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多发性硬化症和 COVID-19:一项双向孟德尔随机化研究。

Multiple sclerosis and COVID-19: a bidirectional Mendelian randomization study.

机构信息

School of Basic Medical Sciences, Guangdong Pharmaceutical University, Guangzhou, China.

School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.

出版信息

Front Immunol. 2024 Oct 18;15:1451347. doi: 10.3389/fimmu.2024.1451347. eCollection 2024.

Abstract

This study aimed to investigate the potential relationship between multiple sclerosis (MS) and coronavirus disease 2019 (COVID-19) outcomes using Mendelian randomization analysis. Specifically, it evaluates whether genetic factors, including the single-nucleotide polymorphism (SNP) rs10191329, influence the susceptibility of MS patients to three COVID-19 outcomes [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, hospitalized COVID-19, and severe COVID-19]. This study utilized genome-wide association study summary statistics from the International Multiple Sclerosis Genetics Consortium to conduct a Mendelian randomization analysis. SNPs strongly associated with MS were selected to examine their impact on COVID-19 outcomes. The analysis focused on identifying any causal associations between MS and COVID-19 severity, as well as assessing the role of interferon beta (IFNβ) treatment in modifying these outcomes. The results suggest a potential association between MS and an increased risk of COVID-19, but individuals carrying the rs10191329 SNP appeared less likely to develop severe COVID-19. This SNP, located within the DYSF-ZNF638 locus, may influence immune responses and MS severity, highlighting its relevance for personalized treatment strategies. Importantly, no significant causal relationship was found between IFNβ treatment and the three COVID-19 outcomes, indicating that the findings in treated patients differ from those observed in untreated patients. This suggests that IFNβ may offer protective effects against SARS-CoV-2 in MS patients. These findings underscore the importance of genetic factors, such as rs10191329, in shaping the clinical outcomes of MS patients in the context of COVID-19. Further research should explore targeted therapies and personalized approaches for managing MS during the ongoing pandemic.

摘要

本研究旨在通过孟德尔随机化分析探讨多发性硬化症(MS)与 2019 年冠状病毒病(COVID-19)结局之间的潜在关系。具体来说,评估包括单核苷酸多态性(SNP)rs10191329 在内的遗传因素是否影响 MS 患者对 COVID-19 三种结局[严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染、住院 COVID-19 和重症 COVID-19]的易感性。本研究利用国际多发性硬化症遗传学联合会的全基因组关联研究汇总统计数据进行孟德尔随机化分析。选择与 MS 强烈相关的 SNP 来检查它们对 COVID-19 结局的影响。该分析重点识别 MS 与 COVID-19 严重程度之间的任何因果关系,并评估干扰素-β(IFNβ)治疗在修饰这些结局中的作用。结果表明 MS 与 COVID-19 风险增加之间存在潜在关联,但携带 rs10191329 SNP 的个体发生重症 COVID-19 的可能性较低。该 SNP 位于 DYSF-ZNF638 基因座内,可能影响免疫反应和 MS 严重程度,突出其对个体化治疗策略的相关性。重要的是,未发现 IFNβ 治疗与 COVID-19 三种结局之间存在显著的因果关系,表明治疗患者的发现与未治疗患者的观察结果不同。这表明 IFNβ 可能为 MS 患者提供对 SARS-CoV-2 的保护作用。这些发现强调了遗传因素(如 rs10191329)在 COVID-19 背景下塑造 MS 患者临床结局的重要性。进一步的研究应探索针对 MS 的靶向治疗和个体化方法,以在当前大流行期间进行管理。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0198/11527686/5fcf7eb3c338/fimmu-15-1451347-g001.jpg

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