Human metapneumovirus: an emerging public health threat and harbinger of a new pandemic

Role of respiratory pathogens in infants hospitalized for a first episode of wheezing and their impact on recurrences

Respiratory syncytial virus (RSV) is a major cause of serious acute lower respiratory tract infection in infants and the elderly. The lack of a licensed RSV vaccine calls for the development of vaccines with other targets and vaccination strategies. Here, we construct a recombinant protein, designated P-KFD1, comprising RSV phosphoprotein (P) and the E.-coli-K12-strain-derived flagellin variant KFD1. Intranasal immunization with P-KFD1 inhibits RSV replication in the upper and lower respiratory tract and protects mice against lung disease without vaccine-enhanced disease (VED). The P-specific CD4+ Tcells provoked by P-KFD1 intranasal (i.n.) immunization either reside in or migrate to the respiratory tract and mediate protection against RSV infection. Single-cell RNA sequencing (scRNA-seq) and carboxyfluorescein succinimidyl ester (CFSE)-labeled cell transfer further characterize the Th1 and Th17 responses induced by P-KFD1. Finally, we find that anti-viral protection depends on either interferon-γ (IFN-γ) or interleukin-17A (IL-17A). Collectively, P-KFD1 is a promising safe and effective mucosal vaccine candidate for the prevention of RSV infection.

Underestimation of Influenza Viral Infection in Childhood Asthma Exacerbations

An off-season outbreak of human metapneumovirus infections after ending of a COVID-19 lockdown

Pathogenesis and current advancement in treatment and prevention strategies for Human metapneumovirus.

Infections, Immunity & their Effects on Asthma

Human metapneumovirus was discovered recently respiratory virus implicated in both upper and lower respiratory tract infection. In children, the clinical symptoms of human metapneumovirus are similar to those produced by respiratory syncytial virus, ranging from mild to severe diseases such as bronchiolitis and pneumonia. The aim of the present study was to describe the prevalence of human metapneumovirus and other common respiratory viruses among admitted to hospital infants. From January 2006 to June 2006, 99 nasopharyngeal aspirates were collected from hospitalized children younger than 12 months in order to study respiratory viruses. Human metapneumovirus detection was performed by cell culture and two RT‐PCR targeting on polymerase and fusion genes. The latter gene was used for phylogenetic analysis. In 67/99 children (67%) at least one viral pathogen was identified, the viruses detected most frequently were respiratory syncytial virus (35%), human metapneumovirus (25%) and rhinovirus (19%). The results obtained in this study, show that: (1) human metapneumovirus is one of the most important viruses among children less than 12 months; (2) children infected with human metapneumovirus were significantly older than those infected by respiratory syncytial virus; (3) human metapneumovirus was associated more frequently with pneumonia whereas respiratory syncytial virus was only detected in patients with bronchiolitis; (4) there was a clear epidemiological succession pattern with only a small overlap among the viruses detected most frequently; (5) all human metapneumovirus samples were clustered within sublineage A2. J. Med. Virol. 80:1452–1460, 2008. © 2008 Wiley‐Liss, Inc.

Comparison of Epidemiologic and Clinical Features between Respiratory Syncytial Virus and Human Metapneumovirus in Korean Children

