Association Between Chest CT Features and Disease Severity in Children With Human Bocavirus Mono-infection: A Retrospective Cohort Study

Technical Summary: Association Between Chest CT Features and Disease Severity in Children With Human Bocavirus Mono-infection

Problem Statement
Human bocavirus (HBoV) is a recognized cause of pediatric lower respiratory tract infection (LRTI), ranging from mild illness to severe pneumonia requiring intensive care. While the virus demonstrates tropism for airway epithelial cells and induces airway-centered injury in experimental models, the specific radiological correlates of disease severity in clinical cohorts remain poorly characterized. Previous imaging studies have been limited by small sample sizes, the inclusion of mixed viral infections, and a lack of severity stratification. Consequently, it is uncertain which chest computed tomography (CT) findings truly reflect clinically meaningful disease severity in immunocompetent children with confirmed HBoV mono-infection. Specifically, it is unclear whether diffuse parenchymal abnormalities (e.g., ground-glass opacities) or features reflecting ventilation heterogeneity (e.g., airway obstruction) are better predictors of critical illness.

Methodology
This retrospective cohort study analyzed 194 hospitalized children (<18 years) with PCR-confirmed HBoV mono-infection admitted to the Children's Hospital, Zhejiang University School of Medicine, between September 2022 and December 2023.

• Cohort Selection: Patients were included if they had a clinical diagnosis of LRTI, PCR-confirmed HBoV mono-infection (excluding co-detection of other respiratory pathogens), and a final diagnosis established by pediatricians.
• Severity Stratification: Cases were classified as moderate, severe, or critical based on institutional pediatric pneumonia criteria. Critical disease was defined by pSOFA score ≥2, ARDS, GCS ≤12, or oxygen saturation ≤90% despite therapy.
• Imaging Analysis: Chest CT images were independently reviewed by two blinded pediatric radiologists. Findings included ground-glass opacity (GGO), consolidation, atelectasis, emphysema, mediastinal emphysema, uneven lung inflation, tracheobronchial stenosis, air bronchogram sign, pleural effusion, and lobar involvement.
• Statistical Analysis: Associations between imaging findings and critical disease were evaluated using univariate and multivariate logistic regression (adjusted for age and sex). Kaplan–Meier analysis with log-rank testing assessed the association between imaging findings and hospitalization duration. Viral genomic analysis (whole-genome sequencing) was performed on a subset of patients.

Key Contributions

• Specific Cohort Characterization: The study isolates a population of immunocompetent children with PCR-confirmed HBoV mono-infection, removing the confounding effects of co-infections that often obscure radiological phenotypes in previous literature.
• Severity-Stratified Imaging Spectrum: It provides a detailed breakdown of CT findings across moderate, severe, and critical disease states, moving beyond general descriptions of "viral pneumonia."
• Differentiation of Pathological Mechanisms: The study distinguishes between diffuse parenchymal involvement and airway-centric dysfunction, testing the hypothesis that ventilation heterogeneity is more closely linked to severity than diffuse GGO.

Results

• Cohort Demographics: The study included 124 moderate (63.9%), 46 severe (23.7%), and 24 critical (12.4%) cases. Clinical symptoms such as wheezing, cyanosis, and dyspnea increased significantly with severity.
• Prevalence of GGO: Ground-glass opacity (GGO) was the most common finding across all severity groups (>90%) and showed no statistically significant association with critical disease (P=0.185).
• Ventilation Heterogeneity: "Uneven lung inflation" increased stepwise with severity: 24.2% in moderate, 54.3% in severe, and 66.7% in critical cases (P<0.001). Atelectasis was absent in moderate cases but present in severe (23.9%) and critical (20.8%) cases.
• Predictive Modeling:
  • Uneven Lung Inflation: Independently associated with critical disease after adjustment for age and sex (Adjusted OR: 3.74; 95% CI: 1.53–9.82; P=0.005).
  • Atelectasis: Also independently associated with critical illness (Adjusted OR: 3.51; 95% CI: 0.99–11.08; P=0.038).
  • Other Findings: GGO, consolidation, emphysema, and lobar involvement were not independently associated with critical disease in multivariate analysis.
• Clinical Outcomes: Kaplan–Meier analysis revealed that uneven lung inflation was associated with a longer duration of hospitalization (log-rank P=0.048), with a median stay of 14 days for affected patients. Atelectasis showed a similar trend but did not reach statistical significance (P=0.088).
• Viral Load and Mutations: Viral DNA load and gene mutation frequency did not show significant associations with disease severity.

Significance and Claims
The paper claims that in children with HBoV mono-infection, chest CT features reflecting ventilation heterogeneity and airway dysfunction (specifically uneven lung inflation and atelectasis) are more strongly associated with disease severity and critical illness than diffuse parenchymal abnormalities like GGO.

• Clinical Relevance: GGO appears to be a non-specific marker of viral lung involvement present regardless of severity. In contrast, uneven lung inflation serves as a potential imaging biomarker for identifying children at risk of critical illness and prolonged hospitalization.
• Pathophysiological Insight: The findings support a model where airway injury and obstruction, rather than diffuse alveolar involvement alone, drive clinical deterioration in severe HBoV infection.
• Limitations and Scope: The authors acknowledge the study's retrospective, single-center nature and the relatively small number of critical cases. They do not claim that CT is necessary for all HBoV infections, suggesting it may be most useful in patients with marked respiratory distress or worsening clinical status. The study concludes that these specific CT features may provide greater clinical relevance for severity assessment than GGO alone, but calls for future multicenter validation.