切换至 "中华医学电子期刊资源库"
高级检索
中华危重症医学杂志(电子版)

中华危重症医学杂志(电子版) ›› 2024, Vol. 17 ›› Issue (01) : 3 -9. doi: 10.3877/cma.j.issn.1674-6880.2024.01.001

论著

危重型新型冠状病毒感染合并侵袭性肺曲霉病的临床特征和高危因素分析
钱雅君1, 虞竹溪1, 徐颖1, 董丹江1, 顾勤1,†()   
  1. 1. 210009　南京，南京大学医学院附属南京鼓楼医院重症医学科
  • 收稿日期:2023-04-26 出版日期:2024-02-29
  • 通信作者: 顾勤
  • 基金资助:
    江苏省科技计划项目(BE2018700)

Clinical characteristics and risk factors of invasive pulmonary aspergillois in critically ill corona virus disease 2019 patients

Yajun Qian1, Zhuxi Yu1, Ying Xu1, Danjiang Dong1, Qin Gu1,†()   

  1. 1. Department of Intensive Care Unit, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210009, China
  • Received:2023-04-26 Published:2024-02-29
  • Corresponding author: Qin Gu
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

钱雅君, 虞竹溪, 徐颖, 董丹江, 顾勤. 危重型新型冠状病毒感染合并侵袭性肺曲霉病的临床特征和高危因素分析[J]. 中华危重症医学杂志(电子版), 2024, 17(01): 3-9.

Yajun Qian, Zhuxi Yu, Ying Xu, Danjiang Dong, Qin Gu. Clinical characteristics and risk factors of invasive pulmonary aspergillois in critically ill corona virus disease 2019 patients[J]. Chinese Journal of Critical Care Medicine(Electronic Edition), 2024, 17(01): 3-9.

目的

确定ICU中新型冠状病毒感染（COVID-19）相关性肺曲霉菌病（CAPA）的患病率与预后，并分析CAPA的高危因素，为早期诊断、及时治疗提供依据。

方法

选择南京鼓楼医院重症医学科2022年12月至2023年1月诊断为危重型COVID-19的74例患者，根据诊断标准分为CAPA组（22例）和非CAPA组（52例），比较两组患者的基本信息、起病症状、实验室检查、影像特征，分析其疾病严重程度及预后指标。采用多因素logistic回归模型分析CAPA的危险因素。

结果

22例CAPA中确诊病例1例，临床拟诊21例；诊断CAPA的时间为入院后（8 ± 5）d。CAPA组和非CAPA组患者淋巴细胞[（0.33 ± 0.25）× 109/L vs.（0.58 ± 0.55）× 109/L，t = 4.233，P = 0.019]、C反应蛋白[（95 ± 80）mg/L vs.（63 ± 45）mg/L，t = 8.940，P = 0.012]、白细胞介素6（IL-6）[225（14，15 432）ng/L vs. 52（5，2 245）ng/L，Z = 4.949，P = 0.024]、人类白细胞DR抗原（HLA-DR）[（31 ± 24）% vs.（42 ± 27）%，t = 4.553，P = 0.042]、激素治疗时间≥ 7 d（13/22 vs. 16/52，χ2 = 5.200，P = 0.023）、应用托珠单抗治疗（4/22 vs. 1/52，χ2 = 4.157，P = 0.041）及预后不良情况（16/22 vs. 24/52，χ2 = 4.401，P = 0.036）比较，差异均有统计学意义。多因素logistic回归分析结果显示，入院时淋巴细胞< 0.35 × 109/L[比值比（OR）= 1.970，95%置信区间（CI）（1.044，3.675），P = 0.038]、C反应蛋白> 63.5 mg/L[OR = 3.441，95%CI（1.609，7.324），P = 0.006]及激素治疗时间≥ 7 d[OR = 4.276，95%CI（2.043，8.433），P = 0.012]为CAPA发生的危险因素。

结论

1/4以上的危重型COVID-19患者合并CAPA，并导致不良的临床预后。淋巴细胞减少、严重炎症反应及长时间应用糖皮质激素均可导致CAPA的发生，临床需针对高危人群及早筛查及治疗，改善预后。

关键词: 危重型新型冠状病毒感染, 新型冠状病毒感染相关性肺曲霉菌病, 临床特征, 细胞因子风暴, 高危因素
Objective

To determine the prevalence and prognosis of corona virus disease 2019 (COVID-19) associated pulmonary aspergillosis (CAPA) in the ICU, and to analyze the risk factors of CAPA, to provide a basis for early diagnosis and timely treatment.

