糖皮质激素治疗一例2019冠状病毒病(COVID-19)危重型患者炎症反应动态观察

doi:10.3785/j.issn.1008-9292.2020.03.10

浙江大学学报（医学版）

2020, Vol. 49

Issue (2): 220-226 DOI: 10.3785/j.issn.1008-9292.2020.03.10

原著

糖皮质激素治疗一例2019冠状病毒病(COVID-19)危重型患者炎症反应动态观察

张胜¹(

),李丹萍²,陈华忠³,郑丹¹,周益萍¹,陈葆国⁴,石卫武⁴,林荣海^1,*(

)

1. 浙江大学台州医院重症医学科, 浙江台州 317000
2. 浙江大学台州医院科教部, 浙江台州 317000
3. 浙江大学台州医院感染科, 浙江台州 317000
4. 浙江大学台州医院中心实验室, 浙江台州 317000

Dynamic inflammatory response in a critically ill COVID-19 patient treated with corticosteroids

ZHAGN Sheng¹(

),LI Danping²,CHEN Huazhong³,ZHENG Dan¹,ZHOU Yiping¹,CHEN Baoguo⁴,SHI Weiwu⁴,LIN Ronghai^1,*(

)

1. Department of Critical Care Medicine, Taizhou Hospital of Zhejiang University, Taizhou 317000, Zhejiang Province, China
2. Department of Science and Education, Taizhou Hospital of Zhejiang University, Taizhou 317000, Zhejiang Province, China
3. Department of Infectious Diseases, Taizhou Hospital of Zhejiang University, Taizhou 317000, Zhejiang Province, China
4. Central Laboratory, Taizhou Hospital of Zhejiang University, Taizhou 317000, Zhejiang Province, China

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摘要：

目的: 探讨糖皮质激素治疗对2019冠状病毒病（COVID-19）危重型患者炎症反应和临床预后的影响。方法: 回顾性分析浙江省首例COVID-19危重型患者的流行病学史、诊疗经过和患者预后。患者于入院第2天开始采用甲泼尼龙80 mg治疗，其后适时调整剂量，累计使用13 d。动态监测激素治疗前后患者淋巴细胞亚群（CD4⁺T、CD8⁺T、NK细胞、B细胞）和淋巴细胞因子（IL-2、IL-4、IL-6、IL-10、TNF-α、γ干扰素）变化情况。结果: 入院第1天，患者外周血CD3⁺T、CD4⁺T、CD8⁺T、NK细胞数较正常值范围明显降低；随着病情改善，CD3⁺T、CD8⁺T和CD4⁺T细胞数量逐渐恢复，呈线性增长趋势（线性拟合方程：Y=18.59X+109.4，P < 0.05）。入院第2天，患者IL-6、IL-10显著高于正常值，γ干扰素处于正常高值，随后迅速降低；IL-2、IL-4、TNF-α均在正常值范围。入院第6、7天，患者IL-6、IL-10首次降至正常值范围。入院第18天，患者痰液病毒核酸检测首次阴性，粪便病毒核酸检测仍为阳性；入院第20天，患者痰液和粪便病毒核酸检测均为阴性。入院第34天，患者痊愈出院，出院时肌力评分44分，日常生活能力评分90分。结论: 缺少有效抗病毒药物的情况下，COVID-19危重型患者早期使用合适剂量的糖皮质激素能够迅速减轻炎症反应程度、改善临床症状，但这在一定程度上会减少T细胞数量，须及时调整剂量。

关键词： 2019冠状病毒病; 严重急性呼吸综合征冠状病毒2; 新型冠状病毒肺炎; 糖皮质激素类; 危重病; 炎症因子

Abstract:

