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托珠单抗治疗不同类型 COVID-19 细胞因子风暴综合征的疗效。

Efficacy of Tocilizumab Therapy in Different Subtypes of COVID-19 Cytokine Storm Syndrome.

机构信息

Department of Anaesthesiology and Intensive Care, Bogomolets National Medical University, 01601 Kyiv, Ukraine.

Department of Emergency Medicine, Pope John II State School of Higher Education in Biala Podlaska, 21-500 Biala Podlaska, Poland.

出版信息

Viruses. 2021 Jun 3;13(6):1067. doi: 10.3390/v13061067.


DOI:10.3390/v13061067
PMID:34205217
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8229480/
Abstract

BACKGROUND: Cytokine storm in COVID-19 is heterogenous. There are at least three subtypes: cytokine release syndrome (CRS), macrophage activation syndrome (MAS), and sepsis. METHODS: A retrospective study comprising 276 patients with SARS-CoV-2 pneumonia. All patients were tested for ferritin, interleukin-6, D-Dimer, fibrinogen, calcitonin, and C-reactive protein. According to the diagnostic criteria, three groups of patients with different subtypes of cytokine storm syndrome were identified: MAS, CRS or sepsis. In the MAS and CRS groups, treatment results were assessed depending on whether or not tocilizumab was used. RESULTS: MAS was diagnosed in 9.1% of the patients examined, CRS in 81.8%, and sepsis in 9.1%. Median serum ferritin in patients with MAS was significantly higher (5894 vs. 984 vs. 957 ng/mL, < 0.001) than in those with CRS or sepsis. Hypofibrinogenemia and pancytopenia were also observed in MAS patients. In CRS patients, a higher mortality rate was observed among those who received tocilizumab, 21 vs. 10 patients ( = 0.043), RR = 2.1 (95% CI 1.0-4.3). In MAS patients, tocilizumab decreased the mortality, 13 vs. 6 patients ( = 0.013), RR = 0.50 (95% CI 0.25-0.99). CONCLUSIONS: Tocilizumab therapy in patients with COVID-19 and CRS was associated with increased mortality, while in MAS patients, it contributed to reduced mortality.

摘要

背景:COVID-19 中的细胞因子风暴具有异质性。至少有三种亚型:细胞因子释放综合征(CRS)、巨噬细胞活化综合征(MAS)和脓毒症。

方法:这是一项回顾性研究,纳入了 276 例 SARS-CoV-2 肺炎患者。所有患者均检测了铁蛋白、白细胞介素 6、D-二聚体、纤维蛋白原、降钙素和 C 反应蛋白。根据诊断标准,确定了三种不同细胞因子风暴综合征亚型的患者群体:MAS、CRS 或脓毒症。在 MAS 和 CRS 组中,根据是否使用托珠单抗评估治疗结果。

结果:所检查的患者中,9.1%诊断为 MAS,81.8%诊断为 CRS,9.1%诊断为脓毒症。MAS 患者的血清铁蛋白中位数明显更高(5894 比 984 比 957ng/mL,<0.001)。MAS 患者还存在低纤维蛋白原血症和全血细胞减少症。在 CRS 患者中,接受托珠单抗治疗的患者死亡率更高,21 例比 10 例(=0.043),RR=2.1(95%CI 1.0-4.3)。在 MAS 患者中,托珠单抗降低了死亡率,13 例比 6 例(=0.013),RR=0.50(95%CI 0.25-0.99)。

结论:COVID-19 合并 CRS 患者的托珠单抗治疗与死亡率增加相关,而 MAS 患者的托珠单抗治疗则降低了死亡率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9837/8229480/a65bc9feae33/viruses-13-01067-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9837/8229480/a65bc9feae33/viruses-13-01067-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9837/8229480/a65bc9feae33/viruses-13-01067-g001.jpg

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引用本文的文献

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[2]
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[4]
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Biomedicines. 2021-8-5

本文引用的文献

[1]
Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence.

Int J Mol Sci. 2021-3-17

[2]
Tocilizumab in Hospitalized Patients with Severe Covid-19 Pneumonia.

N Engl J Med. 2021-4-22

[3]
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

N Engl J Med. 2021-4-22

[4]
Systematic review and meta-analysis of anakinra, sarilumab, siltuximab and tocilizumab for COVID-19.

Thorax. 2021-9

[5]
Potential immuno-nanomedicine strategies to fight COVID-19 like pulmonary infections.

Nano Today. 2021-2

[6]
Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial.

BMJ. 2021-1-20

[7]
Cytokine Storm.

N Engl J Med. 2020-12-3

[8]
Ferritin as a Marker of Severity in COVID-19 Patients: A Fatal Correlation.

Isr Med Assoc J. 2020-8

[9]
Efficacy of Tocilizumab in Patients Hospitalized with Covid-19.

N Engl J Med. 2020-10-21

[10]
Effect of Tocilizumab vs Usual Care in Adults Hospitalized With COVID-19 and Moderate or Severe Pneumonia: A Randomized Clinical Trial.

JAMA Intern Med. 2021-1-1

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