Association of human adenovirus load and viral genotype diversity with respiratory disease severity in children: a systematic review and meta-analysis.

Background: Human adenoviruses (HAdVs) are one of the most prevalent viruses in pediatric outpatients worldwide. The correlation between different genotypes of HAdVs and disease severity requires further investigation. The aim of this meta-analysis was to determine the association among HAdV load, viral genotypic diversity, and respiratory disease severity in children. Methods: We conducted subject-term searches in English language databases, including Web of Science, PubMed, American Medical Association (AMA), Cochrane Library, and European Society for Clinical Nutrition and Metabolism (ESPEN), in addition to a Chinese language database, China National Knowledge Infrastructure (CNKI). We assessed the quality of the literature and performed a meta-analysis using RevMan 5.3 and STATA version 15.1. The study indicators were HAdV load, viral type, and disease severity. We assessed effect sizes using odds ratio (OR), standard error, and diagnostic efficacy indicators. We also performed heterogeneity tests, sensitivity analyses, and publication and bias assessments. Results: We retrieved 12 papers on HAdV load, genotyping, and severity of respiratory disease in children. Four papers on viral load indicated that a high viral load was associated with an increased risk of severe pneumonia [combined OR =2.02; 95% confidence interval (CI): 1.64-2.47]. Six papers on B3 subtype viruses reported a combined sensitivity of 0.42 and specificity of 0.99. Eight publications on B7 subtype viruses reported a combined sensitivity of 0.71 and specificity of 0.97. The combined OR increased with sample size, but the association was not significant for the B3 subtype and was more significant for the B7 subtype. For severe pneumonia, the combined sensitivity of quantitative polymerase chain reaction (qPCR) was 0.20 for B3 (95% CI: 0.13-0.28) and 0.48 for B7 (95% CI: 0.43-0.53), while the combined specificity for B3 was 0.96 (95% CI: 0.95-0.97) and 0.92 for B7 (95% CI: 0.85-0.98), which were higher than those of other polymerase chain reaction (PCR) methods. Conclusions: In children, we found a significant association among HAdV load, the B3 and B7 subtypes, and respiratory disease severity. qPCR showed high sensitivity and specificity for detecting the B3 and B7 virus subtypes, suggesting its suitability for clinical use. This study provides important insights into the role of HAdVs in childhood respiratory infections and may guide clinical diagnosis and therapeutic strategies.