Objective: To investigate the effect of corticosteroids therapy on the inflammatory response in a critically ill coronavirus disease 2019 (COVID-19) patient. Methods: A 55-year old female patient with critical ill COVID-19 was admitted in Taizhou Hospital on January 19, 2020. The patient was treated with methylprednisolone 80 mg on the 2nd day after admission. Thereafter, the dose was adjusted in a timely manner and the therapy lasted for 13 days. The peripheral lymphocyte subsets (CD3⁺T, CD4⁺ T, CD8⁺ T, NK cells, B cells), as well as serum levels of lymphocyte factors (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) were dynamically monitored. Results: On D1 of admission, the numbers of peripheral blood CD3⁺ T, CD4⁺ T, CD8⁺ T, and NK cells were significantly lower than the normal range. With the improvement of the disease, the numbers of CD3⁺ T, CD8⁺ T and CD4 ⁺ T cells gradually recovered and showed a linear growth trend (linear fitting equation: Y=18.59X+109.4, P < 0.05). On D2 of admission, the patient's IL-6 and IL-10 levels were significantly higher than normal values, IFN-γ was at a normal high value, and then rapidly decreased; IL-2, IL-4, and TNF-α were all in the normal range. On the D6 and D7, the IL-6 and IL-10 decreased to the normal range for the first time. On the D18, the sputum virus nucleic acid test was negative for the first time, and the fecal virus nucleic acid test was still positive; on the D20 the sputum and fecal virus nucleic acid test were both negative. On D34, the patient recovered and was discharged. At the discharge the muscle strength score of the patient was 44 and the daily life ability evaluation was 90. Conclusion: In the absence of effective antiviral drugs, early use of appropriate doses of corticosteroids in critically ill patient with COVID-19 can quickly alleviate inflammatory response and improve clinical symptoms, however, it may reduce the number of T cells, and to adjust the dose in time is necessary.

Key words: Coronavirus disease 2019 Severe acute respiratory syndrome coronavirus 2 Novel coronavirus pneumonia Glucocorticoids Critical illness Inflammatory factor

收稿日期: 2020-03-09 出版日期: 2020-03-24

R563.8

基金资助: 浙江省医药卫生科技计划(2017KY163)

通讯作者: 林荣海 E-mail: zhangs@enzemed.com;linrh@enzemed.com

作者简介: 张胜(1980—), 男, 硕士, 副主任医师, 主要从事危重病体外生命支持以及氧代谢研究; E-mail:zhangs@enzemed.com; https://orcid.org/0000-0002-0164-7186

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引用本文:

张胜,李丹萍,陈华忠,郑丹,周益萍,陈葆国,石卫武,林荣海. 糖皮质激素治疗一例2019冠状病毒病(COVID-19)危重型患者炎症反应动态观察[J]. 浙江大学学报（医学版）, 2020, 49(2): 220-226.

ZHAGN Sheng,LI Danping,CHEN Huazhong,ZHENG Dan,ZHOU Yiping,CHEN Baoguo,SHI Weiwu,LIN Ronghai. Dynamic inflammatory response in a critically ill COVID-19 patient treated with corticosteroids. J Zhejiang Univ (Med Sci), 2020, 49(2): 220-226.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2020.03.10 或 http://www.zjujournals.com/med/CN/Y2020/V49/I2/220

图 1 本例2019冠状病毒病危重型患者胸部CT影像学表现动态变化

表 1 本例2019冠状病毒病危重型患者用药情况(2020年1月19日至2月2日)

