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甲泼尼龙对重症新型冠状病毒肺炎患者死亡率及临床病程的影响:一项倾向评分匹配分析

Effect of Methylprednisolone on Mortality and Clinical Courses in Patients with Severe COVID-19: A Propensity Score Matching Analysis.

作者信息

Li Xiaoyan, Yuan Xin, Xu Zhe, Shi Lei, Huang Lei, Lu Xuechun, Fu Junliang

机构信息

Medical School of Chinese PLA, Beijing 100853, China.

Senior Department of Infectious Diseases, the Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China.

出版信息

Infect Dis Immun. 2023 Jan;3(1):20-28. doi: 10.1097/ID9.0000000000000076. Epub 2022 Oct 21.

Abstract

BACKGROUND

Whether methylprednisolone therapy can reduce the mortality rate of patients with severe coronavirus disease 2019 (COVID-19) remains controversial, and its effects on the length of hospital stay and virus shedding time are also unknown. This retrospective study investigates the previous issues to provide more evidence for methylprednisolone treatment in severe COVID-19.

METHODS

This retrospective study included 563 of 4827 patients with confirmed COVID-19 admitted to Wuhan Huoshenshan Hospital or Wuhan Guanggu Hospital between February 3, 2020 and March 30, 2020 who met the screening criteria. The participants' epidemiological and demographic data, comorbidities, laboratory test results, treatments, outcomes, and vital clinical time points were extracted from electronic medical records. The primary outcome was in-hospital death, and the secondary outcomes were 2 clinical courses: length from admission to viral clearance and discharge. Univariate and multivariate logistic or linear regression analyses were used to assess the role of methylprednisolone in different outcomes. Propensity score matching was performed to control for confounding factors.

RESULTS

Of the 563 patients who met the screening criteria and were included in the subsequent analysis, 138 were included in the methylprednisolone group and 425 in the nonmethylprednisolone group. The in-hospital death rate between the methylprednisolone and nonmethylprednisolone groups showed a significant difference (23.91% 1.65%, < 0.001), which was maintained after propensity score matching (13.98% 5.38%, = 0.048). However, univariate logistic analysis in the matched groups showed that methylprednisolone treatment (odds ratio [OR], 5.242; 95% confidence interval [CI], 0.802 to 34.246; = 0.084) was not a risk factor for in-hospital death in severe patients. Further multivariate logistic regression analysis found comorbidities (OR, 3.327; 95% CI, 1.702 to 6.501; < 0.001), lower lymphocyte count (OR, 0.076; 95% CI, 0.012 to 0.461; = 0.005), higher lactate dehydrogenase (LDH) levels (OR, 1.008; 95% CI, 1.003 to 1.013; = 0.002), and anticoagulation therapy (OR, 11.187; 95% CI, 2.459 to 50.900; = 0.002) were associated with in-hospital mortality. Multivariate linear regression analysis in the matched groups showed that methylprednisolone treatment was not a risk factor for a prolonged duration from admission to viral clearance (β Value 0.081; 95% CI, -1.012 to 3.657; = 0.265) or discharge (β Value 0.114; 95% CI, -0.723 to 6.408; = 0.117). d-dimer (β Value, 0.144; 95% CI, 0.012 to 0.817; = 0.044), LDH (β Value 0.260; 95% CI, 0.010 to 0.034; < 0.001), and antiviral therapy (β Value 0.220; 95% CI, 1.373 to 6.263; = 0.002) were associated with a longer length from admission to viral clearance. The lymphocyte count (β Value -0.206; 95% CI, -6.248 to -1.197; = 0.004), LDH (β Value 0.231; 95% CI, 0.012 to 0.048; = 0.001), antiviral therapy (β Value 0.143; 95% CI, 0.058 to 7.497; = 0.047), and antibacterial therapy (β Value 0.152; 95% CI, 0.133 to 8.154; = 0.043) were associated with a longer hospitalization duration from admission to discharge. Further stratified analysis revealed that the low daily dose group (≤60 mg/d) and the low total dose group (≤200 mg) had shorter duration from admission to viral clearance (Z=-2.362, = 0.018; Z=-2.010, = 0.044) and a shorter hospital stay (Z=-2.735, = 0.006; Z=-3.858, < 0.001).