PurposeWe aimed to study the changes in respiratory virus detection rates during the control of the COVID-19 outbreak and to elucidate possible epidemiologic disturbances after the lifting of control measures.MethodsSevere acute respiratory infection (SARI) specimens were collected from hospitalized children in Baiyin, China, from 2021 to 2023. We conducted real-time fluorescence quantitative PCR (RT-qPCR) to detect various respiratory viruses, including influenza virus (IFV), human respiratory syncytial virus (HRSV), human rhinovirus (HRV), human parainfluenza virus (HPIV), human metapneumovirus (HMPV), human adenovirus (HADV), enterovirus (EV), and human coronavirus (HCoV). The results were statistically analyzed using SPSS 26.0 software.ResultsA total of 1353 nasopharyngeal swab specimens were collected from children with SARI between 2021 and 2023. The male-to-female ratio of 1.49:1, the total virus detection rate of 33.85% (458/1353). Data were analyzed by comparing two distinct periods: before the lifting of the COVID-19 control measures (January 1, 2021 – December 6, 2022) and after the lifting of the control measures (December 7, 2022 – December 31, 2023). During the three-year study period, there was no significant difference in the detection rate of pathogen positivity between the ≤ 1 year (OR: 0.986, 95% CI: 0.960–1.013) and 1–3 years (OR: 1.018, 95% CI: 0.997–1.060) age groups (P > 0.05). However, there were significant differences in pathogen positivity rates between the 3–6 years (OR: 1.097, 95% CI: 1.049–1.146) and > 6 years (OR: 1.099, 95% CI: 1.063–1.138) age groups (P < 0.05). Significant differences in pathogen positivity rates were observed between male (OR: 1.293, 95% CI: 1.156–1.445) and female (OR: 1.354, 95% CI: 1.157–1.583) children (P < 0.05). The positive detection rates for various viruses showed a decreasing trend in January and February 2023; however, IFV showed a significant rebound in 2023. Following the lifting of COVID-19 control measures, the overall positive detection rate for respiratory viruses increased significantly from 27.84 to 45.03% (OR: 1.313, 95% CI: 1.198–1.438) (P < 0.05). Prior to the lifting of control measures, the ranking of positive detection rates for respiratory viruses in children was as follows: HPIV > HRSV > HADV > HRV > HMPV > EV > HCOV > influenza virus (IFV). After the measures were lifted, the order was as follows: EV > IFV > HADV > HCOV > HPIV > HRV > HMPV > HRSV. The peak detection periods for HRV, HMPV, HADV, and EV shifted to later time points compared to those before the measures were lifted. After the lifting of control measures, the positive detection rates of IFV (OR: 1.090, 95% CI: 1.059–1.122), EV (OR: 1.102, 95% CI: 1.064–1.141), HCOV (OR: 1.043, 95% CI: 1.017–1.070), and HADV (OR: 1.028, 95% CI: 0.999–1.059) all significantly increased (P < 0.05); HRV (OR: 1.019, 95% CI: 0.994–1.044) and HMPV (OR: 1.010, 95% CI: 0.989–1.032) showed non-significant increases in positive detection rates (P > 0.05); HRSV (OR: 0.965, 95% CI: 0.946–0.985) was significantly reduced (P < 0.05), while the positive detection rate for HPIV (OR: 0.971, 95% CI: 0.943–1.001) showed no significant decrease(P > 0.05).ConclusionsThese findings help clarify that social interventions can influence the prevalence of respiratory viruses in children during unique historical periods. The implementation of COVID-19 control measures may have curbed the spread of respiratory viruses in children during the study period. After the lifting of control measures, monitoring of respiratory pathogens must be strengthened to reduce the harm caused by respiratory viruses to children’s health.

Human metapneumovirus and community-acquired respiratory illness in children.

We compared the clinical and demographic features of children with lower respiratory tract infection (LRI) caused by human metapneumovirus (HMPV), respiratory syncytial virus (RSV) and influenza A virus and sought to determine whether coinfection by HMPV and other respiratory viruses leads to increased disease severity. Nasal wash specimens were prospectively obtained from 516 children hospitalized for LRI during a 1-year period and tested for the presence of HMPV by reverse transcription-polymerase chain reaction and for RSV and influenza A by direct immunofluorescence. HMPV was detected in 68 (13%) patients and was the third most common viral pathogen; 16 of 68 HMPV-positive children (24%) had coinfection with other respiratory viruses (HMPVco).HMPV patients were older than RSV patients (17.6 +/- 16.8 months versus 10.5 +/- 11.8 months, P = 0.02). HMPV was associated with wheezing and hypoxemia at a rate similar to that of RSV and higher than that of influenza A. Atelectasis was more common among HMPV (40%) than among RSV and influenza patients (13%, P < 0.05 for each). HMPV infection was more often associated with a diagnosis of pneumonia than RSV and influenza A and was more often associated with a diagnosis of asthma and less often associated with a diagnosis of bronchiolitis than RSV infection (P < 0.05 for each), even when corrected for age. Children with HMPVco had a higher rate of gastrointestinal symptoms but did not show a more severe respiratory picture. The clinical pattern of HMPV more closely resembles that of RSV than that of influenza A LRI, yet the differences in age, radiographic findings and clinical diagnosis suggest that HMPV pathogenesis may differ from that of RSV.

