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We looked at the interactions between viral loads, coinfection rates and disease severity for children infected with two pneumoviruses: human metapneumovirus (HMPV) and respiratory syncytial virus (RSV). The HMPV RNA load in nasopharyngeal swabs of hospitalized children was significantly higher in mono‐infections compared to coinfections but this was not the case for RSV, which could be explained by different innate immune responses. Also, the viral load of neither of the two viruses was associated with disease severity although RSV‐infected children had higher severity scores than HMPV‐infected children. [ABSTRACT FROM AUTHOR]

This study evaluated the epidemiological and clinical characteristics of human metapneumovirus (hMPV) infection among hospitalized patients with acute respiratory infections during 2015–2021 and assessed the impact of the coronavirus disease 2019 pandemic on hMPV infection. A single‐center, retrospective cohort study was performed, including pediatric and adult patients with laboratory‐confirmed hMPV. Of a total of 990 patients, 253 (25.6%), 105 (10.6%), 121 (12.2%), and 511 (51.6%) belonged to age groups 0–2, 3–17, 18–59, and ≥60 years, respectively. The highest percentage (23.0%) of patients were hospitalized during 2019 and the lowest (4.7%) during 2020. Patients < 18 years experienced high rates of comorbidities (immunodeficiencies: 14.4% and malignancies: 29.9%). Here, 37/39 (94.9%) of all bronchiolitis cases were diagnosed in patients < 2 years, whereas more patients in older age groups were diagnosed with pneumonia. A greater proportion of hMPV patients diagnosed with viral coinfection (mostly respiratory syncytial virus and adenovirus) were <18 years. The highest percentages of intensive care unit admissions were recorded among patients < 18 years. Our findings demonstrate that hMPV is an important cause of morbidity in young children and a possibly underestimated cause of morbidity among older adults. [ABSTRACT FROM AUTHOR]

Background: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician‐rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient‐reported outcomes (PROs). Methods: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ‐5D‐5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. Results: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between‐pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician‐rated symptoms. Conclusions: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well‐being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza. [ABSTRACT FROM AUTHOR]

Introduction: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are significant contributors to the burden of acute respiratory infections in children, but data on hMPV from Southeast Asia are limited despite its potential for serious disease. This study aimed to compare the clinical presentation, resource utilisation and outcomes between hMPV and RSV infections in hospitalised Malaysian children. Methods: This retrospective, observational study included children aged ≤12 years old hospitalised with hMPV or RSV, confirmed via direct fluorescent antibody (DFA) methods, between 1 July to 30 October 2022 at Hospital Tuanku Ja'afar Seremban, Malaysia. Demographic, clinical presentation, resource utilisation and outcome data were analysed. Propensity score matching was used to balance cohorts based on key demographic and clinical characteristics. Results: This study included 192 patients, comprising 112 with hMPV and 80 with RSV. hMPV patients were older (median age 20.5 vs. 9.4 months, p < 0.001) and had a higher incidence of comorbidities (24.1% vs. 7.5%, p = 0.003). Fever was more common in the hMPV group (97.3% vs. 73.8%, p < 0.001), but the other clinical manifestations were similar. Postmatching analysis showed higher corticosteroid use in the hMPV group (p = 0.01). No significant differences were observed in the use of other resources, PICU admissions, duration of hospitalisation or mortality rates between both groups. Conclusion: hMPV and RSV infections in children share similar clinical manifestations and outcomes, with hMPV affecting older children and showing higher corticosteroid usage. These findings emphasise the need for equal clinical vigilance for both hMPV and RSV in paediatric respiratory infections. [ABSTRACT FROM AUTHOR]

