14/12/2020
Viral pneumonia increases patients’ susceptibility to bacterial and fungal superinfections, including invasive pulmonary aspergillosis (IPA). Influenza-associated pul- monary aspergillosis (IAPA) has complicated the clinical course of many critically ill patients with acute respi- ratory distress syndrome (ARDS).1,2 By use of the European Organisation for Research and Treatment of Cancer and the Mycosis Study Group Education and Research Consortium definitions for invasive fungal disease (IFD), it was found that many patients with IAPA could not be classified, leading to missed diagnoses and raising the question of whether current definitions for IFD adequately address all patient populations.3 In December, 2019, COVID-19 emerged from Wuhan, China, and has become pandemic.4 There have been several reports of COVID-19-associated pulmonary aspergillosis (CAPA), raising concerns about this superinfection as an additional contributing factor to mortality.5–10 Indeed, in a prospective cohort of 108 critically ill patients with ARDS, a higher 30-day mortality was observed in patients with CAPA than in patients without aspergillosis (44% vs 19%), and the association of COVID-19-associated fungal disease with mortality was also supported by another study.11,12 The population of patients with CAPA harbours many baseline prognostic factors with negative effects on survival,13 which might be further compromised by azole-resistant CAPA, with an increasing number of patients reported in the literature.
Respiratory viruses cause direct damage to the airway epithelium, enabling aspergillus to invade tissue.17 Further- more, viral infection hampers ciliary clearance and leads to immune dysfunction or dysregulation, or both, locally or systemically.18 The extent of dysregulation that is asso- ciated with ARDS is not yet fully understood, however, some patients develop pronounced immunosuppression, facilitating bacterial and fungal superinfection. Moreover,a distinctive immune-cell event that is observed in patients with COVID-19 is the decrease of T-cell populations, especially in patients with severe disease.19 Decline of lymphocyte counts can be accompanied by defective function. Severe lymphopenia has been established as a factor predicting the risk of invasive mould disease in patients with haematological malignancies.20
Early case series of patients with presumed CAPA indicate that obtaining a diagnosis can be challenging. Although host factors, clinical factors (including radio- logy), and mycological evidence are often used to diagnose and classify patients with IFD, patients with CAPA might not have host factors and typical radiological features.5–11 Obtaining mycological evidence of airway- invasive aspergillosis in patients with COVID-19 is complicated by decreased use of diagnostic bronchos- copy, which is necessary to protect health-care workers from aerosol exposure,21,22 and the low sensitivity of detection of circulating galactomannan in serum.11 Further, detection of aspergillus in specimens of the upper respiratory tract, such as sputum or tracheal aspirate, often does not distinguish between aspergillus colonisation and invasive disease.
Given the challenges that are associated with diagnosis and management of patients with CAPA, there is an urgent need to study the epidemiology and characteristics of this secondary infection. Therefore, the European Confederation for Medical Mycology and the Inter- national Society for Human and Animal Mycology instituted a group of experts to propose consensus criteria for a case definition of CAPA and to provide up-to-date management recommendations for the diagnosis and treatment of patients with CAPA.
