Incidence and outcomes of influenza-associated pulmonary aspergillosis and the role of antifungal prophylaxis: a structured literature review

BACKGROUND: Influenza-associated pulmonary aspergillosis (IAPA) is a frequent and often fatal complication of severe influenza in critically ill patients. Despite increased recognition, its real global burden and optimal prevention strategies remain uncertain. METHODS: A structured literature review of studies published between January 2000 and June 2025 was conducted to summarize IAPA incidence, fatality rate and study heterogeneity. Continuous variables were summarized as trimmed medians (central 80%) with bootstrapped 95% confidence intervals. Between-study heterogeneity and methodological diversity were quantified using the I² and Shannon diversity indices. Non-parametric tests assessed subgroup differences and correlations. RESULTS: Fifty-three studies (527,475 patients) were included. The trimmed median IAPA incidence was 14.55% (95% CI, 11.16–19.21), and the case-fatality rate was 50.00% (95% CI, 42.86–58.54). IAPA occurred more frequently in ICU-only cohorts (p = 0.011) and was associated with higher mortality (p = 0.025). Heterogeneity across studies was substantial (I² = 96.1% for incidence; 79.6% for fatality), reflecting differences in diagnostic definitions and patient selection. Universal antifungal prophylaxis, including posaconazole, did not confer a significant survival benefit. CONCLUSIONS: IAPA affects approximately one in six critically ill influenza patients and carries a mortality of around 50%. Rather than a one-size-fits-all approach, future studies are needed to evaluate more individualized therapy concepts that account for patient- and disease-specific factors and may improve overall outcomes.