Background: The hospitalized acute respiratory tract infection (HARTI) study used the Respiratory Intensity and Impact Questionnaire (RiiQ™) Symptom Scale, derived from FluiiQ™, to assess and compare the burden of respiratory infection symptoms for patients with influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) infection, with or without core risk factors (CRF) (age ≥65; chronic heart, renal, obstructive pulmonary disease; asthma). Methods: This was a prospective cohort study in adult patients hospitalized with acute respiratory tract infection (40 centers, 12 countries) during two consecutive influenza/RSV/hMPV seasons (2017–2019). The RiiQ™ Symptom Scale and EuroQol 5‐Dimensions 5‐Levels (EQ‐5D‐5L) were assessed by interview at two timepoints during hospitalization and at 1, 2, and 3 months post‐discharge. Results: Mean lower respiratory tract (LRT) symptom scores were higher for RSV and hMPV participants compared to influenza at 48 h after enrollment/early discharge (p = 0.001) and 3 months post‐discharge (p = 0.007). This was driven by LRT symptoms, including shortness of breath (SOB) (p < 0.01) and wheezing (p < 0.01) during hospitalization, and SOB (p < 0.05) and cough (p < 0.05) post‐discharge. Participants with CRF reported more moderate‐to‐severe SOB (p < 0.05) and wheezing (p < 0.05) compared to CRF(−) participants post‐discharge. EQ‐5D‐5L scores were moderately associated with RiiQ™ LRT and systemic symptoms domains. Conclusions: Results from the HARTI study suggest that in the study population, LRT symptoms were more severe for RSV and hMPV groups and for patients with CRF. RiiQ™ Symptom Scale scores shows a moderate association with EQ‐5D‐5L indicating that the RiiQ™ may provide useful insights and offer advantages over other measures for use in interventional RSV adult clinical studies. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (HMPV) is a leading cause of lower respiratory tract infection (LRTI) in pediatric and geriatric populations. We recently found that two PDZ‐binding motifs of the M2‐2 protein, 29‐DEMI‐32 and 39‐KEALSDGI‐46, play a significant role in mediating HMPV immune evasion in airway epithelial cells (AECs). However, their role in the overall pulmonary responses to HMPV infection has not been investigated. In this study, we found that two recombinant HMPVs (rHMPV) lacking the individual M2‐2 PDZ‐binding motif are attenuated in mouse lungs. Mice infected with mutants produce more cytokines/chemokines in bronchoalveolar lavage (BAL) fluid compared to mice infected with wild‐type rHMPV. In addition, both mutants are able to enhance the pulmonary recruitment of dendritic cells (DCs) and T cells and induce effective protections against the HMPV challenge. The DC maturation is also significantly improved by the motif mutation. Taken together, our data provide proof‐of‐principle for two live‐attenuated M2‐2 mutants to be promising HMPV vaccine candidates that are effective in inducing higher pulmonary innate immunity and generating protection against HMPV infection. Highlights: HMPV is a major pathogen causing hospitalization in children with bronchiolitis and pneumonia. The infection does not induce long‐lasting immunity. Herein, we identified two M2‐2 mutants which are effective in inducing higher pulmonary innate immunity and producing protection against HMPV infection. [ABSTRACT FROM AUTHOR]

Acute respiratory infection (ARI) is the second leading cause of death in children less than 5 years of age worldwide. Human Metapneumovirus (hMPV) is associated with around 5‐7% of the total pneumonia admissions in children. The aim of this study was to determine the magnitude of hMPV associated hospitalizations among children, in Karachi, Pakistan. A 3 years prospective study was conducted at the Aga Khan University Hospital (AKUH), from August 2009 to June 2012. Children less than 5 years of age, admitted with ARIs, were enrolled. Throat swabs were collected and tested for hMPV using real‐time PCR. Multivariable log binomial regression analysis was performed. Out of 1150 children enrolled, hMPV was detected among 84/1150 (7%). About 87% of the enrolled children presented with cough, followed by fever (73%), nasal congestion (69%) and shortness of breath (68%). Of the hMPV positive subjects, most (56/84, 67%) were less than 12 months of age. The most common diagnosis in hMPV positive infants was pneumonia, followed by asthma and bronchiolitis. HMPV was identified year round, with peaks during February and August. Sore throat was found to be significantly associated with the hMPV infection (Adjusted RR 2.23; 95%CI 1.42‐3.52). The proportion of hMPV was higher among hospitalized infants with ARI. Pneumonia was the primary discharge diagnoses of patients who tested positive for hMPV. hMPV could be a target for future vaccine to further decrease the burden of ARI morbidity and possibly mortality in developing countries. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are capable of killing various pathogens upon stimulation of activating receptors. Human metapneumovirus (HMPV) is a respiratory virus, which was discovered in 2001 and is responsible for acute respiratory tract infection in infants and children worldwide. HMPV infection is very common, infecting around 70% of all children under the age of five. Under immune suppressive conditions, HMPV infection can be fatal. Not much is known on how NK cells respond to HMPV. In this study, using reporter assays and NK-cell cytotoxicity assays performed with human and mouse NK cells, we demonstrated that the NKp46-activating receptor and its mouse orthologue Ncr1, both members of the natural cytotoxicity receptor (NCR) family, recognized an unknown ligand expressed by HMPV-infected human cells. We demonstrated that MHC class I is upregulated and MICA is downregulated upon HMPV infection. We also characterized mouse NK-cell phenotype in the blood and the lungs of HMPV-infected mice and found that lung NK cells are more activated and expressing NKG2D, CD43, CD27, KLRG1, and CD69 compared to blood NK cells regardless of HMPV infection. Finally, we demonstrated, using Ncr1-deficient mice, that NCR1 plays a critical role in controlling HMPV infection. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (hMPV) is a leading cause of acute respiratory tract infections in children and the elderly. The mechanism by which this virus triggers an inflammatory response still remains unknown. Here, we evaluated whether the thymic stromal lymphopoietin (TSLP) pathway contributes to lung inflammation upon hMPV infection. We found that hMPV infection promotes TSLP expression both in human airway epithelial cells and in the mouse lung. hMPV infection induced lung infiltration of OX40L+CD11b+ DCs. Mice lacking the TSLP receptor deficient mice ( tslpr−/−) showed reduced lung inflammation and hMPV replication. These mice displayed a decreased number of neutrophils as well a reduction in levels of thymus and activation-regulated chemokine/CCL17, IL-5, IL-13, and TNF-α in the airways upon hMPV infection. Furthermore, a higher frequency of CD4+ and CD8+ T cells was found in tslpr−/− mice compared to WT mice, which could contribute to controlling viral spread. Depletion of neutrophils in WT and tslpr−/− mice decreased inflammation and hMPV replication. Remarkably, blockage of TSLP or OX40L with specific Abs reduced lung inflammation and viral replication following hMPV challenge in mice. Altogether, these results suggest that activation of the TSLP pathway is pivotal in the development of pulmonary pathology and pulmonary hMPV replication. [ABSTRACT FROM AUTHOR]

