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The Lancet. Microbe Sep 2023Human metapneumovirus (hMPV) is one of the leading causes of respiratory infection. Since its discovery in 2001, no specific antiviral or vaccine has been available in... (Review)
Review
Human metapneumovirus (hMPV) is one of the leading causes of respiratory infection. Since its discovery in 2001, no specific antiviral or vaccine has been available in contrast to its closely related family member human respiratory syncytial virus (hRSV). Neutralising monoclonal antibodies (nMAbs) are the core effectors of vaccines and are essential therapeutic immune drugs against infectious pathogens. The development of nMAbs against hMPV has accelerated in recent years as a result of breakthroughs in viral fusion (F) protein structural biology and experience with hRSV and other enveloped viruses. We provide an overview of the potent F-specific nMAbs of hMPV, generalise their targeting F antigen epitopes, and discuss the nMAb development strategy and future directions for hMPV and broad-spectrum hMPV, hRSV nMabs, and vaccine research and development.
PubMed: 37499668
DOI: 10.1016/S2666-5247(23)00134-9 -
The Journal of Infection Aug 2023Human metapneumovirus (HMPV) is an important aetiologic agent of respiratory tract infection (RTI). This study aimed to describe the prevalence, genetic diversity, and...
BACKGROUND
Human metapneumovirus (HMPV) is an important aetiologic agent of respiratory tract infection (RTI). This study aimed to describe the prevalence, genetic diversity, and evolutionary dynamics of HMPV.
METHODS
Laboratory-confirmed HMPV were characterised based on partial-coding G gene sequences with MEGA.v6.0. WGS was performed with Illumina, and evolutionary analyses with Datamonkey and Nextstrain.
RESULTS
HMPV prevalence was 2.5%, peaking in February-April and with an alternation in the predominance of HMPV-A and -B until the emergence of SARS-CoV-2, not circulating until summer and autumn-winter 2021, with a higher prevalence and with the almost only circulation of A2c. G and SH proteins were the most variable, and 70% of F protein was under negative selection. Mutation rate of HMPV genome was 6.95 × 10 substitutions/site/year.
CONCLUSION
HMPV showed a significant morbidity until the emergence of SARS-CoV-2 pandemic in 2020, not circulating again until summer and autumn 2021, with a higher prevalence and with almost the only circulation of A2c, probably due to a more efficient immune evasion mechanism. The F protein showed a very conserved nature, supporting the need for steric shielding. The tMRCA showed a recent emergence of the A2c variants carrying duplications, supporting the importance of virological surveillance.
Topics: Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Spain; Genotype; COVID-19; SARS-CoV-2; Respiratory Tract Infections; Phylogeny
PubMed: 37178807
DOI: 10.1016/j.jinf.2023.05.004 -
Archives of Disease in Childhood Sep 2023Bronchiolitis is the main acute lower respiratory tract infection in infants. Data regarding SARS-CoV-2-related bronchiolitis are limited.
BACKGROUND
Bronchiolitis is the main acute lower respiratory tract infection in infants. Data regarding SARS-CoV-2-related bronchiolitis are limited.
OBJECTIVE
To describe the main clinical characteristics of infants with SARS-CoV-2-related bronchiolitis in comparison with infants with bronchiolitis associated with other viruses.
SETTING, PATIENTS, INTERVENTIONS
A multicentre retrospective study was conducted in 22 paediatric emergency departments (PED) in Europe and Israel. Infants diagnosed with bronchiolitis, who had a test for SARS-CoV-2 and were kept in clinical observation in the PED or admitted to hospital from 1 May 2021 to 28 February 2022 were considered eligible for participation. Demographic and clinical data, diagnostic tests, treatments and outcomes were collected.
MAIN OUTCOME MEASURES
The main outcome was the need for respiratory support in infants testing positive for SARS-CoV-2 compared with infants testing negative.
RESULTS
2004 infants with bronchiolitis were enrolled. Of these, 95 (4.7%) tested positive for SARS-CoV-2. Median age, gender, weight, history of prematurity and presence of comorbidities did not differ between the SARS-CoV-2-positive and SARS-CoV-2-negative infants. Human metapneumovirus and respiratory syncytial virus were the viruses most frequently detected in the group of infants negative for SARS-CoV-2.Infants testing positive for SARS-CoV-2 received oxygen supplementation less frequently compared with SARS-CoV-2-negative patients, 37 (39%) vs 1076 (56.4%), p=0.001, OR 0.49 (95% CI 0.32 to 0.75). They received less ventilatory support: 12 (12.6%) high flow nasal cannulae vs 468 (24.5%), p=0.01; 1 (1.0%) continuous positive airway pressure vs 125 (6.6%), p=0.03, OR 0.48 (95% CI 0.27 to 0.85).
