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

doi:10.3877/cma.j.issn.1674-6880.2024.01.001

Abstract

Abstract:

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

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.

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References 25

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组别	例数	年龄（岁， ± s）	性别（例，男/女）	基础疾病（例）
组别	例数	年龄（岁， ± s）	性别（例，男/女）	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

组别	例数	年龄（岁， ± s）	性别（例，男/女）	基础疾病（例）
组别	例数	年龄（岁， ± s）	性别（例，男/女）	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

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）
组别	例数	发热	咳嗽咳痰	呼吸衰竭	发病至入院时间（d）	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
组别	例数	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

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）
组别	例数	发热	咳嗽咳痰	呼吸衰竭	发病至入院时间（d）	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
组别	例数	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

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

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