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BMJ Paediatrics Open Jun 2024During the COVID-19 pandemic, the introduction of non-pharmaceutical interventions (NPIs) resulted in an unprecedented reduction in the transmission of the respiratory... (Observational Study)
Observational Study
During the COVID-19 pandemic, the introduction of non-pharmaceutical interventions (NPIs) resulted in an unprecedented reduction in the transmission of the respiratory syncytial virus (RSV), the predominant cause of bronchiolitis. As NPIs were eased, it was speculated that RSV transmission would return with an increase in the severity of bronchiolitis. In a large tertiary hospital, a dramatic reduction in the incidence of bronchiolitis was seen during the COVID-19 pandemic. The easing of NPIs correlated with an increase in RSV transmission particularly in the community; however, there was no evidence of an increase in the severity of bronchiolitis.
Topics: Humans; Respiratory Syncytial Virus Infections; COVID-19; Infant; SARS-CoV-2; Female; Male; Bronchiolitis; Incidence; Infant, Newborn; Respiratory Syncytial Virus, Human
PubMed: 38897622
DOI: 10.1136/bmjpo-2024-002603 -
Scientific Reports Jun 2024We report the first cryoEM structure of the Hendra henipavirus nucleoprotein in complex with RNA, at 3.5 Å resolution, derived from single particle analysis of a...
We report the first cryoEM structure of the Hendra henipavirus nucleoprotein in complex with RNA, at 3.5 Å resolution, derived from single particle analysis of a double homotetradecameric RNA-bound N protein ring assembly exhibiting D14 symmetry. The structure of the HeV N protein adopts the common bi-lobed paramyxoviral N protein fold; the N-terminal and C-terminal globular domains are bisected by an RNA binding cleft containing six RNA nucleotides and are flanked by the N-terminal and C-terminal arms, respectively. In common with other paramyxoviral nucleocapsids, the lateral interface between adjacent N and N protomers involves electrostatic and hydrophobic interactions mediated primarily through the N-terminal arm and globular domains with minor contribution from the C-terminal arm. However, the HeV N multimeric assembly uniquely identifies an additional protomer-protomer contact between the N N-terminus and N C-terminal arm linker. The model presented here broadens the understanding of RNA-bound paramyxoviral nucleocapsid architectures and provides a platform for further insight into the molecular biology of HeV, as well as the development of antiviral interventions.
Topics: Cryoelectron Microscopy; Hendra Virus; Nucleoproteins; Nucleocapsid; Models, Molecular; RNA, Viral; Nucleocapsid Proteins
PubMed: 38890308
DOI: 10.1038/s41598-024-58243-z -
Scientific Reports Jun 2024Respiratory syncytial virus is the major cause of acute lower respiratory tract infections in young children, causing extensive mortality and morbidity globally, with...
Respiratory syncytial virus is the major cause of acute lower respiratory tract infections in young children, causing extensive mortality and morbidity globally, with limited therapeutic or preventative options. Cathelicidins are innate immune antimicrobial host defence peptides and have antiviral activity against RSV. However, upper respiratory tract cathelicidin expression and the relationship with host and environment factors in early life, are unknown. Infant cohorts were analysed to characterise early life nasal cathelicidin levels, revealing low expression levels in the first week of life, with increased levels at 9 months which are comparable to 2-year-olds and healthy adults. No impact of prematurity on nasal cathelicidin expression was observed, nor were there effects of sex or birth mode, however, nasal cathelicidin expression was lower in the first week-of-life in winter births. Nasal cathelicidin levels were positively associated with specific inflammatory markers and demonstrated to be associated with microbial community composition. Importantly, levels of nasal cathelicidin expression were elevated in infants with mild RSV infection, but, in contrast, were not upregulated in infants hospitalised with severe RSV infection. These data suggest important relationships between nasal cathelicidin, upper airway microbiota, inflammation, and immunity against RSV infection, with interventional potential.
Topics: Cathelicidins; Respiratory Syncytial Virus Infections; Humans; Female; Male; Infant; Infant, Newborn; Respiratory Syncytial Virus, Human; Nasal Mucosa
PubMed: 38886476
DOI: 10.1038/s41598-024-64446-1 -
BMC Infectious Diseases Jun 2024Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infection in children worldwide. Understanding its prevalence, variations, and...
INTRODUCTION
Respiratory Syncytial Virus (RSV) is a leading cause of acute lower respiratory infection in children worldwide. Understanding its prevalence, variations, and characteristics is vital, particularly in the context of the COVID-19 pandemic.
OBJECTIVE
The study aimed to investigate the RSV positivity rate, subtype prevalence, age and gender distribution, symptomatology, and co-infection rates during pre-pandemic and pandemic periods.
METHODS
We analyzed data from 15,381 patients tested for RSV between 2017 and 2023.
RESULTS
Our analysis revealed a 7.2% average RSV positivity rate in the pre-pandemic period, with significant fluctuations during the pandemic (1.5% in 2020 to 32.0% in 2021). We observed variations in RSVA and RSVB detection rates. The 0-4 years' age group was consistently the most affected, with a slight male predominance. Fever and cough were common symptoms. Therapeutic interventions, particularly antiviral usage and ventilation requirements, decreased during the pandemic. We also identified variations in co-infection rates with other respiratory viruses.
