Objective:

To determine the frequency, associated mortality, and risk factors for influenza-associated pulmonary aspergillosis (IAPA) among critically ill adults with influenza A pneumonia in post-COVID-19 China.

Approach:

• Study Design: A retrospective cohort study across 21 ICUs in Jiangsu Province, China, including 542 adults admitted with acute respiratory failure due to laboratory-confirmed influenza A pneumonia between November 2024 and February 2025.
• Data Collection: Researchers collected demographic, clinical, laboratory, microbiological, treatment, and outcome data. Mycological testing was performed at clinicians’ discretion.
• IPA Diagnosis: Invasive pulmonary aspergillosis (IPA) was defined using the 2024 FUNDICU criteria, requiring compatible clinical and radiological findings plus mycological evidence.
• Statistical Analysis: Multivariable logistic regression assessed factors associated with IPA. Propensity score matching compared mortality between groups, while Cox frailty models assessed mortality-associated factors within the IPA cohort. The primary outcome was 60-day all-cause mortality.

Key Findings:

• IPA was diagnosed in 179 of 542 patients (33.0%). The median interval from influenza diagnosis to IPA diagnosis was 2 days.
• Sixty-day mortality was 47.5% among patients with IPA versus 32.0% among those without IPA. The difference remained significant after matching.
• Renal replacement therapy, diabetes, bacterial coinfection, pre-ICU systemic glucocorticoid use, and steroid use during ICU admission were independently associated with IPA.
• Among patients with IPA, hematologic disorders and higher C-reactive protein levels were independently associated with mortality.

Interpretation:

Clinically detected IAPA is frequent and associated with higher mortality in this cohort. The findings support timely diagnostic evaluation but do not establish mortality directly attributable to IPA.

Limitations:

• Clinician-directed testing introduces detection bias; the reported frequency reflects clinically detected disease rather than true prevalence.
• Propensity score matching cannot fully eliminate immortal time bias.
• FUNDICU criteria limit comparisons with studies using older definitions.
• Some patients meeting diagnostic criteria may have had colonization rather than invasive infection.

Conclusion:

The authors call for protocolized screening and timely diagnostic strategies in critically ill patients with influenza A pneumonia. Diagnosis should integrate clinical, radiological, and microbiological findings.