Methods

A total of 74 patients with severe COVID-19 admitted to the ICU of Nanjing Drum Tower Hospital from December 2022 to January 2023 were selected. According to the diagnostic criteria, patients were divided into a CAPA group (n = 22) and a non-CAPA group (n = 52). Then the basic information, onset symptoms, laboratory examinations and imaging characteristics of patients in the two groups were compared, and the disease severity and prognostic indicators were analyzed. A multivariate logistic regression model was used to analyze the risk factors of CAPA.

Results

Among the 22 CAPA patients, one was confirmed and 21 were clinically suspected. The diagnostic time of CAPA was mostly (8 ± 5) d after admission. The lymphocyte count [(0.33 ± 0.25) × 109/L vs. (0.58 ± 0.55) × 109/L, t = 4.233, P = 0.019], C-reactive protein [(95 ± 80) mg/L vs. (63 ± 45) mg/L, t = 8.940, P = 0.012], interleukin-6 (IL-6) [225 (14, 15 432) ng/L vs. 52 (5, 2 245) ng/L, Z = 4.949, P = 0.024], human leukocyte DR antigen (HLA-DR) [(31 ± 24)% vs. (42 ± 27)%, t = 4.553, P = 0.042], duration of hormone therapy ≥ 7 d (13/22 vs. 16/52, χ2 = 5.200, P = 0.023), tocilizumab treatment (4/22 vs. 1/52, χ2 = 4.157, P = 0.041) and poor prognosis (16/22 vs. 24/52, χ2 = 4.401, P = 0.036) in the CAPA and non-CAPA groups showed statistically significant differences. Multivariate logistic regression analysis showed that the lymphocytes at admission < 0.35 × 109/L [odds ratio (OR) = 1.970, 95% confidence interval (CI) (1.044, 3.675), P = 0.038], C-reactive protein > 63.5 mg/L [OR = 3.441, 95%CI (1.609, 7.324), P = 0.006] and duration of hormone therapy ≥ 7 d [OR = 4.276, 95%CI (2.043, 8.433), P = 0.012] were risk factors for the occurrence of CAPA.

Conclusions

More than a quarter of critically ill COVID-19 patients are associated with CAPA, which leads to poor clinical outcomes. The low lymphocyte count, severe inflammatory response and long-term use of glucocorticoid may induce the occurrence of CAPA. Early screening and treatment for high-risk groups are needed to improve the prognosis.

