Background: Bacterial superinfections are well-described complications of influenza infection, however few data exist on invasive fungal infections in this setting. The pathogenesis of invasive fungal infections may be related to respiratory epithelium disruption and viral-induced lymphopenia.
Methods: A retrospective study was conducted among severe influenza cases requiring ICU admission at a large academic hospital (2015-2016). Data collected included respiratory cultures; medical conditions; laboratory/radiographic data; and outcome. Aspergillosis was defined using EORTC guidelines. A systematic literature review (PubMed; 1963-2015) of cases in the English language of aspergillosis complicating influenza was conducted.
Results: Of the 48 ICU patients tested, 8 were diagnosed with influenza infection. Of these, six (75%) had Aspergillus sp. (4 A. fumigatus, 1 A. fumigatus and A. versicolor, and 1 A. niger) isolated from respiratory cultures a median of 4.5 days (range 0-12) after influenza diagnosis [3 influenza A(H1N1); 3 B]. Since A. niger was of unknown pathogenicity, it was excluded. Of the 40 patients influenza negative, none had Aspergillus isolated. No patient with Aspergillus was immunosuppressed. Galactomannan and/or β-glucan levels were positive in 75% of cases tested, and all cases had diffuse pulmonary consolidative infiltrates. All except one Aspergillus case had lymphopenia (median 459/µl) vs. those without aspergillosis (1095/µl). Mortality was 60% among influenza-aspergillus co-infected patients, with the two survivors having respiratory failure >30 days. Review of literature and current cases yielded n=57 (EORTC: 37% proven, 25% probable, and 39% possible cases). An increasing number of cases were noted since 2010 mostly linked to influenza A (H1N1); only 1/3 had classic underlying conditions for aspergillosis; 86% had lymphopenia; 78-88% had a positive fungal serologic marker; overall mortality rate was 46%.
Conclusion: Aspergillosis is an emerging complication of severe influenza infections even among immunocompetent hosts. Risks may include viral-induced lymphopenia and H1N1 strains, although further studies are needed. Prompt diagnosis (using respiratory cultures and potentially preemptive galactomannan and/or β-glucan testing) and antifungal therapy are recommended given the high mortality rate.