危重症患者中新型冠状病毒肺炎相关侵袭性肺曲霉病的临床特征与预后:一项单中心研究

Clinical characteristics and prognosis of COVID-19- associated invasive pulmonary aspergillosis in critically patients: a single-center study.

作者信息

Xiao Shuang, Xu Jie, Xiao Han, Li Yonggang, Chen Xu, Chen Li, Zhao Weifeng

机构信息

Department of Infectious Diseases, The First Affiliated Hospital of Soochow University, Suzhou, China.

Center of Clinical Laboratory, The First Affiliated Hospital of Soochow University, Suzhou, China.

出版信息

Front Cell Infect Microbiol. 2025 Apr 22;15:1522217. doi: 10.3389/fcimb.2025.1522217. eCollection 2025.

Abstract

OBJECTIVE

A single-center retrospective study was conducted according to the latest diagnostic criteria of the European Consortium for Mycology in Medicine/International Society for Human and Animal Mycoses (ECMM/ISHAM) Consensus, which describes the clinical characteristics, factors influencing and prognosis of a group of patients with COVID-19 (Omicron variant) combined with invasive pulmonary mycoses with onset of disease at the end of 2022.

METHODS

This study retrospectively analyzed data related to 58 hospitalized patients with severe pneumonia due to COVID-19 infection admitted to the ICU of critical care medicine, respiratory ICU, and ICU of the Department of Infections at the First Affiliated Hospital of Soochow University from December 1, 2022, to January 31, 2023. CAPA was defined according to the ECMM/ISHAM consensus criteria. Our study compared the clinical and microbiological characteristics and associated risk factors of fungal infections and pulmonary fungal infections and performed univariate and multivariate analyses of factors associated with mortality in patients with COVID-19-Associated Pulmonary Aspergillosis (CAPA).

RESULTS

17 (29.3%) of the 58 critically ill patients were diagnosed with CAPA, of which 10 (58.82%) patients were Probable CAPA and 7 (41.18%) patients were Possible CAPA. Among this strains, strains were found in 13 cases (76.47%) and strains in 4 cases (23.53%). 7 (41.18%) patients had concomitant bacterial fungal infections with a mortality rate of 57.14% (4/7), of which was the most common pathogen. Among the patients with CAPA, galactomannan assay of bronchoalveolar lavage fluid (BALF) was performed in 5 patients with a 100% (5/5) positivity rate, and two or more serum galactomannan (GM) assays were performed in 17 patients, with a probability of favorable results in both cases of 41.2% (7/17). The 60-day mortality rate in patients with CAPA was 52.9% (9/17), whereas the non-CAPA patients had a 60-day mortality rate of 24.4% (10/41), which was statistically different (P = 0.035). Diabetes mellitus (P = 0.018, OR: 5.040 (95% CI: 1.314-19.337)), renal insufficiency (P=0.002, OR: 11.259 (95% CI: 2.480-51.111)), chronic obstructive pulmonary disease (COPD) (P = 0.003, OR: 6.939 (95% CI: 1.963-24.531)), elevated interleukin-6 (IL-6) (P = 0.022, OR: 4.160 (95% CI: 1.22614.113)), mechanical ventilation (P = 0.002, OR: 8.100 (95%CI: 2.13230.777)), increased duration of steroids use (P = 0.022, OR: 1.071 (95%CI: 1.0101.135)), increased cumulative dose of steroids use ((P < 0.001, OR: 1.012 (95%CI: 1.0091.015)), use of tocilizumab (P = 0.020, OR: 11.480 (95%CI: 2.48051.111)), and increased length of hospitalization in ICU (P = 0.021, OR: 1.038 (95% CI: 1.006 to 1.071)), and increase in the type of antibiotics used (P = 0.002, OR: 1.603 (95% CI: 1.181 to 2.176)) were the risk factors for the occurrence of fungal infections, whereas the use of steroids or not, the use of baricitinib or not, and hypertension did not have a significant effect on the occurrence of fungal infections (P > 0.05). Patients with CAPA had a higher mortality rate, and their hospitalization was prolonged compared to non-CAPA patients. The all-cause mortality rate for patients with CAPA was 52.9%. We also performed univariate and multivariate analyses of potential factors associated with mortality, including the use of mechanical ventilation (P = 0.040 OR: 10.500, (95% CI: 1.115 to 98.914)), advanced age (P = 0.043 OR: 1.212, (95% CI: 1.006 to 1.460)), and a significantly higher CRP level (P = 0.042 OR: 1.043, (95% CI: 1.0021.078)) had a worse prognosis. Steroids use, gender, and diabetes mellitus were not associated with patient death (P > 0.05).

