COVID-19-associated pulmonary aspergillosis (CAPA) has been reported to be an emerging and potentially fatal complication of severe COVID-19. However, risk factors for CAPA have not been systematically addressed to date. In this systematic review and meta-analysis to identify factors associated with CAPA, we comprehensively searched five medical databases: Ovid MEDLINE; Ovid Embase; the Cochrane Database of Systematic Reviews; the Cochrane Central Register of Controlled Trials; and the WHO COVID-19 Database. All case-control and cohort studies in adults (aged >18 years) that described at least six cases of CAPA and evaluated any risk factors for CAPA, published from Dec 1, 2019, to July 27, 2023, were screened and assessed for inclusion. Only studies with a control population of COVID-19-positive individuals without aspergillosis were included. Two reviewers independently screened search results and extracted outcome data as summary estimates from eligible studies. The primary outcome was to identify the factors associated with CAPA. Meta-analysis was done with random-effects models, with use of the Mantel–Haenszel method to assess dichotomous outcomes as potential risk factors, or the inverse variance method to assess continuous variables for potential association with CAPA. Publication bias was assessed with funnel plots for factors associated with CAPA. The study is registered with PROSPERO, CRD42022334405. Of 3561 records identified, 28 articles were included in the meta-analysis. 8009 patients with COVID-19 were included, of whom 1398 (17·5%) were diagnosed with CAPA. Diagnosis rates of CAPA ranged from 2·5% (14 of 566 patients) to 47·2% (58 of 123). We identified nine risk factors for CAPA. These factors included pre-existing comorbidities of chronic liver disease (odds ratio [OR] 2·56 [95% CI 1·30–5·05], p=0·007; =47%), haematological malignancies (OR 2·47 [1·27–4·83], p=0·008; =50%), chronic obstructive pulmonary disease (OR 1·92 [1·42–2·60], p<0·0001; =22%), cerebrovascular disease (OR 1·31 [1·01–1·71], p=0·05; =46%), and diabetes (OR 1·26 [1·04–1·53], p=0·02; =37%). Use of invasive mechanical ventilation (OR 2·73 [1·89–3·94]; p<0·0001; =69%), use of renal replacement therapy (OR 2·26 [1·76–2·90], p<0·0001; =14%), treatment of COVID-19 with interleukin-6 inhibitors (OR 2·69 [1·47–4·90], p=0·001; =88%), and treatment of COVID-19 with corticosteroids (OR 1·72 [1·10–2·68], p=0·02; =77%) were also associated with CAPA. Patients with CAPA were typically older than those without CAPA (mean age 66·0 years [SD 4·4] 63·1 years [5·4]; mean difference 2·72 [1·33–4·12], p=0·0001; =86%). The duration of mechanical ventilation in patients with CAPA was longer than in those without CAPA (n=7 studies; mean duration 19·3 days [8·9] vs 13·5 days [6·8]; mean difference 5·53 days [1·30–9·77], p=0·01; =88%). In post-hoc analysis, patients with CAPA had higher all-cause mortality than those without CAPA (n=21 studies; OR 2·63 [2·06–3·34], p<0·0001; =48%). The identified risk factors for CAPA could eventually be addressed with targeted antifungal prophylaxis in patients with severe COVID-19. None.

中文翻译：

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COVID-19相关肺曲霉病的危险因素：系统评价和荟萃分析


据报道，与 COVID-19 相关的肺曲霉病 (CAPA) 是严重 COVID-19 的一种新出现的、可能致命的并发症。然而，迄今为止，CAPA 的风险因素尚未得到系统解决。在这项旨在确定与 CAPA 相关因素的系统回顾和荟萃分析中，我们全面检索了五个医学数据库：Ovid MEDLINE；奥维德大使馆； Cochrane 系统评价数据库；科克伦对照试验中央登记册；和世界卫生组织 COVID-19 数据库。 2019年12月1日至2023年7月27日发表的所有描述至少六例CAPA病例并评估CAPA任何危险因素的成人（年龄>18岁）病例对照和队列研究均经过筛选和评估以纳入研究。仅纳入了以没有曲霉病的 COVID-19 阳性个体为对照人群的研究。两名评审员独立筛选搜索结果并提取结果数据作为符合条件的研究的总结估计。主要结果是确定与 CAPA 相关的因素。使用随机效应模型进行荟萃分析，使用 Mantel-Haenszel 方法评估二分结果作为潜在风险因素，或使用逆方差方法评估连续变量与 CAPA 的潜在关联。通过漏斗图评估与 CAPA 相关的因素的发表偏倚。该研究已在 PROSPERO 注册，CRD42022334405。在确定的 3561 条记录中，荟萃分析纳入了 28 篇文章。纳入了 8009 名 COVID-19 患者，其中 1398 名 (17·5%) 被诊断为 CAPA。 CAPA 的诊断率范围为 2·5%（566 名患者中的 14 名）至 47·2%（123 名患者中的 58 名）。我们确定了 CAPA 的九个风险因素。 这些因素包括先前存在的慢性肝病合并症（优势比 [OR] 2·56 [95% CI 1·30–5·05]，p=0·007；=47%）、血液系统恶性肿瘤（OR 2· 47 [1·27–4·83]，p=0·008；=50%)，慢性阻塞性肺疾病（OR 1·92 [1·42–2·60]，p<0·0001；=22% ）、脑血管疾病（OR 1·31 [1·01–1·71]，p=0·05；=46%）和糖尿病（OR 1·26 [1·04–1·53]，p=0 ·02；=37%）。使用有创机械通气（OR 2·73 [1·89–3·94]；p<0·0001；=69%），使用肾脏替代疗法（OR 2·26 [1·76–2·90] ，p<0·0001；=14%），用白细胞介素 6 抑制剂治疗 COVID-19（OR 2·69 [1·47–4·90]，p=0·001；=88%），以及治疗使用皮质类固醇治疗 COVID-19 的效果（OR 1·72 [1·10–2·68]，p=0·02；=77%）也与 CAPA 相关。患有 CAPA 的患者通常比没有 CAPA 的患者年龄更大（平均年龄 66·0 岁 [SD 4·4] 63·1 岁 [5·4]；平均差 2·72 [1·33–4·12]，p= 0·0001；=86%）。患有 CAPA 的患者机械通气持续时间比未患有 CAPA 的患者更长（n = 7 项研究；平均持续时间 19·3 天 [8·9] vs 13·5 天 [6·8]；平均差异 5·53 天[1·30–9·77]，p=0·01；=88%）。在事后分析中，患有 CAPA 的患者比不患有 CAPA 的患者具有更高的全因死亡率（n=21 项研究；OR 2·63 [2·06–3·34]，p<0·0001；=48%）。已确定的 CAPA 危险因素最终可以通过对重症 COVID-19 患者进行有针对性的抗真菌预防来解决。没有任何。