HMPV has been identified a leading cause of ARTIs since it was discovered in 2001. According to a serological study, HMPV infection has existed for at least 70 years . Almost all children eventually become infected by HMPV, and adults can be re-infected by HMPV throughout their lives due to incomplete immunity. The prevalence of HMPV in children is approximately 2.0–18.2% [4, 14,15,16]. In this study, we explored the epidemiology and genotypic diversity of HMPV within hospitalized children in Beijing, China from April 2017 to March 2018. Of the 1276 children, 52 (4.1%) were positive for HMPV, while 2% in southern China (Guangzhou, 2014–2016) and 7.14% in northern China (Beijing, 2010) [4, 17], indicating that the prevalence of HMPV could be different in across regions and years. Therefore, it is necessary to establish continuous epidemiological surveillance in a wider area. The detection rates of HMPV infection between male and female patients in our study were not significantly different (p = 0.251), but there was a significance difference in the detection rates among age groups, with patients aged ≤ 4 years (4.8%) having a higher rate of detection compared with the patients aged 5–14 years (1.7%) (p = 0.001). Notably, 90.4% of HMPV infections detected in this study occurred in patients aged ≤ 4 years, which is consistent with findings from prior studies [4, 15]. The peak age range for HMPV infections was 1–2 years (6.6%).
HMPV infections have a clear tendency toward seasonal distribution, supported by the result of the present study (p = 0.000), but they vary based on different climate and geography factors. Here, HMPV was detected most frequently in the winter and spring. The HMPV detection rate was highest in March 2018, which is similar to findings from studies in Lanzhou (China) and Korea [18, 19].
Co-infection with respiratory viruses and bacteria is commonly seen in cases of ARTIs. Coinfections of HMPV with other respiratory viruses have been reported many times, and patients with such co-infections are more likely to have a fever, lead to severe pneumonia, and cause higher hospitalization rates [4, 18, 20]. The proportion of co-infection in this study was 36.5%. IFV and RSV were the most frequently co-infected viruses, which may be related to the overlap between the epidemic season of HMPV with those of IFV and RSV . There was no significance difference observed between the co-infection group and mono-infection group in any of the assessed clinical manifestations, diagnoses, or hospital stay length. Peng et al. indicated that a high HMPV copy number is correlated with disease severity and hospital stay duration ; however, we did not find any relationship between the HMPV viral load and clinical features. There are also studies reporting that the viral load of asymptomatic children infected with HMPV is significantly lower than that of symptomatic children , which needs to be verified in future studies.
HMPV infection can cause both URTI and LRTI . The risk factors associated with severe HMPV infection include preterm birth, early age, low immune function, nosocomial infection, and chronic pulmonary, cardiopathy, or neurological disease . In the present study, all HMPV-infected patients had an URTI, 55.8% had pneumonia, and 44.2% had bronchitis. Additionally, 94.2% of HMPV-positive children had an abnormal chest radiograph, and the main clinical characteristics of HMPV infection were cough, fever, and rhinorrhoea. No severe cases were found in our cohort, and 78.9% of our patients were discharged within 7 days.
HMPV can be divided into genotypes A and B. Vicente et al. reported that type A HMPV is more virulent than type B, whereas Papenburg et al. concluded that type B HMPV was associated with severe infection [25, 26], and some studies found no evidence for differential severity among different HMPV genotypes . In the present study, we found patients with HMPV genotype A infection had a higher viral load compared to genotype B patients (p = 0.029), which is consistent with Oong’s report . However, there was no significant difference between HMPV genotypes A and B in terms of their epidemiological characteristics, hospital stay, or viral loads. We analysed the distribution of HMPV subtypes in Beijing based on a partial sequence of the N gene. Subtypes A2b, B1, and B2 were detected, but subtypes A1 and A2a were not found. The most prevalent subtype was B1 (54.5%), followed by A2b (40.9%), which is consistent with previous work conducted in Beijing, Changsha, Kuala Lumpur, and Jordanian [7, 14, 28, 29].
Finally, to study the genome variation of HMPV epidemic strains in Beijing, we obtained five complete HMPV genome sequences with 80.1–99.6% identity, and four of them have an identity of 99.1–99.6%. Phylogenetic tree results show that four strains belong to sublineage A2b and have the closest genetic distance to the gz-01 (China) strain, one strain belongs to sublineage B1, which is the first report of whole genome sequence of HMPV-B1 isolated in China. No recombination events or mutations in important function sites were found.
The study is limited by the lack of a control group without ARTIs and its short research duration. Follow-up studies with long-term continuous monitoring that include a control group are needed to analyse the clinical features more accurately.