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中华肺部疾病杂志(电子版)

中华肺部疾病杂志(电子版) ›› 2020, Vol. 13 ›› Issue (05) : 586 -591. doi: 10.3877/cma.j.issn.1674-6902.2020.05.002

论著

糖皮质激素辅助治疗重型新型冠状病毒肺炎的回顾性分析
刘熙1, 朱天怡2, 王美菊1, 李聪聪2, 徐瑜1, 郭亮1, 张文静1, 王斌1, 胡明冬1, 李琦1,†(), 马壮2,†(), 宋青3,†()   
  1. 1. 400037　重庆，陆军（第三）军医大学第二附属医院呼吸与危重症医学中心
    2. 110016　沈阳，中国人民解放军北部战区总医院呼吸与重症医学科
    3. 100853　北京，中国人民解放军总医院第一医学中心急危重症中心
  • 收稿日期:2020-04-17 出版日期:2020-10-25
  • 通信作者: 李琦, 马壮, 宋青
  • 基金资助:
    国家自然科学基金青年科学基金项目(81700072)

A retrospective analysis of adjuvant glucocorticoid therapy for severe COVID-19

Xi Liu1, Tianyi Zhu2, Meiju Wang1, Congcong Li2, Yu Xu1, Liang Guo1, Wenjing Zhang1, Bin Wang1, Mingdong Hu1, Qi Li1,†(), Zhuang Ma2,†(), Qing Song3,†()   

  1. 1. Center of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Army Medical University, Chongqing 400037, China
    2. Department of Respiratory and Critical Care Medicine, Northern Theater General Hospital of PLA, Shenyang 110016, China
    3. Department of Critical Care Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing 100853, China
  • Received:2020-04-17 Published:2020-10-25
  • Corresponding author: Qi Li, Zhuang Ma, Qing Song
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引用本文：

刘熙, 朱天怡, 王美菊, 李聪聪, 徐瑜, 郭亮, 张文静, 王斌, 胡明冬, 李琦, 马壮, 宋青. 糖皮质激素辅助治疗重型新型冠状病毒肺炎的回顾性分析[J]. 中华肺部疾病杂志(电子版), 2020, 13(05): 586-591.

Xi Liu, Tianyi Zhu, Meiju Wang, Congcong Li, Yu Xu, Liang Guo, Wenjing Zhang, Bin Wang, Mingdong Hu, Qi Li, Zhuang Ma, Qing Song. A retrospective analysis of adjuvant glucocorticoid therapy for severe COVID-19[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2020, 13(05): 586-591.

目的

探讨糖皮质激素辅助治疗对重型新型冠状病毒肺炎(COVID-19)患者的影响，为进一步优化COVID-19的治疗策略提供参考。

方法

纳入某医院普通病区2020年2月28日在院且被确诊为重型COVID-19的195例患者，根据有无糖皮质激素用药史分为激素组和非激素组。回顾性分析各组患者一般资料、激素用药情况、病程中不同阶段的体温、当日最佳指氧饱和度、血常规相关信息、C反应蛋白(CRP)、降钙素原(PCT)及相关不良反应发生情况、咽拭子SARS-CoV-2核酸转阴时间和转归。

结果

激素组和非激素组患者均以男性为主，平均年龄相近(63.01±11.93 vs. 62.20±14.26)岁，临床症状、合并基础疾病、病程、抗病毒治疗、体温等情况基本一致(P>0.05)。激素组指氧饱和度低于非激素组[96(92～98)vs. 97(95～98)，P<0.05]。激素组白细胞计数和中性粒细胞绝对值在正常范围但明显高于非激素组(P<0.05)，淋巴细胞绝对值明显低于非激素组[0.90(0.68～1.10)vs. 1.29(0.93～1.62)，P<0.05]，CRP明显高于非激素组[34.56(9.69～62.27)vs. 7.60(2.19～37.28)，P<0.05]。经治疗，激素组(激素干预后)指氧饱和度较非激素组(入院后1周)更优[99(98～99)vs. 98(97～99)，P<0.05]，白细胞计数和中性粒细胞绝对值有所增加且明显高于非激素组(入院1周后)(P<0.05)但仍在正常范围内，淋巴细胞计数明显回升且与非激素组(入院后1周)相近[1.39(1.08～2.18)vs. 1.36(1.05～1.82)，P>0.05]；CRP值回落且与非激素组(入院后1周)相近(P>0.05)。对激素组按激素累积剂量行亚组分析无阳性发现。各组患者咽拭子SARS-CoV-2核酸转阴时间中位数相近[20.00(15.00～26.00)d vs. 19.00(13.00～23.00)d]，组间无差异(P>0.05)。激素组共报告6例、8人次不良反应，男性为主，年龄多在70岁以上，均报告血糖较基线水平明显升高，其中2例还出现血压较基线水平明显升高。非激素组无不良反应报告。各组患者均好转出院，无病情恶化和死亡报告。因数据缺失较多，为避免偏倚，PCT未予纳入分析。

