Background and aim Patients with influenza or Coronavirus disease 2019 (COVID-19) are at risk of developing invasive pulmonary aspergillosis (IPA). Whether the clinical profiles and outcomes differ between influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) remains unclear, hindering efforts to optimize management. This study aimed to compare the demographic, clinical, laboratory characteristics, and outcomes of patients with IPA following influenza A/B versus COVID-19 during the same period. Methods We conducted a single-center retrospective cohort study in China from December 1, 2022, to September 1, 2024. The study included 45 patients with IAPA and 82 patients with CAPA. We compared demographics, clinical features, management, and mortality between the IAPA and CAPA patients. Group comparisons utilized Student’s t -test or the Mann-Whitney U test for continuous variables, the Chi-square or Fisher’s exact test for categorical variables, and Kaplan-Meier survival curves, and time-dependent Cox proportional hazards model for survival data. Results Compared to IAPA patients, CAPA patients had significantly lower lymphocytes, especially in CD4 + T cells, CD8 + T cells, and B cells (all p 0.05). Corticosteroid use was more frequent among CAPA patients than IAPA patients. The median time from viral diagnosis to IPA detection was longer in CAPA patients than in IAPA patients. Respiratory co-infections (bacterial) were more common in the CAPA group ( p = 0.030). After adjusting for confounders, the risk of death within the first 14 days following IPA diagnosis was 4.92 times higher in the CAPA group than in the IAPA group (HR = 4.92, 95% CI: 1.35–18.01, p = 0.016). Conclusion CAPA was independently associated with an approximately five-fold increase in the risk of death within the first 14 days following IPA diagnosis. This early hazard, together with the higher frequency of corticosteroid use, respiratory co-infections (bacterial), and severe lymphopenia, underscores a critical window for early therapeutic intervention in patients with CAPA.
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