Multi-organ post-acute sequelae of major respiratory and Aedes -borne arboviral diseases: a systematic review and meta-analysis
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Background
Post-acute sequelae are well described following COVID-19 but may also occur after other respiratory infections and Aedes -borne infections. Evidence remains fragmented due to heterogeneity in study design, populations, and exposure, outcome, and follow-up definitions.
Methods
We synthesized and compared post-acute sequelae across influenza, RSV-ARI, dengue fever, chikungunya, Zika, and yellow fever. We searched five databases from inception to 25-08-2025 for articles quantifying risk, incidence, or rates of post-acute sequelae following these diseases. Eligible non-randomized observational studies assessed post-acute neurological, psychiatric, gastrointestinal, cardiovascular, respiratory, renal, musculoskeletal, autoimmune, or endocrine outcomes after confirmed infection. Risk of bias was assessed using ROBINS-E. Random-effects meta-analyses with restricted maximum likelihood estimation were conducted when ≥ 3 comparable effect estimates were available (PROSPERO #CRD420251124994).
Findings
51 studies were included, predominantly from high-income regions. Most were retrospective cohorts using ICD-coded diagnoses; prospective studies used laboratory-confirmed infections. Data sources, comparator groups, exposure definitions, outcome ascertainment, and follow-up periods varied substantially. Meta-analyses were feasible for RSV, influenza, and dengue fever. All RSV-ARI studies were pediatric and assessed infections during infancy, which were associated with higher pooled odds of physician-diagnosed asthma (OR:2.93 [95%CI: 2.12–4.06]). Influenza studies used COVID-19-positive comparators; pooled estimates showed lower risk for neurological (HR:0.82 [0.76–0.89]) and composite outcomes (RR:0.88 [0.82–0.95]), with other organ systems non-significant. Dengue fever studies spanned all ages and showed increased risks of anxiety (HR:1.34 [1.01–1.78]), dementia (HR:1.61 [1.10–2.35]), autoimmune (RR:1.39 [1.17–1.67]), cardiovascular (HR:1.51 [1.27–1.80]), psychiatric (HR:1.17 [1.07–1.28]), and any sequelae (HR:1.19 [1.13–1.25]) versus those without prior infection.
Interpretations
Post-acute sequelae contribute to overall disease burden following RSV-ARI and dengue fever. The evidence remains limited by heterogeneity in study design, exposure and outcome definitions, comparator selection, and follow-up duration. Greater standardization in study design and reporting is needed to improve comparability and strengthen causal inference.
