Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2022 Apr 20;60(4):e0229821.
doi: 10.1128/jcm.02298-21. Epub 2022 Mar 24.

Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a Post Hoc Analysis from the European Confederation of Medical Mycology (ECMM) COVID-19-Associated Pulmonary Aspergillosis Study

Daniele Roberto Giacobbe #  1   2 , Juergen Prattes #  3 , Joost Wauters  4 , Silvia Dettori  1   2 , Alessio Signori  5 , Jon Salmanton-García  6   7 , Johan Maertens  4 , Marc Bourgeois  8 , Marijke Reynders  8 , Lynn Rutsaert  9 , Niels Van Regenmortel  9 , Piet Lormans  10 , Simon Feys  4 , Nikolay Klimko  11 , Olga Shadrivova  11 , Oliver A Cornely  6   12   13   14 , Riina Rautemaa-Richardson  15   16 , Philipp Koehler  6   7 , Katrien Lagrou  17   18 , Matteo Bassetti #  1   2 , Martin Hoenigl #  3   19   20 ; ECMM-CAPA Study Group
Affiliations
Observational Study

Prognostic Impact of Bronchoalveolar Lavage Fluid Galactomannan and Aspergillus Culture Results on Survival in COVID-19 Intensive Care Unit Patients: a Post Hoc Analysis from the European Confederation of Medical Mycology (ECMM) COVID-19-Associated Pulmonary Aspergillosis Study

Daniele Roberto Giacobbe et al. J Clin Microbiol. .

Abstract

Critically ill patients with coronavirus disease 2019 (COVID-19) may develop COVID-19-associated pulmonary aspergillosis (CAPA), which impacts their chances of survival. Whether positive bronchoalveolar lavage fluid (BALF) mycological tests can be used as a survival proxy remains unknown. We conducted a post hoc analysis of a previous multicenter, multinational observational study with the aim of assessing the differential prognostic impact of BALF mycological tests, namely, positive (optical density index of ≥1.0) BALF galactomannan (GM) and positive BALF Aspergillus culture alone or in combination for critically ill patients with COVID-19. Of the 592 critically ill patients with COVID-19 enrolled in the main study, 218 were included in this post hoc analysis, as they had both test results available. CAPA was diagnosed in 56/218 patients (26%). Most cases were probable CAPA (51/56 [91%]) and fewer were proven CAPA (5/56 [9%]). In the final multivariable model adjusted for between-center heterogeneity, an independent association with 90-day mortality was observed for the combination of positive BALF GM and positive BALF Aspergillus culture in comparison with both tests negative (hazard ratio, 2.53; 95% CI confidence interval [CI], 1.28 to 5.02; P = 0.008). The other independent predictors of 90-day mortality were increasing age and active malignant disease. In conclusion, the combination of positive BALF GM and positive BALF Aspergillus culture was associated with increased 90-day mortality in critically ill patients with COVID-19. Additional study is needed to explore the possible prognostic value of other BALF markers.

Keywords: Aspergillus; BALF; CAPA; COVID-19; GM; biomarker; galactomannan.

PubMed Disclaimer

Conflict of interest statement

The authors declare a conflict of interest. Outside the submitted work, D.R.G. reports an unconditional grant from Correvio Italia, and investigator-initiated grants from Pfizer Inc and Gilead Italia. J.P. has received personal fees from Gilead Sciences and Pfizer, research funding from MSD outside of the submitted work and is stakeholder of AbbVie and Novo Nordisk. J.W. reports grants and personal fees from Gilead and Pfizer: investigator-initiated grants, personal fees and also non-financial support from MSD, outside the submitted work. J.M. reports grants, personal fees and non-financial support from MSD, grants, personal fees and non-financial support from Pfizer Inc., grants, personal fees and non-financial support from Gilead Sciences, personal fees and non-financial support from Astellas Pharma, personal fees and non-financial support from Cidara, personal fees and non-financial support from F2G, personal fees and non-financial support from Mundipharma, personal fees and non-financial support from Takeda/Shire, outside of the submitted work. O.A.C 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, Seres; Honoraria for lectures from Abbott, Al-Jazeera Pharmaceuticals, Astellas, Grupo Biotoscana/United Medical/Knight, Hikma, MedScape, MedUpdate, Merck/MSD, Mylan, 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, Shionogi; A pending patent currently reviewed at the German Patent and Trade Mark Office; Other interests from DGHO, DGI, ECMM, ISHAM, MSG-ERC, Wiley, outside the submitted work. J.S.-G. has received lecture honoraria from Gilead and Pfizer, outside the submitted work. M. Bassetti has received funding for scientific advisory boards, travel and speaker honoraria from Angelini, Astellas, Bayer, BioMèrieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer and Shionogi. R.R.-R. has received speaker honoraria from Astellas Pharma, Gilead Sciences, Pfizer, and research funding from Associates of Cape Cod. P.K. reports grants or contracts from German Federal Ministry of Research and Education and the State of North Rhine-Westphalia; Consulting fees 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, Pfizer Pharma; A pending patent currently reviewed at the German Patent and Trade Mark Office; Other non-financial interests from Elsevier, Wiley and Taylor & Francis online outside the submitted work. K.L. received consultancy fees from SMB Laboratoires Brussels, MSD and Gilead, travel support from Pfizer, speaker fees from FUJIFILM WAKO, Pfizer and Gilead and a service fee from Thermo Fisher Scientific. M.H. received research funding from Gilead Sciences, Astellas, Scynexis, F2G, MSD, and Pfizer, all outside the submitted work. All other authors declare no conflict of interest for this study.

