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Active EBV infection in children: associations between DNA load, infection status, immune status, and disease
Haipeng Yan1, Xun Li2, Xiaohui Zeng1
1Internation 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), Changsha, China.
Insights
High Epstein-Barr virus (EBV) DNA levels in children significantly increase mortality risk and organ injury. Monitoring EBV DNA, antibodies, and immune status is crucial for early intervention in critical cases.
Area of Science:
- Pediatric Infectious Diseases
- Virology
- Immunology
Background:
- Epstein-Barr virus (EBV) is a common human herpesvirus.
- Active EBV infection in children can lead to significant morbidity and mortality.
- Understanding the relationship between EBV DNA load and clinical outcomes is essential.
Purpose of the Study:
- To investigate active EBV infection in pediatric patients.
- To examine associations between EBV DNA load, infection types, disease severity, and immune characteristics.
- To identify risk factors for adverse outcomes in children with EBV infection.
Main Methods:
- Analysis of EBV DNA load testing data from 35,956 pediatric patients.
- Categorization of patients based on EBV DNA levels and infection status.
- Spearman's rank correlation and Gaussian mixture model clustering for immune profiling.
Main Results:
- Elevated EBV DNA load (>1 × 10^5 copies/mL) correlated with increased mortality and organ injuries (AKI, respiratory failure, liver injury).
- Mortality risk was significantly higher with EBV DNA >1 × 10^5 copies/mL (aOR: 10.53).
- Two immune clusters were identified: Cluster 0 showed higher inflammation, lower immune cells, and increased mortality, particularly in activation-IgG+ cases.
Conclusions:
- High EBV DNA load in children is a critical indicator of increased mortality and severe complications.
- Immune dysregulation, characterized by high pro-inflammatory/anti-inflammatory markers and low immune cells, signifies a critical condition.
- Integrated assessment of EBV DNA, antibodies, and immune status is recommended for risk stratification and management, especially in children with high EBV DNA levels.
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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