Institute of Infection and Immunity, St George's University of London, London, UK
Clinical Infection Unit, St George's University Hospitals NHS Foundation Trust, London, UK.
Thorax. 2023 Dec 15;79(1):75-82. doi: 10.1136/thorax-2023-220002.
Invasive pulmonary aspergillosis is a complication of severe COVID-19, with regional variation in reported incidence and mortality. We describe the incidence, risk factors and mortality associated with COVID-19-associated pulmonary aspergillosis (CAPA) in a prospective, multicentre UK cohort.
From March 2020 to March 2021, 266 mechanically ventilated adults with COVID-19 were enrolled across 5 UK hospital intensive care units (ICUs). CAPA was defined using European Confederation for Medical Mycology and the International Society for Human and Animal Mycology criteria and fungal diagnostics performed on respiratory and serum samples.
Twenty-nine of 266 patients (10.9%) had probable CAPA, 14 (5.2%) possible CAPA and none proven CAPA. Probable CAPA was diagnosed a median of 9 (IQR 7-16) days after ICU admission. Factors associated with probable CAPA after multivariable logistic regression were cumulative steroid dose given within 28 days prior to ICU admission (adjusted OR (aOR) 1.16; 95% CI 1.01 to 1.43 per 100 mg prednisolone-equivalent), receipt of an interleukin (IL)-6 inhibitor (aOR 2.79; 95% CI 1.22 to 6.48) and chronic obstructive pulmonary disease (COPD) (aOR 4.78; 95% CI 1.13 to 18.13). Mortality in patients with probable CAPA was 55%, vs 46% in those without. After adjustment for immortal time bias, CAPA was associated with an increased risk of 90-day mortality (HR 1.85; 95% CI 1.07 to 3.19); however, this association did not remain statistically significant after further adjustment for confounders (adjusted HR 1.57; 95% CI 0.88 to 2.80). There was no difference in mortality between patients with CAPA prescribed antifungals (9 of 17; 53%) and those who were not (7 of 12; 58%) (p=0.77).
In this first prospective UK study, probable CAPA was associated with corticosteroid use, receipt of IL-6 inhibitors and pre-existing COPD. CAPA did not impact mortality following adjustment for prognostic variables.
侵袭性肺曲霉病是严重 COVID-19 的一种并发症，其发病率和死亡率在不同地区存在差异。我们描述了在一项前瞻性、多中心英国队列中与 COVID-19 相关的肺曲霉病 (CAPA) 的发病率、风险因素和死亡率。
2020 年 3 月至 2021 年 3 月，5 家英国医院重症监护病房 (ICU) 纳入了 266 名接受机械通气的 COVID-19 成年患者。使用欧洲医学真菌学联合会和国际人类和动物真菌学学会标准以及呼吸道和血清样本的真菌诊断来定义 CAPA。
266 名患者中有 29 名（10.9%）患有可能的 CAPA，14 名（5.2%）患有可能的 CAPA，没有确诊的 CAPA。在 ICU 入院后中位数 9（IQR 7-16）天诊断出可能的 CAPA。多变量逻辑回归后，与可能的 CAPA 相关的因素包括在 ICU 入院前 28 天内给予的累积类固醇剂量（校正优势比 (aOR) 1.16；每 100mg 泼尼松龙等效物增加 1.01 至 1.43）、使用白细胞介素 (IL)-6 抑制剂（aOR 2.79；95%CI 1.22 至 6.48）和慢性阻塞性肺疾病 (COPD)（aOR 4.78；95%CI 1.13 至 18.13）。可能的 CAPA 患者的死亡率为 55%，而无 CAPA 的患者为 46%。在对不朽时间偏倚进行调整后，CAPA 与 90 天死亡率增加相关（HR 1.85；95%CI 1.07 至 3.19）；然而，在进一步调整混杂因素后，这种关联不再具有统计学意义（调整后的 HR 1.57；95%CI 0.88 至 2.80）。接受抗真菌药物治疗的 CAPA 患者（17 例中的 9 例；53%）与未接受治疗的患者（12 例中的 7 例；58%）之间的死亡率无差异（p=0.77）。
在这项英国首例前瞻性研究中，可能的 CAPA 与皮质类固醇的使用、IL-6 抑制剂的使用和既往 COPD 相关。在调整预后变量后，CAPA 并未影响死亡率。