摘要

目的

根据欧洲医学真菌学联盟/国际人类和动物真菌病学会(ECMM/ISHAM)共识的最新诊断标准进行了一项单中心回顾性研究,该研究描述了一组在2022年末发病的新型冠状病毒肺炎(奥密克戎变异株)合并侵袭性肺真菌病患者的临床特征、影响因素及预后。

方法

本研究回顾性分析了2022年12月1日至2023年1月31日苏州大学附属第一医院重症医学科、呼吸重症监护病房及感染科重症监护病房收治的58例因新型冠状病毒感染导致的重症肺炎住院患者的数据。根据ECMM/ISHAM共识标准定义确诊为新冠病毒相关肺曲霉病(CAPA)。本研究比较了真菌感染和肺部真菌感染的临床及微生物学特征及相关危险因素,并对CAPA患者的死亡相关因素进行单因素和多因素分析。

结果

58例重症患者中17例(29.3%)诊断为CAPA,其中10例(58.82%)为疑似CAPA,7例(41.18%)为可能CAPA。在这17例患者中,13例(76.47%)检出[具体真菌名称未给出]菌株,4例(23.53%)检出[具体真菌名称未给出]菌株。7例(41.18%)患者合并细菌真菌感染,死亡率为57.14%(4/7),其中[具体细菌名称未给出]是最常见的病原体。在CAPA患者中,5例患者进行了支气管肺泡灌洗(BALF)液半乳甘露聚糖检测,阳性率为100%(5/5),17例患者进行了两次或更多次血清半乳甘露聚糖(GM)检测,两次检测结果均为阳性的概率为41.2%(7/17)。CAPA患者60天死亡率为52.9%(9/17),而非CAPA患者60天死亡率为24.4%(10/41),差异有统计学意义(P = 0.035)。糖尿病(P = 0.018,OR:5.040(95%CI:1.314 - 19.337))、肾功能不全(P = 0.002,OR:11.259(95%CI:2.480 - 51.111))、慢性阻塞性肺疾病(COPD)(P = 0.003,OR:6.939(95%CI:1.963 - 24.531))、白细胞介素-6(IL-6)升高(P = 0.022,OR:4.160(95%CI:1.22614.113))、机械通气(P = 0.002,OR:8.100(95%CI:2.13230.777))、类固醇使用时间延长(P = 0.022,OR:1.071(95%CI:1.0101.135))、类固醇累积剂量增加((P < 0.001,OR:1.012(95%CI:1.0091.015))、使用托珠单抗(P = 0.020,OR:11.480(95%CI:2.48051.111))、ICU住院时间延长(P = 0.021,OR:1.038(95%CI:1.006至1.071))以及使用抗生素种类增加(P = 0.002,OR:1.603(95%CI:1.181至2.176))是真菌感染发生的危险因素,而是否使用类固醇、是否使用巴瑞替尼以及高血压对真菌感染的发生无显著影响(P > 0.05)。与非CAPA患者相比,CAPA患者死亡率更高,住院时间更长。CAPA患者的全因死亡率为52.9%。我们还对与死亡相关的潜在因素进行了单因素和多因素分析,包括使用机械通气(P = 0.040,OR:10.500,(95%CI:1.115至98.914))、高龄(P = 0.043,OR:1.212,(95%CI:1.006至1.460))以及C反应蛋白(CRP)水平显著升高(P = 0.042,OR:1.043,(95%CI:1.0021.078))预后较差。类固醇使用、性别和糖尿病与患者死亡无关(P > 0.05)。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4141/12052734/66f74147e6dc/fcimb-15-1522217-g001.jpg

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