CONCLUSION
Our study offers critical insights into the impact of the COVID-19 pandemic on RSV prevalence, subtype distribution, patient characteristics, and clinical management. These findings underscore the need for ongoing surveillance and adaptive public health responses.
Topics: Humans; COVID-19; Respiratory Syncytial Virus Infections; India; Male; Female; Infant; Child, Preschool; Coinfection; Child; Prevalence; Respiratory Syncytial Virus, Human; Infant, Newborn; SARS-CoV-2; Adolescent; Adult; Middle Aged; Young Adult; Pandemics
PubMed: 38877428
DOI: 10.1186/s12879-024-09426-6 -
Frontiers in Immunology 2024Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current...
Newcastle disease virus vector-based SARS-CoV-2 vaccine candidate AVX/COVID-12 activates T cells and is recognized by antibodies from COVID-19 patients and vaccinated individuals.
INTRODUCTION
Several effective vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and implemented in the population. However, the current production capacity falls short of meeting global demand. Therefore, it is crucial to further develop novel vaccine platforms that can bridge the distribution gap. AVX/COVID-12 is a vector-based vaccine that utilizes the Newcastle Disease virus (NDV) to present the SARS-CoV-2 spike protein to the immune system.
METHODS
This study aims to analyze the antigenicity of the vaccine candidate by examining antibody binding and T-cell activation in individuals infected with SARS-CoV-2 or variants of concern (VOCs), as well as in healthy volunteers who received coronavirus disease 2019 (COVID-19) vaccinations.
RESULTS
Our findings indicate that the vaccine effectively binds antibodies and activates T-cells in individuals who received 2 or 3 doses of BNT162b2 or AZ/ChAdOx-1-S vaccines. Furthermore, the stimulation of T-cells from patients and vaccine recipients with AVX/COVID-12 resulted in their proliferation and secretion of interferon-gamma (IFN-γ) in both CD4+ and CD8+ T-cells.
DISCUSSION
The AVX/COVID-12 vectored vaccine candidate demonstrates the ability to stimulate robust cellular responses and is recognized by antibodies primed by the spike protein present in SARS-CoV-2 viruses that infected patients, as well as in the mRNA BNT162b2 and AZ/ChAdOx-1-S vaccines. These results support the inclusion of the AVX/COVID-12 vaccine as a booster in vaccination programs aimed at addressing COVID-19 caused by SARS-CoV-2 and its VOCs.
Topics: Humans; COVID-19; SARS-CoV-2; Antibodies, Viral; Newcastle disease virus; COVID-19 Vaccines; Spike Glycoprotein, Coronavirus; Lymphocyte Activation; Adult; Female; Male; Middle Aged; T-Lymphocytes; BNT162 Vaccine; Vaccination; Genetic Vectors; Interferon-gamma
PubMed: 38873610
DOI: 10.3389/fimmu.2024.1394114 -
PloS One 2024Respiratory syncytial virus (RSV) is one of the major pathogens frequently associated with severe respiratory tract infections in younger children and older adults...
BACKGROUND
Respiratory syncytial virus (RSV) is one of the major pathogens frequently associated with severe respiratory tract infections in younger children and older adults globally. There is an unmet need with a lack of routine country-specific databases and/or RSV surveillance systems on RSV disease burden among adults in most low- and middle-income countries, including Cameroon. We aim to estimate the adult RSV burden needed to develop a framework for establishing an RSV surveillance database in Cameroon.
METHODS AND ANALYSIS
A two-phase study approach will be implemented, including a literature review and a review of medical records. First, a systematic review of available literature will provide insights into the current burden of RSV in adults in Cameroon, searching the following databases: Global Health, PubMed, CINAHL, Embase, African Journal Online Library, Scopus, Global Index Medicus, Cochrane databases, and grey literature search. Identified studies will be included if they reported on the RSV burden of disease among Cameroonian adults aged ≥18 years from 1st January 1990 to 31st December 2023. A narrative synthesis of the evidence will be provided. A meta-analysis will be conducted using a random effect model, when feasible. Two co-authors will independently perform data screening, extraction, and synthesis and will be reported according to the PRISMA-P guidelines for writing systematic review protocols. Secondly, a retrospective cohort design will permit data analysis on RSV among adults in the laboratory registers at the National Influenza Center. Medical records will be reviewed to link patients' files from emanating hospitals to capture relevant demographic, laboratory, and clinical data. The International Classification of Diseases and Clinical Modifications 10th revision (ICD-10-CM) codes will be used to classify the different RSV outcomes retrospectively.
RESULTS
The primary outcome is quantifying the RSV burden among the adult population, which can help inform policy on establishing an RSV surveillance database in Cameroon. The secondary outcomes include (i) estimates of RSV prevalence among Cameroonian adult age groups, (ii) RSV determinants, and (iii) clinical outcomes, including proportions of RSV-associated morbidity and/or death among age-stratified Cameroonian adults with medically attended acute respiratory tract infections.
