TY - JOUR
T1 - Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients
T2 - a multinational observational study by the European Confederation of Medical Mycology
AU - ECMM-CAPA Study Group
AU - Prattes, Juergen
AU - Wauters, Joost
AU - Giacobbe, Daniele Roberto
AU - Salmanton-García, Jon
AU - Maertens, Johan
AU - Bourgeois, Marc
AU - Reynders, Marijke
AU - Rutsaert, Lynn
AU - Van Regenmortel, Niels
AU - Lormans, Piet
AU - Feys, Simon
AU - Reisinger, Alexander Christian
AU - Cornely, Oliver A
AU - Lahmer, Tobias
AU - Valerio, Maricela
AU - Delhaes, Laurence
AU - Jabeen, Kauser
AU - Steinmann, Joerg
AU - Chamula, Mathilde
AU - Bassetti, Matteo
AU - Hatzl, Stefan
AU - Rautemaa-Richardson, Riina
AU - Koehler, Philipp
AU - Lagrou, Katrien
AU - Hoenigl, Martin
N1 - Funding Information:
RR was supported by the NIHR Manchester Biomedical Research Centre . PK 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 the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. MH is supported by NIH ( UL1TR001442 ) and investigator initiated grants from Astellas , Gilead and Pfizer .
Funding Information:
RR was supported by the NIHR Manchester Biomedical Research Centre. PK 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 the Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, Cologne, Germany. MH is supported by NIH (UL1TR001442) and investigator initiated grants from Astellas, Gilead and Pfizer.JP 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. JW reports grants and personal fees from Gilead and Pfizer: investigator-initiated grants, personal fees and also on-financial support from MSD, outside the submitted work. DRG reports an unconditional grant from Correvio Italia and a grant for his institution by Pfizer Inc. outside the submitted work. JM 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 Pharam, 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. OAC reports grants and personal fees from Actelion, personal fees from Allecra Therapeutics, personal fees from Al-Jazeera Pharmaceuticals, grants and personal fees from Amplyx, grants and personal fees from Astellas, grants and personal fees from Basilea, personal fees from Biosys, grants and personal fees from Cidara, grants and personal fees from DaVolterra, personal fees from Entasis, grants and personal fees from F2G, grants and personal fees from Gilead, personal fees from Grupo Biotoscana, personal fees from IQVIA, grants from Janssen, personal fees from Matinas, grants from Medicines Company, grants and personal fees from Medpace, grants from Melinta Therapeutics, personal fees from Menarini, grants and personal fees from Merck/MSD, personal fees from Mylan, personal fees from Nabriva, personal fees from Noxxon, personal fees from Octapharma, personal fees from Paratek, grants and personal fees from Pfizer, personal fees from PSI, personal fees from Roche Diagnostics, grants and personal fees from Scynexis, personal fees from Shionogi, grants from DFG, German Research Foundation, grants from German Federal Ministry of Research and Education, grants from Immunic, personal fees from Biocon, personal fees from CoRe Consulting, personal fees from Molecular Partners, from MSG-ERC, from Seres, other from Wiley (Blackwell), outside the submitted work. LD has received personal fees from Gilead Sciences outside the submitted work. JS has received lecture honoraria from Gilead and Pfizer, outside the submitted work. MB has received funding for scientific advisory boards, travel and speaker honoraria from Angelini, Astellas, Bayer, BioM?rieux, Cidara, Cipla, Gilead, Menarini, MSD, Pfizer and Shionogi. RRR has received speaker honoraria from Astellas Pharma, Gilead Sciences, Pfizer and research funding from Associates of Cape Cod. PK 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 f?r 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. KL 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. MH received research funding from Gilead Sciences, Astellas, Scynexis, F2G and Pfizer, all outside the submitted work. All other authors declare no conflict of interest for this study.
Funding Information:
JP 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 . JW reports grants and personal fees from Gilead and Pfizer : investigator-initiated grants, personal fees and also on-financial support from MSD , outside the submitted work. DRG reports an unconditional grant from Correvio Italia and a grant for his institution by Pfizer Inc. outside the submitted work. JM 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 Pharam , 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. OAC reports grants and personal fees from Actelion , personal fees from Allecra Therapeutics , personal fees from Al-Jazeera Pharmaceuticals , grants and personal fees from Amplyx , grants and personal fees from Astellas , grants and personal fees from Basilea , personal fees from Biosys , grants and personal fees from Cidara , grants and personal fees from DaVolterra , personal fees from Entasis , grants and personal fees from F2G , grants and personal fees from Gilead , personal fees from Grupo Biotoscana , personal fees from IQVIA , grants from Janssen , personal fees from Matinas , grants from Medicines Company , grants and personal fees from Medpace , grants from Melinta Therapeutics , personal fees from Menarini , grants and personal fees from Merck/MSD , personal fees from Mylan , personal fees from Nabriva , personal fees from Noxxon , personal fees from Octapharma , personal fees from Paratek , grants and personal fees from Pfizer , personal fees from PSI , personal fees from Roche Diagnostics , grants and personal fees from Scynexis , personal fees from Shionogi , grants from DFG , German Research Foundation , grants from German Federal Ministry of Research and Education , grants from Immunic , personal fees from Biocon , personal fees from CoRe Consulting , personal fees from Molecular Partners , from MSG-ERC , from Seres , other from Wiley (Blackwell) , outside the submitted work. LD has received personal fees from Gilead Sciences outside the submitted work. JS has received lecture honoraria from Gilead and Pfizer , outside the submitted work. MB has received funding for scientific advisory boards, travel and speaker honoraria from Angelini , Astellas , Bayer , BioMérieux , Cidara , Cipla , Gilead , Menarini , MSD , Pfizer and Shionogi . RRR has received speaker honoraria from Astellas Pharma , Gilead Sciences , Pfizer and research funding from Associates of Cape Cod . PK 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. KL 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 . MH received research funding from Gilead Sciences , Astellas , Scynexis , F2G and Pfizer , all outside the submitted work. All other authors declare no conflict of interest for this study.