CONCLUSIONS
SARS-CoV-2 rarely causes bronchiolitis in infants. SARS-CoV-2-related bronchiolitis mostly has a mild clinical course.
Topics: Infant; Child; Humans; SARS-CoV-2; Retrospective Studies; COVID-19; Bronchiolitis; Hospitalization
PubMed: 37130726
DOI: 10.1136/archdischild-2023-325448 -
Journal of Asthma and Allergy 2023Asthma is a common airway disease, affecting millions of people worldwide. Although most asthma patients experience mild symptoms, it is characterized by variable... (Review)
Review
Asthma is a common airway disease, affecting millions of people worldwide. Although most asthma patients experience mild symptoms, it is characterized by variable airflow limitation, which can occasionally become life threatening in the case of a severe exacerbation. The commonest triggers of asthma exacerbations in both children and adults are viral infections. In this review article, we will try to investigate the most common viruses triggering asthma exacerbations and their role in asthma immunopathogenesis, since viral infections in young adults are thought to trigger the development of asthma either right away after the infection or at a later stage of their life. The commonest viral pathogens associated with asthma include the respiratory syncytial virus, rhinoviruses, influenza and parainfluenza virus, metapneumovirus and coronaviruses. All these viruses exploit different molecular pathways to infiltrate the host. Asthmatics are more prone to severe viral infections due to their unique inflammatory response, which is mostly characterized by T2 cytokines. Unlike the normal T1 high response to viral infection, asthmatics with T2 high inflammation are less potent in containing a viral infection. Inhaled and/or systematic corticosteroids and bronchodilators remain the cornerstone of asthma exacerbation treatment, and although many targeted therapies which block molecules that viruses use to infect the host have been used in a laboratory level, none has been yet approved for clinical use. Nevertheless, further understanding of the unique pathway that each virus follows to infect an individual may be crucial in the development of targeted therapies for the commonest viral pathogens to effectively prevent asthma exacerbations. Finally, biologic therapies resulted in a complete change of scenery in the treatment of severe asthma, especially with a T2 high phenotype. All available data suggest that monoclonal antibodies are safe and able to drastically reduce the rate of viral asthma exacerbations.
PubMed: 37791040
DOI: 10.2147/JAA.S277455 -
Viruses Sep 2023Among the respiratory pathogens of birds, the Avian Metapneumovirus (aMPV) is one of the most relevant, as it is responsible for causing infections of the upper... (Review)
Review
Among the respiratory pathogens of birds, the Avian Metapneumovirus (aMPV) is one of the most relevant, as it is responsible for causing infections of the upper respiratory tract and may induce respiratory syndromes. aMPV is capable of affecting the reproductive system of birds, directly impacting shell quality and decreasing egg production. Consequently, this infection can cause disorders related to animal welfare and zootechnical losses. The first cases of respiratory syndromes caused by aMPV were described in the 1970s, and today six subtypes (A, B, C, D, and two more new subtypes) have been identified and are widespread in all chicken and turkey-producing countries in the world, causing enormous economic losses for the poultry industry. Conventionally, immunological techniques are used to demonstrate aMPV infection in poultry, however, the identification of aMPV through molecular techniques helped in establishing the traceability of the virus. This review compiles data on the main aMPV subtypes present in different countries; aMPV and bacteria co-infection; vaccination against aMPV and viral selective pressure, highlighting the strategies used to prevent and control respiratory disease; and addresses tools for viral diagnosis and virus genome studies aiming at improving and streamlining pathogen detection and corroborating the development of new vaccines that can effectively protect herds, preventing viral escapes.
PubMed: 37766366
DOI: 10.3390/v15091960 -
Emerging Microbes & Infections Dec 2023Upper respiratory tract infection (URTI) is common in humans. We sought to profile sputum pathogen spectrum and impact of URTI on acute exacerbation of bronchiectasis...
