Review of influenza-associated pulmonary aspergillosis in ICU patients and proposal for a case definition: an expert opinion

Abstract

Purpose: Invasive pulmonary aspergillosis is increasingly reported in patients with influenza admitted to the intensive care unit (ICU). Classification of patients with influenza-associated pulmonary aspergillosis (IAPA) using the current definitions for invasive fungal diseases has proven difficult, and our aim was to develop case definitions for IAPA that can facilitate clinical studies. Methods: A group of 29 international experts reviewed current insights into the epidemiology, diagnosis and management of IAPA and proposed a case definition of IAPA through a process of informal consensus. Results: Since IAPA may develop in a wide range of hosts, an entry criterion was proposed and not host factors. The entry criterion was defined as a patient requiring ICU admission for respiratory distress with a positive influenza test temporally related to ICU admission. In addition, proven IAPA required histological evidence of invasive septate hyphae and mycological evidence for Aspergillus. Probable IAPA required the detection of galactomannan or positive Aspergillus culture in bronchoalveolar lavage (BAL) or serum with pulmonary infiltrates or a positive culture in upper respiratory samples with bronchoscopic evidence for tracheobronchitis or cavitating pulmonary infiltrates of recent onset. The IAPA case definitions may be useful to classify patients with COVID-19-associated pulmonary aspergillosis (CAPA), while awaiting further studies that provide more insight into the interaction between Aspergillus and the SARS-CoV-2-infected lung.

Bacterial and fungal superinfections in critically ill patients with COVID-19

“…More than 30 cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been published to date [9]. Overall, the possible development of invasive pulmonary aspergillosis in some critically ill COVID-19 patients is somewhat expected, considering the following, likely cumulative risk factors: (1) the epithelial lung damage caused by either the virus or the dysregulated host response; (2) the frequent use of corticosteroids [10]; (3) a possible similarity with influenza-associated invasive aspergillosis (IAPA) [11]. However, some clinically relevant differences between IAPA and CAPA have been described.…”

“…In addition, different effects of the two different viruses on the host immune response could possibly explain a usually worse disease progression in IAPA than in CAPA. Finally, the diagnostic performance of fungal antigens tests could be different (e.g., lower sensitivity of serum galactomannan in CAPA than in IAPA) [11,12]. Very importantly, all of this also stands against the backdrop of a lack of a standardization in the definition of non-proven invasive aspergillosis in non-neutropenic critically ill patients, which itself contribute in further fueling the uncertainty regarding the true prevalence of CAPA.…”

COVID-19 Associated Invasive Pulmonary Aspergillosis: Diagnostic and Therapeutic Challenges

“…from a BALF as the entry criteria. Recently, a panel of experts proposed case definitions for influenza-associated pulmonary aspergillosis that might also be considered for the classification of CAPA patients, while awaiting further histopathological studies that will provide more insight into the interaction between Aspergillus and SARS-CoV-2-infected lungs [ 35 ]. Patients with confirmed severe COVID-19 infection and pulmonary infiltrates on chest imaging should trigger investigation for the presence of Aspergillus infection by the culture of respiratory samples and/or the detection of GM either in serum or BALF, if and when bronchoscopy is performed.…”

“…Excluding the six proven CAPA cases, 18 of the remaining 32 cases reviewed here fulfilled the case definition of probable CAPA, as suggested by the expert panel [ 35 ]; 11 had putative IPA utilizing the Asp ICU criteria [ 38 ]; and one had probable CAPA utilizing EORTC/MSGERC definitions [ 37 ]. Two patients with chronic obstructive pulmonary disease (COPD) could be classified as probable CAPA, following definitions by Bulpa et al for COPD patients [ 36 ].…”

COVID-19-Associated Invasive Aspergillosis: Data from the UK National Mycology Reference Laboratory

“…Invasive aspergillosis (IA) complicating severe influenza pneumonia is well-described from anecdotal case reports, and more recently from cross-centre and large cohort studies (1)(2)(3)(4)(5). Of particular note, mortality was significantly higher in patients with influenza/aspergillosis than those with influenza alone (2,4).…”