Search Results (78)

Background: Human metapneumovirus (hMPV) is a respiratory pathogen that causes illness ranging from mild upper respiratory tract infections to severe pneumonia, particularly in individuals with comorbidities. Fatal cases of hMPV-induced hemorrhagic pneumonia are rare and likely under-reported. Diagnosis is often delayed due to overlapping symptoms with other respiratory viruses and the rapid progression of the disease. Case presentation: We report the case of a 55-year-old man with a complex medical history, including liver cirrhosis and diabetes mellitus, who developed acute viral pneumonia. Initial symptoms appeared three days before a sudden clinical deterioration marked by shortness of breath, hemoptysis, and respiratory failure. A nasopharyngeal swab taken on the third day of illness tested positive for hMPV by qRT-PCR. The patient died the following day. Postmortem molecular testing confirmed hMPV in lung tissue and alveolar contents. Autopsy revealed bilateral hemorrhagic pneumonia with regional lymphadenopathy. Histopathological examination showed alveolar hemorrhage, multinucleated cells, neutrophilic infiltration, activated autophagy in macrophages, and numerous cytoplasmic eosinophilic viral inclusions. Conclusions: This is the first documented case of fatal hMPV pneumonia in Armenia. It highlights the potential severity of hMPV in adults with chronic health conditions and emphasizes the need for timely molecular diagnostics. Postmortem identification of characteristic viral inclusions may serve as a cost-effective histopathological marker of hMPV-associated lung pathology. Full article

Macrophages are a principal pulmonary source of type I and III interferons (IFNs), initiating and coordinating the early antiviral response to respiratory viral infections. Yet the contribution of macrophage-derived IFNs to host defense during human metapneumovirus (HMPV) infection remains poorly defined. Here, we use human primary monocyte-derived macrophages (MDMs) and THP-1-derived macrophages to analyze the IFN responses induced by HMPV compared to its closely related human pneumovirus, respiratory syncytial virus (RSV). We show that HMPV induced a robust response of type I and type III IFNs and ISGs, whereas RSV elicited only a modest, delayed IFN response despite strong IRF activation; instead, RSV preferentially activates NF-κB and exhibits a pronounced proinflammatory cytokine output. Our results highlight the role of macrophages as key modulators of the IFN and proinflammatory responses during HMPV and RSV infection. Full article

Human metapneumovirus (hMPV), a member of the Pneumoviridae subfamily, has emerged as a significant etiological agent of acute respiratory tract infections across diverse age groups, particularly affecting infants, the elderly, and immunocompromised individuals. Since its initial identification in 2001, hMPV has been recognized globally for its seasonal circulation pattern, predominantly in late winter and spring. hMPV is a leading etiological agent, accounting for approximately 5% to 10% of hospitalizations among pediatric patients with acute respiratory tract infections. hMPV infection can result in severe bronchiolitis and pneumonia, particularly in young children, with clinical manifestations often indistinguishable from those caused by human RSV. Primary hMPV infection typically occurs during early childhood; however, re-infections are frequent and may occur throughout an individual’s lifetime. hMPV is an enveloped, negative-sense RNA virus transmitted through respiratory droplets and aerosols, with a 3–5-day incubation period. The host immune response is marked by elevated pro-inflammatory cytokines, which contribute to disease severity. Advances in molecular diagnostics, particularly reverse transcription–quantitative polymerase chain reaction (RT-qPCR) and metagenomic next-generation sequencing (mNGS), have improved detection accuracy and efficiency. Despite these advancements, treatment remains largely supportive, as no specific antiviral therapy has yet been approved. Promising developments in vaccine research, including mRNA-based candidates, are currently undergoing clinical evaluation. This review synthesizes current knowledge on hMPV, highlighting its virological, epidemiological, and clinical characteristics, along with diagnostic advancements and emerging therapeutic strategies, while underscoring the critical role of continued research and sustained preventive measures—including vaccines, monoclonal antibodies, and non-pharmaceutical interventions—in mitigating the global burden of hMPV-related disease. Full article

This study explored the distribution and genetic characteristics of respiratory pathogens in outpatients with acute respiratory infections (ARIs) in Yangon, Myanmar, during the 2023 rainy season. Among 267 patients who tested negative for influenza, RSV, and SARS-CoV-2 using rapid diagnostic tests, 84.6% were positive for at least one pathogen according to a multiplex polymerase chain reaction (PCR) assay, the BioFire^® FilmArray^® Respiratory Panel 2.1. The most common viruses detected were rhinovirus/enterovirus (RV/EV) at 37.8%, respiratory syncytial virus (RSV) at 22.4%, and human metapneumovirus (hMPV) at 10.0%. These pathogens co-circulated mainly from July to September, with RV/EV consistently predominant. Symptom comparison among RV/EV-, RSV-, and hMPV-infected patients showed similar clinical features, though fever was more common in hMPV cases. Among RV/EV-positive patients, 59.3% had single infections, while 40.7% experienced co-infections, especially with RSV and adenovirus. Genotyping identified 28 types from five species, primarily RV-A and RV-C, which were genetically diverse. One EV-D68 case was also found, emphasizing its potential risk. This study underscores the genetic diversity and clinical impact of RV/EV and stresses the importance of ongoing molecular surveillance in Myanmar’s post-COVID-19 context to inform effective public health responses. Full article

