Purpose: Invasive pulmonary aspergillosis (IPA) is increasingly reported in patients with severe coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Diagnosis and management of COVID-19 associated pulmonary aspergillosis (CAPA) are challenging and our aim was to develop practical guidance. Methods: A group of 28 international experts reviewed current insights in the epidemiology, diagnosis and management of CAPA and developed recommendations using GRADE methodology. Results: The prevalence of CAPA varied between 0 and 33%, which may be partly due to variable case definitions, but likely represents true variation. Bronchoscopy and bronchoalveolar lavage (BAL) remain the cornerstone of CAPA diagnosis, allowing for diagnosis of invasive Aspergillus tracheobronchitis and collection of the best validated specimen for Aspergillus diagnostics. Most patients diagnosed with CAPA lack traditional host factors, but pre-existing structural lung disease and immunomodulating therapy may predispose to CAPA risk. Computed tomography seems to be of limited value to rule CAPA in or out, and serum biomarkers are negative in 85% of patients. As the mortality of CAPA is around 50%, antifungal therapy is recommended for BAL positive patients, but the decision to treat depends on the patients’ clinical condition and the institutional incidence of CAPA. We recommend against routinely stopping concomitant corticosteroid or IL-6 blocking therapy in CAPA patients. Conclusion: CAPA is a complex disease involving a continuum of respiratory colonization, tissue invasion and angioinvasive disease. Knowledge gaps including true epidemiology, optimal diagnostic work-up, management strategies and role of host-directed therapy require further study.
Bibliographical noteFunding Information:
PE Verweij reported grants from Gilead Sciences, MSD, Pfizer, Mundipharma, ThermoFisher, and F2G, and non-financial support from OLM and IMMY, outside the submitted work. All contracts were through Radboudumc, and all payments were invoiced by Radboudumc. RJM Brüggemann served as consultant to Astellas Pharma, Inc., F2G, Amplyx, Gilead Sciences, Merck Sharp & Dohme Corp., and Pfizer, Inc., and has received unrestricted and research grants from Astellas Pharma, Inc., Gilead Sciences, Merck Sharp & Dohme Corp., and Pfizer, Inc. All contracts were through Radboudumc, and all payments were invoiced by Radboudumc. E Azoulay has received fees for lectures from Pfizer, Gilead, MSD, Alexion and Baxter. His institution received research support from Fisher&Payckle, Jazz pharma and Gilead. M Bassetti has received funding for scientific advisory boards, travel and speaker honoraria from Angelini, Astellas, Bayer, BioMèrieux, Cidara, Correvio, Menarini, MSD, Nabriva, Pfizer, Roche and Shionogi. S Blot received research funding from Pfizer and MSD, travel support from Pfizer, MSD, and Gilead, and invited speaker for Pfizer and Gilead. J.B. Buil T Calandra reported advisory board membership from Astellas, Basilea, Cidara, MSD, Sobi, ThermoFisher, and GE Healthcare and data monitoring board membership from Novartis, all outside the submitted work. Fees are paid to its institution. T Chiller reported no conflicts of interest. CJ Clancy has been awarded investigator-initiated research grants from Astellas, Merck, Melinta, and Cidara for projects unrelated to this project, served on advisory boards or consulted for Astellas, Merck, the Medicines Company, Cidara, Scynexis, Shionogi, Qpex and Needham & Company, and spoken at symposia sponsored by Merck and T2Biosystems. OA Cornely is supported by the German Federal Ministry of Research and Education and the European Commission, and has received research grants from, is an advisor to, or received lecture honoraria from Actelion, Allecra Therapeutics, Amplyx, Astellas, Basilea, Biosys UK Limited, Cidara, Da Volterra, Entasis, F2G, Gilead, Grupo Biotoscana, Janssen Pharmaceuticals, Matinas, Medicines Company, MedPace, Melinta Therapeutics, Menarini Ricerche, Merck/MSD, Octapharma, Paratek Pharmaceuticals, Pfizer, PSI, Rempex, Scynexis, Seres Therapeutics, Tetraphase, Vical. P Depuydt reported no conflicts of interest. P Koehler is supported by the German Federal Ministry of Research and Education and the State of North Rhine-Westphalia, Germany and has received non-financial scientific grants from Miltenyi Biotec GmbH, Bergisch Gladbach, Germany, and the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany, and received lecture honoraria from and/or is advisor to Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, MSD Sharp & Dohme GmbH, Noxxon N.V., and University Hospital, LMU Munich outside the submitted work. K Lagrou received consultancy fees from MSD, SMB Laboratories Brussels and Gilead Sciences, travel support from Pfizer, grant from Thermo Fisher Scientific and speaker fees from Gilead Sciences, Pfizer, and FUJIFILM WAKO. D de Lange C Lass-Flörl received research funding from Pfizer, Gilead and Egger, travel support from Pfizer, MSD, and Gilead, and has served as invited speaker for MSD, Pfizer, Gilead, Basilea and Angelini. RE Lewis has received research support from Merck, and has served an invited speaker for Gilead, Cidara. O Lortholary has served as an invited speaker for Gilead, MSD, Pfizer, Astellas Pharma, and is a consultant for Gilead, Novartis and F2G. P Wei-Lun Liu has received research grants from MSD, Pfizer, and has served as an invited speaker for Gilead, MSD, Pfizer, Astellas Pharma, and is an advisor to Pfizer, Gilead. J Maertens reported personal fees and non-financial support from Basilea Pharmaceuticals, Bio-Rad Laboratories, Cidara, F2G Ltd, Gilead Sciences, Merck, Astellas, Scynexis, and Pfizer Inc. and grants from Gilead Sciences, IMMY and OLM. MH Nguyen receives research grants from the National Institute of Health, Astellas, Pulmocide, Scynexis,and Mayne, and participates in clinical trials funded by the Mycosis Study Group and F2G. TF Patterson received research grants or clinical trial support to UT Health San Antonio from Cidara and F2G and is an NIH ACTT and ACTIV investigator; is a consultant for Appili, Basilea, F2G Gilead, Mayne, Merck, Pfizer, Scynexis, and Sfunga. B Rijnders was investigator for studies supported by Gilead Sciences, Janssen-Cilag, MSD, Pfizer, ViiV; has received research grants from Gilead and MSD; was invited speaker for Gilead, MSD, Pfizer, Jansen-Cilag, BMS; and advisory board member for BMS, Abbvie, MSD, Gilead, Jansen-Cilag; he received travel support from BMS, Abbvie, MSD, Gilead, Jansen-Cilag. A Rodríguez report research grant from Gilead Science and fees for lectures from Pfizer, Gilead, ThermoFisher, Biomerieux and MSD. J Schouten reported grants from MSD and Pfizer, outside the submitted work. All contracts were through Radboudumc, and all payments were invoiced by Radboudumc. J Wauters reports grants, personal fees and other from MSD, Gilead Sciences, Pfizer, outside the submitted work. F van de Veerdonk reports grants from Gilead Sciences, grants from Sobi, outside the submitted work. I Martin-Loeches reported grants from Gilead, MSD and Pfizer, outside the submitted work.
© 2021, The Author(s).