Key words: Critically ill corona virus disease 2019, Corona virus disease 2019 associated pulmonary aspergillosis, Clinical characteristics, Cytokine storm, Risk factors
表1 两组COVID-19患者一般资料比较
组别 例数 年龄（岁， ± s） 性别（例，男/女） 基础疾病（例）
高血压 糖尿病 COPD 自身免疫性疾病 移植术后
CAPA组 22 77 ± 9 20/2 15 14 8 6 3
非CAPA组 52 71 ± 18 46/6 27 21 7 8 2
t/χ2值   1.792 0.012 1.673 3.348 3.703 0.751 1.053
P值   0.187 0.921 0.197 0.067 0.054 0.385 0.304
表2 两组COVID-19患者临床特征比较（ ± s）
组别 例数 起病症状（例） 发病至入院时间（d） 影像学表现（例） 初始治疗（例）
发热 咳嗽咳痰 呼吸衰竭 磨玻璃 结节及空洞 抗病毒 广谱抗细菌药 糖皮质激素 激素治疗时间≥ 7 d 应用托珠单抗
CAPA组 22 15 14 11 8 ± 4 21 5 12 21 18 13 4
非CAPA组 52 35 27 19 8 ± 5 46 3 24 47 38 16 1
t/χ2/Z值   0.008 0.859 1.162 0.027 0.256 3.023 0.443 0.067 0.639 5.200 4.157
P值   0.941 0.354 0.281 0.855 0.614 0.082 0.509 0.791 0.423 0.023 0.041
组别 例数 实验室检查
白细胞（× 109/L） 中性粒细胞（× 109/L） 淋巴细胞（× 109/L） 降钙素原[μg/L，M（P25，P75）] 血小板计数（× 109/L） C反应蛋白（mg/L） IL-6[ng/L，M（P25，P75）] D-二聚体[mg/L，M（P25，P75）] CD4+/CD8+ HLA-DR（%）
CAPA组 22 11.2 ± 5.8 10 ± 5 0.33 ± 0.25 19.5（4.1，75.6） 161 ± 84 95 ± 80 225（14，15 432） 9.0（4.8，41.2） 2.9 ± 2.0 31 ± 24
非CAPA组 52 11.1 ± 5.9 10 ± 6 0.58 ± 0.55 3.4（1.2，33.5） 155 ± 98 63 ± 45 52（5，2 245） 7.5（0.2，33.1） 2.0 ± 1.7 42 ± 27
t/χ2/Z值   0.963 1.615 4.233 3.221 0.263 8.940 4.949 0.114 1.919 4.553
P值   0.334 0.208 0.019 0.064 0.611 0.012 0.024 0.755 0.168 0.042
表3 两组COVID-19患者疾病严重程度及预后比较（ ± s）
组别 例数 APACHEⅡ评分（分） SOFA评分（分） 氧合指数（mmHg） 机械通气（例） 机械通气时间[d，M（P25，P75）] 合并器官功能障碍≥ 2个（例） 合并耐药细菌感染（例） ICU治疗时间（d） 预后不良（例）
CAPA组 22 23 ± 7 10 ± 5 133 ± 86 20 13（7，28） 17 15 20 ± 17 16
非CAPA组 52 22 ± 7 8±4 148 ± 66 39 7（4，11） 29 29 19 ± 14 24
t/χ2/Z值   0.038 0.103 2.267 1.543 2.321 3.035 0.992 0.324 4.401
P值   0.839 0.748 0.144 0.215 0.136 0.081 0.320 0.572 0.036
表4 继发CAPA的多因素logistic回归分析
变量 回归系数 标准误 Wald值 OR值 95%CI P值
淋巴细胞<0.35 × 109/L 0.678 0.112 4.541 1.970 1.044 ~ 3.675 0.038
C反应蛋白>63.5 mg/L 1.233 0.214 9.788 3.441 1.609 ~ 7.324 0.006
IL-6>77.2 ng/L 0.029 0.034 0.866 1.030 0.844 ~ 2.301 0.355
HLA-DR<38.6% 0.760 0.571 1.774 2.123 0.678 ~ 5.331 0.186
激素治疗时间≥ 7 d 1.768 0.328 6.533 4.276 2.043 ~ 8.433 0.012
托珠单抗应用 0.622 0.541 1.421 1.874 0.648 ~ 4.214 0.246
1
Bartoletti M, Pascale R, Cricca M, et al. Epidemiology of invasive pulmonary aspergillosis among intubated patients with COVID-19: a prospective study[J]. Clin Infect Dis, 2021, 73 (11): e3606-e3614.
2
Koehler P, Bassetti M, Chakrabarti A, et al. Defining and managing COVID-19-associated pulmonary aspergillosis: the 2020 ECMM/ISHAM consensus criteria for research and clinical guidance[J]. Lancet Infect Dis, 2021, 21 (6): e149-e162.
3
