Cao Yuan, Hu Xinhua, Li Jun, Zheng Yumin
Department of Neurology, People's Hospital of Xinjin District, Chengdu, Sichuan, People's Republic of China.
Department of Urology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, People's Republic of China.
J Multidiscip Healthc. 2025 May 27;18:2957-2967. doi: 10.2147/JMDH.S518008. eCollection 2025.
Increased incidences of herpes zoster (HZ) have been reported among COVID-19 patients, but the underlying causal mechanisms remain unclear. Inspired by an atypical case of HZ in a COVID-19 patient, we conducted a bidirectional Mendelian randomization (MR) analysis to investigate potential causal relationships.
The genetic statistics were extracted from the COVID19-hg GWAS meta-analyses and the IEU GWAS database. MR analyses were performed using the inverse-variance weighted (IVW) method as the primary approach, with MR-Egger, weighted median, simple mode, and weighted mode methods as supplementary strategies. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept, and MR-PRESSO analysis, while outliers were evaluated with MR-radial plots.
The MR analysis did not support a significant causal relationship between COVID-19 and HZ. In the forward analysis, the IVW method revealed no significant associations between COVID-19 susceptibility (β = -0.053, SE = 0.182, P = 0.77), hospitalization (β = 0.060, SE = 0.069, P = 0.38), or severity (β = 0.015, SE = 0.048, P = 0.75) and HZ. Similarly, the reverse analysis showed no significant effect of HZ on COVID-19 susceptibility (β = 0.006, SE = 0.006, P = 0.33), hospitalization (β = -0.012, SE = 0.012, P = 0.32), or severity (β = -0.015, SE = 0.020, P = 0.46). Sensitivity analyses confirmed these findings, showing no substantial heterogeneity or horizontal pleiotropy.
Our findings provide no evidence of a causal relationship between genetic predisposition to COVID-19 and the risk of HZ reactivation. The observed clinical association may be attributable to non-genetic factors, such as immune suppression or stress related to COVID-19 and its treatment. Further studies are warranted to explore these alternative mechanisms and improve clinical management of HZ in the context of COVID-19.
已有报道称新冠病毒病（COVID-19）患者中带状疱疹（HZ）的发病率有所增加，但其潜在因果机制仍不清楚。受一名COVID-19患者出现非典型HZ病例的启发，我们进行了双向孟德尔随机化（MR）分析，以研究潜在的因果关系。
从COVID19-hg全基因组关联研究（GWAS）荟萃分析和IEU GWAS数据库中提取遗传统计学数据。MR分析采用逆方差加权（IVW）法作为主要方法，以MR-Egger法、加权中位数法、简单模式法和加权模式法作为补充策略。使用Cochran's Q检验、MR-Egger截距和MR-PRESSO分析评估异质性和多效性，并通过MR径向图评估异常值。
MR分析不支持COVID-19与HZ之间存在显著因果关系。在前瞻性分析中，IVW法显示COVID-19易感性（β = -0.053，标准误 = 0.182，P = 0.77）、住院情况（β = 0.060，标准误 = 0.069，P = 0.38）或严重程度（β = 0.015，标准误 = 0.048，P = 0.75）与HZ之间无显著关联。同样，反向分析显示HZ对COVID-19易感性（β = 0.006，标准误 = 0.006，P = 0.33）、住院情况（β = -0.012，标准误 = 0.012，P = 0.32）或严重程度（β = -0.015，标准误 = 0.020，P = 0.46）无显著影响。敏感性分析证实了这些发现，表明不存在实质性异质性或水平多效性。
我们的研究结果没有提供证据表明COVID-19的遗传易感性与HZ再激活风险之间存在因果关系。观察到的临床关联可能归因于非遗传因素，如与COVID-19及其治疗相关的免疫抑制或应激。有必要进一步研究以探索这些替代机制，并改善COVID-19背景下HZ的临床管理。
