Abstract：
UNASSIGNED: Objective: We conducted a two-sample bidirectional Mendelian randomization (MR) study to investigate the causal relationships between herpes viruses and sepsis. Methods: Publicly available genome-wide association study data were used. Four viruses, HSV-1, HSV-2, EBV, and CMV, were selected, with serum positivity and levels of antibody in serum as the herpes virus data. Results: In forward MR, susceptibility to HSV-1 was a risk factor for sepsis. The susceptibility to CMV showed a severity-dependent effect on sepsis and was a risk factor for the 28-day mortality from sepsis, and was also a risk factor for 28-day sepsis mortality in critical care admission. The EBV EA-D antibody level after EBV infection was a protective factor for 28-day sepsis mortality in critical care admission, and CMV pp28 antibody level was a risk factor for 28-day sepsis mortality in critical care admission. No statistically significant causal relationships between HSV-2 and sepsis were found. No exposures having statistically significant association with sepsis critical care admission as an outcome were found. In reverse MR, the sepsis critical care admission group manifested a decrease in CMV pp52 antibody levels. No causal relationships with statistical significance between sepsis exposure and other herpes virus outcomes were found. Conclusion: Our study identifies HSV-1 susceptibility as a sepsis risk, with CMV susceptibility elevating severity. Varied effects of EBV and CMV antibodies on sepsis severity are noted. Severe sepsis results in a decline in CMV antibody levels. Our results help prognostic and predictive enrichment and offer valuable information for precision sepsis treatment.
摘要：
目的：我们进行了双样本双向孟德尔随机化（MR）研究，以调查疱疹病毒与败血症之间的因果关系。
方法：使用公开的全基因组关联研究（GWAS）数据。四种病毒,HSV-1，HSV-2，EBV和CMV，被选中,血清阳性和血清抗体水平作为疱疹病毒数据。
结果：在正向MR中，HSV-1易感性是脓毒症的危险因素.对CMV的易感性对脓毒症表现出严重程度依赖性影响，并且是脓毒症28天死亡率的危险因素。也是重症监护住院患者28日脓毒症死亡率的危险因素.EBV感染后EBVEA-D抗体水平是重症监护患者28天脓毒症死亡率的保护因素，CMVpp28抗体水平是重症监护患者28天脓毒症死亡率的危险因素.未发现HSV-2与脓毒症之间有统计学意义的因果关系。没有发现与脓毒症重症监护入院有统计学意义的暴露。在反向MR中，脓毒症重症监护组出现CMVpp52抗体水平下降.未发现脓毒症暴露与其他疱疹病毒结局之间具有统计学意义的因果关系。
结论：我们的研究将HSV-1易感性确定为脓毒症风险，CMV易感性严重程度升高。注意到EBV和CMV抗体对脓毒症严重程度的不同影响。严重脓毒症导致CMV抗体水平下降。我们的结果有助于预后和预测性富集，并为精确脓毒症治疗提供有价值的信息。
方法：使用公开的全基因组关联研究（GWAS）数据。四种病毒,HSV-1，HSV-2，EBV和CMV，被选中,血清阳性和血清抗体水平作为疱疹病毒数据。
结果：在正向MR中，HSV-1易感性是脓毒症的危险因素.对CMV的易感性对脓毒症表现出严重程度依赖性影响，并且是脓毒症28天死亡率的危险因素。也是重症监护住院患者28日脓毒症死亡率的危险因素.EBV感染后EBVEA-D抗体水平是重症监护患者28天脓毒症死亡率的保护因素，CMVpp28抗体水平是重症监护患者28天脓毒症死亡率的危险因素.未发现HSV-2与脓毒症之间有统计学意义的因果关系。没有发现与脓毒症重症监护入院有统计学意义的暴露。在反向MR中，脓毒症重症监护组出现CMVpp52抗体水平下降.未发现脓毒症暴露与其他疱疹病毒结局之间具有统计学意义的因果关系。
结论：我们的研究将HSV-1易感性确定为脓毒症风险，CMV易感性严重程度升高。注意到EBV和CMV抗体对脓毒症严重程度的不同影响。严重脓毒症导致CMV抗体水平下降。我们的结果有助于预后和预测性富集，并为精确脓毒症治疗提供有价值的信息。