结论

在缺乏高级别循证医学证据支持的抗病毒药物情况下，在强化治疗的基础上给予重症COVID-19患者适当剂量和疗程的激素治疗，可能改善氧合，使患者更多临床获益，且用药风险可控，转归预期好。但本项目存在一定局限性，开展激素辅助治疗COVID-19的随机对照研究是必要的。

关键词: 重型新型冠状病毒肺炎, 严重急性呼吸综合征冠状病毒-2, 糖皮质激素, 回顾性分析
Objective

To analyze the effects of adjuvant glucocorticoid therapy on severe patients with COVID-19 in order to optimize the treatment for severe COVID-19.

Methods

195 patients confirmed as severe COVID-19 in non-ICU wards of one Hospital hospitalizing on Feb 28, 2020, were enrolled and divided into glucocorticoid treatment group(GC group) and non-glucocorticoid treatment group(non-GC group) by medication history. We retrospectively analyzed all patients′data including general information, glucocorticoid therapy information, temperature and best value of SpO2 in one day when recorded, some results of complete blood count, values of C reaction protein(CRP) and procalcitonin(PCT), glucocorticoid associated adverse reaction, pharyngeal swab SARS-CoV-2 nucleic acid negative time and final outcomes.

Results

Patients in both groups were characterized by male, similar average age(63.01±11.93 vs. 62.20±14.26, years) and with no significant difference on clinical characters, comorbidity, clinical course, antiviral therapy and temperature. Value of SPO2 in GC group was lower than which in non-GC group[96(92-98)vs. 97(95-98), (P<0.05)]. Values of WBC and absolute neutrophil count (ANC) in GC group were normal but significantly higher than which in non-GC group. Compared with non-GC group, value of absolute lymphocyte count in GC group was significantly lower [0.90(0.68-1.10)vs. 1.29(0.93-1.62), P<0.05] and value of CRP in the same group was significantly higher [34.56(9.69-62.27)vs. 7.60(2.19-37.28), P<0.05]. After treating, value of SpO2 in GC group was significantly higher than which in non-GC group [99(98-99)vs. 98(97-99), P<0.05)] admitted into hospital one week later. Mean while, values of WBC and ANC in GC group rose respectively, compared to the baseline level, and were significantly higher than which in non-GC group but normal. And value of absolute lymphocyte count in GC group rose significantly and was similar to which in non-GC group [1.39(1.08-2.18)vs.1.36(1.05-1.82), P>0.05], after treating, but with no difference. GC group′s patients′value of CRP significantly fell down and was similar to which in non-GC group admitted into hospital one week later. Analyses of subgroups divided by the accumulated dose of glucocorticoid showed no significant difference. Pharyngeal swab SARS-CoV-2 nucleic acid negative median time in both groups were similar with no statistical difference. Six cases of hyperglycemia, including blood pressure significantly higher than baseline level in two of the above, were observed in GC group, characterized by male and elder than 70 years. No case with adverse reaction was observed in non-GC group. All patients in both groups were discharged from hospital after recovery with no deterioration and death. Values of PCT in both groups were not analysed in order to avoiding bias for data missing.

Conclusion

The appropriate dose and course of glucocorticoid with other intensive treating may improve oxygenation of severe COIVD-19 patients and help the patients obtain more clinical benefits with controlled risk and favorable outcomes, for the absence of high grade level evidence-based medical recommendation for antiviral therapy. However, there are some limitations in our study and it is necessary to research the adjuvant glucocorticoid therapy for COVID-19 by a randomized controlled trial.