检测指标	正常值范围	1月19日(D1)	1月20日(D2)	1月22日(D4)	1月23日(D5)	1月24日(D6)	1月25日(D7)	1月26日(D8)	1月27日(D9)	1月29日(D11)	1月31日(D13)	2月1日(D14)	2月2日(D15)
D：用药天数；1 mmHg=0.133 kPa; “—”无数据.
白细胞计数(×10⁹/L)	3.5~9.5	6.9	8.4	7.1	9.2	5.6	2.4	5.2	6.6	14.9	16.3	17.1	17.2
中性粒细胞比例(%)	40.0~75.0	92.5	92.3	87.2	89.2	85.7	82.3	89.4	87.5	86.9	91.2	87.0	83.8
淋巴细胞比例(%)	20.0~50.0	5.4	6.3	8.5	8.0	11.0	12.6	5.7	5.0	6.0	5.0	3.6	6.2
淋巴细胞绝对值(×10⁹/L)	1.1~3.2	0.4	0.5	0.6	0.7	0.6	0.3	0.3	0.3	0.9	0.8	0.6	1.1
血红蛋白(g/L)	115~156	123	129	111	107	102	99	92	99	102	105	104	110
血小板计数(×10⁹/L)	125~350	125	156	157	177	149	150	189	242	340	363	356	351
肌酐(μmol/L)	45~84	58	62	—	57	63	54	43	47	44	46	50	45
天冬氨酸转氨酶(U/L)	15~40	56	64	—	31	—	50	31	21	29	37	36	20
总胆红素(mmol/L)	3.4~20.5	6.1	5.9	—	6.1	—	9.3	10.6	11.5	11.3	15.7	—	17.9
乳酸脱氢酶E(U/L)	100~198	529	794	—	653	—	452	398	320	202	121	—	—
血糖(mmol/L)	3.89~5.83	10.7	7.4	8.9	12.5	10.0	13.7	12.0	11.7	10.5	9.7	9.4	8.4
肌红蛋白(U/L)	＜106	29.5	—	—	138.5	—	123.0	125.6	102.0	76.0	—	—	—
D-二聚体(mg/L)	0.00~0.50	2.05	2.98	—	2.63	2.61	2.61	2.88	2.15	2.01	1.88	—	2.47
凝血酶原时间(s)	11.0~14.5	13.6	13.0	—	13.6	14.0	12.0	13.9	12.0	13.7	13.0	13.0	13.0
活化部分凝血活酶时间(s)	28.0~42.0	45.3	39.8	—	28.8	32.0	29.2	29.0	28.3	31.2	28.9	26.0	25.8
降钙素原(ng/mL)	＜0.05	0.39	0.39	—	0.19	0.33	0.23	0.11	0.07	0.06	0.09	0.05	0.06
C反应蛋白(mg/L)	＜8.0	188.6	185.0	66.3	23.7	89.2	208.0	76.8	32.8	3.4	11.3	10.9	8.2
酸碱度	7.35~7.45	7.44	7.45	7.43	7.46	7.47	7.43	7.44	7.47	7.44	7.48	7.43	7.49
二氧化碳分压(mmHg)	35~45	33	32	38	43	42	54	47	46	42	42	48	46
氧分压(mmHg)	83~108	80	62	91	57	82	78	123	81	97	111	114	142
血氧饱和度(%)	93~98	97	94	98	93	97	97	99	98	98	99	99	99
碳酸氢根浓度(mmol/L)	22.0~26.0	23.5	26.0	25.6	29.8	29.9	33.9	30.7	32.6	27.5	30.9	30.2	33.7
碱剩余(mmol/L)	-3.0~+3.0	-1.6	-3.2	-3.2	6.2	6.1	10.5	7.1	8.8	3.5	7.1	6.8	10.4
乳酸(mmol/L)	0.5~1.6	1.0	3.2	1.8	2.9	2.5	1.6	2.1	1.8	1.2	1.3	2.2	1.3
吸氧浓度	—	0.60	0.90	0.55	0.60	0.55	0.55	0.60	0.45	0.40	0.40	0.40	0.40
氧合指数(mmHg)	—	133	69	165	95	149	142	205	180	243	278	285	355

表 2 本例2019冠状病毒病危重型患者实验室检查结果(2020年1月19日至2月2日)

图 2 本例2019冠状病毒病危重型患者外周血CD4+ T细胞数量动态变化

表 3 本例2019冠状病毒病危重型患者淋巴细胞亚群和淋巴细胞因子动态检测结果(2020年1月19日至2月2日)

图 3 本例2019冠状病毒病危重型患者外周血IL-6、IL-10、γ干扰素水平动态变化

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