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

Abstract

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.

Invasive pulmonary aspergillosis among intubated patients with SARS-CoV-2 or influenza pneumonia: a European multicenter comparative cohort study

“…Another potential explanation for the high incidence of IPA reported in these studies is the false positive results of galactomannan in some patients, which is supported by the absence of positive impact of antifungal treatment on mortality, and the fact that some patients with CAPA survived in spite of absence of any antifungal treatment [ 13 ]. On the other hand, other well-performed single and multicenter studies reported lower incidence of IPA in influenza and COVID-19 patients [ 9 , 10 , 18 , 25 ], which is in line with our findings. Geographical distribution and different case definitions might explain the variation in IPA incidence.…”

The Impacts of Aspergillosis on Outcome, Burden and Risks for Mortality in Influenza Patients with Critical Illness

“…Secondly, in line with previous studies investigating the coinfection between IPA and influenza among critically ill patients, the morbidity and mortality of this population were high [7,9,11,16,23]. Septic shock, acute kidney injury, and acute respiratory failure requiring mechanical ventilation were common complications, and the mortality rate was as high as 50% in this study.…”

“…Although IPA typically occurs in immunocompromised patients, more and more IPA cases reportedly develop in non-classically immunocompromised hosts [4][5][6]. The risk factors of IPA in critically ill patients without immunocompromised conditions include the use of corticosteroids, chronic obstructive pulmonary disease, acute respiratory distress syndrome, hepatic failure, and multiple organ dysfunction [4,5]; moreover, influenza itself is an independent risk factor of IPA and is associated with high mortality [7][8][9][10][11][12][13]. IPA might affect up to 23-29% of severe influenza patients [14][15][16].…”

A Visual and Comprehensive Review on COVID-19-Associated Pulmonary Aspergillosis (CAPA)

“…The importance of performing proper BAL sampling as part of the routine work-up for invasive aspergillosis in the ICU must be emphasized. Studies reporting very low incidences of aspergillosis in ICU patients typically have very low rates of bronchoscopy or BAL sampling, or do not include the use of BAL GM testing to diagnose IPA [97][98][99]. An important issue confounding our knowledge on CAPA incidence is the lack of reporting on the fraction of patients that received a proper fungal work-up (i.e., at least one BAL sampling for fungal culture and GM testing).…”