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新型冠状病毒肺炎患者 2 型糖尿病的免疫学特征。

Immunological Characteristics in Type 2 Diabetes Mellitus Among COVID-19 Patients.

机构信息

Department and Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Endocrinol (Lausanne). 2021 Mar 11;12:596518. doi: 10.3389/fendo.2021.596518. eCollection 2021.

Abstract

CLINICAL TRIAL REGISTRATION

www.ClinicalTrials.gov, identifier: NCT04365634.

CONTEXT

Diabetes mellitus was associated with increased severity and mortality of disease in COVID-19 pneumonia. So far the effect of type 2 diabetes (T2DM) or hyperglycemia on the immune system among COVID-19 disease has remained unclear.

OBJECTIVE

We aim to explore the clinical and immunological features of type 2 diabetes mellitus (T2DM) among COVID-19 patients.

DESIGN AND METHODS

In this retrospective study, the clinical and immunological characteristics of 306 hospitalized confirmed COVID-19 patients (including 129 diabetic and 177 non-diabetic patients) were analyzed. The serum concentrations of laboratory parameters including cytokines and numbers of immune cells were measured and compared between diabetic and non-diabetic groups.

RESULTS

Compared with non-diabetic group, diabetic cases more frequently had lymphopenia and hyperglycemia, with higher levels of urea nitrogen, myoglobin, D-dimer and ferritin. Diabetic cases indicated the obviously elevated mortality and the higher levels of cytokines IL-2R, IL-6, IL-8, IL-10, and TNF-α, as well as the distinctly reduced Th1/Th2 cytokines ratios compared with non-diabetic cases. The longitudinal assays showed that compared to that at week 1, the levels of IL-6 and IL-8 were significantly elevated at week 2 after admission in non-survivors of diabetic cases, whereas there were greatly reductions from week 1 to week 2 in survivors of diabetic cases. Compared with survival diabetic patients, non-survival diabetic cases displayed distinct higher serum concentrations of IL-2R, IL-6, IL-8, IL-10, TNF-α, and lower Th1/Th2 cytokines ratios at week 2. Samples from a subset of participants were evaluated by flow cytometry for the immune cells. The counts of peripheral total T lymphocytes, CD4 T cells, CD8 T cells and NK cells were markedly lower in diabetic cases than in non-diabetic cases. The non-survivors showed the markedly declined counts of CD8 T cells and NK cells than survivors.

CONCLUSION

The elevated cytokines, imbalance of Th1/Th2 cytokines ratios and reduced of peripheral numbers of CD8 T cells and NK cells might contribute to the pathogenic mechanisms of high mortality of COVID-19 patients with T2DM.

摘要

临床试验注册

www.ClinicalTrials.gov,标识符:NCT04365634。

背景

糖尿病与 COVID-19 肺炎的疾病严重程度和死亡率增加有关。迄今为止,2 型糖尿病(T2DM)或高血糖对 COVID-19 疾病免疫系统的影响仍不清楚。

目的

我们旨在探讨 2 型糖尿病(T2DM)COVID-19 患者的临床和免疫学特征。

设计和方法

在这项回顾性研究中,分析了 306 例住院确诊 COVID-19 患者(包括 129 例糖尿病患者和 177 例非糖尿病患者)的临床和免疫学特征。测量并比较了糖尿病组和非糖尿病组之间实验室参数(包括细胞因子和免疫细胞数量)的血清浓度。

结果

与非糖尿病组相比,糖尿病组更频繁地出现淋巴细胞减少和高血糖症,且血尿素氮、肌红蛋白、D-二聚体和铁蛋白水平较高。糖尿病组的死亡率明显升高,细胞因子 IL-2R、IL-6、IL-8、IL-10 和 TNF-α水平明显升高,Th1/Th2 细胞因子比值明显降低。纵向检测显示,与第 1 周相比,糖尿病组非幸存者第 2 周的 IL-6 和 IL-8 水平明显升高,而幸存者第 2 周的水平则从第 1 周大幅降低。与存活的糖尿病患者相比,非存活的糖尿病患者在第 2 周时显示出明显更高的血清 IL-2R、IL-6、IL-8、IL-10、TNF-α浓度和更低的 Th1/Th2 细胞因子比值。对一部分参与者的样本进行流式细胞术检测免疫细胞。糖尿病组外周总 T 淋巴细胞、CD4 T 细胞、CD8 T 细胞和 NK 细胞计数明显低于非糖尿病组。非幸存者的 CD8 T 细胞和 NK 细胞计数明显低于幸存者。

结论

升高的细胞因子、Th1/Th2 细胞因子比值失衡以及外周 CD8 T 细胞和 NK 细胞数量减少可能有助于解释 T2DM COVID-19 患者高死亡率的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f1b/7992040/950af8238497/fendo-12-596518-g001.jpg

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