Respiratory Syncytial Virus (RSV), Human metapneumovirus (HMPV), and Rhinoviruses (RV) are frequent causes of respiratory tract infections in young children. We compared laboratory and clinical findings in children with comparable age distribution and hospitalized due to RSV, HMPV or RV infections. Viral pathogens were detected by a quantitative real time PCR from nasopharyngeal aspirates. No significant differences in the admission diagnosis, laboratory parameters, patient demographics and treatment measures between the three viral causes of respiratory illness were found. No correlation between viral load and disease severity was observed however, there was a significantly lower concentration of the nasopharyngeal interleukin 8 (IL-8) in children with RV compared to HMPV and RSV, indicating a milder proinflammatory reaction. Moreover, RV-infected children had significantly lower body temperature, higher leucocyte counts in peripheral blood, and a tendency to have a shorter stay in hospital than children with either HMPV or RSV infection. Taken together, clinical presentation of the infections with RSV, HMPV, and RV is similar among children of the same age group and not clearly distinguishable by standard clinical or laboratory findings. Therefore, virus specific testing should be included regularly for routine diagnosis of children with respiratory tract infections. J. Med. Virol. 87:275-280, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Human metapneumovirus (hMPV) causes acute respiratory infections in children. The prevalence and clinical characteristics of hMPV were determined in nasopharyngeal aspirates of children in Changsha, China. Reverse transcription-polymerase chain reaction (RT-PCR) or PCR was employed to screen for both hMPV and other common respiratory viruses in 1,165 nasopharyngeal aspirate specimens collected from children with lower respiratory tract infections from September 2007 to August 2008. All PCR products were sequenced, and demographic and clinical data were collected from all patients. Seventy-six of 1,165 (6.5%) specimens were positive for hMPV, of which 85.5% (65/76) occurred in the winter and spring seasons. The hMPV coinfection rate was 57.9% (44/76), and human bocavirus was the most common virus detected in conjunction with hMPV. Phylogenetic analysis revealed that 94.7% of the hMPV detected were of subgroup A2, 5.3% were subgroup B2, and none belonged to either the A1 or B1 subgroups. No significant differences were found in terms of the frequency of diagnosis and clinical signs between either the co- and mono-infection groups, or between patients with and without underlying diseases. It was concluded that hMPV is an important viral pathogen in pediatric patients with lower respiratory tract infections in Changsha. Only hMPV genotypes A2 and B2 were co-circulating in this locality; human bocavirus was the most common coinfecting virus, and coinfection did not affect disease severity. J. Med. Virol. 85:546-553, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Summary: Respiratory infections, especially those of the lower respiratory tract, remain a foremost cause of mortality and morbidity of children greater than 5 years in developing countries including Pakistan. Ignoring these acute‐level infections may lead to complications. Particularly in Pakistan, respiratory infections account for 20% to 30% of all deaths of children. Even though these infections are common, insufficiency of accessible data hinders development of a comprehensive summary of the problem. The purpose of this study was to determine the prevalence rate in various regions of Pakistan and also to recognize the existing viral strains responsible for viral respiratory infections through published data. Respiratory viruses are detected more frequently among rural dwellers in Pakistan. Lower tract infections are found to be more lethal. The associated pathogens comprise respiratory syncytial virus (RSV), human metapneumovirus (HMPV), coronavirus, enterovirus/rhinovirus, influenza virus, parainfluenza virus, adenovirus, and human bocavirus. RSV is more dominant and can be subtyped as RSV‐A and RSV‐B (BA‐9, BA‐10, and BA‐13). Influenza A (H1N1, H5N1, H3N2, and H1N1pdm09) and Influenza B are common among the Pakistani population. Generally, these strains are detected in a seasonal pattern with a high incidence during spring and winter time. The data presented include pneumonia, bronchiolitis, and influenza. This paper aims to emphasise the need for standard methods to record the incidence and etiology of associated pathogens in order to provide effective treatment against viral infections of the respiratory tract and to reduce death rates. [ABSTRACT FROM AUTHOR]