疱疹病毒感染对重症肺炎患者临床预后及呼吸道微生态的影响

doi:10.6040/j.issn.1671-7554.0.2024.1059

摘要/Abstract

摘要： 目的探讨疱疹病毒感染对重症肺炎患者临床预后及下呼吸道微生态的影响。方法纳入114例ICU住院的重症肺炎患者,根据宏基因组二代测序(metagenomic next-generation sequencing, mNGS)结果分为疱疹病毒阳性组和疱疹病毒阴性组,收集其基本人口统计学及临床特征资料,使用独立样本t检验、Mann-Whitney U检验及χ2检验比较两组资料之间的差异,使用Cox回归模型分析影响预后的因素,使用Kaplan-Meier法进行生存分析,使用对数秩(Log-Rank)检验比较两组生存曲线,绘制柱状图及热图比较两组之间下呼吸道微生物菌群的差异。结果疱疹病毒阳性组急性生理学和慢性健康评分(acute physiololgy and chronic health evaluation, APACHE Ⅱ)高于疱疹病毒阴性组,差异有统计学意义(Z=-2.260,P=0.024),其他临床特征差异无统计学意义。疱疹病毒感染是影响重症肺炎患者临床预后的独立危险因素;疱疹病毒阳性组30 d死亡率高于阴性组(44.64% vs. 27.57%, χ2=4.040,P=0.044),差异有统计学意义;其中人类α疱疹病毒Ⅰ型(herpes simplex virus-1, HSV-1)、Epstein-Barr病毒(Epstein-Barr virus, EBV)、人类β疱疹病毒5型即巨细胞病毒(cytomegalovirus, CMV)阳性患者30 d死亡率均高于对应疱疹病毒阴性患者,差异有统计学意义(χ2=3.982,P=0.046; χ2=4.991,P=0.025; χ2=6.791,P=0.009)。疱疹病毒阳性组和疱疹病毒阴性组的微生物菌群分布上存在差异,各组优势菌群略有不同,疱疹病毒阳性组更易合并纹带棒杆菌、嗜肺军团菌、曲霉菌、耶氏肺孢子菌等病原体。结论疱疹病毒感染是重症肺炎患者临床预后的独立危险因素,与重症肺炎患者的30 d死亡率密切相关,尤其是HSV-1、EBV、CMV的存在与30 d死亡率增加有关。疱疹病毒阳性的重症肺炎患者呼吸道中富集了更多的条件致病菌,提示疱疹病毒可能通过改变微生态来影响疾病预后。

关键词: 重症肺炎, 疱疹病毒感染, 下呼吸道微生态, 30 d死亡率, 宏基因组二代测序

Abstract: Objective To investigate the effect of herpesvirus infection on the clinical prognosis and the microbiota of the lower respiratory tract in patients with severe pneumonia. Methods According to the results of metagenomic next-generation sequencing(mNGS), 114 patients with severe pneumonia hospitalized in ICU were divided into herpesvirus-positive group and herpesvirus-negative group. The basic demographic and clinical characteristics were collected. Differences between the two sets of information were compared using the independent samples t test, Mann-Whitney U test, and χ2 test. Cox regression model was used to analyze the factors affecting prognosis. Kaplan-Meier method was used to conduct the survival analysis, and the Log-Rank test was applied to compare survival curves. Histograms and heat maps were generated to illustrate the differences in the lower respiratory tract microbiota between the two groups. Results The acute physiololgy and chronic health evaluation(APACHE II)score of the herpesvirus-positive group was higher than that of the negative group, and the difference was statistically significant(Z=-2.260, P=0.024). There were no significant differences in other clinical characteristics. Herpesvirus infection was an independent risk factor affecting the clinical prognosis of patients with severe pneumonia. The 30-day mortality rate of the herpesvirus-positive group was higher than that of the herpesvirus-negative group(44.64 % vs. 27.57 %, χ2=4.040, P=0.044), with a statistically significant difference. The 30-day mortality rate of herpes simplex virus-1(HSV-1),Epstein-Barr virus(EBV)and cytomegalovirus(CMV)positive groups were higher than that of the corresponding herpesvirus-negative groups, with a statistically significant difference(χ2=3.982, P=0.046; χ2=4.991, P=0.025; χ2=6.791, P=0.009). There were observable differences in the distribution of microbial flora between the herpesvirus-positive and herpesvirus-negative groups, with a distinct predominance of certain species in each group. The herpesvirus-positive group showed a higher likelihood of co-occurrence with pathogens such as Corynebacterium striatum, Legionella pneumophila, Aspergillus and Pneumocystis japonicus. Conclusion Herpesvirus infection is an independent risk factor for the clinical prognosis of patients with severe pneumonia, and is closely associated with the 30-day mortality of patients with severe pneumonia, particularly the presence of HSV-1, EBV, and CMV, which correlate with increased 30-day mortality rates. Furthermore, patients with severe pneumonia who were positive for herpesviruses tend to have a higher presence of conditional pathogenic bacteria in their respiratory tracts, suggesting that herpesviruses may influence disease prognosis by altering the microbiota.

Key words: Severe pneumonia, Herpesvirus infection, Lower respiratory tract microbiota, 30-day mortality, Metagenomic next-generation sequencing

中图分类号:

R563

葛雪,赵红艳. 疱疹病毒感染对重症肺炎患者临床预后及呼吸道微生态的影响[J]. 山东大学学报 (医学版), 2025, 63(6): 27-37.

GE Xue, ZHAO Hongyan. Effect of herpesvirus infection on clinical prognosis and respiratory microbiota in patients with severe pneumonia[J]. Journal of Shandong University (Health Sciences), 2025, 63(6): 27-37.

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