Active EBV infection in children: associations between DNA load, infection status, immune status, and disease severity

Abstract Background This study investigated active Epstein-Barr virus (EBV) infection in children and examined the associations among EBV deoxyribonucleic acid (DNA) load, infection types, disease severity, and immune characteristics. Methods A total of 35,956 pediatric patients who underwent EBV DN...

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Main Authors: Haipeng Yan, Xun Li, Xiaohui Zeng, Ting Luo, Xiao Li, Longlong Xie, Xiangyu Wang, Yufan Yang, Lan Luo, Xiulan Lu, Zhenghui Xiao
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Virology Journal
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Online Access:https://doi.org/10.1186/s12985-025-02741-7
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author Haipeng Yan
Xun Li
Xiaohui Zeng
Ting Luo
Xiao Li
Longlong Xie
Xiangyu Wang
Yufan Yang
Lan Luo
Xiulan Lu
Zhenghui Xiao
author_facet Haipeng Yan
Xun Li
Xiaohui Zeng
Ting Luo
Xiao Li
Longlong Xie
Xiangyu Wang
Yufan Yang
Lan Luo
Xiulan Lu
Zhenghui Xiao
author_sort Haipeng Yan
collection DOAJ
description Abstract Background This study investigated active Epstein-Barr virus (EBV) infection in children and examined the associations among EBV deoxyribonucleic acid (DNA) load, infection types, disease severity, and immune characteristics. Methods A total of 35,956 pediatric patients who underwent EBV DNA load testing were included. Patients were categorized based on their EBV DNA levels and infection status. Results Spearman’s rank correlation analysis revealed a positive association between EBV DNA levels and the mortality rate, as well as the incidence rates of acute kidney injury (AKI), respiratory failure, cardiovascular complications, coagulation abnormalities, and liver injury. Mortality risk significantly increased when EBV DNA exceeded 1 × 105 copies/mL (adjusted odds ratio: 10.53, 95% confidence interval: 2.38–46.59, P < 0.05). As EBV DNA levels increase, the rise in mortality rate during activation- immunoglobulin G (IgG+) was more pronounced than that observed during primary infections. Gaussian mixture model clustering identified two immune clusters. Cluster 0 exhibited elevated pro-inflammatory indicators (IFN-γ, IL-6) and anti-inflammatory indicator (IL-10) levels, along with reduced immune cell counts. This cluster showed higher activation-IgG+ and mortality rates compared with Cluster 1. Conclusions An elevated EBV DNA load (> 1 × 105 copies/mL) in children is associated with increased mortality risk. High pro-inflammatory and anti-inflammatory states, coupled with low immune cell numbers, indicate critical condition. Simultaneous examinations of EBV DNA, antibodies, and immune status are recommended, especially for children with EBV DNA > 1 × 105 copies/mL, emphasizing the need for caution in those with activation-IgG+ and immune dysregulation.
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spelling doaj-art-079da98d1cec42bdb238557aacd3720e2025-08-20T03:14:02ZengBMCVirology Journal1743-422X2025-04-0122111410.1186/s12985-025-02741-7Active EBV infection in children: associations between DNA load, infection status, immune status, and disease severityHaipeng Yan0Xun Li1Xiaohui Zeng2Ting Luo3Xiao Li4Longlong Xie5Xiangyu Wang6Yufan Yang7Lan Luo8Xiulan Lu9Zhenghui Xiao10Internation Inpatient Ward & Hunan Provincial Key Laboratory of Emergency Medicine for Children, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital)Pediatrics Research Institute of Hunan Province & Pediatric Intensive Care Unit & Hunan Provincial Key Laboratory of Emergency Medicine for Children, School of Medicine, The Affiliated Children’s Hospital of Xiangya, Central South University (Hunan Children’s Hospital)Internation Inpatient Ward & Hunan Provincial Key Laboratory of Emergency Medicine for Children, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital)Pediatrics Research Institute of Hunan Province & Pediatric Intensive Care Unit & Hunan Provincial Key Laboratory of Emergency Medicine for Children, School of Medicine, The Affiliated Children’s Hospital of Xiangya, Central South University (Hunan Children’s Hospital)Pediatric Intensive Care Unit & Hunan Provincial Key Laboratory of Emergency Medicine for Children, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital)Pediatrics