The frequency and diversity of serious fungal infections is increasing [ 1 x 1 Nucci, M, Garnica, M, Gloria, AB et al. Invasive fungal diseases in haematopoietic cell transplant recipients and in patients with acute myeloid leukaemia or myelodysplasia in Brazil. Clin Microbiol Infect. 2013; 19: 745–751 Abstract | Full Text | Full Text PDF | PubMed | Scopus (43) | Google Scholar See all References , 2 x 2 Nucci, M and Anaissie, E. Fusarium infections in immunocompromised patients. Clin Microbiol Rev. 2007; 20: 695–704 Crossref | PubMed | Scopus (413) | Google Scholar See all References , 3 x 3 Nucci, M and Anaissie, E. Emerging fungi. Infect Dis Clin North Am. 2006; 20: 563–579 Abstract | Full Text | Full Text PDF | PubMed | Scopus (0) | Google Scholar See all References ]. Severely immunocompromised patients are particularly vulnerable to infection from unusual moulds and yeasts, which are present in the environment. Clinical manifestations range from colonization to chronic localized lesions to acute invasive and/or disseminated diseases. Localized infections may occur following penetrating trauma in healthy individuals; dissemination usually occurs among immunocompromised patients and the outcome is closely related to the degree and persistence of immunosuppression [ 4 x 4 Nucci, M, Anaissie, EJ, Queiroz-Telles, F et al. Outcome predictors of 84 patients with hematologic malignancies and Fusarium infection. Cancer. 2003; 98: 315–319 Crossref | PubMed | Scopus (163) | Google Scholar See all References 4 ]. Diagnosis usually requires isolation and identification of the infecting pathogen; however, serology, imaging techniques and clinical manifestations are not specific, and pan-fungal and species-specific PCR are useful investigational tools. Many of the emerging opportunistic moulds demonstrate in vitro and in vivo resistance to various antifungals. As a result, successful treatment may require adjunctive surgical debridement and, when possible, reconstitution of the host immune system.

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. Conclusion A consensus case definition of IAPA is proposed, which will facilitate research into the epidemiology, diagnosis and management of this emerging acute and severe Aspergillus disease, and may be of use to study CAPA.

Like severe influenza, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome (ARDS) has emerged as an important disease that predisposes patients to secondary pulmonary aspergillosis, with 35 cases of COVID-19 associated pulmonary aspergillosis (CAPA) published until June 2020. The release of danger-associated molecular patterns during severe COVID-19 results in both pulmonary epithelial damage and inflammatory disease, which are predisposing risk factors for pulmonary aspergillosis. Moreover, collateral effects of host recognition pathways required for the activation of antiviral immunity may, paradoxically, contribute to a highly permissive inflammatory environment that favors fungal pathogenesis. Diagnosis of CAPA remains challenging, mainly because bronchoalveolar lavage fluid galactomannan testing and culture, which represent the most sensitive diagnostic tests for aspergillosis in the ICU, are hindered by the fact that bronchoscopies are rarely performed in COVID-19 patients due to the risk of disease transmission. Similarly, autopsies are rarely performed, which may result in an underestimation of the prevalence of CAPA. Finally, the treatment of CAPA is complicated by drug–drug interactions associated with broad spectrum azoles, renal tropism and damage caused by SARS-CoV-2, which may challenge the use of liposomal amphotericin B, as well as the emergence of azole-resistance. This clinical reality creates an urgency for new antifungal drugs currently in advanced clinical development with more promising pharmacokinetic and pharmacodynamic profiles.