Mechanistic Basis of Super-Infection: Influenza-Associated Invasive Pulmonary Aspergillosis

Abstract

Influenza infection is a risk factor for invasive pulmonary aspergillosis in both immunocompetent and immunocompromised hosts. The purpose of this review is to highlight the epidemiology of influenza-associated invasive pulmonary aspergillosis and the mechanistic studies that have been performed to delineate how influenza increases susceptibility to this invasive fungal infection.

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.…”

Pathological Diagnosis of Pulmonary Aspergillosis

“…Another severe presentation of pulmonary aspergillosis is the context of viral coinfection, namely influenza-associated pulmonary aspergillosis (IAPA) and coronavirus disease 2019-associated pulmonary aspergillosis (CAPA), in which Aspergillus invasion arises secondary to severe viral disease, mainly in intensive care unit (ICU)-hospitalized patients. 59 60 61 The mechanisms that predispose these viral patients to Aspergillus infection is not clearly understood, but several factors altering the antifungal immunity have been proposed to be implicated, i.e., impaired mucociliary clearance, damages to the respiratory epithelium, inhibition of phagocytic activity, as well as decreased immunological response as a result of treatment with corticosteroids and immunomodulatory drugs. 59 60 62 63 Recently, Feys et al demonstrated that Aspergillus hyphae invaded the respiratory mucosa through damaged epithelium, which was concurrently or had recently been infected with severe acute respiratory syndrome coronavirus 2, highlighting the importance of epithelial impairment as a predisposing factor for fungal invasion.…”

“…59 60 61 The mechanisms that predispose these viral patients to Aspergillus infection is not clearly understood, but several factors altering the antifungal immunity have been proposed to be implicated, i.e., impaired mucociliary clearance, damages to the respiratory epithelium, inhibition of phagocytic activity, as well as decreased immunological response as a result of treatment with corticosteroids and immunomodulatory drugs. 59 60 62 63 Recently, Feys et al demonstrated that Aspergillus hyphae invaded the respiratory mucosa through damaged epithelium, which was concurrently or had recently been infected with severe acute respiratory syndrome coronavirus 2, highlighting the importance of epithelial impairment as a predisposing factor for fungal invasion. 64 Similar to the IPA monoinfection, the diagnosis of IAPA and CAPA can be divided into proven, probable, or possible coinfection based on the level of diagnostic certainty.…”

Pathogenicity and virulence of Aspergillus fumigatus

“…Superinfections caused by Streptococcus pneumonia and Staphylococcus aureus have long been recognised as complications of severe influenza and similar figures have been reported during the COVID-19 pandemic [ 417 ]. In these patients, viral-mediated epithelial cell damage and dysregulation of the immune defences at the site of viral infection have been suggested to increase susceptibility to secondary fungal disease [ 418 ]. In a recent publication, using murine models of Aspergillus -Influenza co-infection, it was reported that there is a decrease in neutrophil recruitment to the lungs, which may underpin increased fungal and viral burdens [ 419 ].…”