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新型冠状病毒肺炎相关肺曲霉病(CAPA)

COVID-19-Associated Pulmonary Aspergillosis (CAPA).

作者信息

Dimopoulos George, Almyroudi Maria-Panagiota, Myrianthefs Pavlos, Rello Jordi

机构信息

Department of Critical Care, University Hospital ATTIKON, National and Kapodistrian University of Athens, Athens 12462, Greece.

Department of Emergency Medicine, University Hospital ATTIKON, National and Kapodistrian University of Athens, Athens 12462, Greece.

出版信息

J Intensive Med. 2021 Aug 7;1(2):71-80. doi: 10.1016/j.jointm.2021.07.001. eCollection 2021 Oct.

Abstract

Invasive Pulmonary Aspergillosis (IPA) has been recognized as a possible secondary infection complicating Coronavirus disease 2019 (COVID-19) and increasing mortality. The aim of this review was to report and summarize the available data in the literature concerning the incidence, pathophysiology, diagnosis, and treatment of COVID-19-Associated Pulmonary Aspergillosis (CAPA). Currently, the incidence of CAPA is unclear due to different definitions and diagnostic criteria used among the studies. It was estimated that approximately 8.6% (206/2383) of mechanically ventilated patients were diagnosed with either proven, probable, or putative CAPA. Classical host factors of invasive aspergillosis are rarely recognized in patients with CAPA, who are mainly immuno-competent presenting with comorbidities, while the role of steroids warrants further investigation. Direct epithelial injury and diffuse pulmonary micro thrombi in combination with immune dysregulation, hyper inflammatory response, and immunosuppressive treatment may be implicated. Discrimination between two forms of CAPA (e.g., tracheobronchial and parenchymal) is required, whereas radiological signs of aspergillosis are not typically evident in patients with severe COVID-19 pneumonia. In previous studies, the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria, a clinical algorithm to diagnose Invasive Pulmonary Aspergillosis in intensive care unit patients (AspICU algorithm), and influenza-associated pulmonary aspergillosis (IAPA) criteria were used for the diagnosis of proven/probable and putative CAPA, as well as the differentiation from colonization, which can be challenging. is the most commonly isolated pathogen in respiratory cultures. Bronchoalveolar lavage (BAL) and serum galactomannan (GM), β-d-glucan (with limited specificity), polymerase chain reaction (PCR), and Aspergillus-specific lateral-flow device test can be included in the diagnostic work-up; however, these approaches are characterized by low sensitivity. Early treatment of CAPA is necessary, and 71.4% (135/189) of patients received antifungal therapy, mainly with voriconazole, isavuconazole, and liposomal amphotericin B . Given the high mortality rate among patients with infection, the administration of prophylactic treatment is debated. In conclusion, different diagnostic strategies are necessary to differentiate colonization from bronchial or parenchymal infection in intubated COVID-19 patients with spp. in their respiratory specimens those not infected with severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2). Following confirmation, voriconazole or isavuconazole should be used for the treatment of CAPA.

摘要

侵袭性肺曲霉病(IPA)已被认为是一种可能并发于2019冠状病毒病(COVID-19)的继发感染,并会增加死亡率。本综述的目的是报告并总结文献中有关COVID-19相关肺曲霉病(CAPA)的发病率、病理生理学、诊断和治疗的现有数据。目前,由于各研究中使用的定义和诊断标准不同,CAPA的发病率尚不清楚。据估计,在接受机械通气的患者中,约8.6%(206/2383)被诊断为确诊、很可能或疑似CAPA。侵袭性曲霉病的经典宿主因素在CAPA患者中很少被识别,这些患者主要是具有免疫能力且伴有合并症,而类固醇的作用值得进一步研究。直接上皮损伤和弥漫性肺微血栓与免疫失调、高炎症反应和免疫抑制治疗可能有关。需要区分两种形式的CAPA(如气管支气管型和实质型),而在重症COVID-19肺炎患者中,曲霉病的影像学表现通常不明显。在先前的研究中,欧洲癌症研究与治疗组织/真菌病研究组(EORTC/MSG)标准、一种用于诊断重症监护病房患者侵袭性肺曲霉病的临床算法(AspICU算法)以及流感相关肺曲霉病(IAPA)标准被用于确诊/很可能和疑似CAPA的诊断,以及与定植的鉴别,这可能具有挑战性。 是呼吸道培养中最常分离出的病原体。支气管肺泡灌洗(BAL)和血清半乳甘露聚糖(GM)、β-d-葡聚糖(特异性有限)、聚合酶链反应(PCR)以及曲霉特异性侧流装置检测可纳入诊断检查;然而,这些方法的特点是敏感性低。CAPA的早期治疗是必要的,71.4%(135/189)的患者接受了抗真菌治疗,主要使用伏立康唑、艾沙康唑和脂质体两性霉素B。鉴于 感染患者的高死亡率,预防性治疗的应用存在争议。总之,对于呼吸道标本中存在 属菌的插管COVID-19患者,需要不同的诊断策略来区分定植与支气管或实质感染,以及区分未感染严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的患者。确诊后,应使用伏立康唑或艾沙康唑治疗CAPA。

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