Clinical characteristics and risk factors of severe bocavirus-positive pneumonia in children and a literature review

Abstract

Increasing evidence suggests that human bocavirus (HBoV) is associated with respiratory symptoms in the absence of other identifiable pathogens and may even precipitate severe lower respiratory tract infections. However, only a few studies of severe human bocavirus infections in pediatric patients have been reported. The aim of the current study was to collect and analyze clinical data from children diagnosed with mild pneumonia and severe pneumonia, with an emphasis on those testing positive for HBoV from June 2009 to June 2019. Among the 799 HBoV-positive children included in the study, approximately 5.88% experienced severe pneumonia. Results revealed no significant differences between co-detection and single detection of HBoV-positive pneumonia in the severe and mild groups, supporting the pathogenicity of HBoV. A higher incidence of severe cases was observed in children lacking Bacillus Calmette–Guérin (BCG) vaccination, or with congenital airway or bronchopulmonary dysplasia (P = 0.046, P = 0.017). Overall, these findings indicate that HBoV can be identified in respiratory samples from children with severe pneumonia, denoting its role as a viral pathogen in hospitalized children with this condition. Preterm birth, wheezing history of previous infection, pulmonary underlying diseases such as airway dysplasia or bronchopulmonary dysplasia, and viremia may be the risk factors for severe pneumonia with HBoV positive.

Keywords

bocavirus / children / clinical features / risk factors / severe pneumonia

References

[1] Allander T, Tammi MT, Eriksson M, Bjerkner A, Tiveljung-Lindell A, Andersson B. Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci U S A. 2005; 102(36): 12891-12896.

[2] Kapoor A, Slikas E, Simmonds P, et al. A newly identified bocavirus species in human stool. J Infect Dis. 2009; 199(2): 196-200.

[3] Christensen A, Kesti O, Elenius V, et al. Human bocaviruses and paediatric infections. Lancet Child Adolesc Health. 2019; 3(6): 418-426.

[4] Deng X, Zou W, Xiong M, et al. Human parvovirus infection of human airway epithelia induces pyroptotic cell death by inhibiting apoptosis. J Virol. 2017; 91(24):e01533.

[5] Bhat R, Almajhdi FN. Induction of immune responses and immune evasion by human bocavirus. Int Arch Allergy Immunol. 2021; 182(8): 728-735.

[6] Zhang X, Zheng J, Zhu L, Xu H. Human bocavirus-1 screening in infants with acute lower respiratory tract infection. J Int Med Res. 2021; 49(8):3000605211027739.

[7] Nascimento-Carvalho AC, Vilas-Boas AL, Fontoura MSH, et al. Serologically diagnosed acute human bocavirus 1 infection in childhood community-acquired pneumonia. Pediatr Pulmonol. 2018; 53(1): 88-94.

[8] Choi SH, Huh JW, Hong SB, et al. Severe human bocavirus-associated pneumonia in adults at a referral hospital, Seoul, South Korea. Emerg Infect Dis. 2021; 27(1): 226-228.

[9] Ji K, Sun J, Yan Y, et al. Epidemiologic and clinical characteristics of human bocavirus infection in infants and young children suffering with community acquired pneumonia in Ningxia, China. Virol J. 2021; 18(1): 212.

[10] Bagasi AA, Howson-Wells HC, Clark G, et al. Human Bocavirus infection and respiratory tract disease identified in a UK patient cohort. J Clin Virol. 2020; 129:104453.

[11] Tabatabai J, Fakhiri J, Meyburg J, et al. Severe human bocavirus 1 respiratory tract infection in an immunodeficient child with fatal outcome. Pediatr Infect Dis J. 2019; 38(9): e219-e222.

[12] Ogimi C, Martin ET, Xie H, et al. Role of human bocavirus respiratory tract infection in hematopoietic cell transplant recipients. Clin Infect Dis. 2021; 73(11): e4392-e4399.

[13] National Health Commission of the People’s Republic of China. State Administration of Traditional Chinese Medicine. Guideline for diagnosis and treatment of community-acquired pneumonia in Children (2019 version) (In Chinese). Chin J Clin Infect Dis. 2019; 12: 6-13.

[14] Zhu Y, Xu B, Li C, et al. A multicenter study of viral aetiology of community-acquired pneumonia in hospitalized children in Chinese mainland. Virol Sin. 2021; 36(6): 1543-1553.

[15] Saha S, Fozzard N, Lambert SB, Ware RS, Grimwood K. Human bocavirus-1 infections in Australian children aged < 2 years: a birth cohort study. Eur J Clin Microbiol Infect Dis. 2023; 42(1): 99-108.

[16] Polo D, Lema A, Gándara E, Romalde JL. Prevalence of human bocavirus infections in Europe. A systematic review and meta-analysis. Transbound Emerg Dis. 2022; 69(5): 2451-2461.

[17] Petrarca L, Nenna R, Frassanito A, et al. Human bocavirus in children hospitalized for acute respiratory tract infection in Rome. World J Pediatr. 2020; 16(3): 293-298.