A comparatively newly discovered human metapneumovirus (HMPV) has emerged as an important cause of severe acute respiratory illness (SARI), second only to respiratory syncytial virus (RSV). RSV and HMPV taxonomically belong to same family and subfamily, and their clinical presentation and seasonal distribution are also seemed to be indistinguishable. Present study was planned to know the epidemiology and prevalence of HMPV and RSV in patients presented as SARI in a tertiary care hospital. Nasopharyngeal aspirate of 440 patients fulfilling World Health Organization criteria of SARI, enrolled during a 2-year study period, were collected and tested for the presence of RSV, HMPV and their subtypes A and B by real time polymerase chain reaction along with other respiratory viruses, viz influenza A, B, parainfluenza 1, 2, 3, 4, adenovirus, measles virus and bocavirus. The demographic details, clinical profile, underlying diseases, clinical diagnosis at the time of admission and seasonal distribution were studied and analyzed statistically. Overall positivity of RSV was 14.3% (24.68% in <5 years) and of HMPV was 3.63% (5.1% in <5 years and 5.08% in 6-12 years). Among RSV, subtype A (89%), and among HMPV, genotype B (68.8%) were predominating. Adults having underlying chronic obstructive pulmonary disease were more prone to acquire RSV and HMPV infections. RSV and HMPV positivity was restricted to winter season. We are reporting replacement of RSV with HMPV in this population. HMPV has emerged as an important cause of SARI in children <12 years of age. Alternative predominance of RSV and HMPV is an important observation.

Acute respiratory infections (ARI) constitutes a substantial disease burden in adults and the elderly. We aimed to identify all case-control studies investigating the potential role of respiratory viruses in the etiology of ARI in older adults aged 65 years old or more. We conducted a systematic literature review (across 7 databases) of case-control studies published from 1996 to 2017, which investigated the viral profile of older adults with and without ARI. We then computed a pooled odds ratio (OR) with 95% CI and virus–specific attributable fraction among the exposed (AFE) of 8 common viruses – respiratory syncytial virus (RSV), influenza virus (Flu), parainfluenza virus (PIV), human metapneumovirus (HMPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV). From the 16 studies included, there was strong evidence for association indicating possible causal attribution for RSV (OR 8.5 (3.9-18.5); AFE 88%), Flu (OR 8.3 (4.4-15.9); AFE 88%), PIV (OR not available (NA); AFE ~100%), HMPV (OR 9.8 (2.3-41.0); AFE 90%), AdV (OR NA; AFE ~100%), RV (OR 7.1 (3.7-13.6); AFE 86%) and CoV (OR 2.8 (2.0-4.1); AFE 65%) in older adults presenting with ARI compared to those without respiratory symptoms (asymptomatic) or healthy older adults. However, there was no significant difference in the detection of BoV in cases and controls. This review supports RSV, Flu, PIV, HMPV, AdV, RV and CoV as important causes of ARI in older adults, and provides quantitative estimates of the absolute proportion of virus–associated ARI cases to which a viral cause can be attributed.

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause a high burden of disease, particularly in children and the elderly. With the aim to add knowledge on RSV and HMPV infections in Italy, a prospective, multicenter study was conducted by eight centers of the Working Group on Respiratory Virus Infections (GLIViRe), from December 2018-April 2019. Weekly distribution and patients' demographic and clinical data were compared in 1300 RSV and 222 HMPV-positive cases. Phylogenetic analysis of the G-glycoprotein coding region was performed to characterize circulating strains. RSV positivity ranged from 6.4% in outpatients of all ages to 31.7% in hospitalized children; HMPV positivity was 4-1.2% with no age-association. RSV season peaked in February and ended in mid-April: HMPV circulation was higher when RSV decreased in early spring. RSV was more frequent in infants, whereas HMPV infected comparatively more elderly adults; despite, their clinical course was similar. RSV-B cases were two-thirds of the total and had similar clinical severity compared to RSV-A. Phylogenetic analysis showed the circulation of RSV-A ON1 variants and the predominance of RSV-B genotype BA10. HMPV genotype A2c was the prevalent one and presented insertions of different lengths in G. This first multicenter Italian report on seasonality, age-specific distribution, and clinical presentation of RSV and HMPV demonstrated their substantial disease burden in young patients but also in the elderly. These data may provide the basis for a national respiratory virus surveillance network.

Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription.