Abstract：
BACKGROUND: Pulmonary aspergillosis may complicate coronavirus disease 2019 (COVID-19) and contribute to excess mortality in intensive care unit (ICU) patients. The disease is poorly understood, in part due to discordant definitions across studies.
OBJECTIVE: We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions.
METHODS: PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021.
METHODS: ICU cohort studies and CAPA case series including ≥3 patients were included.
METHODS: Adult patients in ICUs with COVID-19.
METHODS: Patients were reclassified according to four research definitions. We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews.
METHODS: We calculated CAPA prevalence using the Freeman-Tukey random effects method. Correlations between definitions were assessed with Spearman\'s rank test. Associations between antifungals and outcome were assessed with random effects meta-analysis.
RESULTS: Fifty-one studies were included. Among 3297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%; 95% CI 8%-13%). Two hundred seventy-seven patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ = 0.268-0.447; p < 0.001), with the exception of Koehler and Verweij (ρ = 0.893; p < 0.001); 33.9% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 8 days (interquartile range 5-14) in ICUs. Tracheobronchitis occurred in 3% of patients examined with bronchoscopy. The mortality rate was high (59.2%). Applying CAPA research definitions did not strengthen the association between mould-active antifungals and survival.
CONCLUSIONS: The reported prevalence of CAPA is significant but may be exaggerated by nonstandard definitions.
OBJECTIVE: We sought to review the prevalence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA) and compare research definitions.
METHODS: PubMed, Embase, Web of Science, and MedRxiv were searched from inception to October 12, 2021.
METHODS: ICU cohort studies and CAPA case series including ≥3 patients were included.
METHODS: Adult patients in ICUs with COVID-19.
METHODS: Patients were reclassified according to four research definitions. We assessed risk of bias with an adaptation of the Joanna Briggs Institute cohort checklist tool for systematic reviews.
METHODS: We calculated CAPA prevalence using the Freeman-Tukey random effects method. Correlations between definitions were assessed with Spearman\'s rank test. Associations between antifungals and outcome were assessed with random effects meta-analysis.
RESULTS: Fifty-one studies were included. Among 3297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (prevalence 10%; 95% CI 8%-13%). Two hundred seventy-seven patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ = 0.268-0.447; p < 0.001), with the exception of Koehler and Verweij (ρ = 0.893; p < 0.001); 33.9% of patients reported to have CAPA did not fulfill any research definitions. Patients were diagnosed after a median of 8 days (interquartile range 5-14) in ICUs. Tracheobronchitis occurred in 3% of patients examined with bronchoscopy. The mortality rate was high (59.2%). Applying CAPA research definitions did not strengthen the association between mould-active antifungals and survival.
CONCLUSIONS: The reported prevalence of CAPA is significant but may be exaggerated by nonstandard definitions.
摘要：
背景：肺曲霉病可能会使2019年冠状病毒病（COVID-19）复杂化，并导致重症监护病房（ICU）患者的超额死亡率。人们对这种疾病知之甚少，部分原因是研究中定义不一致。
目的：我们试图回顾患病率，诊断,治疗,和COVID-19相关肺曲霉病（CAPA）的结果，并比较研究定义。
方法：PubMed，Embase,WebofScience,和MedRxiv从开始到2021年10月12日进行了搜索。
方法：纳入ICU队列研究和包括≥3名患者的CAPA病例系列。
方法：ICU中患有COVID-19的成年患者。
方法：根据四个研究定义对患者进行重新分类。我们通过对JoannaBriggs研究所队列清单工具进行系统评价来评估偏倚风险。
方法：我们使用Freeman-Tukey随机效应方法计算了CAPA患病率。使用Spearman秩检验评估定义之间的相关性。使用随机效应荟萃分析评估抗真菌药物与结果之间的关联。
结果：纳入51项研究。在ICU队列研究的3297例COVID-19患者中，313例被诊断为CAPA（患病率10%；95%CI8%-13%）。二百七十七名患者的患者水平数据允许重新分类。定义彼此之间的相关性有限(ρ=0.268-0.447；p<0.001)，除Koehler和Verweij外(ρ=0.893;p<0.001);33.9%的报告患有CAPA的患者不符合任何研究定义。患者在ICU中的中位数为8天（四分位距5-14）后被诊断。3％的支气管镜检查患者发生气管支气管炎。死亡率高(59.2%)。应用CAPA研究定义并没有加强霉菌活性抗真菌剂与存活率之间的联系。
结论：报告的CAPA患病率显著，但可能被非标准定义夸大。
目的：我们试图回顾患病率，诊断,治疗,和COVID-19相关肺曲霉病（CAPA）的结果，并比较研究定义。
方法：PubMed，Embase,WebofScience,和MedRxiv从开始到2021年10月12日进行了搜索。
方法：纳入ICU队列研究和包括≥3名患者的CAPA病例系列。
方法：ICU中患有COVID-19的成年患者。
方法：根据四个研究定义对患者进行重新分类。我们通过对JoannaBriggs研究所队列清单工具进行系统评价来评估偏倚风险。
方法：我们使用Freeman-Tukey随机效应方法计算了CAPA患病率。使用Spearman秩检验评估定义之间的相关性。使用随机效应荟萃分析评估抗真菌药物与结果之间的关联。
结果：纳入51项研究。在ICU队列研究的3297例COVID-19患者中，313例被诊断为CAPA（患病率10%；95%CI8%-13%）。二百七十七名患者的患者水平数据允许重新分类。定义彼此之间的相关性有限(ρ=0.268-0.447；p<0.001)，除Koehler和Verweij外(ρ=0.893;p<0.001);33.9%的报告患有CAPA的患者不符合任何研究定义。患者在ICU中的中位数为8天（四分位距5-14）后被诊断。3％的支气管镜检查患者发生气管支气管炎。死亡率高(59.2%)。应用CAPA研究定义并没有加强霉菌活性抗真菌剂与存活率之间的联系。
结论：报告的CAPA患病率显著，但可能被非标准定义夸大。
