| Objective Human Adenovirus(HAdV)can cause severe pneumonia in infants and young children,complicated by severe sequelae and even fatal.It is essential to systematically investigate the clinical and epidemiological characteristics of children with HAdV pneumonia,especially severe patients,and explore the kinetics of viral load and related influencing factors in children with severe HAdV pneumonia,which will provide scientific basis for precise prevention and control and clinical treatment.Methods A retrospective survey was conducted to summarize and analyze the clinical and epidemiological data of children with community acquired pneumonia admitted to the Children’s Medical Center of Hunan Provincial People’s Hospital from 2013 to 2020.We prospectively monitored the kinetics of viral load in children under 14 years of age with severe HAdV pneumonia.Real-time quantitative PCR was used to detect the HAdV DNA of dynamically collected nasopharyngeal aspirate(NPA)samples,and further genotyping was performed by nest-PCR and sequencing.We combined HAdV-7 severe pneumonia children’s viral load kinetics and immune intervention treatment strategies to analyze the effects of different treatments on HAdV DNA kinetics.Results:(1)Among 50805 hospitalized children diagnosed with community-acquired pneumonia from 2013 to 2020,the overall HAdV detection rate was 13.11%(6662 of 50805).The detection rate of HAdV in boys was higher than that in girls(χ2=22.638 P=0.000).In addition,the age group was mainly focus on 4 to 5 years-old children(x2=987.09,16.65%).The incidence of HAdV infection peaked in summer(χ2=143.1 P=0.000).Cough(91.61%)and fever(82.18%)were the main clinical manifestations,and among the fever cases,the temperature more than 39℃accounted for 80.02%.The median HAdV load is 5.20(3.57,6.78)copies/mL.Among patients tested with HAdV-positive,37.89%complicated with leukocytosis,42.73%had elevated C-reactive protein(CRP),54.94%had elevated creatine kinase isoenzymes(CK-MB)and 87.41%had elevated lactate dehydrogenase(LDH).HAdV-positive cases accounted for 24.84%in severe community acquired pneumonia.Severe HAdV pneumonia is more common in boys and mainly focuses on the age group of 6 months to 2 years old.(2)The prospective monitoring study enrolled 132 children with severe HAdV pneumonia for viral load kinetic observation,including 105 cases of HAdV-7 infection and 12 cases of HAdV-3 infection.A total of 1372 qualified NPA samples were collected.There was a significant negative correlation between the viral load in the NPA samples and the course of disease(Spearman r=-0.547,P=0.000).Different HAdV genotypes have different viral dynamic characteristics.HAdV-7 load in NPA samples decreased at a rate of 0.089 log10 copies/mL per day,and the duration of viral shedding was predicted to be 96.9 days(y=8.624-0.089x).However,HAdV-3 load decreased more quickly and the duration of viral shedding was 51.4 days(y=9.558-0.186x).No significant differences in kinetics of viral load were found in different gender,age(>2 years vs ≤2 years),with or without underlying diseases,and bronchiolitis obliterans groups.(3)A total of 105 children with severe pneumonia infected with HAdV-7 were investigated on the effects of different interventions on viral load kinetics.In the high-dose intravenous immunoglobulin(IVIG)group,HAdV-7 load decreased faster,with a daily decline rate of 0.127 log10 copies/mL,and the predicted duration of virus shedding was 73.46 days(y=9.329-0.127x),which was significantly shorter than the low-dose IVIG group with predicted shedding time is 102.3 days(y=102.37-0.083x).There is no significant effect of virus shedding in NPA samples between different doses of glucocorticoid therapy group,different course of glucocorticoid therapy group,continous renal replacement therapy(CRRT)or conventional therapy group.Conclusion HAdV is an important pathogen of severe pneumonia in children under 5 years old in Hunan Province in recent years.Viral shedding in children with severe HAdV pneumonia persisted,among which HAdV-7 lasted longer than 3 months and the viral load decreased slowly than HAdV-3.In children with severe pneumonia infected with HAdV-7,high-dose IVIG therapy might accelerate virus shedding.It is suggested that monitoring the viral load kinetics in children with HAdV pneumonia,especially in severely patients,helps to understand the process of disease infection,and provides an objective basis for adjusting infection control strategies and evaluating treatment effects. |
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