Peng Xiaoqi, Zhuo Lianjia, Ma Yong, Liu Yingxia, Wu Zeming
Department of Emergency, Shenzhen Hospital of Guangzhou University of Traditional Chinese Medicine (Futian), Shenzhen, 518034, Guangdong Province, PR China.
Department of Rehabilitation, Shenzhen General Station Hospital of Immigration Inspection, Shenzhen, 518029, Guangdong Province, PR China.
J Stroke Cerebrovasc Dis. 2025 Jan;34(1):108113. doi: 10.1016/j.jstrokecerebrovasdis.2024.108113. Epub 2024 Nov 7.
Observational studies about the association between coronavirus disease 2019 (COVID-19) vaccination and thrombosis/ischemic stroke are inconsistent. The aim of this study is to assess the causality between COVID-19 vaccination and thrombosis-related biomarkers/thrombosis/ischemic stroke using mendelian randomization (MR) analysis.
A two-sample MR analysis using publicly available genome-wide association study (GWAS) data was conducted. Causal effects were appraised using inverse variance weighted (IVW, as a primary method), with supplementary methods including constrained maximum likelihood and model averaging, MR-Robust Adjusted Profile Score, MR-Egger regression, simple mode, weighted median, and weighted mode. Sensitivity analyses were conducted using Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis.
Genetically predicted COVID-19 vaccination was negatively associated with C-C motif chemokine 3 [CCL3, odds ratio (OR): 0.694, 95% confidence intervals (CI): 0.484-0.995] and multiple coagulation factor deficiency protein 2 (MCFD2, OR: 0.806, 95% CI: 0.675-0.963). Meanwhile, the IVW analysis revealed significant causal effects between genetically predicted COVID-19 vaccination and ischemic stroke (OR: 1.088, 95% CI: 1.006-1.177), large artery stroke (LAS, OR: 1.251, 95% CI: 1.028-1.521). The leave-one-out analysis revealed that no individual SNP exerted a significant effect on the overall causal estimate.
Our study provided evidence supporting a potential causal association of genetically predicted COVID-19 vaccination with CCL3 levels, MCFD2 levels, ischemic stroke risk and LAS risk. These results provide preliminary evidence of potential adverse associations, but further studies are required to fully understand the mechanisms and to validate these findings across broader populations.
关于2019冠状病毒病（COVID-19）疫苗接种与血栓形成/缺血性中风之间关联的观察性研究结果并不一致。本研究的目的是使用孟德尔随机化（MR）分析评估COVID-19疫苗接种与血栓形成相关生物标志物/血栓形成/缺血性中风之间的因果关系。
采用公开可用的全基因组关联研究（GWAS）数据进行两样本MR分析。使用逆方差加权法（IVW，作为主要方法）评估因果效应，补充方法包括约束最大似然法和模型平均法、MR稳健调整轮廓得分法、MR-Egger回归法、简单模式法、加权中位数法和加权模式法。使用Cochran's Q检验、MR-Egger截距检验和留一法进行敏感性分析。
基因预测的COVID-19疫苗接种与C-C基序趋化因子3[CCL3，优势比（OR）：0.694，95%置信区间（CI）：0.484-0.995]和多种凝血因子缺乏蛋白2（MCFD2，OR：0.806，95%CI：0.675-0.963）呈负相关。同时，IVW分析显示基因预测的COVID-19疫苗接种与缺血性中风（OR：1.088，95%CI：1.006-1.177）、大动脉中风（LAS，OR：1.251，95%CI：1.028-1.521）之间存在显著的因果效应。留一法分析显示，没有单个单核苷酸多态性（SNP）对总体因果估计产生显著影响。
我们的研究提供了证据，支持基因预测的COVID-19疫苗接种与CCL3水平、MCFD2水平、缺血性中风风险和LAS风险之间存在潜在因果关联。这些结果提供了潜在不良关联的初步证据，但需要进一步研究以充分了解其机制，并在更广泛的人群中验证这些发现。
