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严重急性呼吸综合征冠状病毒2(SARS-CoV-2)导致患者纤溶系统出现显著异常:病毒突变、变体与血栓形成之间的相关性。

SARS-COV-2 causes significant abnormalities in the fibrinolysis system of patients: correlation between viral mutations, variants and thrombosis.

作者信息

Abudouleh Esra'a, Owaidah Tarek, Alhamlan Fatimah, Al-Qahtani Arwa A, Aljowaie Reem M, Al-Ghnnam Fatimah, Fe Bohol Marie, Al-Qahtani Ahmed A

机构信息

Department of Botany and Microbiology, College of Science, King Saud University, Riyadh, Saudi Arabia.

Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

出版信息

Front Cell Infect Microbiol. 2025 Apr 15;15:1531412. doi: 10.3389/fcimb.2025.1531412. eCollection 2025.

DOI:10.3389/fcimb.2025.1531412
PMID:40302923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12037514/
Abstract

BACKGROUND

Coronavirus disease (COVID-19) is reported as a complex disorder affecting multiple systems and coagulopathy that can cause mortality. In this study, we investigated the correlation of SARS-CoV-2 mutations found in blood samples with various changes in the fibrinolysis system, as well as the severity of the disease based on outcome and whether or not these patients were admitted into the ICU.

MATERIALS AND METHODS

COVID-19 patients (n = 446) admitted to our institute between 2021 and 2022 were recruited. Blood samples were collected, and a sequence analysis of the SARS-CoV-2 spike gene was isolated from the blood. Measured several parameters of fibrinolysis and coagulation, including alpha-2-antiplasmin and plasminogen, thrombin activatable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), D-dimer, and fibrinogen levels.

RESULTS

SARS-CoV-2 RNA was found in 123/446 (27.6%) of the blood samples. The N501Y, D614G, K417N, and P681R mutations among COVID-19 patients were associated with higher admissions to the ICU (P = 0.0057, P = 0.0068, P = 0.0193, and P = 0.018, respectively). Omicron (BA.1.1) variant variants are highly associated with thrombosis (P = 0.002) in hospitalized COVID-19 patients that are unvaccinated and have comorbidity conditions. The plasma levels of tPA, aPTT, and D-dimer were significantly higher in participants who had the N501Y mutation (P = 0.044, P = 0.024, and P = 0.027, respectively).

CONCLUSION

Thrombosis was the most prevalent condition among severe COVID-19 patients. The correlation between specific SARS-CoV-2 new variants and thrombosis warrants more investigation.

摘要

背景

冠状病毒病(COVID-19)被报道为一种影响多个系统的复杂疾病以及可导致死亡的凝血病。在本研究中,我们调查了血液样本中发现的严重急性呼吸综合征冠状病毒2(SARS-CoV-2)突变与纤维蛋白溶解系统的各种变化之间的相关性,以及基于结局的疾病严重程度和这些患者是否被收入重症监护病房(ICU)。

材料与方法

招募了2021年至2022年期间入住我院的COVID-19患者(n = 446)。采集血液样本,并从血液中分离出SARS-CoV-2刺突基因进行序列分析。测量了纤维蛋白溶解和凝血的几个参数,包括α-2-抗纤溶酶和纤溶酶原、凝血酶激活的纤维蛋白溶解抑制剂(TAFI)、组织纤溶酶原激活剂(tPA)、纤溶酶原激活剂抑制剂-1(PAI-1)、D-二聚体和纤维蛋白原水平。

结果

在123/446(27.6%)的血液样本中发现了SARS-CoV-2 RNA。COVID-19患者中的N501Y、D614G、K417N和P681R突变与更高的ICU入院率相关(分别为P = 0.0057、P = 0.0068、P = 0.0193和P = 0.018)。奥密克戎(BA.1.1)变异株与未接种疫苗且患有合并症的住院COVID-19患者的血栓形成高度相关(P = 0.002)。具有N501Y突变的参与者的血浆tPA、活化部分凝血活酶时间(aPTT)和D-二聚体水平显著更高(分别为P = 0.044、P = 0.024和P = 0.027)。

结论

血栓形成是重症COVID-19患者中最普遍的情况。特定SARS-CoV-2新变异株与血栓形成之间的相关性值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a4/12037514/11316cf28e92/fcimb-15-1531412-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a4/12037514/11316cf28e92/fcimb-15-1531412-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a4/12037514/9dd2a8eb2b89/fcimb-15-1531412-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10a4/12037514/2809d5e9d9a6/fcimb-15-1531412-g003.jpg
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