CONCLUSIONS

In patients with severe COVID-19, methylprednisolone is safe and does not prolong the duration from admission to viral clearance or discharge. Low-dose, short-term methylprednisolone treatment may be more beneficial in shortening the disease course.

摘要

背景

甲基强的松龙治疗能否降低重症2019冠状病毒病(COVID-19)患者的死亡率仍存在争议,其对住院时间和病毒清除时间的影响也尚不明确。这项回顾性研究对上述问题进行调查,旨在为重症COVID-19患者使用甲基强的松龙治疗提供更多证据。

方法

这项回顾性研究纳入了2020年2月3日至2020年3月30日期间收治于武汉火神山医院或武汉光谷医院的4827例确诊COVID-19患者中的563例,这些患者符合筛选标准。从电子病历中提取参与者的流行病学和人口统计学数据、合并症、实验室检查结果、治疗方法、结局及重要临床时间点。主要结局为院内死亡,次要结局为两个临床病程:从入院到病毒清除的时长和出院时长。采用单因素和多因素逻辑回归或线性回归分析评估甲基强的松龙在不同结局中的作用。进行倾向得分匹配以控制混杂因素。

结果

在符合筛选标准并纳入后续分析的563例患者中,138例被纳入甲基强的松龙组,425例被纳入非甲基强的松龙组。甲基强的松龙组和非甲基强的松龙组的院内死亡率存在显著差异(23.91% 对1.65%,P<0.001),倾向得分匹配后该差异仍然存在(13.98% 对5.38%,P = 0.048)。然而,匹配组的单因素逻辑分析显示,甲基强的松龙治疗(比值比[OR],5.242;95%置信区间[CI],0.802至34.246;P = 0.084)并非重症患者院内死亡的危险因素。进一步的多因素逻辑回归分析发现,合并症(OR,3.327;95% CI,1.702至6.501;P<0.001)、较低的淋巴细胞计数(OR,0.076;95% CI,0.012至0.461;P = 0.005)、较高的乳酸脱氢酶(LDH)水平(OR,1.008;95% CI,1.003至1.013;P = 0.002)以及抗凝治疗(OR,11.187;95% CI,2.459至50.900;P = 0.002)与院内死亡率相关。匹配组的多因素线性回归分析显示,甲基强的松龙治疗并非从入院到病毒清除(β值0.081;95% CI,-1.012至3.657;P = 0.265)或出院(β值0.114;95% CI,-0.723至6.408;P = 0.117)时长延长的危险因素。D-二聚体(β值,0.144;95% CI,0.012至0.817;P = 0.044)、LDH(β值0.260;95% CI,0.010至0.034;P<0.001)以及抗病毒治疗(β值0.220;95% CI,1.373至6.263;P = 0.002)与从入院到病毒清除的较长时长相关。淋巴细胞计数(β值-0.206;95% CI,-6.248至-1.197;P = 0.004)、LDH(β值0.231;95% CI,0.012至0.048;P = 0.001)、抗病毒治疗(β值0.143;95% CI,0.058至7.497;P = 0.047)以及抗菌治疗(β值0.152;95% CI,0.133至8.154;P = 0.043)与从入院到出院的较长住院时长相关。进一步的分层分析显示,低日剂量组(≤60 mg/d)和低总剂量组(≤200 mg)从入院到病毒清除的时长较短(Z=-2.362,P = 0.018;Z=-2.010,P = 0.044),住院时间也较短(Z=-2.735,P = 0.006;Z=-3.858,P<0.001)。

结论

对于重症COVID-19患者,甲基强的松龙是安全的,且不会延长从入院到病毒清除或出院的时长。低剂量、短期的甲基强的松龙治疗可能更有助于缩短病程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2091/9912987/d770932bca45/idi-3-20-g001.jpg

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