DEN when compared with normal controls, suggesting a protective role against DEN. In addition, DRB1*11 (OR = 4.10, 95% CI = 1.23-13.69) was positively associated with severe dengue (SD) when compared with dengue fever, whereas DRB1*03 (OR = 0.48, 95% CI = 0.28-0.82) and DRB1*09 (OR = 0.73, 95% CI = 0.55-0.96) were negatively associated with SD when compared with normal controls. The meta-analysis confirmed that HLA-A*0203, A*24, A*33, DRB1*03, DRB1*09, and DRB1*11 have significantly affected dengue disease, and the associations are related to race and regions.