Incidence, risk factors and mortality of invasive pulmonary aspergillosis in patients with influenza: A systematic review and meta‐analysis

Abstract

Background An increasing number of cases of invasive pulmonary aspergillosis (IPA) complicating influenza have been described. We performed a meta‐analysis to estimate the incidence, risk factors and outcomes of IPA in patients with influenza. Methods A systematic search was conducted in the PubMed, EMBASE and Cochrane Library databases from their inception to 31 August 2021 for eligible studies. Data on the incidence and risk factors of and mortality due to IPA in influenza patients were pooled using a random‐effects model. Sensitivity analyses restricted to severe influenza requiring intensive care unit (ICU) support and multiple subgroup analyses were performed. Results Fourteen studies involving 6024 hospitalised patients with influenza were included. IPA was estimated to occur in 10% of influenza patients, with a mortality rate of 52%. Similar incidence (11%) and mortality (54%) estimates for IPA were observed in the sensitivity analysis including severe cases requiring ICU support. Subgroup analysis by geographical location showed a similar IPA rate between European (10%) and non‐European (11%) studies. The IPA rate in the subset of nine studies using the modified AspICU criteria was 13%. Most subgroup analyses showed ≥50% mortality in IPA patients. Several predictors for IPA susceptibility were identified, including male sex, smoking history, chronic lung disease, influenza A (H1N1), severe conditions requiring supportive therapy, corticosteroid use before admission, solid organ transplant and haematological malignancy. Conclusions The IPA is common in individuals with severe influenza, and the prognosis is particularly poor. Influenza patients, especially those with high‐risk factors, should be thoroughly screened for IPA.

Higher risk for influenza-associated pulmonary aspergillosis (IAPA) in asthmatic patients. A Swiss multicenter cohort study on IAPA in critically ill influenza patients.

“…High mortality in patients with IAPA has been reported by us and others 1, 14 . Interestingly, influenza A was associated with poor outcome that was also shown in a recent metaanalysis of 14 studies of IAPA 28 . An association of influenza A with an increased risk of bacterial respiratory infections and mortality has been previously suggested [29][30][31] , even though it was recently challenged 32 .…”

Invasive pulmonary aspergillosis with candidiasis: usefulness of molecular and ultrastructural morphological analysis on FFPE tissue for invasive fungal infections

“…IPA accounts for more than 90% of cases of IA, and viral infections such as infections with SARS-CoV-2 and influenza viruses have recently been reported to be risks for IPA [ 7 , 11 ]. Influenza virus infection is known to induce 'influenza-associated pulmonary aspergillosis (IAPA)', which can progress to IPA, and the incidence of IAPA has been increasing [ 5 , 6 ]. Our patient died of IPA after influenza infection, which is presumed to have occurred via IAPA based on the clinical course of the case.…”

Higher risk for influenza‐associated pulmonary aspergillosis (IAPA) in asthmatic patients: A Swiss multicenter cohort study on IAPA in critically ill influenza patients

“…1,14 Interestingly, influenza A was associated with poor outcome that was also shown in a recent metaanalysis of 14 studies of IAPA. 28 An association of influenza A with an increased risk of bacterial respiratory infections and mortality has been previously suggested, [29][30][31] even though it was recently challenged. 32 The proportion of IAPA among influenza patients requiring ICU care in Switzerland was similar in the 2017/2018 and the 2019/2020 seasons, 14 which were characterized by influenza B with Yamagata (2017/2018) predominance versus similar presence of influenza A(H1N1)pdm09 and B Victoria (2019/2020).…”

“… 1 , 14 Interestingly, influenza A was associated with poor outcome that was also shown in a recent meta‐analysis of 14 studies of IAPA. 28 An association of influenza A with an increased risk of bacterial respiratory infections and mortality has been previously suggested, 29 , 30 , 31 even though it was recently challenged. 32 …”