Human Bocavirus in Childhood: A True Respiratory Pathogen or a “Passenger” Virus? A Comprehensive Review

Abstract

Recently, human bocavirus (HBoV) has appeared as an emerging pathogen, with an increasing number of cases reported worldwide. HBoV is mainly associated with upper and lower respiratory tract infections in adults and children. However, its role as a respiratory pathogen is still not fully understood. It has been reported both as a co-infectious agent (predominantly with respiratory syncytial virus, rhinovirus, parainfluenza viruses, and adenovirus), and as an isolated viral pathogen during respiratory tract infections. It has also been found in asymptomatic subjects. The authors review the available literature on the epidemiology of HBoV, the underlying risk factors associated with infection, the virus’s transmission, and its pathogenicity as a single pathogen and in co-infections, as well as the current hypothesis about the host’s immune response. An update on different HBoV detection methods is provided, including the use of quantitative single or multiplex molecular methods (screening panels) on nasopharyngeal swabs or respiratory secretions, tissue biopsies, serum tests, and metagenomic next-generations sequencing in serum and respiratory secretions. The clinical features of infection, mainly regarding the respiratory tract but also, though rarely, the gastrointestinal one, are extensively described. Furthermore, a specific focus is dedicated to severe HBoV infections requiring hospitalization, oxygen therapy, and/or intensive care in the pediatric age; rare fatal cases have also been reported. Data on tissue viral persistence, reactivation, and reinfection are evaluated. A comparison of the clinical characteristics of single infection and viral or bacterial co-infections with high or low HBoV rates is carried out to establish the real burden of HBoV disease in the pediatric population.

Analysis of a Cohort of 165 Pediatric Patients with Human Bocavirus Infection and Comparison between Mono-Infection and Respiratory Co-Infections: A Retrospective Study

“…The HBoV1 virions can infect human airway epithelial cells, inducing airway epithelial damage and inflammation. It has also been demonstrated the genome of HBoV could persist in epithelial cells for months even up to a year after an acute infection [6]. This persistence may explain the detection of viral genomes in about 5-44% of respiratory samples obtained from asymptomatic children [20].…”

“…Human bocavirus (HBoV) is a parvovirus, mainly affecting the lower respiratory and gastrointestinal tracts in childhood all over the world [1][2][3]. It is a small, icosahedral, linear, non-enveloped, single-stranded DNA virus measuring between 18 and 26 nm [4][5][6]. Four strains of the virus have been detected: HBoV1, HBoV2, HBoV3, and HBoV4 [7,8]; the former has been found primarily in samples from the respiratory tract, responsible for upper and lower respiratory tract infections (RTIs) [9]; instead, HBoV 2-4 have been identified mainly in stool, causing gastrointestinal tract infections [10,11].…”

“…Appetite loss, vomiting, and diarrhea, as well as skin rash, and stomatitis are more rarely described [16][17][18]. Blood exams are usually evocative of viral infection, with C-reactive protein (CRP) and white blood cells (WBC) normal or just slightly elevated [6,18]. Chest radiography frequently shows peribronchial or interstitial infiltrates, hyperinflation, or atelectasis [19].…”

“…However, in the most recent studies, there is good evidence supporting the hypothesis that HBoV is a genuine pathogenic agent, even when it is the sole infectious agent [6,[23][24][25]. Furthermore, viral persistence hinders the diagnosis of acute HBoV infection, making the detection of viral DNA in nasal swabs highly sensitive but little specific.…”

“…To overcome the concern about diagnosis of acute infection, it has been proposed the detection of HBoV in nasopharyngeal swab (HBoV high DNA load on secretion or HBoV mRNA on secretion) and serologic confirmation, with at least one of the following: serum positive IgM, low IgG avidity, or >4-fold IgG titre [6].…”