Aspergillus tracheobronchitis in COVID-19 patients with acute respiratory distress syndrome: a cohort study

Abstract

Comprehensive work-up is needed for COVID-19 ARDS patients, especially when suspecting invasive fungal infections. Aspergillus tracheobronchitis has a substantial prevalence in patients with CAPA accounting for an overall mortality of 75% in this study. https://bit.ly/3uF3FZU

Trial registration: ClinicalTrials.gov NCT01731353.

Conflict of interest statement

Conflict of interest: P. Koehler reports grants or contracts from German Federal Ministry of Research and Education and the State of North Rhine-Westphalia; consulting fees from Ambu GmbH, Gilead Sciences, Noxxon N.V. and Pfizer Pharma; honoraria for lectures from Akademie für Infektionsmedizin e.V., Ambu GmbH, Astellas Pharma, BioRad Laboratories Inc., European Confederation of Medical Mycology, Gilead Sciences, GPR Academy Ruesselsheim, medupdate GmbH, MedMedia, MSD Sharp & Dohme GmbH, Pfizer Pharma GmbH, Scilink Comunicación Científica SC and University Hospital and LMU Munich; participation on an advisory board from Ambu GmbH, Gilead Sciences and Pfizer Pharma; a pending patent currently reviewed at the German patent and trade mark office (official file number DE 10 2021 113 007.7); other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. Conflict of interest: S. von Stillfried has nothing to disclose. Conflict of interest: J. Garcia Borrega reports scientific grants and travel expenses from Kite/Gilead outside the submitted work. Conflict of interest: F. Fuchs has a clinician scientist position supported by the dean's office, medical faculty, University of Cologne. Conflict of interest: J. Salmanton-García has nothing to disclose. Conflict of interest: F. Pult has nothing to disclose. Conflict of interest: B. Böll reports honoraria, travel expenses and advisory role from/for Astellas, Celgene, Johnson & Johnson, Kite/Gilead, MSD, Novartis, Pfizer and Takeda, and financing of scientific research by Astellas, Celgene, Kite/Gilead, MSD and Takeda outside the submitted work. Conflict of interest: D.A. Eichenauer received honoraria from Sanofi and Takeda outside the submitted work. Conflict of interest: A. Shimabukuro-Vornhagen reports travel grants from Gilead Sciences outside the submitted work. Conflict of interest: O. Kurzai reports payment or honoraria for lectures, presentations or speakers' bureaus by Gilead and Pfizer, and receipt of equipment, materials, drugs, medical writing, gifts or other services by Pfizer, MSD, Basilea, Gilead, Virotech and Wako Fujifilm outside the submitted work. Conflict of interest: P. Boor has nothing to disclose. Conflict of interest: M. Kochanek reports payment or honoraria for lectures, presentations or speakers' bureaus by Gilead, MSD and Pfizer outside the submitted work. Conflict of interest: O.A. Cornely reports grants or contracts from Amplyx, Basilea, BMBF, Cidara, DZIF, EU-DG RTD (101037867), F2G, Gilead, Matinas, MedPace, MSD, Mundipharma, Octapharma, Pfizer, Scynexis; consulting fees from Amplyx, Biocon, Biosys, Cidara, Da Volterra, Gilead, Matinas, MedPace, Menarini, Molecular Partners, MSG-ERC, Noxxon, Octapharma, PSI, Scynexis and Seres; honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan and Pfizer; payment for expert testimony from Cidara; participation on a data safety monitoring board or advisory board from Actelion, Allecra, Cidara, Entasis, IQVIA, Jannsen, MedPace, Paratek, PSI and Shionogi; a pending patent currently reviewed at the German patent and trade mark office (official file number DE 10 2021 113 007.7); other interests from DGHO, DGI, ECMM, ISHAM, MSG-ERC, Wiley outside the submitted work.

Figures

FIGURE 1

Aspergillus tracheobronchitis. a) Bronchoscopy image of a patient with Aspergillus tracheobronchitis with tracheal ulceration and plaque formation (arrow). Bird's-eye view from the middle section of the trachea down into the primary bronchi separated by the carina (#). Notice the mucosa as it should be at the carina (#) and at the surrounding of the arrowhead, which points to the ventral part of the trachea. b) Macroscopic image of tracheal luminal surface at autopsy from a patient with invasive Aspergillus tracheobronchitis and invasive pulmonary aspergillosis. Note erosion and ulceration of tracheal mucosa with exposition of tracheal cartilage (arrowhead), partially covered by detached cellular detritus (arrow, histology shown in panel c). c) Images from tracheal and lung autopsy tissue from a coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) patient with Aspergillus tracheobronchitis and invasive pulmonary aspergillosis. Fungal invasion of the tracheal mucosa, fungal hyphae with 45° branching, 2–4 µm in diameter, consistent with Aspergillus spp. ¶: tracheal cartilage, PAS 4×, scale bar 200 µm; insert I: detached cellular detritus with fungal hyphae (arrowheads), PAS 40×, scale bar 30 µm; insert II: tracheal luminal surface with invasive growth of fungal hyphae with 45° branching, 2–4 µm in diameter, consistent with Aspergillus spp., PAS 40×, scale bar 30 µm. Due to ossification of tracheal cartilage, tissue was decalcified in formic acid overnight. d) Aspergillus invasion of the bronchial mucosa, fungal hyphae with 45° branching, 2–4 µm in diameter, typical for Aspergillus spp. +: bronchial cartilage, PAS 4×, scale bar 200 µm; insert I: detached cellular detritus with fungal hyphae (arrowheads), PAS 40×, scale bar 30 µm; insert II: bronchial wall with invasive growth of fungal hyphae (arrowheads) reaching bronchial cartilage, PAS 40×, scale bar 30 µm. e) Pulmonary vascular invasion of Aspergillus, fungal hyphae with 45° branching, 2–4 µm in diameter, typical for Aspergillus spp. §: vascular lumen, arrows: vascular wall with fungal invasion, HE 4×, scale bar 200 µm; insert: fungal hyphae with 45° branching, typical for Aspergillus spp. (arrowheads), HE 40×, scale bar 30 µm. b–e) Courtesy of S. von Stillfried and P. Boor (both Institute of Pathology, RWTH Aachen University Hospital, Aachen, Germany).