Background: Pneumoviruses are etiologic agents of respiratory tract infections and a major cause of morbidity and mortality worldwide, particularly affecting young children, the elderly, and individuals with underlying clinical conditions. These viruses are associated with a significant burden, particularly in low- and middle-income countries, where reported deaths attributable to respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) in young children are important. Recent developments have been noted in the prevention of pneumoviral infections. Method: In this review, we analyzed clinical trials of the approved RSV vaccines, as well as the recent prominent platform technologies used in RSV vaccine research. In addition, we discussed combination vaccines targeting RSV, HMPV, and Human Parainfluenza Virus Type 3 (HPIV3) that have entered clinical trials. Results: Recent advancements include the approval of three RSV vaccine candidates: AREXVY^®(GSK), ABRYSVO^®(Pfizer), and mRESVIA^®(Moderna). These vaccines are primarily intended for older adults, with ABRYSVO^® also capable of providing passive immunization to infants via maternal administration. The review highlights RSV vaccine platform technologies and combination vaccines currently being evaluated in clinical settings. Conclusions: While significant progress has been made in RSV vaccine development, especially with three approved candidates, the development of vaccines for HMPV remains an unmet medical need. Ongoing research in combination vaccines holds promise for broader protection against multiple respiratory viruses in the future. Full article

Background/Objectives: Human metapneumovirus (hMPV) is a leading cause of respiratory infections in the elderly, with high morbidity and mortality and with no vaccines or specific therapies available. The primary protective antigen of hMPV is the fusion protein, and its prefusion conformation (pre-F) is considered the most promising target for vaccine development. Methods: Utilizing computational design strategies focused on intraprotomer interface stabilization, we designed hMPV pre-F recombinant subunit vaccine candidates based on the most prevalent A2 subtype and characterized them in vitro and in vivo, benchmarking to the prototypical hMPV pre-F stabilized by an introduction of a proline at site 185. Results: The top candidate (N46V_T160F) yielded 14.4 mg/L with a melting temperature of 79.3 °C as compared to 5.7 mg/L and 70.4 °C for the benchmark. By employing monoclonal antibody binding to all six antigenic sites of hMPV pre-F, we confirmed this construct retained all pre-F specific antigenic sites and that the key sites Ø and V were stable at 4 °C for up to 6 months. When immunogenicity of N46V_T160F was evaluated in mice, it induced higher binding and neutralizing antibody titers than the benchmark, which stemmed in part from increased levels of site Ø and site II targeting Abs. Further, this A2 based construct induced cross-neutralizing Abs against all four hMPV subtypes. Lastly, our construct exhibited similar immunogenicity as the recently published next-generation hMPV pre-F constructs, DS-CavEs2 and v3B_Δ12_D454C-V458C. Conclusions: N46V_T160F is a promising hMPV vaccine candidate paving the way for further development and optimization. Full article

Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are pneumoviruses causing lower respiratory tract infections, primarily in infants and children rather than in healthy adults. Human bronchial epithelial cells serve as a viral replication target and source of the innate immune response to these viruses. To better understand the immune responses induced by RSV and HMPV in the pediatric airway epithelium, we comparatively studied pediatric and adult epithelial responses. We used normal human bronchial epithelial (NHBE) cells cultured in an air–liquid interface culture system (ALI), which helps to mimic the architecture of the human lower respiratory tract epithelium. Our results demonstrate differential viral replication patterns and reduced interferons; and inflammatory cytokines’ expression in pediatric cells compared to adult cells. However, pediatric epithelial cells expressed an increased mucus response and induced a stronger pro-inflammatory response in monocyte-derived dendritic cells. These findings reveal age-dependent immune epithelial responses that may contribute to more severe infections by HMPV and RSV. Full article