Research Institute of Hunan Province & Pediatric Intensive Care Unit & Hunan Provincial Key Laboratory of Emergency Medicine for Children, School of Medicine, The Affiliated Children’s Hospital of Xiangya, Central South University (Hunan Children’s Hospital)Pediatrics Research Institute of Hunan Province & Pediatric Intensive Care Unit & Hunan Provincial Key Laboratory of Emergency Medicine for Children, School of Medicine, The Affiliated Children’s Hospital of Xiangya, Central South University (Hunan Children’s Hospital)Pediatric Intensive Care Unit & Hunan Provincial Key Laboratory of Emergency Medicine for Children, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital)Internation Inpatient Ward & Hunan Provincial Key Laboratory of Emergency Medicine for Children, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital)Pediatric Intensive Care Unit & Hunan Provincial Key Laboratory of Emergency Medicine for Children, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital)Pediatric Intensive Care Unit & Hunan Provincial Key Laboratory of Emergency Medicine for Children, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital)Abstract Background This study investigated active Epstein-Barr virus (EBV) infection in children and examined the associations among EBV deoxyribonucleic acid (DNA) load, infection types, disease severity, and immune characteristics. Methods A total of 35,956 pediatric patients who underwent EBV DNA load testing were included. Patients were categorized based on their EBV DNA levels and infection status. Results Spearman’s rank correlation analysis revealed a positive association between EBV DNA levels and the mortality rate, as well as the incidence rates of acute kidney injury (AKI), respiratory failure, cardiovascular complications, coagulation abnormalities, and liver injury. Mortality risk significantly increased when EBV DNA exceeded 1 × 105 copies/mL (adjusted odds ratio: 10.53, 95% confidence interval: 2.38–46.59, P < 0.05). As EBV DNA levels increase, the rise in mortality rate during activation- immunoglobulin G (IgG+) was more pronounced than that observed during primary infections. Gaussian mixture model clustering identified two immune clusters. Cluster 0 exhibited elevated pro-inflammatory indicators (IFN-γ, IL-6) and anti-inflammatory indicator (IL-10) levels, along with reduced immune cell counts. This cluster showed higher activation-IgG+ and mortality rates compared with Cluster 1. Conclusions An elevated EBV DNA load (> 1 × 105 copies/mL) in children is associated with increased mortality risk. High pro-inflammatory and anti-inflammatory states, coupled with low immune cell numbers, indicate critical condition. Simultaneous examinations of EBV DNA, antibodies, and immune status are recommended, especially for children with EBV DNA > 1 × 105 copies/mL, emphasizing the need for caution in those with activation-IgG+ and immune dysregulation.https://doi.org/10.1186/s12985-025-02741-7Epstein-Barr virusImmune responseImmune dysregulationEpstein-Barr virus DNA load
spellingShingle Haipeng Yan
Xun Li
Xiaohui Zeng
Ting Luo
Xiao Li
Longlong Xie
Xiangyu Wang
Yufan Yang
Lan Luo
Xiulan Lu
Zhenghui Xiao
Active EBV infection in children: associations between DNA load, infection status, immune status, and disease severity
Virology Journal
Epstein-Barr virus
Immune response
Immune dysregulation
Epstein-Barr virus DNA load
title Active EBV infection in children: associations between DNA load, infection status, immune status, and disease severity
title_full Active EBV infection in children: associations between DNA load, infection status, immune status, and disease severity
title_fullStr Active EBV infection in children: associations between DNA load, infection status, immune status, and disease severity
title_full_unstemmed Active EBV infection in children: associations between DNA load, infection status, immune status, and disease severity
title_short Active EBV infection in children: associations between DNA load, infection status, immune status, and disease severity
title_sort active ebv infection in children associations between dna load infection status immune status and disease severity
topic Epstein-Barr virus
Immune response
Immune dysregulation
Epstein-Barr virus DNA load
url https://doi.org/10.1186/s12985-025-02741-7
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