Verweij PE, Brüggemann RJM, Azoulay E, et al. Taskforce report on the diagnosis and clinical management of COVID-19 associated pulmonary aspergillosis[J]. Intensive Care Med, 2021, 47 (8): 819-834.
4
Alanio A, Dellière S, Fodil S, et al. Prevalence of putative invasive pulmonary aspergillosis in critically ill patients with COVID-19[J]. Lancet Respir Med, 2020, 8 (6): e48-e49.
5
中华人民共和国国家卫生健康委员会.新型冠状病毒感染诊疗方案（试行第十版）[J].国际流行病学传染病学杂志，2023，50（1）：1-7.
6
祁慧，顾勤，许莹，等.血清半乳甘露聚糖抗原对不同影像类型侵袭性肺曲霉病患者的诊断价值[J/CD].中华危重症医学杂志（电子版），2019，12（6）：402-405.
7
段伊珊，陈雨莎，梁斌苗，等.重症H1N1流感合并侵袭性肺曲霉病的队列研究[J].中国呼吸与危重监护杂志，2021，20（5）：310-314.
8
Xu Y, Shao M, Liu N, et al. Invasive pulmonary aspergillosis is a frequent complication in patients with severe fever with thrombocytopenia syndrome: a retrospective study[J]. Int J Infect Dis, 2021, 105 (7): 646-652.
9
Schauwvlieghe AFAD, Rijnders BJA, Philips N, et al. Invasive aspergillosis in patients admitted to the intensive care unit with severe influenza: a retrospective cohort study[J]. Lancet Respir Med, 2018, 6 (10): 782-792.
10
Prattes J, Wauters J, Giacobbe DR, et al. Risk factors and outcome of pulmonary aspergillosis in critically ill coronavirus disease 2019 patients-a multinational observational study by the European Confederation of Medical Mycology[J]. Clin Microbiol Infect, 2022, 28 (4): 580-587.
11
Duan Y, Ou X, Chen Y, et al. Severe influenza with invasive pulmonary aspergillosis in immunocompetent hosts: a retrospective cohort study[J]. Front Med (Lausanne), 2021 (7): 602732.
12
Bian XW, COVID-19 Pathology Team. Autopsy of COVID-19 patients in China[J]. Natl Sci Rev, 2020, 7 (9): 1414-1418.
13
Stein SR, Ramelli SC, Grazioli A, et al. SARS-CoV-2 infection and persistence in the human body and brain at autopsy[J]. Nature, 2022, 612 (7941): 758-763.
14
Hartemink KJ, Paul MA, Spijkstra JJ, et al. Immunoparalysis as a cause for invasive aspergillosis?[J]. Intensive Care Med, 2003, 29 (11): 2068-2071.
15
戴敏惠，潘频华.重症监护室侵袭性支气管肺曲霉病高危因素研究进展[J/CD].中华危重症医学杂志（电子版），2016，9（5）：352-355.
16
Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China[J]. Lancet, 2020, 395 (10223): 497-506.
17
Merad M, Blish CA, Sallusto F, et al. The immunology and immunopathology of COVID-19[J]. Science, 2022, 375 (6585): 1122-1127.
18
Que Y, Hu C, Wan K, et al. Cytokine release syndrome in COVID-19: a major mechanism of morbidity and mortality[J]. Int Rev Immunol, 2022, 41 (2): 217-230.
19
Shekhawat J, Gauba K, Gupta S, et al. Interleukin-6 perpetrator of the COVID-19 cytokine storm[J]. Indian J Clin Biochem, 2021, 36 (4): 440-450.
20
