The Extent of Aspergillosis in Critically Ill Patients With Severe Influenza Pneumonia: A Multicenter Cohort Study

OBJECTIVES: To determine the frequency and prognosis of invasive pulmonary aspergillosis in critically ill patients with severe influenza pneumonia. DESIGN: Retrospective multicenter cohort study. SETTING: Five French ICUs. PATIENTS: Patients with influenza admitted to ICU between 2009 and 2018. MEASUREMENTS AND MAIN RESULTS: Of the 524 patients admitted for severe influenza diagnosed with a positive airway reverse-transcriptase polymerase chain reaction test, 450 (86%) required mechanical ventilation. A lower respiratory tract sample yielded with Aspergillus (Asp+) in 28 patients (5.3%). Ten patients (1.9%) were diagnosed with putative or proven invasive pulmonary aspergillosis, based on the validated AspICU algorithm. A multivariate model was built to identify independent risk factors for Aspergillus -positive pulmonary culture. Factors independently associated with Aspergillus -positive culture were liver cirrhosis (odds ratio = 6.7 [2.1–19.4]; p < 0.01), hematologic malignancy (odds ratio = 3.3 [1.2–8.5]; p = 0.02), Influenza A(H1N1)pdm09 subtype (odds ratio = 3.9 [1.6–9.1]; p < 0.01), and vasopressor requirement (odds ratio = 4.1 [1.6–12.7]; p < 0.01). In-hospital mortality of Asp+ patients was 36% versus 21% in patients without Aspergillus -positive pulmonary culture ( p = 0.09). CONCLUSIONS: In this large retrospective multicenter cohort of critically ill patients, putative invasive pulmonary aspergillosis according to AspICU algorithm was a relatively rare complication of influenza. Patients at higher risk of Aspergillus pulmonary colonization included those with liver cirrhosis, hematologic malignancy, H1N1pdm09 influenza A virus, and requiring vasopressors. Our results provide additional data on the controversial association between severe influenza and invasive pulmonary aspergillosis. Reaching a consensual definition of invasive pulmonary aspergillosis becomes mandatory and confers further prospective research.