Please wait a minute...
J Zhejiang Univ (Med Sci)  2020, Vol. 49 Issue (2): 220-226    DOI: 10.3785/j.issn.1008-9292.2020.03.10
    
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 Ronghai1,*()
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
Download: HTML( 17 )   PDF(4582KB)
Export: BibTeX | EndNote (RIS)      

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 wordsCoronavirus disease 2019      Severe acute respiratory syndrome coronavirus 2      Novel coronavirus pneumonia      Glucocorticoids      Critical illness      Inflammatory factor     
Received: 09 March 2020      Published: 24 March 2020
CLC:  R563.8  
Corresponding Authors: LIN Ronghai     E-mail: zhangs@enzemed.com;linrh@enzemed.com
Cite this article:

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.

URL:

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


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

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 
Fig 1 Chest imaging picture of this critical ill COVID-19 patient
项目 1月19日(D1) 1月20日(D2) 1月21日(D3) 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28日(D10) 1月29日(D11) 1月30日(D12) 1月31日(D13) 2月1日(D14) 2月2日(D15)
  D:用药天数.
体温(℃) 39.6 38.5 37.5 37 37.5 38.3 36.5 36.5 36.8 37.2 37.2 37.1 37.0 37.1 37.3
液体平衡(mL/24 h) 530 1370 180 545 -450 -565 -60 -500 110 70 30 70 10 15
抗菌药物
抗病毒药物
免疫调节剂
血管活性药物
Tab 1 Clinical drug use of this critical ill COVID-19 patient (January 19 to February 2, 2020)
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
Tab 2 Laboratory examination of this critical ill COVID-19 patient (January 19 to February 2, 2020)
Fig 2 Dynamic changes in the number of CD4+ T cells of this critical ill COVID-19 patient
检测指标 正常值范围 1月19日(D1) 1月20日(D2) 1月23日(D5) 1月24日(D6) 1月25日(D7) 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;“—”无数据.
CD3+T(个/μL) 770~2041 192 230 476 324 192 210 585 512 486 869
CD4+T(个/μL) 414~1123 120 140 287 252 105 114 351 280 246 561
CD8+T(个/μL) 238~874 68 70 210 78 90 96 207 208 234 308
CD4/CD8 0.7~2.5 1.76 2.00 1.37 3.23 1.17 1.19 1.70 1.76 1.05 1.82
B细胞(个/μL) 90~560 100 81 81 51 180 112 187 165
NK细胞(个/μL) 150~1100 80 18 24 27 126 40 66 44
IL-2(pg/mL) 1.1~9.8 2.34 1.94 2.34 1.80 1.99 2.05 2.28 2.25 2.25
IL-4(pg/mL) 0.1~3.0 2.36 2.24 2.17 1.99 2.05 1.81 2.24 2.05 2.24
IL-6(pg/mL) 1.7~16.6 251.80 141.26 57.06 10.20 5.15 17.58 9.04 7.49 18.00
IL-10(pg/mL) 2.6~4.9 39.53 12.20 15.84 6.90 4.87 7.84 3.66 4.06 5.04
TNF-α(pg/mL) 0.1~5.2 2.27 1.34 2.54 1.98 1.69 2.12 1.69 1.98 2.02
γ干扰素(pg/mL) 1.6~17.3 13.55 3.77 2.61 2.38 2.66 2.66 3.43 3.77 2.66
Tab 3 Dynamic changes of lymphocyte subsets and lymphokines of this critical ill COVID-19 patient (January 19 to February 2, 2020)
Fig 3 Dynamic changes of IL-6, IL-10, and INF-γ levels of this critical ill COVID-19 patient
[1]   World Health Organization. Coronavirus disease (COVID-2019) situation reports[EB/OL].[2020-02-22]. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/.
[2]   YANG X , YU Y , XU J et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study[J]. Lancet Respir Med, 2020,
doi: 10.1016/S2213-2600(20)30079-5
