COVID-19 Associated Pulmonary Aspergillosis (CAPA)—From Immunology to Treatment
Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ 07110, USA
Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, 4710-057 Braga, Portugal
ICVS/3B’s—PT Government Associate Laboratory, 4710-057 Braga, Portugal
Department of Internal Medicine, Radboud University Medical Center, 6525 Nijmegen, The Netherlands
Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, 6525Nijmegen, The Netherlands
Department of Medicine, University of California San Diego, San Diego, CA 92103, USA
Clinical and Translational Fungal-Working Group, University of California San Diego, La Jolla, CA 92093, USA
Department I of Internal Medicine, Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, 50937Cologne, Germany
Section of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Medical University of Graz, 8036 Graz, Austria
Zentrum fuer klinische Studien (ZKS) Köln, Clinical Trials Centre Cologne, 50937 Cologne, Germany
German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Medical Faculty and University Hospital Cologne, University of Cologne, 50937 Cologne, Germany
Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, 6020 Innsbruck, Austria
Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, San Diego, CA 92093, USA
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
J. Fungi 2020, 6(2), 91; https://doi.org/10.3390/jof6020091
Received: 5 June 2020 / Revised: 19 June 2020 / Accepted: 22 June 2020 / Published: 24 June 2020
(This article belongs to the Special Issue Fungal Infections Complicating COVID-19)
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.