Enterovirus D68 and Acute Neurologic Outcomes: A Systematic Review and Meta-Analysis (2010-2025).

Area of Science:

• Virology
• Epidemiology
• Neurology

Background:

• Enterovirus D68 (EV-D68) is associated with acute flaccid myelitis (AFM) and severe respiratory illness.
• The consistency and magnitude of this association across different settings and over time require further investigation.

Purpose of the Study:

• To quantify the association between EV-D68 detection and acute neurologic outcomes, particularly AFM.
• To explore heterogeneity in this association based on study design and temporal factors.

Main Methods:

• Systematic review and meta-analysis of observational studies following PRISMA 2020 and MOOSE guidelines.
• Random effects meta-analysis with meta-regression to assess moderators and heterogeneity.
• Evaluation of small-study effects using funnel plots and bias-adjusted models.

Main Results:

• Pooled analysis of 98 studies showed an overall odds ratio (OR) of 1.39 (95% CI 1.14-1.69) for EV-D68 association with neurologic outcomes, with high heterogeneity (I² = 98.9%).
• Respiratory surveillance studies indicated a stronger association (OR 1.59) compared to AFM case-control studies (OR 0.86).
• Study design and calendar year explained 47% of the variance, with predicted ORs declining from 2014 to 2022.

Conclusions:

• The association between EV-D68 and neurologic outcomes is context-dependent and varies over time.
• Surveillance data during outbreaks drives the pooled association, whereas case-control studies yield attenuated estimates.
• Standardizing diagnostics and integrating design-specific surveillance are crucial for improving risk estimation and preparedness for AFM.