Figures

FIG 1
FIG 1
Flowchart of the patient inclusion process. BALF, bronchoalveolar lavage fluid; CAPA, COVID-19-associated pulmonary aspergillosis; COVID-19, coronavirus disease 2019; GM, galactomannan; PCR, polymerase chain reaction.
See this image and copyright information in PMC

References

    1. Permpalung N, Chiang TP, Massie AB, Zhang SX, Avery RK, Nematollahi S, Ostrander D, Segev DL, Marr KA. 9 March 2021. COVID-19 associated pulmonary aspergillosis in mechanically ventilated patients. Clin Infect Dis 74:83–91. doi:10.1093/cid/ciab223. - DOI - PMC - PubMed
    1. Prattes J, Wauters J, Giacobbe DR, Salmanton-Garcia J, Maertens J, Bourgeois M, Reynders M, Rutsaert L, Van Regenmortel N, Lormans P, Feys S, Reisinger AC, Cornely OA, Lahmer T, Valerio M, Delhaes L, Jabeen K, Steinmann J, Chamula M, Bassetti M, Hatzl S, Rautemaa-Richardson R, Koehler P, Lagrou K, Hoenigl M, the ECMM-CAPA Study Group. 25 August 2021. Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients—a multinational observational study by the European Confederation of Medical Mycology. Clin Microbiol Infect. doi:10.1016/j.cmi.2021.08.014. - DOI - PMC - PubMed
    1. Salmanton-Garcia J, Sprute R, Stemler J, Bartoletti M, Dupont D, Valerio M, Garcia-Vidal C, Falces-Romero I, Machado M, de la Villa S, Schroeder M, Hoyo I, Hanses F, Ferreira-Paim K, Giacobbe DR, Meis JF, Gangneux JP, Rodriguez-Guardado A, Antinori S, Sal E, Malaj X, Seidel D, Cornely OA, Koehler P, FungiScope European Confederation of Medical Mycology/The International Society for Human and Animal Mycology Working Group. 2021. COVID-19-associated pulmonary aspergillosis, March–August 2020. Emerg Infect Dis 27:1077–1086. doi:10.3201/eid2704.204895. - DOI - PMC - PubMed
    1. Bartoletti M, Pascale R, Cricca M, Rinaldi M, Maccaro A, Bussini L, Fornaro G, Tonetti T, Pizzilli G, Francalanci E, Giuntoli L, Rubin A, Moroni A, Ambretti S, Trapani F, Vatamanu O, Ranieri VM, Castelli A, Baiocchi M, Lewis R, Giannella M, Viale P, PREDICO Study Group. 2021. Epidemiology of invasive pulmonary aspergillosis among COVID-19 intubated patients: a prospective study. Clin Infect Dis 73:e3606–e3614. doi:10.1093/cid/ciaa1065. - DOI - PMC - PubMed
    1. Borman AM, Palmer MD, Fraser M, Patterson Z, Mann C, Oliver D, Linton CJ, Gough M, Brown P, Dzietczyk A, Hedley M, McLachlan S, King J, Johnson EM. 2020. COVID-19-associated invasive aspergillosis: data from the UK National Mycology Reference Laboratory. J Clin Microbiol 59:e02136-20. doi:10.1128/JCM.02136-20. - DOI - PMC - PubMed

Publication types