[18] Moesker FM, van Kampen JJ, van der Eijk AA, et al. Human bocavirus infection as a cause of severe acute respiratory tract infection in children. Clin Microbiol Infect. 2015; 21(10): 964.e1-964.e9648.

[19] Hao R, Ni K, Xia Q, et al. Correlation between nucleotide mutation and viral loads of human bocavirus 1 in hospitalized children with respiratory tract infection. J Gen Virol. 2013; 94(Pt 5): 1079-1085.

[20] Zhou L, Zheng S, Xiao Q, et al. Single detection of human bocavirus 1 with a high viral load in severe respiratory tract infections in previously healthy children. BMC Infect Dis. 2014; 14: 424.

[21] Silva PE, Figueiredo CA, Luchs A, et al. Human bocavirus in hospitalized children under 5 years with acute respiratory infection, São Paulo, Brazil, 2010. Arch Virol. 2018; 163(5): 1325-1330.

[22] Alkhalf H, Almutairi AR, Almutairi A, et al. Prevalence and clinical characterization of bocavirus infection in a specialized children’s hospital in Saudi Arabia. Cureus. 2022; 14(2):e22127.

[23] Endo R, Ishiguro N, Kikuta H, et al. Seroepidemiology of human bocavirus in Hokkaido prefecture, Japan. J Clin Microbiol. 2007; 45(10): 3218-3223.

[24] Sun H, Sun J, Ji W, et al. Impact of RSV coinfection on human bocavirus in children with acute respiratory infections. J Trop Pediatr. 2019; 65(4): 342-351.

[25] Fleck A, Raines G, Hawker F, et al. Increased vascular permeability: a major cause of hypoalbuminaemia in disease and injury. Lancet. 1985; 1(8432): 781-784.

[26] Levitt DG, Levitt MD. Human serum albumin homeostasis: a new look at the roles of synthesis, catabolism, renal and gastrointestinal excretion, and the clinical value of serum albumin measurements. Int J Gen Med. 2016; 9: 229-255.

[27] Aroor S, Mundkur S, Kumar S. Clinico-radiological profile and outcome of children with viral pneumonia admitted to paediatric intensive care unit in the pre COVID 19 period. J Nepal Paedtr Soc. 2022; 42(1): 26-32.

[28] Akhmerov A, Marbán E. Covid-19 and the heart. Circ Res. 2020; 126(10): 1443-1455.

[29] Li H, Liu L, Zhang D, et al. SARS-CoV-2 and viral sepsis: observations and hypotheses. Lancet. 2020; 395(10235): 1517-1520.

[30] Uršič T, Krivec U, Kalan G, Petrovec M. Fatal human bocavirus infection in an 18-month-old child with chronic lung disease of prematurity. Pediatr Infect Dis J. 2015; 34(1): 111-112.

[31] O’Neill LAJ, Netea MG. BCG-induced trained immunity: can it offer protection against COVID-19? Nat Rev Immunol. 2020; 20(6): 335-337.

[32] Aaby P, Andersen A, Ravn H, Zaman K. Co-administration of BCG and Diphtheria-tetanus-pertussis (DTP) vaccinations may reduce infant mortality more than the WHO-schedule of BCG first and then DTP. A re-analysis of demographic surveillance data from rural Bangladesh. EBioMedicine. 2017; 22: 173-180.

[33] Christensen A, Nordbø SA, Krokstad S, Rognlien AGW, Døllner H. Human bocavirus in children: mono-detection, high viral load and viraemia are associated with respiratory tract infection. J Clin Virol. 2010; 49(3): 158-162.

[34] Liao J, Yang Z, He Y, et al. Respiratory tract infection of fatal severe human bocavirus 1 in a 13-month-old child: a case report and literature review. Front Pediatr. 2022; 10:949817.

[35] Xu M, Arku B, Jartti T, et al. Comparative diagnosis of human bocavirus 1 respiratory infection with messenger RNA reverse-transcription polymerase chain reaction (PCR), DNA quantitative PCR, and serology. J Infect Dis. 2017; 215(10): 1551-1557.

[36] Xu M, Perdomo MF, Mattola S, et al. Persistence of human bocavirus 1 in tonsillar germinal centers and antibody-dependent enhancement of infection. mBio. 2021; 12(1):e03132.

[37] Kols NI, Aatola H, Peltola V, et al. Comparison of phenotypic and genotypic diagnosis of acute human bocavirus 1 infection in children. J Clin Virol. 2019; 120: 17-19.

[38] Schlaberg R, Ampofo K, Tardif KD, et al. Human bocavirus capsid messenger RNA detection in children with pneumonia. J Infect Dis. 2017; 216(6): 688-696.

RIGHTS & PERMISSIONS

2025 The Author(s). Pediatric Discovery published by John Wiley & Sons Australia, Ltd on behalf of Children's Hospital of Chongqing Medical University.