Upper respiratory tract infection (URTI) is common in humans. We sought to profile sputum pathogen spectrum and impact of URTI on acute exacerbation of bronchiectasis (AE). Between March 2017 and December 2021, we prospectively collected sputum from adults with bronchiectasis. We stratified AEs into events related (URTI-AE) and unrelated to URTI (non-URTI-AE). We captured URTI without onset of AE (URTI-non-AE). We did bacterial culture and viral detection with polymerase chain reaction, and explored the pathogen spectrum and clinical impacts of URTI-AE via longitudinal follow-up. Finally, we collected 479 non-AE samples (113 collected at URTI-non-AE and 225 collected at clinically stable) and 170 AE samples (89 collected at URTI-AE and 81 collect at non-URTI-AE). The viral detection rate was significantly higher in URTI-AE (46.1%) than in non-URTI-AE (4.9%) and URTI-non-AE (11.5%) (both < 0.01). Rhinovirus [odds ratio (OR): 5.00, 95% confidence interval (95%CI): 1.06-23.56, = 0.03] detection was independently associated with URTI-AE compared with non-URTI-AE. URTI-AE tended to yield higher viral load and detection rate of rhinovirus, metapneumovirus and bacterial shifting compared with URTI-non-AE. URTI-AE was associated with higher initial viral loads (esp. rhinovirus, metapneumovirus), greater symptom burden (higher scores of three validated questionnaires) and prolonged recovery compared to those without. Having experienced URTI-AE predicted a greater risk of future URTI-AE (OR: 10.90, 95%CI: 3.60-33.05). In summary, URTI is associated with a distinct pathogen spectrum and aggravates bronchiectasis exacerbation, providing the scientific rationale for the prevention of URTI to hinder bronchiectasis progression.
Topics: Adult; Humans; Prospective Studies; Sputum; Respiratory Tract Infections; Bronchiectasis; Rhinovirus
PubMed: 37038356
DOI: 10.1080/22221751.2023.2202277 -
Virus Genes Aug 2023Human metapneumovirus (HMPV) is a major pathogen of acute respiratory tract infections (ARTIs) in children. Whole genome sequence analyses could help understand the...
Human metapneumovirus (HMPV) is a major pathogen of acute respiratory tract infections (ARTIs) in children. Whole genome sequence analyses could help understand the evolution and transmission events of this virus. In this study, we sequenced HMPV whole genomes to improve the identification of molecular epidemiology in Beijing, China. Nasopharyngeal aspirates of hospitalized children aged < 14 years old with ARTIs were screened for HMPV infection using qPCR. Fourteen pairs of overlapping primers were used to amplify whole genome sequences of HMPV from positive samples with high viral loads. The epidemiology of HMPV was analysed and 27 HMPV whole genome sequences were obtained. Sequence identity and the positional entropy analyses showed that most regions of HMPV genome are conserved, whereas the G gene contained many variations. Phylogenetic analysis identified 25 HMPV sequences that belonged to a newly defined subtype A2b1; G gene sequences from 24 of these contained a 111-nucleotide duplication. HMPV is an important respiratory pathogen in paediatric patients. The new subtype A2b1 with a 111-nucleotide duplication has become predominate in Beijing, China.
Topics: Whole Genome Sequencing; Metapneumovirus; Evolution, Molecular; Humans; Male; Female; Infant; Child, Preschool; Child; Adolescent; Paramyxoviridae Infections; Phylogeny
PubMed: 37150780
DOI: 10.1007/s11262-023-02001-2 -
European Journal of Clinical... Jul 2023Acute respiratory infections (ARIs) are caused by a variety of microorganisms. Of all ARIs, 80% are caused by viruses such as human respiratory syncytial virus,...
Acute respiratory infections (ARIs) are caused by a variety of microorganisms. Of all ARIs, 80% are caused by viruses such as human respiratory syncytial virus, metapneumovirus, influenza, parainfluenza, rhinovirus, and, more recently, Sars-CoV-2, which has been responsible for the COVID-19 pandemic. The objective of our study was to evaluate clinical data from a viral panel performed in children hospitalized with SARS or COVID-19 in the infirmary or ICU of 5 pediatric hospitals in the city of Goiânia, Goiás, Brazil. Demographic, clinical, and laboratory data were collected for analysis, and data on the outcomes underwent statistical treatment. A total of 128 patients were selected for the study, 54% of whom were male and 46% female. The viral panel included rhinovirus, COVID-19, metapneumovirus, adenovirus, and parainfluenza. Descriptive analyses of age profile showed differences in the involvement of particular viruses. The percentage of patients who required hospitalization in the ICU, infirmary, as well as individuals who were discharged after therapy or who died, were described. Our work shows that epidemiological surveillance measures are indispensable, especially if used in the continued analysis of viral panels in all pediatric patients with SARS.
Topics: Child; Humans; Male; Female; Infant; Pandemics; COVID-19; SARS-CoV-2; Viruses; Respiratory Tract Infections; Paramyxoviridae Infections; Metapneumovirus; Rhinovirus
PubMed: 37160574
DOI: 10.1007/s10096-023-04615-8