Dengue is a widespread arboviral disease endemic in tropical and subtropical regions and historically considered an acute, self-limiting illness. Emerging evidence, however, suggests cardiovascular sequelae may persist beyond the acute phase. Reported manifestations include major adverse cardiovascular events, arrhythmias, thromboembolic complications, subclinical myocardial dysfunction, endothelial dysfunction, and vascular changes. Studies to date show heterogeneity in design, populations, outcome definitions, and follow-up durations. This protocol outlines a systematic review to appraise and synthesise evidence on post-acute and long-term cardiovascular outcomes following dengue infection, to describe the spectrum of outcomes, estimate comparative risk where possible, and identify determinants.
This review will include human studies of any age that report cardiovascular outcomes assessed at least 4 weeks after acute dengue illness or recovery. Eligible study designs are cohort, case-control, cross-sectional, and case-series. Comparative studies that include dengue-negative or clearly defined reference groups will be used to estimate comparative effects; non-comparative follow-up studies will be included for descriptive synthesis.
The review will prioritise laboratory-confirmed dengue for primary comparative analyses. Studies relying on clinical diagnosis will be used in descriptive synthesis and considered in subgroup or sensitivity analyses when appropriate. Outcomes to be captured include major clinical cardiovascular and cerebrovascular events (for example myocardial infarction, stroke, transient ischaemic attack, heart failure), arrhythmias, thromboembolic events, subclinical cardiac or vascular abnormalities (including residual left ventricular impairment), and cardiovascular-related biomarkers such as inflammatory and endothelial markers where reported.
Electronic searches will be run in PubMed/MEDLINE, Scopus, Cochrane Library, CINAHL, ScienceDirect, ProQuest, and Google Scholar. Two reviewers will independently perform title/abstract screening, full-text review, data extraction, and risk-of-bias and methodological quality assessments. Heterogeneity across study designs, comparator definitions, dengue diagnostic criteria, outcome definitions, and follow-up timing will be assessed and explicitly considered when interpreting results.
Evidence will be synthesised narratively across outcomes and study types. Where studies are sufficiently comparable in design, population, and outcome measures, random-effects meta-analysis will be conducted. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework will be applied to assess the certainty of the evidence when pooled estimates are produced.
The planned review aims to summarise post-dengue cardiovascular sequelae and to identify gaps in the literature. Given substantial global dengue burden and recent observational findings suggesting elevated risks of adverse cardiovascular outcomes beyond the acute phase, a comprehensive synthesis may clarify magnitude and timing of risk, highlight higher-risk subgroups, and inform future epidemiological studies, clinical follow-up strategies, and public health planning in dengue-endemic settings.
Dengue virus (four serotypes: DENV-1 to DENV-4), transmitted primarily by Aedes mosquitoes, is endemic in over 100 countries. Approximately half the world’s population is at risk, with an estimated 100–400 million infections annually. Reported dengue cases have increased markedly over recent decades; the World Health Organization recorded over 14 million cases in 2024, including severe cases and deaths, representing the highest reported global burden to date.
Although dengue has traditionally been considered an acute illness with limited long-term consequences, multiple observational studies have reported potential associations with cardiovascular outcomes after the acute phase. Examples cited by the authors include population-based cohorts showing increased risks of myocardial infarction, stroke, heart failure, dysrhythmias, and thrombotic events in the months following dengue infection, as well as studies reporting subclinical left ventricular impairment among recovered individuals.
The evidence base is fragmented by variation in study design, diagnostic criteria, comparator selection, outcome definitions, and follow-up duration, underlining the need for systematic synthesis.
Primary objective
To systematically review and synthesise available evidence on post-acute and long-term cardiovascular consequences of dengue virus infection, encompassing clinical cardiovascular and cerebrovascular events, subclinical cardiac or vascular changes, and related biomarkers, and to estimate comparative cardiovascular risk where suitable data exist.
Specific objectives
Methodological quality, risk of bias, and heterogeneity will be assessed for all objectives and incorporated into interpretation of findings.
This protocol is prospectively registered with PROSPERO (registration number CRD420261354181). The protocol was prepared and reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. A PRISMA-P checklist is provided as supporting information in the original source.
If important protocol amendments occur after PROSPERO registration, the authors will document the date, description, and rationale for each amendment in an amendment log, update the PROSPERO record where applicable, and report amendments in the final systematic review manuscript.
The review is planned in four phases. Literature searching and title/abstract screening were scheduled for June 2026. Full-text review, study selection, data extraction, and risk-of-bias/critical appraisal were planned to commence in July 2026. Data synthesis, including narrative synthesis and any meta-analyses, subgroup or sensitivity analyses, was planned from August 2026. Manuscript drafting and submission were planned for October–November 2026. The timeline may be adjusted based on article retrieval, study volume, and reviewer consensus processes; regular team meetings will monitor progress.
Primary comparative question: Among human participants of any age, is documented dengue infection associated with post-acute and long-term cardiovascular outcomes compared with individuals without documented recent or index dengue infection or with general-population comparison groups?
Secondary descriptive question: What post-acute and long-term cardiovascular manifestations, including clinical events, subclinical abnormalities, and cardiovascular-related biomarkers, have been reported among individuals with prior dengue infection?
The review will consider outcomes assessed at least 4 weeks after acute illness. For synthesis, outcomes will be grouped by timing where data permit: post-acute (4 weeks to <3 months) and long-term (≥3 months). These thresholds are pragmatic and not intended as strict biological boundaries; where studies use different timing definitions the original definitions will be retained and timing heterogeneity considered in synthesis.
Eligibility follows a PECOS-informed framework (Population, Exposure, Comparator, Outcomes, Study design) adapted from established guidance for exposure–health outcome reviews. Both comparative and non-comparative descriptive studies will be eligible to capture the full range of evidence.
Human participants of any age, including children, adolescents, adults, and mixed-age populations. Studies restricted to specific age groups will be considered as reported by the study authors.