Arboviral Coinfection and Clinical Severity in the Americas: An Integrative Review of Dengue, Chikungunya, and Zika Virus Interactions

Background: Dengue virus (DENV), chikungunya virus (CHIKV), and Zika virus (ZIKV) co-circulate across the Americas and share Aedes mosquito vectors, creating conditions for concurrent infections. Whether coinfection increases clinical severity remains uncertain because clinical syndromes overlap, diagnostic windows are short, and flavivirus serology is prone to cross-reactivity. Objective: To synthesize evidence on the association between DENV, CHIKV, and ZIKV coinfection and clinical severity in the Americas. Methods: An integrative review was structured according to the framework proposed by Whittemore and Knafl. PubMed/MEDLINE, Scopus, Web of Science, LILACS, and SciELO were searched for publications from 2015 to 2026. Eligible studies involved human populations in the Americas and laboratory-confirmed dual or triple infection. Evidence was narratively synthesized by epidemiology, clinical severity, laboratory phenotype, neurologic or perinatal outcomes, diagnostic validity, and methodological quality. Results: Coinfection was repeatedly documented in settings of intense arboviral co-circulation, particularly when multiplex molecular assays were used. Evidence does not support a uniform increase in hemodynamic severity or mortality in all coinfected patients. Instead, DENV-CHIKV coinfection appears to produce a mixed phenotype combining dengue-like hematologic abnormalities with chikungunya-like arthralgia, whereas DENV-ZIKV interactions raise greater concern for diagnostic misclassification and immune-mediated neurologic or congenital outcomes. Conclusions: Arboviral coinfection in the Americas is better understood as a context-dependent interaction shaped by vector ecology, timing of infection, host immune history, and diagnostic method than as a simple additive syndrome. Prospective multicenter studies using standardized severity definitions and multiplex molecular confirmation are needed.