Background. Influenza remains a significant public health issue, with seasonal trends varying across regions. This study provides a comprehensive analysis of influenza virus trends in Italy, leveraging epidemiological and virological data from the Istituto Superiore di Sanità (ISS). The primary objective is to assess influenza activity at both national and regional levels, highlighting variations in incidence rates and viral subtype circulation during the 2023/2024 season. Methods. We conducted a systematic approach to data collection, processing, and visualization, utilizing influenza surveillance data from ISS. Incidence rates, subtype distribution, and co-circulating respiratory viruses were analyzed to identify key trends. Results. Our findings reveal a significant increase in influenza cases during the 2023/2024 season, with incidence rates surpassing pre-pandemic levels. Notably, changes in the circulation of influenza A(H3N2) and influenza B were observed, alongside the presence of other respiratory viruses such as RSV and rhinovirus. Conclusions. This study underscores the importance of real-time surveillance, transparent data sharing, and advanced visualization tools in guiding public health responses. By integrating lessons from COVID-19, we highlight the necessity of standardized surveillance frameworks to enhance preparedness for future seasonal outbreaks and potential pandemics. Full article

Background: Human metapneumovirus (HMPV) is a significant cause of respiratory infections, particularly in children, the elderly, and immunocompromised individuals. However, data on HMPV infection in people living with HIV (PLWH) are limited, and cases of co-infection with influenza A virus in this population have not been previously described. Case Presentation: We reported the case of a 73-year-old HIV-positive man with multiple comorbidities, including insulin-dependent diabetes mellitus, who presented with fever, asthenia, and glycometabolic decompensation. Despite an initially unremarkable chest computed tomography (CT) scan, the patient developed progressive respiratory failure, requiring high-flow oxygen therapy. Molecular testing using the BIOFIRE^® FILMARRAY^® Pneumonia Panel Plus identified HMPV and influenza A virus as the causative pathogens. Bacterial cultures were negative, allowing for the discontinuation of empirical antibiotic therapy. The patient was successfully weaned off oxygen therapy and discharged after clinical improvement. Conclusions: This case highlights the potential severity of HMPV and influenza A co-infection in PLWH, emphasizing the importance of molecular diagnostics in distinguishing viral from bacterial infections. Rapid and accurate pathogen identification is essential for guiding appropriate antimicrobial stewardship and optimizing patient outcomes in community-acquired pneumonia. Full article

Background: Human metapneumovirus (hMPV) is a respiratory pathogen that has gained increasing recognition due to advancements in molecular diagnostic tools, which have improved its detection and characterization. While severe disease manifestations are traditionally associated with pediatric, elderly, or immunocompromised patients, hMPV-related pneumonia in immunocompetent adults remains underexplored. Methods: This case report describes a 68-year-old male who developed severe community-acquired pneumonia (CAP) caused by hMPV despite being immunocompetent and having no significant comorbidities. The diagnosis was confirmed via multiplex RT-PCR, excluding bacterial and viral coinfections. Laboratory and imaging findings supported a viral etiology, while empirical antibiotics were initially prescribed due to diagnostic uncertainty. Results: The patient presented with respiratory symptoms that progressed to hypoxia, productive cough, and fatigue, requiring hospitalization. Imaging revealed bilateral ground-glass opacities and consolidations typical of viral pneumonia. Molecular diagnostics enabled accurate pathogen identification and guiding appropriate management, and the patient fully recovered with supportive care. Conclusion: This case underscores the importance of rapid molecular diagnostics for hMPV, reducing unnecessary antibiotics and enhancing management. Routine incorporation of hMPV testing into clinical protocols could improve the diagnosis and resource use. The development of vaccines, such as the IVX-A12 in phase II trials, offers hope for targeted prevention, underscoring the need for further research and therapeutic innovations. Full article

Acute respiratory infections (ARIs) are a leading cause of death in children under five globally. The seasonal trends and profiles of respiratory viruses vary by region and season. Due to limited information and the population’s vulnerability, we conducted the hospital-based surveillance of respiratory viruses in Eastern Uttar Pradesh. Throat and nasal swabs were collected from outpatients and inpatients in the Department of Paediatrics, Baba Raghav Das (BRD) Medical College, Gorakhpur, between May 2022 and April 2023. A total of 943 samples from children aged 1 to 60 months were tested using multiplex real-time PCR for respiratory viruses in cases of ARI and SARI. Out of 943 samples tested, the highest positivity was found for parainfluenza virus [105 (11.13%) PIV-1 (79), PIV-2 (18), PIV-4 (18)], followed by adenovirus [82 (8.7%), RSV-B, [68 (7.21%)], influenza-A [46(4.9%): H1N1 = 29, H3N2 = 14), SARS CoV-2 [28 (3%)], hMPV [13(1.4%), RSV-A [4 (0.42%), and influenza-B (Victoria lineage) 1 (0.10%). The maximum positivity of respiratory viruses was seen in children between 1 to 12 months. The wide variation in prevalence of these respiratory viruses was seen in different seasons. This study enhances understanding of the seasonal and clinical trends of respiratory virus circulation and co-infections in Eastern Uttar Pradesh. The findings highlight the importance of targeted interventions to reduce the burden of respiratory infections in this region. Full article

