Review 1 : "Obesity is Associated with Increased Pediatric Dengue Virus Infection and Disease: A 9-year Cohort Study in Managua, Nicaragua"

RR:C19 Evidence Scale rating by reviewer:

• Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review: The research establishes a correlation between obesity and heightened susceptibility to both Dengue virus (DENV) infection and dengue disease. Findings indicate that children classified as obese exhibit increased odds of DENV infection and are more likely to develop dengue disease post-infection, irrespective of age, sex, or pre-infection DENV antibody levels. Furthermore, obese children infected with DENV are more prone to experiencing symptoms such as fever, headache, and rash compared to their counterparts with normal weight.

The study offers valuable insights into the link between pediatric obesity and susceptibility to Dengue virus (DENV) infection and non-severe dengue disease. By analyzing data spanning 9 years from the Pediatric Dengue Cohort Study in Nicaragua, which included a substantial cohort of 5,940 children, the research gains strength and credibility. The prospective cohort design, coupled with serial serosurveys, enables a thorough exploration of the relationship between obesity and DENV infection over time.

A notable strength of the study lies in its ability to establish a clear correlation between obesity and heightened susceptibility to both DENV infection and dengue disease. It demonstrates that obese children face increased odds of DENV infection and are more prone to developing symptomatic dengue following infection, regardless of age, sex, or pre-infection DENV antibody levels. Additionally, the research highlights the heightened vulnerability of obese children to experiencing symptoms such as fever, headache, and rash compared to their normal-weight counterparts. This sheds new light on an aspect of pediatric health and disease dynamics that has not been extensively explored previously. The chosen statistical analysis is deemed appropriate for addressing the research question. Notably, the unrestricted analyses enable comparisons of the results with those of other studies or public health surveillance systems that predominantly rely on clinically apparent infection, without the capacity to control for differences in infection rates across BMI categories.

Identifying the association between obesity and pediatric DENV infection or non-severe dengue represents a significant contribution to the field. It fills a critical gap in the literature and lays the groundwork for further exploration of the interplay between obesity and infectious diseases, particularly in pediatric populations. Nonetheless, it is important to acknowledge the limitations highlighted by the authors, including the low sample size for assessing associations with severe dengue and the underpowered analysis regarding the relationship between underweight and dengue. Exploring these aspects further could enhance our understanding of the intricate relationship between weight status and dengue outcomes. The study underscores the public health implications of its findings, especially in light of the existing burden of noncommunicable diseases among individuals with obesity. The heightened risk of DENV infection and disease among this population emphasizes the need for a multidisciplinary approach to disease prevention and control. Overall, this study makes a substantial contribution to our understanding of the relationship between pediatric obesity and susceptibility to DENV infection and disease. Its findings carry significant implications for public health policy and highlight the necessity for further research in this area.

The key finding of this preprint is the observed link between pediatric obesity and heightened susceptibility to both Dengue virus (DENV) infection and non-severe dengue disease, complementing existing research on the association between obesity and severe dengue. This highlights the need for targeted public health interventions tailored towards obese children, emphasizing the critical role of addressing obesity as a risk factor for infectious diseases like Dengue. These findings emphasize the significance of comprehensive approaches to disease prevention and control.