Publisher Copyright:
© 2021 European Society of Clinical Microbiology and Infectious Diseases
PY - 2022/4
Y1 - 2022/4
N2 - Objectives: Coronavirus disease 2019 (COVID-19) -associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. The objectives of this multinational study were to determine the prevalence of CAPA in patients with COVID-19 in intensive care units (ICU) and to investigate risk factors for CAPA as well as outcome. Methods: The European Confederation of Medical Mycology (ECMM) conducted a multinational study including 20 centres from nine countries to assess epidemiology, risk factors and outcome of CAPA. CAPA was defined according to the 2020 ECMM/ISHAM consensus definitions. Results: A total of 592 patients were included in this study, including 11 (1.9%) patients with histologically proven CAPA, 80 (13.5%) with probable CAPA, 18 (3%) with possible CAPA and 483 (81.6%) without CAPA. CAPA was diagnosed a median of 8 days (range 0–31 days) after ICU admission predominantly in older patients (adjusted hazard ratio (aHR) 1.04 per year; 95% CI 1.02–1.06) with any form of invasive respiratory support (HR 3.4; 95% CI 1.84–6.25) and receiving tocilizumab (HR 2.45; 95% CI 1.41–4.25). Median prevalence of CAPA per centre was 10.7% (range 1.7%–26.8%). CAPA was associated with significantly lower 90-day ICU survival rate (29% in patients with CAPA versus 57% in patients without CAPA; Mantel–Byar p < 0.001) and remained an independent negative prognostic variable after adjusting for other predictors of survival (HR 2.14; 95% CI 1.59–2.87, p ≤ 0.001). Conclusion: Prevalence of CAPA varied between centres. CAPA was significantly more prevalent among older patients, patients receiving invasive ventilation and patients receiving tocilizumab, and was an independent strong predictor of ICU mortality.
AB - Objectives: Coronavirus disease 2019 (COVID-19) -associated pulmonary aspergillosis (CAPA) has emerged as a complication in critically ill COVID-19 patients. The objectives of this multinational study were to determine the prevalence of CAPA in patients with COVID-19 in intensive care units (ICU) and to investigate risk factors for CAPA as well as outcome. Methods: The European Confederation of Medical Mycology (ECMM) conducted a multinational study including 20 centres from nine countries to assess epidemiology, risk factors and outcome of CAPA. CAPA was defined according to the 2020 ECMM/ISHAM consensus definitions. Results: A total of 592 patients were included in this study, including 11 (1.9%) patients with histologically proven CAPA, 80 (13.5%) with probable CAPA, 18 (3%) with possible CAPA and 483 (81.6%) without CAPA. CAPA was diagnosed a median of 8 days (range 0–31 days) after ICU admission predominantly in older patients (adjusted hazard ratio (aHR) 1.04 per year; 95% CI 1.02–1.06) with any form of invasive respiratory support (HR 3.4; 95% CI 1.84–6.25) and receiving tocilizumab (HR 2.45; 95% CI 1.41–4.25). Median prevalence of CAPA per centre was 10.7% (range 1.7%–26.8%). CAPA was associated with significantly lower 90-day ICU survival rate (29% in patients with CAPA versus 57% in patients without CAPA; Mantel–Byar p < 0.001) and remained an independent negative prognostic variable after adjusting for other predictors of survival (HR 2.14; 95% CI 1.59–2.87, p ≤ 0.001). Conclusion: Prevalence of CAPA varied between centres. CAPA was significantly more prevalent among older patients, patients receiving invasive ventilation and patients receiving tocilizumab, and was an independent strong predictor of ICU mortality.
KW - Aspergillus
KW - coronavirus disease 2019
KW - coronavirus disease 2019-associated pulmonary aspergillosis
KW - intensive care unit
KW - survival
UR - http://www.scopus.com/inward/record.url?scp=85114353749&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/e4c68e90-830f-31b2-be9a-21920646a3d3/
U2 - 10.1016/j.cmi.2021.08.014
DO - 10.1016/j.cmi.2021.08.014
M3 - Article
C2 - 34454093
SN - 1469-0691
VL - 28
SP - 580
EP - 587
JO - Clinical Microbiology and Infection
JF - Clinical Microbiology and Infection
IS - 4
ER -