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与 COVID-19 不良结局相关的变异的遗传特征-一项多中心观察性研究。

Genetic signatures of variants associated with worse COVID-19 outcomes - a multicentric observational study.

机构信息

Laboratório de Imunofarmacologia e Biologia Molecular, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.

Laboratório de Imunologia e Biologia Molecular, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Salvador, Brazil.

出版信息

Front Immunol. 2024 Oct 8;15:1422349. doi: 10.3389/fimmu.2024.1422349. eCollection 2024.

DOI:10.3389/fimmu.2024.1422349
PMID:39439795
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11493623/
Abstract

INTRODUCTION

The COVID-19, triggered by the SARS-CoV-2 virus, has varied clinical manifestations, ranging from mild cases to severe forms such as fatal pneumonia and acute respiratory distress syndrome (ARDS). Disease severity is influenced by an exacerbated immune response, characterized by high pro-inflammatory cytokine levels. Inhibition of AKT can potentially suppress pathological inflammation, cytokine storm and platelet activation associated with COVID-19. In this study, we aimed to investigate the rs2494746 and rs1130214 variants in the gene associated with severe COVID-19 outcomes.

METHODS

Peripheral blood samples and sociodemographic data from 508 individuals with COVID-19, measuring plasma cytokine concentrations using ELISA and genotyped the variants.

RESULTS

The rs2494746-C allele was associated with severity, ICU admission, and death from COVID-19. The C allele at rs1130214 was linked to increased TNF and D-dimer levels. Moreover, both variants exhibited an increased cumulative risk of disease severity, ICU admission, and mortality caused by COVID-19. In the predictive analysis, the rs2494746 obtained an accuracy of 71%, suggesting a high probability of the test determining the severity of the disease.

DISCUSSION

Our findings contribute to understanding the influence of the gene variants on the immunological damage in individuals infected with SARS-CoV-2.

摘要

简介

由 SARS-CoV-2 病毒引发的 COVID-19 具有不同的临床表现,从轻症到严重形式不等,如致命性肺炎和急性呼吸窘迫综合征(ARDS)。疾病严重程度受加剧的免疫反应影响,其特征是促炎细胞因子水平升高。AKT 抑制可能会抑制与 COVID-19 相关的病理性炎症、细胞因子风暴和血小板激活。在这项研究中,我们旨在研究与严重 COVID-19 结局相关的 基因中的 rs2494746 和 rs1130214 变体。

方法

从 508 名 COVID-19 患者中采集外周血样本和社会人口统计学数据,使用 ELISA 测量血浆细胞因子浓度,并对 变体进行基因分型。

结果

rs2494746-C 等位基因与 COVID-19 的严重程度、入住 ICU 和死亡相关。rs1130214 处的 C 等位基因与 TNF 和 D-二聚体水平升高有关。此外,这两种变体都增加了 COVID-19 导致的疾病严重程度、入住 ICU 和死亡率的累积风险。在预测分析中,rs2494746 的准确性为 71%,表明该测试确定疾病严重程度的可能性很高。

讨论

我们的发现有助于了解 基因变体对 SARS-CoV-2 感染个体免疫损伤的影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d319/11493623/6752d535e08c/fimmu-15-1422349-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d319/11493623/d4fea215c7a0/fimmu-15-1422349-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d319/11493623/67a9c37139e6/fimmu-15-1422349-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d319/11493623/6752d535e08c/fimmu-15-1422349-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d319/11493623/d4fea215c7a0/fimmu-15-1422349-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d319/11493623/67a9c37139e6/fimmu-15-1422349-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d319/11493623/6752d535e08c/fimmu-15-1422349-g003.jpg

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