Department of Critical Care Medicine, Zhongda Hospital Lishui Branch, Nanjing Lishui People's Hospital, Southeast University, Nanjing, 211200, China.
Department of Gastroenterology, Jiangsu Province People' s Hospital, Nanjing, 211029, China.
Virol J. 2024 Nov 6;21(1):280. doi: 10.1186/s12985-024-02548-y.
Current observational data indicates that ischemic stroke (IS) affects a significant proportion of people with COVID-19. The current study sought to evaluate the causal relationship between COVID-19 and IS.
A two-sample Mendelian randomization (2 S-MR) approach was used to probe the relationship between genetic determinants of three COVID-19 parameters (SARS-CoV-2 infection, COVID-19 hospitalization, and severe COVID-19) and the incidence of IS based on genome-wide association studies (GWAS) data. Using this 2 S-MR technique, expression quantitative trait loci (eQTL) and GWAS studies were further assessed for overlap to identify common causative genes associated with severe COVID-19 and IS.
IVW approaches indicated the genetic variants linked to COVID-19 hospitalization (OR 1.04, 95% CI 1.01-1.08, p = 0.023) and severe COVID-19 (OR 1.03, 95% CI 1.01-1.05, p = 0.007) were both significantly linked to greater odds of IS. In contrast, there was no causal association between genetic SARS-CoV-2 infection susceptibility and the occurrence of IS (OR 0.99, 95% CI 0.92-1.06, p = 0.694). Ten shared causal genes (TNFSF8, CFL2, TPM1, C15orf39, LHFPL6, FAM20C, SPAG9, KCNJ2, PELI1, and HLA-L) were established as possible mediators of the interplay between severe COVID-19 and the development of IS, with these genes primarily being enriched in immune-related and renin-angiotensin-aldosterone system pathways.
These findings indicate a possible causative relationship between IS risk and COVID-19 severity, offering crucial new information for managing COVID-19 patients. Promising options for therapeutic therapies for severe COVID-19 complicated by IS include the common genes found in the present study.
目前的观察性数据表明，新冠病毒（COVID-19）感染会影响相当一部分缺血性脑卒中（IS）患者。本研究旨在评估 COVID-19 与 IS 之间的因果关系。
采用两样本 Mendelian 随机化（2S-MR）方法，基于全基因组关联研究（GWAS）数据，探讨三种 COVID-19 参数（SARS-CoV-2 感染、COVID-19 住院和重症 COVID-19）的遗传决定因素与 IS 发生率之间的关系。利用该 2S-MR 技术，进一步评估表达数量性状基因座（eQTL）和 GWAS 研究的重叠情况，以识别与重症 COVID-19 和 IS 相关的共同致病基因。
IVW 方法表明，与 COVID-19 住院（OR 1.04，95%CI 1.01-1.08，p=0.023）和重症 COVID-19（OR 1.03，95%CI 1.01-1.05，p=0.007）相关的遗传变异均与 IS 发生的几率增加显著相关。相比之下，遗传易感性 SARS-CoV-2 感染与 IS 的发生无因果关联（OR 0.99，95%CI 0.92-1.06，p=0.694）。确定了 10 个共享的因果基因（TNFSF8、CFL2、TPM1、C15orf39、LHFPL6、FAM20C、SPAG9、KCNJ2、PELI1 和 HLA-L）作为严重 COVID-19 和 IS 发展之间相互作用的可能介导因子，这些基因主要富集在免疫相关和肾素-血管紧张素-醛固酮系统途径中。
这些发现表明 IS 风险与 COVID-19 严重程度之间可能存在因果关系，为 COVID-19 患者的管理提供了重要的新信息。对于治疗 COVID-19 患者并发的重症 COVID-19，本研究发现的共同基因可能为治疗提供新的思路。