[3]   中华人民共和国国家卫生健康委员会办公厅, 国家中医药管理局办公室.新型冠状病毒感染的肺炎诊疗方案(试行第六版)[A/OL].国卫办医函〔2020〕145号.(2020-02-18)[2020-02-28].http://www.nhc.gov.cn/yzygj/s7653p/202002/8334a8326dd94d329df351d7da8aefc2.shtml.
General Office of National Health Commission of the People's Republic of China, Office of National Administration of Traditional Chinese Medicine. Diagnosis and treatment of novel coronavirus pneumonia (trial version 6)[A/OL]. No.145〔2020〕 of the General Office of the National Health Commission. (2020-02-18)[2020-02-28]. http://www.nhc.gov.cn/yzygj/s7653p/202002/8334a8326dd94d329df351d7da8aefc2.shtml. (in Chinese)
[4]   RUSSELL C D , MILLAR J E , BAILLIE J K . Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury[J]. Lancet, 2020, 395 (10223): 473- 475
doi: 10.1016/S0140-6736(20)30317-2
[5]   XU Z , SHI L , WANG Y et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome[J]. Lancet Respir Med, 2020,
doi: 10.1016/S2213-2600(20)30076-X
[6]   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
doi: 10.1016/S0140-6736(20)30183-5
[7]   CHANNAPPANAVAR R , PERLMAN S . Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology[J]. Semin Immunopathol, 2017, 39 (5): 529- 539
doi: 10.1007/s00281-017-0629-x
[8]   WONG C K , LAM C W , WU A K et al. Plasma inflammatory cytokines and chemokines in severe acute respiratory syndrome[J]. Clin Exp Immunol, 2004, 136 (1): 95- 103
doi: 10.1111/j.1365-2249.2004.02415.x
[9]   MAHALLAWI W H , KHABOUR O F , ZHANG Q et al. MERS-CoV infection in humans is associated with a pro-inflammatory Th1 and Th17 cytokine profile[J]. Cytokine, 2018, 104 8- 13
doi: 10.1016/j.cyto.2018.01.025
[10]   郝东, 何礼贤, 瞿介明 et al. SARS冠状病毒N蛋白致大鼠肺部炎症及糖皮质激素对其的作用[J]. 中华内科杂志, 2005, 44 (12): 890- 893
HAO Dong , HE Lixian , QU Jieming et al. A study of pulmonary inflammatory reaction induced by N-protein of SARS-CoV in rat models and effects of glucocorticoids on it[J]. Chinese Journal of Internal Medicine, 2005, 44 (12): 890- 893
doi: 10.3760/j.issn:0578-1426.2005.12.004
[11]   BURNHAM E L , JANSSEN W J , RICHES D W et al. The fibroproliferative response in acute respiratory distress syndrome: mechanisms and clinical significance[J]. Eur Respir J, 2014, 43 (1): 276- 285
doi: 10.1183/09031936.00196412
[12]   RUSSELL C D , MILLAR J E , BAILLIE J K . Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury[J]. Lancet, 2020, 395 (10223): 473- 475
doi: 10.1016/S0140-6736(20)30317-2
[1] WANG Jincheng,LIU Jinpeng,WANG Yuanyuan,LIU Wei,CHEN Xiaoqun,SUN Chao,SHEN Xiaoyong,WANG Qidong,WU Yaping,LIANG Wenjie,RUAN Lingxiang. Dynamic changes of chest CT imaging in patients with COVID-19[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 191-197.
[2] ZHANG Xiaoyan, SUN Wei, SHANG Shiqiang, MAO Jianhua, FU Junfen, SHU Qiang, JIANG Kewen. Principles and suggestions on biosafety protection of biological specimen preservation during prevalence of COVID-19[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 170-177.
[3] CAO Shengli,FENG Peihua,SHI Pengpeng. Study on the epidemic development of COVID-19 in Hubei province by a modified SEIR model[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 178-184.
