Clinical characteristics, risk stratification, and subgroup-dependent IVIG efficacy in hospitalized children with infectious mononucleosis: a single-center retrospective study.
- 1Department of Pediatrics, The First People's Hospital of Chuzhou, Chuzhou, China.
Abstract
Infectious mononucleosis (IM) is a common Epstein-Barr virus (EBV)-related illness in Chinese children, yet comprehensive data on its clinical presentation, complications, and treatment response are limited. This study aimed to describe clinical characteristics, identify risk factors for hepatic dysfunction and splenomegaly, establish a risk stratification model based on EBV-DNA load and CD4+/CD8+ ratio, and identify subgroups that may benefit from intravenous immunoglobulin (IVIG). A total of 515 children with IM (2020-2025) were enrolled. Hepatic dysfunction was defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of normal (>40 U/L); Splenomegaly was confirmed by ultrasound. Based on EBV-DNA load (threshold: 50×102 copies/mL) and CD4+/CD8+ ratio (threshold: 0.4), patients were cross-classified into four groups: Low-risk, Immune dysregulation, High viral load, and Synergistic high-risk. Multivariate logistic regression and subgroup analyses were used to evaluate risk stratification and IVIG efficacy. The median age was 5.2 years [interquartile range (IQR), 3.1-7.8 years], with male predominance (56.7%) and summer peak (31.1%). Common findings included fever (93.2%), cervical lymphadenopathy (88.2%), and tonsillar enlargement (88.0%). Laboratory evaluation revealed lymphocytosis (lymphocyte% 61.2%), elevated ALT or AST, and reduced CD4+/CD8+ ratio (0.4). Independent risk factors for both complications included age ≥6 years, CD4+/CD8+ <0.4, and EBV-DNA ≥50×102 copies/mL. In the four-tier stratification, the Synergistic high-risk group had the highest complication rates (hepatic dysfunction: 49.4%; persistent splenomegaly >7 days: 23.3%), with adjusted odds ratios (ORs) of 7.15 and 3.21 versus the Low-risk group (P for trend <0.001). Notably, IVIG showed subgroup-dependent efficacy: significant benefit was confined to children with CD4+/CD8+ <0.4. In the Synergistic high-risk group, IVIG reduced persistent splenomegaly from 42.4% to 13.3% (P<0.001) and shortened hospital stay from 11.0 to 8.0 days (P<0.05); in the Immune dysregulation group, IVIG reduced persistent splenomegaly from 27.3% to 12.5% (P<0.05). No benefit was observed in groups with preserved immune regulation. Pediatric IM in our cohort predominantly affects preschool-aged boys with summer peak. Hepatic dysfunction and splenomegaly are driven by synergistic interaction between high viral load and immune dysregulation. The four-tier stratification model effectively predicts complication risk. IVIG demonstrates subgroup-dependent efficacy, with benefit confined to children with CD4+/CD8+ <0.4-particularly the Synergistic high-risk subgroup. Routine IVIG is not recommended for all IM patients, but may be considered in selected patients, but these findings require prospective validation in those with immune dysregulation. Prospective trials in biomarker-selected populations are warranted.
Related
- Epidemiological characteristics and in-hospital burden of infectious mononucleosis among hospitalized children in China, 2021–2023
- Acyclovir and ganciclovir exposure and short-term outcomes in hospitalized children with EBV-associated mononucleosis-like illness: a retrospective cohort study using inverse probability of treatment weighting
- IL27RA ubiquitination by CBL E3 ligase regulates IL27 dependent immune response against EBV- induced infectious mononucleosis
- Age-related clinical characteristics of respiratory syncytial virus infection in hospitalized children: a retrospective study
- Palmoplantar Maculopapular Rash Mimicking Secondary Syphilis in Infectious Mononucleosis After Sequential Antibiotic Exposure: A Case Report
BibTeX
@article{zhan2026clinical,
title = {{Clinical characteristics, risk stratification, and subgroup-dependent IVIG efficacy in hospitalized children with infectious mononucleosis: a single-center retrospective study.}},
author = {Feng Zhan and Taimei Sun and Si Wang and Chong Zhong},
journal = {Translational pediatrics},
year = {2026},
month = sep,
doi = {10.21037/tp-2026-0629},
url = {https://europepmc.org/article/MED/42996731},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Clinical characteristics, risk stratification, and subgroup-dependent IVIG efficacy in hospitalized children with infectious mononucleosis: a single-center retrospective study.
AU - Feng Zhan
AU - Taimei Sun
AU - Si Wang
AU - Chong Zhong
PY - 2026
DA - 2026/09/30
JO - Translational pediatrics
DO - 10.21037/tp-2026-0629
UR - https://europepmc.org/article/MED/42996731
AB - Infectious mononucleosis (IM) is a common Epstein-Barr virus (EBV)-related illness in Chinese children, yet comprehensive data on its clinical presentation, complications, and treatment response are limited. This study aimed to describe clinical characteristics, identify risk factors for hepatic dysfunction and splenomegaly, establish a risk stratification model based on EBV-DNA load and CD4+/CD8+ ratio, and identify subgroups that may benefit from intravenous immunoglobulin (IVIG). A total of 515 children with IM (2020-2025) were enrolled. Hepatic dysfunction was defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) above the upper limit of normal (>40 U/L); Splenomegaly was confirmed by ultrasound. Based on EBV-DNA load (threshold: 50×102 copies/mL) and CD4+/CD8+ ratio (threshold: 0.4), patients were cross-classified into four groups: Low-risk, Immune dysregulation, High viral load, and Synergistic high-risk. Multivariate logistic regression and subgroup analyses were used to evaluate risk stratification and IVIG efficacy. The median age was 5.2 years [interquartile range (IQR), 3.1-7.8 years], with male predominance (56.7%) and summer peak (31.1%). Common findings included fever (93.2%), cervical lymphadenopathy (88.2%), and tonsillar enlargement (88.0%). Laboratory evaluation revealed lymphocytosis (lymphocyte% 61.2%), elevated ALT or AST, and reduced CD4+/CD8+ ratio (0.4). Independent risk factors for both complications included age ≥6 years, CD4+/CD8+ <0.4, and EBV-DNA ≥50×102 copies/mL. In the four-tier stratification, the Synergistic high-risk group had the highest complication rates (hepatic dysfunction: 49.4%; persistent splenomegaly >7 days: 23.3%), with adjusted odds ratios (ORs) of 7.15 and 3.21 versus the Low-risk group (P for trend <0.001). Notably, IVIG showed subgroup-dependent efficacy: significant benefit was confined to children with CD4+/CD8+ <0.4. In the Synergistic high-risk group, IVIG reduced persistent splenomegaly from 42.4% to 13.3% (P<0.001) and shortened hospital stay from 11.0 to 8.0 days (P<0.05); in the Immune dysregulation group, IVIG reduced persistent splenomegaly from 27.3% to 12.5% (P<0.05). No benefit was observed in groups with preserved immune regulation. Pediatric IM in our cohort predominantly affects preschool-aged boys with summer peak. Hepatic dysfunction and splenomegaly are driven by synergistic interaction between high viral load and immune dysregulation. The four-tier stratification model effectively predicts complication risk. IVIG demonstrates subgroup-dependent efficacy, with benefit confined to children with CD4+/CD8+ <0.4-particularly the Synergistic high-risk subgroup. Routine IVIG is not recommended for all IM patients, but may be considered in selected patients, but these findings require prospective validation in those with immune dysregulation. Prospective trials in biomarker-selected populations are warranted.
SN - 2224-4336
SN - 2224-4344
ER -