新冠病毒感染後侵襲性肺麴菌病

COVID-19-associated Pulmonary Aspergillosis

急性呼吸窘迫症候群（Acute Respiratory Distress Syndrome）是發生COVID-19重症的主要併發症。這些重症的COVID-19病人，後續的麴菌感染更增加了病人的死亡率，成為醫護照顧重症病人的另一個危機。而後發生的侵襲性肺麴菌病我們稱為CAPA（COVID-19 associated pulmonary aspergillosis）。SARS-CoV-2病毒感染本身會造成呼吸道上皮細胞的直接損害，以及由病毒和藥物所造成的免疫失調，使得麴菌又機會深入組織而造成後續的感染。本篇的重點在介紹產生CAPA的風險因子，CAPA的發生率和死亡率。此外，BAL（bronchial alveolar lavage）aspergillosisgalactomannan antigen（GM）titer，PCR以及培養能提供最佳的麴菌感染診斷敏感度。然而，因為COVID-19的高傳染染性，臨床上限制了支氣管鏡的應用。本篇文章也介紹European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium（EORTC/MSGERC）對於CAPA的診斷定義。最後，voriconazole與isavuconazole為治療首選藥物。但是臨床上需考慮藥物交互作用。觀察性研究中發現，預防性抗黴菌藥的使用可以減少未來重症COVID-19病人發生CAPA的機會。然而存活率卻沒有顯著差異。未來，需要進行隨機對照試驗來評估抗黴菌預防性用藥在COVID-19重症病人使用的有效性及安全性。

Acute respiratory distress syndrome (ARDS) is a major complication of coronavirus disease 2019 (COVID-19). Patients presenting with ARDS can rapidly develop invasive pulmonary aspergillosis. Reports of COVID-19-associated pulmonary aspergillosis (CAPA) have raised concerns about it worsening the COVID-19 disease course and increasing mortality rates. Immune dysregulation and epithelial lung damage arising from COVID-19 immunopathology are likely predisposing mechanisms for CAPA. This article introduces the prevalence and incidence of CAPA and its associated risk factors. The diagnosis of CAPA remains challenging, mainly because the bronchoalveolar lavage fluid galactomannan test, culture, and polymerase chain reaction are the most sensitive diagnostic tests for aspergillosis. However, because of the risk of disease transmission, bronchoscopies are rarely performed for patients with COVID-19. We discuss the definition of CAPA provided by the European Organization for the Research and Treatment of Cancer/Mycoses Study Group Education and Research Consortium. Finally, voriconazole and isavuconazole are the first-line treatment choices for possible, probable, and proven CAPA cases. However, drug-drug interactions associated with broad-spectrum azoles require consideration. Antifungal prophylaxis was associated with a significantly reduced CAPA incidence, but this did not translate into improved survival rates. Therefore, further randomized controlled trials are warranted.