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,Clinical Microbiology and Infection

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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
Clinical Microbiology and Infection ( IF 10.9 ) Pub Date : 2021-08-26 , DOI: 10.1016/j.cmi.2021.08.014
Juergen Prattes ₁ , Joost Wauters ₂ , Daniele Roberto Giacobbe ₃ , Jon Salmanton-García ₄ , Johan Maertens ₂ , Marc Bourgeois ₅ , Marijke Reynders ₅ , Lynn Rutsaert ₆ , Niels Van Regenmortel ₆ , Piet Lormans ₇ , Simon Feys ₇ , Alexander Christian Reisinger ₈ , Oliver A Cornely ₄ , Tobias Lahmer ₉ , Maricela Valerio ₁₀ , Laurence Delhaes ₁₁ , Kauser Jabeen ₁₂ , Joerg Steinmann ₁₃ , Mathilde Chamula ₁₄ , Matteo Bassetti ₃ , Stefan Hatzl ₈ , Riina Rautemaa-Richardson ₁₄ , Philipp Koehler ₁₅ , Katrien Lagrou ₂ , Martin Hoenigl ₁₆ ,

Affiliation

Medical University of Graz, Department of Infectious Diseases, Excellence Centre for Medical Mycology (ECMM), Graz, Austria.
Universitair Ziekenhuis Leuven, Leuven, Belgium.
San Martino Polyclinic Hospital IRCCS, Genoa, Italy; Department of Health Sciences, University of Genoa, Genoa, Italy.
University of Cologne, Medical Faculty and University Hospital Cologne, Department I of Internal Medicine, Excellence Centre for Medical Mycology (ECMM), Cologne, Germany; University of Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
Algemeen Ziekenhuis Sint-Jan Brugge-Oostende, Bruges, Belgium.
Ziekenhusnetwerk Antwerp, Campus Stuivenberg, Antwerp, Belgium.
Algemeen Ziekenhuis Delta, Roeselare, Belgium.
Medical University of Graz, Department of Internal Medicine, Intesive Care Unit, Graz, Austria.
Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
Clinical Microbiology and Infectious Diseases Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, Madrid, Spain.
Centre Hospitalier Universitaire de Bordeaux, ISERM U1045, Bordeaux, France.
Aga Khan University, Karachi, Pakistan.
Institute of Clinical Hygiene, Medical Microbiology and Infectiology, Paracelsus Medical University, Klinikum Nürnberg, Nuremberg, Germany.
Manchester University NHS Foundation Trust, Wythenshawe Hospital and Division of Infection, Immunity and Respiratory Medicine, Faculty of Biology, Medicine and Health, University of Manchester, UK.
University of Cologne, Medical Faculty and University Hospital Cologne, Department I of Internal Medicine, Excellence Centre for Medical Mycology (ECMM), Cologne, Germany.
Medical University of Graz, Department of Infectious Diseases, Excellence Centre for Medical Mycology (ECMM), Graz, Austria; Division of Infectious Diseases and Global Public Health, University of California San Diego, San Diego, CA, USA; Clinical and Translational Fungal-Working Group, University of California San Diego, San Diego, CA, USA.

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.

中文翻译：

2019 年重症冠状病毒病患者肺曲霉病的危险因素和结果——欧洲医学真菌学联合会的一项多国观察性研究

目标

2019 年冠状病毒病 (COVID-19) 相关的肺曲霉病 (CAPA) 已成为 COVID-19 重症患者的并发症。这项跨国研究的目的是确定重症监护病房 (ICU) 中 COVID-19 患者的 CAPA 患病率，并调查 CAPA 的危险因素和结果。

方法

欧洲医学真菌学联合会 (ECMM) 进行了一项多国研究，包括来自 9 个国家的 20 个中心，以评估 CAPA 的流行病学、风险因素和结果。CAPA 是根据 2020 ECMM/ISHAM 共识定义定义的。

结果

本研究共纳入 592 名患者，其中 11 名 (1.9%) 患者经组织学证实为 CAPA，80 名 (13.5%) 患者为可能的 CAPA，18 名 (3%) 可能为 CAPA，483 名 (81.6%) 为无 CAPA。CAPA 在入住 ICU 后的中位时间为 8 天（范围 0-31 天），主要在接受任何形式有创呼吸支持（HR 3.4 ; 95% CI 1.84–6.25) 和接受托珠单抗治疗 (HR 2.45; 95% CI 1.41–4.25)。每个中心的 CAPA 患病率中位数为 10.7%（范围 1.7%–26.8%）。CAPA 与 90 天 ICU 生存率显着降低相关（CAPA 患者为 29%，非 CAPA 患者为 57%；Mantel-Byar p < 0.001），并且在调整其他生存预测因子（HR 2.14；95% CI 1.59–2。