Causal Effects of COVID-19 on the Risk of Thrombosis: A Two-Sample Mendel Randomization Study.

IF 5 2区 医学 Q1 HEMATOLOGY Thrombosis and haemostasis Pub Date : 2024-08-01 Epub Date: 2024-02-07 DOI:10.1055/a-2263-8514
Zhengran Li, Minghui Zeng, Tong Wu, Zijin Wang, Yuxin Sun, Ziran Zhang, Fanye Wu, Zejun Chen, Min Fu, Fanke Meng
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Abstract

Background:  Coronavirus disease 2019 (COVID-19) and thrombosis are linked, but the biomolecular mechanism is unclear. We aimed to investigate the causal relationship between COVID-19 and thrombotic biomarkers.

Methods:  We used two-sample Mendelian randomization (MR) to assess the effect of COVID-19 on 20 thrombotic biomarkers. We estimated causality using inverse variance weighting with multiplicative random effect, and performed sensitivity analysis using weighted median, MR-Egger regression and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) methods. All the results were examined by false discovery rate (FDR) with the Benjamin and Hochberg method for this correction to minimize false positives. We used R language for the analysis.

Results:  All COVID-19 classes showed lower levels of tissue factor pathway inhibitor (TFPI) and interleukin-1 receptor type 1 (IL-1R1). COVID-19 significantly reduced TFPI (odds ratio [OR] = 0.639, 95% confidence interval [CI]: 0.435-0.938) and IL-1R1 (OR = 0.603, 95% CI = 0.417-0.872), nearly doubling the odds. We also found that COVID-19 lowered multiple coagulation factor deficiency protein 2 and increased C-C motif chemokine 3. Hospitalized COVID-19 cases had less plasminogen activator, tissue type (tPA) and P-selectin glycoprotein ligand 1 (PSGL-1), while severe cases had higher mean platelet volume (MPV) and lower platelet count. These changes in TFPI, tPA, IL-1R1, MPV, and platelet count suggested a higher risk of thrombosis. Decreased PSGL-1 indicated a lower risk of thrombosis.

Conclusion:  TFPI, IL-1R, and seven other indicators provide causal clues of the pathogenesis of COVID-19 and thrombosis. This study demonstrated that COVID-19 causally influences thrombosis at the biomolecular level.

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COVID-19 对血栓风险的因果效应:双样本孟德尔随机研究
背景:COVID-19与血栓形成有关,但其生物分子机制尚不清楚。我们旨在研究 COVID-19 与血栓形成生物标志物之间的因果关系:我们采用双样本孟德尔随机化(MR)方法评估了 COVID-19 对 20 个血栓生物标志物的影响。我们使用带有乘法随机效应的反方差加权法估计因果关系,并使用加权中位数、MR Egger回归和MR pleiotropy residual sum and outlier(MR-PRESSO)方法进行了敏感性分析。我们使用 R 语言进行分析:所有 COVID-19 类药物的组织因子通路抑制剂(TFPI)和白细胞介素-1 受体 1 型(IL-1R1)水平均较低。COVID-19可显著降低TFPI(OR=0.639,95%CI:0.435-0.938)和IL-1R1(OR=0.603,95%CI=0.417-0.872),几率几乎翻倍。我们还发现,COVID-19 降低了多凝血因子缺乏蛋白 2 (MCFD2),增加了 C-C motif 趋化因子 3 (CCL3)。COVID-19住院病例的组织型纤溶酶原激活因子(tPA)和P-选择素糖蛋白配体1(PSGL-1)含量较低,而重症病例的平均血小板体积(MPV)和血小板计数较低。TFPI、tPA、IL-1R1、MPV 和血小板计数的这些变化表明血栓形成的风险较高。PSGL-1的降低表明血栓形成的风险较低:本研究表明,COVID-19 主要通过降低 TFPI 和 IL-1R1 在生物分子水平上对血栓形成产生因果影响。其他三个生物标志物也暗示 COVID-19 会增加血栓风险。我们证实了血小板数量和MPV的减少,为COVID-19和血栓形成的发病机制提供了线索。我们的研究结果可能对COVID-19患者血栓并发症的预防和治疗有意义。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Thrombosis and haemostasis
Thrombosis and haemostasis 医学-外周血管病
CiteScore
11.90
自引率
9.00%
发文量
140
审稿时长
1 months
期刊介绍: Thrombosis and Haemostasis publishes reports on basic, translational and clinical research dedicated to novel results and highest quality in any area of thrombosis and haemostasis, vascular biology and medicine, inflammation and infection, platelet and leukocyte biology, from genetic, molecular & cellular studies, diagnostic, therapeutic & preventative studies to high-level translational and clinical research. The journal provides position and guideline papers, state-of-the-art papers, expert analysis and commentaries, and dedicated theme issues covering recent developments and key topics in the field.
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