Key words: Severe coronavirus disease 2019, Severe acute respiratory syndrome coronavirus 2, Glucocorticoid, Retrospective analysis
表1 各组患者一般资料比较[±s，M(Q1-Q3)]
临床资料 激素组(n＝72) 非激素组(n＝123) χ2/t P值
性别(n，男/女) 72(48/24) 123(63/60) 3.812 0.051
年龄(岁) 63.01±11.93 62.20±14.26 0.410 0.682
临床症状        
  咳嗽[n(%)] 61(84.72) 94(76.42) 1.919 0.166
  发热[n(%)] 58(80.56) 97(78.86) 0.080 0.777
  咳痰[n(%)] 13(18.06) 19(15.45) 0.225 0.635
  乏力[n(%)] 47(65.28) 88(71.54) 0.837 0.360
  咽痛[n(%)] 2(2.78) 2(1.63) 0.300 0.584
  呼吸困难[n(%)] 48(66.67) 67(54.47) 2.792 0.095
  肌痛[n(%)] 31(43.06) 51(41.46) 0.047 0.828
基础疾病        
  高血压[n(%)] 29(40.28) 44(35.77) 0.394 0.530
  糖尿病[n(%)] 14(19.44) 25(20.33) 0.022 0.882
  慢阻肺[n(%)] 2(2.78) 0(0.00) 3.452 0.063
  冠心病[n(%)] 3(4.17) 11(8.94) 1.555 0.212
  慢性肾病[n(%)] 1(1.39) 1(0.81) 0.148 0.700
  脑血管病[n(%)] 1(1.39) 3(2.44) 0.249 0.618
病程        
  (起病至开始治疗，天) 15(11～19) 17(11～26) 1.753 0.080
  抗病毒治疗        
  单用1种药物[n(%)] 20(27.78) 41(33.33) 0.652 0.419
  联用2种药物[n(%)] 18(25.00) 40(32.52) 1.229 0.268
  联用2种以上药物[n(%)] 23(31.94) 31(25.20) 1.031 0.310
体温(℃) 36.83±0.68 36.67±0.53 1.833 0.068
指氧饱和度(%) 96(92～98) 97(95～98) 2.285 0.022
白细胞计数(×109/L) 6.90 5.90 -2.617 0.009
5．40～9.10 4．70～7.80
中性粒细胞绝 5.13 3.91 -4.425 0.000
对值(×109/L) 3．97～7.97 2．84～5.50
淋巴细胞绝 0.90 1.29 4.920 0.000
对值(×109/L) 0．68～1.10 0．93～1.62
CRP(mg/L) 34.56 7.60 -4.276 0.000
9．69～62.27 2．19～37.28
表2 激素组(激素干预后)与非激素组(入院后1周)结果相关指标比较[±s，M(Q1-Q3)]
临床资料 激素组(激素干预后)(n＝72) 非激素组(入院后1周)(n＝123) t/Z P值
体温(℃) 36.6(36.3～36.9) 36.5(36.3～36.8) -0.567 0.571
指氧饱和度(%) 99(98～99) 98(97～99) -2.304 0.021
白细胞计数(×109/L) 7.60(6.13～9.20) 5.70(4.50～7.00) -5.372 0.000
中性粒细胞绝对值(×109/L) 5.30(4.25～7.36) 3.71(2.81～5.04) -5.427 0.000
淋巴细胞绝对值(×109/L) 1.39(1.08～2.18) 1.36(1.05～1.82) -1.214 0.225
CRP(mg/L) 6.19(2.47～22.32) 6.32(2.48～15.30) -0.528 0.598
表3 不同激素剂量亚组干预后相关指标结果比较(±s)
激素累积剂量 指氧饱和度(%) 白细胞计数(×109/L) 淋巴细胞绝对值(×109/L)
<200 mg 98.63±0.96 7.25±3.59 1.41±0.67
200～399 mg 98.43±1.03 8.15±2.38 1.48±0.53
400～799 mg 98.36±1.25 8.86±4.20 1.70±0.83
>800 mg 98.00±0.58 7.66±1.72 2.01±0.70
F值 0.638 0.845 1.698
P值 0.593 0.474 0.176
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