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液体活检作为预测严重 COVID-19 和住院社区获得性肺炎的工具。

Liquid biopsy as a tool for predicts of severe COVID-19 and hospitalised community-acquired pneumonia.

机构信息

Lugansk State Medical University, Rubizhne, Ukraine.

出版信息

Pol Merkur Lekarski. 2022 Jun 24;50(297):155-159.

PMID:35801596
Abstract

UNLABELLED

Cell-free DNA (cfDNA) is released into the circulation after apoptosis, necrosis, and active secretion from cells. In a healthy individual, cfDNA is present in small amounts, has a short half-life, and is predominantly derived from circulating hematopoietic cells. The composition and quantity of cfDNA dramatically changes during pathological conditions. Indeed, several studies reported elevated cfDNA concentration as a potential noninvasive biomarker in many diseases.

AIM

The aim of the study was evaluation of the circulating cell-free DNA in patients with severe Covid-19 in comparison with patients with hospitalised community-acquired pneumonia (with and without hyperglycemia and type 2 diabetes mellitus) to determine the specificity, sensitivity and cutoff value of cfDNA for each nosology.

MATERIALS AND METHODS

The studies were carried out on the basis of city and regional hospitals in the Luhansk region between 2015 to 2021. Were examined in the study 28 patients with a positive diagnosis of COVID-19 according to PCR analysis (14 women and 14 men), 60 patients with community- acquired pneumonia (CAP) (30 women and 30 men), 101 patients with community-acquired pneumonia and hyperglicemia (CAP+HH) (44 women and 57 men), 70 patients with type 2 diabetes mellitus (T2DM) (37 women and 33 men), 42 patients with community-acquired pneumonia in combination with type 2 diabetes mellitus (CAP+T2DM) (27 women and 15 men). The control group consisted of 81 healthy volunteer donor (46 women and 35 men). DNA fragmentation was measured with the diphenylamine assay. Statistical and graphical analyses were done using Statistica 7.0 StatSoft software and using GraphPad Prism version 9.0 (GraphPad Software, La Jolla, CA, USA) software.

RESULTS

We found 3-4-fold higher concentration of serum cfDNA levels in COVID-19 patients (womens and mens) compared with healthy controls. Similarly, the levels of cfDNA were 1,5- to 2-fold higher in pneumoniawomens and pneumonia-mens, pneumonia+hyperglycemia-womens and pneumonia+hyperglycemia-mens pneumonia+Type2 Diabetes-womens and pneumonia+Type2 Diabetes-mens, compared with healthy controls. Our results indicate cfDNA profiles on admission can discriminate between patients with COVID-19 and community-acquired pneumonia at risk of severe disease and death with better performance than previously reported inflammatory markers.

CONCLUSIONS

Circulating cell-free nucleic acids (cfDNA) are novel potential biomarkers of COVID-19 and community-acquired pneumonia identified. Our study is one of the first to analyze cfDNA level (the cutoff value of cfDNA concentration) for prediction of COVID-19 and community-acquired pneumonia (with and without complications and comorbidity diseases).

摘要

目的

评估严重 COVID-19 患者与住院社区获得性肺炎(伴或不伴高血糖和 2 型糖尿病)患者循环游离 DNA(cfDNA),以确定 cfDNA 对每种诊断的特异性、敏感性和截断值。

材料和方法

该研究于 2015 年至 2021 年在卢甘斯克地区的市级和地区医院进行。研究中检查了 28 例经 PCR 分析确诊为 COVID-19 的患者(14 名女性和 14 名男性),60 例社区获得性肺炎(CAP)患者(30 名女性和 30 名男性),101 例社区获得性肺炎和高血糖患者(CAP+HH)(44 名女性和 57 名男性),70 例 2 型糖尿病患者(T2DM)(37 名女性和 33 名男性),42 例社区获得性肺炎合并 2 型糖尿病患者(CAP+T2DM)(27 名女性和 15 名男性)。对照组由 81 名健康志愿者捐赠者(46 名女性和 35 名男性)组成。DNA 片段化采用二苯胺法测量。统计和图形分析使用 Statistica 7.0 StatSoft 软件和 GraphPad Prism 版本 9.0(GraphPad Software,La Jolla,CA,USA)软件进行。

结果

我们发现 COVID-19 患者(女性和男性)血清 cfDNA 水平高 3-4 倍,与健康对照组相比。同样,与健康对照组相比,肺炎女性和肺炎男性、肺炎+高血糖女性和肺炎+高血糖男性、肺炎+2 型糖尿病女性和肺炎+2 型糖尿病男性的 cfDNA 水平也高 1.5-2 倍。我们的结果表明,入院时的 cfDNA 谱可以区分 COVID-19 患者和有发生严重疾病和死亡风险的社区获得性肺炎,其性能优于先前报道的炎症标志物。

结论

鉴定了新型 COVID-19 和社区获得性肺炎潜在的循环游离核酸(cfDNA)生物标志物。我们的研究是分析 cfDNA 水平(cfDNA 浓度截断值)预测 COVID-19 和社区获得性肺炎(伴或不伴并发症和合并症疾病)的首批研究之一。

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