Bülow Anderberg S, Luther T, Berglund M, et al. Increased levels of plasma cytokines and correlations to organ failure and 30-day mortality in critically ill Covid-19 patients[J]. Cytokine, 2021, 138 (1): 155389.
21
Gupta S, Leaf DE. Tocilizumab in COVID-19: some clarity amid controversy[J]. Lancet, 2021, 397 (10285): 1599-1601.
22
Akoumianaki T, Vaporidi K, Diamantaki E, et al. Uncoupling of IL-6 signaling and LC3-associated phagocytosis drives immunoparalysis during sepsis[J]. Cell Host Microbe, 2021, 29 (8): 1277-1293.e6.
23
Moreno G, Rodríguez A, Reyes LF, et al. Corticosteroid treatment in critically ill patients with severe influenza pneumonia: a propensity score matching study[J]. Intensive Care Med, 2018, 44 (9): 1470-1482.
24
RECOVERY Collaborative Group, Horby P, Lim WS, et al. Dexamethasone in hospitalized patients with Covid-19[J]. N Engl J Med, 2021, 384 (8): 693-704.
25
Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock[J]. N Engl J Med, 2018, 378 (9): 797-808.
[1] 王月丽, 宋砾, 牛宝荣, 陈炎, 张楠, 何怡华. 心脏血管肉瘤的临床及超声心动图特征[J]. 中华医学超声杂志（电子版）, 2023, 20(04): 398-403.
[2] 缪黄泰, 李潇颖, 张明, 聂绍平. 急性心肌梗死后心脏破裂患者院内死亡的危险因素分析[J]. 中华危重症医学杂志(电子版), 2023, 16(03): 187-192.
[3] 董晓燕, 赵琪, 唐军, 张莉, 杨晓燕, 李姣. 奥密克戎变异株感染所致新型冠状病毒感染疾病新生儿的临床特征分析[J]. 中华妇幼临床医学杂志(电子版), 2023, 19(05): 595-603.
[4] 陈滔, 罗洪, 周进军. 老年食管癌单纯放疗及同期放化疗患者急性不良反应影响因素分析[J]. 中华普外科手术学杂志(电子版), 2023, 17(04): 405-407.
[5] 王晓丹, 王媛, 崔向宇, 任晓磊. 上尿路结石内镜手术后尿源性脓毒血症病原菌耐药及死亡高危因素分析[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(06): 611-615.
[6] 刘麒, 曾弘, 徐子昕, 方超, 黄铭, 郑俊炯, 吴少旭, 钟广正, 林天歆, 黄健, 董文. 乳头状肾细胞癌单中心11年临床诊治与预后分析[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 351-355.
[7] 李小娟, 李炜佳, 彭凌燕, 周鹏莹, 李桂娥, 刘相辰. 体检人群中前列腺钙化灶的检出率及临床特征分析[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(04): 336-338.
[8] 周恩竹, 刘敏, 万秋, 刘静文, 唐莉歆. 慢性阻塞性肺疾病与获得性免疫缺陷综合征共病的临床特征分析[J]. 中华肺部疾病杂志(电子版), 2024, 17(01): 78-82.
[9] 王婷, 余江. 1 820例罕见病的临床特征分析[J]. 中华肺部疾病杂志(电子版), 2024, 17(01): 68-72.
[10] 拉周措毛, 山春玲, 李国蓉, 华毛. 青海西宁地区IPF-LC的病理类型及临床特征分析[J]. 中华肺部疾病杂志(电子版), 2024, 17(01): 25-29.
[11] 陈勇, 任建伟, 朱光发, 刘玉磊, 吴绍芹. 非移植患者侵袭性肺曲霉病32例临床特征分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(06): 809-813.
[12] 孟原竹, 蒋国路, 陈小兵, 蒋莉. 肺结核合并侵袭性肺曲霉感染临床特征及危险因素分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(04): 541-543.
[13] 李华娟, 唐英俊, 王赛妮, 徐旺, 林玲, 李羲, 黄华萍. 肺结节临床与CT影像学特征分析及良恶性预测模型构建[J]. 中华肺部疾病杂志(电子版), 2023, 16(03): 318-323.
[14] 田井梅, 何俊, 何永琴, 张玉梅, 郑文红, 袁玉霞. 老年慢性阻塞性肺疾病合并髋部骨折围术期31例临床特征分析[J]. 中华肺部疾病杂志(电子版), 2023, 16(03): 418-420.
[15] 苏琪皓, 解利红, 孟宪梅, 王觅柱, 王晶, 张静洁, 汤泊夫, 江振宇. 消化道毛细血管扩张特征及内镜治疗效果观察[J]. 中华胃肠内镜电子杂志, 2023, 10(03): 180-184.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号