Levels of TREC and KREC molecules significance determining in peripheral blood for predicting the outcome of COVID-19 disease in the acute period

Maria A. Saitgalina, Yu. V. Ostankova, N. A. Arsentieva, Z. R. Korobova, N. E. Liubimova, V. A. Kashchenko, A. N. Kulikov, D. E. Pevtsov, O. V. Stanevich, E. I. Chernykh, Areg A. Totolian
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引用次数: 1

Abstract

The disease caused by the highly contagious SARS-CoV-2 virus novel coronavirus infection (COVID-19) had killed more than 6.5 million people at the end of December 2022. The severity of the manifestation of the infectious process varies from asymptomatic forms to rapid progression to life-threatening conditions requiring emergency measures. One of the factors, the severity of which affects the outcome of the disease, is lymphopenia, the cause of which may be a violation of lymphopoiesis. The identification of laboratory markers of a high risk of mortality in patients with COVID-19 plays an important role in improving patient care algorithms and increasing their survival. Levels of TREC and KREC molecules in peripheral blood, respectively, can serve as molecular markers of the severity of T and B lymphopenias. The aim of our work was a comparative analysis of the levels of TREC and KREC molecules in the peripheral blood of surviving and deceased patients with COVID-19. The material was whole blood samples obtained from 1745 people, including: 1028 patients diagnosed with novel coronavirus infection (COVID-19) (ICD-10 code U07.1), of which 937 patients recovered and 91 died; 717 apparently healthy individuals (control group). The levels of TREC and KREC molecules were assessed by quantitative multiplex Real-time PCR using the TREC/KREC-AMP PS reagent kit (Federal Scientific Research Institute Pasteur, St. Petersburg). Statistically significant differences in the levels of KREC and TREC molecules between the control group and patients, both surviving and deceased, were established. A significant decrease in median concentrations of KREC molecules was shown in patients with a lethal outcome compared with survivors (p = 0.0019, 95% CI). Among the deceased patients, in 63.7% of cases, the levels of TREC or KREC molecules were reduced relative to the corresponding age norms. Of these, in 20.9% of cases, both analytes were reduced in patients. When assessing the diagnostic significance of the levels of the analytes under study for predicting the outcome of the disease, the area under the AUC curve for KREC was 0.630.029, which indicates the average strength of the prognostic model of the patient's death depending on the level of KREC in the blood. The constructed model is statistically significant (p = 0.002). Monitoring laboratory parameters of patients with COVID-19, including those who died, allows you to determine the prognostic factors that are most significant for assessing the outcome of the disease. Based on the assessment of the KREC level, a predictive model with high specificity reflects the risk of death in patients with COVID-19. Thus, the quantitative determination of the level of KREC molecules in the peripheral blood can be attributed to the methods of preventive personalized diagnostics aimed at improving the survival of patients.
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外周血TREC和KREC分子水平对预测COVID-19急性期预后的意义
截至2022年12月底,由高度传染性的SARS-CoV-2病毒引起的新型冠状病毒感染(COVID-19)已造成650多万人死亡。感染过程表现的严重程度各不相同,从无症状形式到迅速进展到需要采取紧急措施的危及生命的情况。其中一个因素是淋巴细胞减少,其严重程度影响疾病的结果,其原因可能是淋巴细胞生成的破坏。识别COVID-19患者死亡高风险的实验室标志物对改进患者护理算法和提高患者生存率具有重要作用。外周血中TREC和KREC分子水平分别可作为T淋巴细胞减少症和B淋巴细胞减少症严重程度的分子标志物。我们的工作目的是比较分析存活和死亡的COVID-19患者外周血中TREC和KREC分子的水平。材料为取自1745人的全血样本,包括:确诊为新型冠状病毒感染(COVID-19) (ICD-10代码U07.1)的患者1028例,其中937例康复,91例死亡;717例明显健康个体(对照组)。采用TREC/KREC- amp PS试剂盒(圣彼得堡巴斯德联邦科学研究所),采用多重实时荧光定量PCR检测TREC和KREC分子水平。在对照组和患者(包括存活患者和死亡患者)之间,KREC和TREC分子水平的差异具有统计学意义。与幸存者相比,致命结局患者的KREC分子中位浓度显著降低(p = 0.0019, 95% CI)。在死亡患者中,63.7%的病例TREC或KREC分子水平相对于相应的年龄标准降低。其中,在20.9%的病例中,两种分析物在患者中都减少了。在评估所研究的分析物水平对预测疾病结局的诊断意义时,KREC的AUC曲线下面积为0.630.029,这表明患者死亡预测模型依赖于血液中KREC水平的平均强度。构建的模型具有统计学意义(p = 0.002)。监测COVID-19患者(包括已死亡患者)的实验室参数,可使您确定对评估疾病结果最重要的预后因素。基于对KREC水平的评估,一个高特异性的预测模型可以反映COVID-19患者的死亡风险。因此,外周血中KREC分子水平的定量测定可归因于旨在提高患者生存率的预防性个性化诊断方法。
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