Abstract
Human bocavirus (HBoV) has been detected primarily in children with acute lower respiratory tract disease (LRTD), but its occurrence, clinical profile, and role as a causative agent of RTD are not clear. The aim of this study was to investigate the prevalence and the potential clinical relevance of HBoV. Using molecular tests, we tested 1352 nasopharyngeal samples obtained between October 1, 2017 and April 30, 2018 from children up to the age of 16 with RTD for the presence of HBoV DNA and 20 other respiratory pathogens at three different hospitals in Belgium. HBoV was detected in 77 children with a median age of 10.6 months. Consecutive samples were available for 15 HBoV-positive children and showed persistent HBoV positivity in four of them. Monoinfection was observed in six infants. Four of them were born prematurely and were infected during hospitalization at the neonatal intensive care unit (NICU). Only one of these six monoinfected children was diagnosed with recurrent wheezing due to HBoV. This child was carried to term and had a high viral load. Coinfections, most frequently with rhinovirus (52.1%) and adenovirus (49.3%), were observed in 72 patients. In seventeen of them in which HBoV was present at high viral load or higher viral load than its copathogens, bronchi(oli)tis (n = 8), recurrent wheezing (n = 8) or episodic wheezing (n = 1) were diagnosed. Our results suggest that HBoV infection at high viral load in infants is associated with wheezing (P = 0.013, Cramer’s V = 0.613).
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Introduction
Respiratory tract diseases (RTDs) are a leading reason for morbidity in young children and are caused by a broad spectrum of microbial agents. Viruses account for the largest number of respiratory tract infections (RTIs). The so-called respiratory viruses include influenza A and B viruses (IAV, IBV), human parainfluenza viruses (HPIVs), human respiratory syncytial virus (HRSV), human adenoviruses (HAdVs), human rhinoviruses (HRVs), human coronaviruses (HCoVs), enteroviruses (EVs) and human parechoviruses (HPeVs). In the 21st century, using large-scale molecular virus screening, several novel viruses have been discovered in patients with respiratory infections. These viruses include human metapneumovirus (hMPV), polyomaviruses KI and WU, several coronaviruses (SARS-CoV, HCoV-NL63, HCoV-HKU1, MERS-CoV) and human bocavirus (HBoV) as described by Allander et al. in 2005 [1,2,3]. The DNA virus HBoV is a member of the family Parvoviridae, genus Bocaparvovirus. HBoV is classified into genotypes 1 through 4. HBoV1 is predominantly found in respiratory tract secretions from children with RTD, and HBoV2-4 are found mainly in stool samples from patients with gastroenteritis [3, 4]. HBoV is predominantly present in winter and spring [5]. The average prevalence of HBoV in respiratory tract samples ranges from 1.0% to 56.8%, depending on the country. The worldwide estimate for the total prevalence of HBoV in respiratory infections is 6.3% [6]. HBoV has been reported worldwide in all age groups; however, it has mainly been detected in children who presented at the hospital with RTD. A high HBoV viral load could be an etiologic agent for severe LRTI, and these patients may develop bronchitis and pneumonia with fever, cough and peribronchial infiltrates detected on a chest X-ray [17].
In order to assess whether HBoV showed characteristics of a respiratory pathogen in the coinfected group, we chose to focus in detail on cases in which HBoV was expressed at a high viral load or a higher viral load then it copathogens. In these patients, a viral URT prodrome followed by breathing difficulties and wheezing were the most frequently reported clinical signs, and bronchi(oli)tis and recurrent wheezing were the leading diagnoses. In this group, a relationship was observed between HBoV and LRTD. Some previous studies have found high viral loads to be associated with more-severe symptoms [9], while others have failed to find a clear relationship [5, 7, 23]. In our opinion, it is not possible to establish a clear relationship between viral load and severity of LRTD. In the past, many scoring systems have been developed in an attempt to quantify respiratory distress objectively, but few have demonstrated any predictive validity [36]. Since clinical parameters such as respiratory rates or use of accessory muscles were sometimes lacking in the medical files, it was not possible to make a 100% correct statement about severity. We may assume that all children who needed hospitalization, and certainly those who developed hypoxia with a need for extra oxygen or ventilator support, had rather severe clinical signs.
In conclusion, HBoV is frequently found in NPSs of children with RTD. In our study, we found that HBoV infection at high viral load in infants is associated with bronchi(oli)tis and recurrent or episodic wheezing (P = 0.013, Cramer’s V = 0.613).
Data availability
The data generated and/or analyzed during the current study are available online: Online Resource 2 Dataset of the 87 nasopharyngeal samples positive for human bocavirus (xls. 447 kB).
Abbreviations
- BPD:
-
Bronchopulmonary dysplasia
- CLD:
-
Chronic lung disease
- CPAP:
-
Continuous positive airway pressure
- Cq:
-
Quantitation cycle
- CRP:
-
C-reactive protein
- EV:
-
Enterovirus
- GI:
-
Gastrointestinal
- HAdV:
-
Human adenoviruses
- HBoV:
-
Human bocavirus
- HCoV-229E:
-
Human coronavirus 229E
- HCoV-HKU1:
-
Human coronavirus HKU1
- HCoV-NL63:
-
Human coronavirus NL63
- HCoV-OC43:
-
Human coronavirus OC43
- hMPV:
-
Human metapneumovirus
- HRV:
-
Human rhinoviruses
- HPeV:
-
Human parechovirus
- HPIV:
-
Human parainfluenza viruses
- HRSV:
-
Human respiratory syncytial virus
- IAV:
-
Human influenza A virus
- IBV:
-
Human influenza B virus
- LRTD:
-
Lower respiratory tract disease
- MP:
-
Mycoplasma pneumoniae
- ND:
-
Not detected
- NICU:
-
Neonatal intensive care unit
- NPS:
-
Nasopharyngeal samples
- PICU:
-
Pediatric intensive care unit
- RTD:
-
Respiratory tract disease
- RTI:
-
Respiratory tract infections
- RT-PCR:
-
Real-time PCR
- SARI:
-
Severe acute respiratory infection
- UH:
-
University Hospital
- URTD:
-
Upper respiratory tract disease
- WBC:
-
White blood cell count
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VV analyzed and interpreted the laboratory and clinical data for all patients of the three participating hospitals included in this study and wrote this manuscript. The microbiologists MR, KF and WV provided the laboratory data from AZ Sint-Jan and AZ Sint-Lucas Hospital of Bruges and helped with the interpretation of the data. The pediatricians SD, KS and FC provided the clinical data from the Ghent University Hospital, the AZ Sint-Jan and AZ Sint-Lucas Hospital of Bruges, respectively, and helped with the interpretation of the data. The study was supervised and coordinated by professor EP. All authors read and approved the final manuscript.
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The study was conducted in accordance with the Declaration of Helsinki and was approved by the Medical Ethics Committee of the three participating hospitals under Belgian Registration number B670201836996.
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Verbeke, V., Reynders, M., Floré, K. et al. Human bocavirus infection in Belgian children with respiratory tract disease. Arch Virol 164, 2919–2930 (2019). https://doi.org/10.1007/s00705-019-04396-6
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DOI: https://doi.org/10.1007/s00705-019-04396-6