[4] CHEN Jun,LIU Danping,LIU Li,LIU Ping,XU Qingnian,XIA Lu,LING Yun,HUANG Dan,SONG Shuli,ZHANG Dandan,QIAN Zhiping,LI Tao,SHEN Yinzhong,LU Hongzhou. A pilot study of hydroxychloroquine in treatment of patients with moderate COVID-19[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 215-219.
[5] CHEN Zhimin,FU Junfen,SHU Qiang,WANG Wei,CHEN Yinghu,HUA Chunzhen,LI Fubang,LIN Ru,TANG Lanfang,WANG Tianlin,WANG Yingshuo,XU Weize,YANG Zihao,YE Sheng,YUAN Tianming,ZHANG Chenmei,ZHANG Yuanyuan. Diagnosis and treatment recommendation for pediatric COVID-19 (the second edition)[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 139-146.
[6] XU Kaijin,CAI Hongliu,SHEN Yihong,NI Qin,CHEN Yu,HU Shaohua,LI Jianping,WANG Huafen,YU Liang,HUANG He,QIU Yunqing,WEI Guoqing,FANG Qiang,ZHOU Jianying,SHENG Jifang,LIANG Tingbo,LI Lanjuan. Management of COVID-19: the Zhejiang experience[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 147-157.
[7] JIANG Saiping,LI Lu,RU Renping,ZHANG Chunhong,RAO Yuefeng,LIN Bin,WANG Rongrong,CHEN Na,WANG Xiaojuan,CAI Hongliu,SHENG Jifang,ZHOU Jianying,LU Xiaoyang,QIU Yunqing. Pharmaceutical care for severe and critically ill patients with COVID-19[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 158-169.
[8] LI Xin,DAI Tian,WANG Hong,SHI Junnian,YUAN Wei,LI Jing,CHEN Lijun,ZHANG Tianming,ZHANG Shanshan,KONG Yan,YUE Ning,SHI Hui,HE Yuping,HU Huifang,LIU Furong,YANG Caixia. Clinical analysis of suspected COVID-19 patients with anxiety and depression[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 203-208.
[9] LUO Song,YANG Lijuan,WANG Chun,LIU Chuanmiao,LI Dianming. Clinical observation of 6 severe COVID-19 patients treated with plasma exchange or tocilizumab[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 227-231.
[10] HONG Dongsheng,NI Jian,SHAN Wenya,LI Lu,HU Xi,YANG Hongyu,ZHAO Qingwei,ZHANG Xingguo. Establishment of a rapid identification of adverse drug reaction program in R language implementation based on monitoring data[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 253-259.
[11] ZHONG Qi,LI Zhi,SHEN Xiaoyong,XU Kaijin,SHEN Yihong,FANG Qiang,CHEN Feng,LIANG Tingbo. CT imaging features of patients with different clinical types of COVID-19[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 198-202.
[12] KANG Xianhui,ZHANG Rong,HE Huiliang,YAO Yongxing,ZHENG Yueying,WEN Xiaohong,ZHU Shengmei. Anesthesia management in cesarean section for patient with COVID-19: a case report[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 249-252.
[13] CHEN Xu,LI Yang,WANG Jinxi,CAI Hongliu,CAO Hongcui,SHENG Jifang. Pregnant women complicated with COVID-19: a clinical analysis of 3 cases[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 240-244.
[14] SHEN Lihua,HUANG Fei,CHEN Xiang,XIONG Zuan,YANG Xiaoyu,LI Hui,CHENG Feng,GUO Jian,GONG Guofu. Diagnostic efficacy of three test kits for SARS-CoV-2 nucleic acid detection[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 185-190.
[15] LI Youjiang,HU Yingying,ZHANG Xiaodong,YU Yuanyuan,LI Bin,WU Jianguo,WU Yingping,XIA Xiaoping,XU Jian. Follow-up testing of viral nucleic acid in discharged patients with moderate type of COVID-19[J]. J Zhejiang Univ (Med Sci), 2020, 49(2): 270-274.