Human metapneumovirus (HMPV) is a significant respiratory pathogen, particularly in vulnerable populations. Background: No vaccine for the prevention of HMPV is currently licensed, although several subunit vaccines are in development. Saponin-based adjuvant systems (AS), including QS-21, have transformed the field of subunit vaccines by dramatically increasing their potency and efficacy, leading to the development of several licensed vaccines. However, naturally sourced tree bark-extracted QS-21 faces supply and manufacturing challenges, hindering vaccine development. Objective: This study reports on an alternative plant cell culture system for the consistent production of highly pure QS-21. Method: We evaluated the efficacy of cultured plant cell (cpc)-produced QS-21 in a novel HMPV vaccine, formulating a recombinant pre-fusion stabilized HMPV F protein (preF) with cpcQS-21 and a synthetic toll-like receptor 4 (TLR4) agonist adjuvant formulation. Results: In mice, TLR4 agonist containing adjuvant formulations with plant cell-produced QS-21 performed equally to licensed adjuvant AS01 containing tree-bark-extracted QS-21 and demonstrated a significant increase in immunogenicity against HMPV preF compared to the unadjuvanted control. Conclusion: Our findings pave the way for a reliable, scalable, and sustainable source of pure QS-21, enabling the development of highly effective HMPV and other vaccines with significant public health impact. Full article

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children. During the COVID-19 pandemic, a significant change in the epidemiology of RSV and other viruses occurred worldwide, leading to a reduction in the circulation of these infectious agents. After the pandemic, the resurgence of seasonal respiratory viruses occurred, but some features of these infections contrast to those registered prior to the pandemic. In the present work, we studied 390 children <5 years old admitted to the hospital to determine the contribution of RSV, SARS-CoV-2, human metapneumovirus (hMPV), and influenza viruses to acute respiratory infections during the 2023–2024 winter season in Mexico. RSV was the most frequently detected virus (n = 160, 41%), followed by SARS-CoV-2 (n = 69, 17.7%), hMPV (n = 68, 17.4%), and influenza A or B (n = 40, 10.26%). Fourteen patients required admission to the intensive care unit, including six (42.8%) with RSV infection. Four children died (1%). At least one of the four viruses was detected in all deceased patients: SARS-CoV-2 in one; SARS-CoV-2 and hMPV in two; and RSV, influenza A, and SARS-CoV-2 in one. The high impact of RSV and other respiratory viruses indicates the need to implement specific preventive programs to reduce the morbidity and mortality associated with them. Full article

The impact of common respiratory virus infections on adults and older individuals in the community is unclear, excluding seasonal influenza viruses. We examined FilmArray® tests performed on 1828 children aged <10 years and 10,803 adults, including cases with few respiratory symptoms, between January 2021 and June 2024. Approximately 80% of the children tested positive for ≥1 viruses, while 9.5% of the adults tested positive mostly for severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). Besides SARS-CoV-2 infection, 66 out of 97 patients (68.0%) aged >60 years with rhinovirus/enterovirus (RV/EV), respiratory syncytial virus (RSV), parainfluenza virus-3 (PIV-3), or human metapneumovirus (hMPV) infection required hospitalization, of whom seven died; 26 out of 160 patients (16.3%) aged <60 years required hospitalization mostly because of deterioration of bronchial asthma, with no reported deaths. In older patients with RV/EV infection, three with few respiratory symptoms died due to worsened heart failure. Although the frequency of common respiratory virus infections in older adults is low, it may be overlooked because of subclinical respiratory symptoms, and its clinical significance in worsening comorbidities in older adults should not be underestimated. Full article

Background: Interferon epsilon (IFN-ε) is a type I IFN that plays a critical role in the host immune response against pathogens. Despite having demonstrated antiviral activity in macrophages and mucosal tissues such as the female reproductive tract and the constitutive expression in mucosal tissues such as the lung, the relevance of IFN-ε against respiratory viral infections remains elusive. Results: We present, for the first time, the expression of IFN-ε in alveolar epithelial cells and primary human bronchial epithelial cells grown in an air–liquid interface (ALI) in response to human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) infection. The molecular characterization of the IFN-ε induction by the viruses indicates that the expression of RIG-I is necessary for an optimal IFN-ε expression. Furthermore, treatment of the airway epithelial cells with rhIFN-ε induced the expression of IFN-stimulated genes (ISGs) and significantly restricted the viral replication of HMPV and RSV. Conclusions: These findings underscore the relevance of IFN-ε against viral infections in the respiratory tract. Full article