Epidemiology and clinical patterns of human bocavirus coinfections: a systematic review and meta-analysis

The global epidemiology, coinfection patterns, and clinical manifestations of human bocavirus (HBoV) exhibit marked variation. We aimed to determine the regional and national status and trends in HBoV prevalence, seasonality, coinfection patterns, and clinical manifestations from 2013 to 2025. A comprehensive search was performed in PubMed and Web of Science, yielding 301 studies. A total of 21 eligible studies, encompassing 74,424 participants and 4,274 HBoV‑positive patients from nine countries across five continents, were identified. Of these, 18 studies that met pre‑specified design criteria (cross‑sectional or consecutive surveillance, with a valid denominator, and excluding studies that exclusively enrolled HBoV‑positive patients) were included in the primary prevalence meta‑analysis. The pooled prevalence was 9.7% (95% confidence interval [CI] 6.4–13.1;95% prediction interval [PI] 0.0–25.1%). The co‑infection analysis comprised 18 studies. The seasonality analysis initially included 12 studies. For summer, the crude proportion of HBoV‑positive cases occurring in summer was 17.2% (95% CI: 10.0–24.5); after excluding three outliers (Ljubin-Sternak et al., 2021; Caporizzi et al., 2024; Zhang et al., 2021) identified by pre-specified criteria (studentized residual > 2.0 and I² reduction > 20% points), the adjusted proportion was 23.2% (95% CI: 17.2–29.1). No outliers were identified for spring, autumn, or winter. The clinical manifestation analysis was based on 9 studies. The higher coinfection proportion in the post-pandemic subgroup was not a statistically significant moderator effect (meta-regression p = 0.721). The seasonal peak was delayed by 1.6 months after the pandemic, and the phase distribution became more concentrated in the post-pandemic era. The overall proportion of coinfections was 65.9%(95% CI 64.3–67.5; 95% PI 18.5–100.0%). Among specific pathogens, Respiratory Syncytial Virus (RSV) had the highest coinfection rate. Patients with coinfections had a significantly higher risk of pneumonia than those with monoinfections (OR = 1.53, 95% CI 1.08–2.18) and coinfection was associated with an average 0.80-day longer hospital stay. However, these clinical analyses were based on only nine studies, the majority from China, and bacterial co‑pathogens were not assessed. HBoV prevalence, seasonality, and coinfection patterns are significantly influenced by geographic region, age, and socioeconomic factors. The finding of increased pneumonia risk in co-infected patients, although statistically significant, must be interpreted with caution due to the limited number of studies, their geographic concentration, and potential residual confounding. Further research incorporating standardized protocols and comprehensive pathogen testing is required to clarify the clinical impact of HBoV coinfections. PROSPERO CRD420261460519.