CONCLUSIONS
The evidence generated from the two projects will be used for further engagement with relevant stakeholders, including policymakers, clinicians, and researchers, to develop a framework for systematically establishing an RSV surveillance database in Cameroon. This study proposal has been registered (CRD42023460616) with the University of York Center for Reviews and Dissemination of the International Prospective Register of Systematic Reviews (PROSPERO).
Topics: Humans; Cameroon; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Adult; Systematic Reviews as Topic
PubMed: 38861519
DOI: 10.1371/journal.pone.0303468 -
Human Vaccines & Immunotherapeutics Dec 2024Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and associated with most bronchiolitis- and...
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children and associated with most bronchiolitis- and pneumonia-related hospitalizations. A new preventive monoclonal antibody (MAb), nirsevimab, has been launched in the United States, Luxembourg, and France, and was recently approved to be given in a population-based manner throughout Spain. This study aimed to have a first pre-immunization insight into the Spanish parental knowledge about bronchiolitis, RSV, and nirsevimab immunization. Parents in Murcia with children <2 years of age up to the date of September 1, 2023, were selected to complete a questionnaire. The primary endpoint was the parental knowledge about bronchiolitis, RSV, and nirsevimab. A total of 3,217 responses were analyzed. The majority (95.8%) were aware of bronchiolitis. Meanwhile, 46.6% of the respondents knew about RSV, most of them only after the first child's birth. Information about RSV or bronchiolitis was mainly obtained from family members, with only 4.8% reporting having been informed by Health care Professionals (HCPs). Only 11.2% of respondents were aware of nirsevimab. Nonetheless, these were not entirely satisfied with the information received (score of 3.3 out of 5) and shared that HCPs should be the primary source of information. The present survey then highlights the need for better and more efficient educational strategies directed to all parents/legal guardians. It also sheds some light on the different factors that should be considered to improve awareness of RSV immunization to decrease its burden in Spain and beyond.
Topics: Humans; Spain; Respiratory Syncytial Virus Infections; Parents; Female; Male; Health Knowledge, Attitudes, Practice; Infant; Surveys and Questionnaires; Adult; Immunization Programs; Respiratory Syncytial Virus, Human; Bronchiolitis; Antibodies, Monoclonal, Humanized; Middle Aged; Young Adult; Infant, Newborn
PubMed: 38857859
DOI: 10.1080/21645515.2024.2357439 -
Bulletin of Mathematical Biology Jun 2024How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains...
How viral infections develop can change based on the number of viruses initially entering the body. The understanding of the impacts of infection doses remains incomplete, in part due to challenging constraints, and a lack of research. Gaining more insights is crucial regarding the measles virus (MV). The higher the MV infection dose, the earlier the peak of acute viremia, but the magnitude of the peak viremia remains almost constant. Measles is highly contagious, causes immunosuppression such as lymphopenia, and contributes substantially to childhood morbidity and mortality. This work investigated mechanisms underlying the observed wild-type measles infection dose responses in cynomolgus monkeys. We fitted longitudinal data on viremia using maximum likelihood estimation, and used the Akaike Information Criterion (AIC) to evaluate relevant biological hypotheses and their respective model parameterizations. The lowest AIC indicates a linear relationship between the infection dose, the initial viral load, and the initial number of activated MV-specific T cells. Early peak viremia is associated with high initial number of activated MV-specific T cells. Thus, when MV infection dose increases, the initial viremia and associated immune cell stimulation increase, and reduce the time it takes for T cell killing to be sufficient, thereby allowing dose-independent peaks for viremia, MV-specific T cells, and lymphocyte depletion. Together, these results suggest that the development of measles depends on virus-host interactions at the start and the efficiency of viral control by cellular immunity. These relationships are additional motivations for prevention, vaccination, and early treatment for measles.
Topics: Measles; Animals; Viremia; Measles virus; Mathematical Concepts; Viral Load; Macaca fascicularis; Likelihood Functions; Humans; Models, Immunological; Models, Biological; T-Lymphocytes; Lymphocyte Activation
PubMed: 38853189
DOI: 10.1007/s11538-024-01305-0 -
Signal Transduction and Targeted Therapy Jun 2024Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific...
Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in young children and the elderly. There are currently no approved RSV-specific therapeutic small molecules available. Using high-throughput antiviral screening, we identified an oral drug, the prenylation inhibitor lonafarnib, which showed potent inhibition of the RSV fusion process. Lonafarnib exhibited antiviral activity against both the RSV A and B genotypes and showed low cytotoxicity in HEp-2 and human primary bronchial epithelial cells (HBEC). Time-of-addition and pseudovirus assays demonstrated that lonafarnib inhibits RSV entry, but has farnesyltransferase-independent antiviral efficacy. Cryo-electron microscopy revealed that lonafarnib binds to a triple-symmetric pocket within the central cavity of the RSV F metastable pre-fusion conformation. Mutants at the RSV F sites interacting with lonafarnib showed resistance to lonafarnib but remained fully sensitive to the neutralizing monoclonal antibody palivizumab. Furthermore, lonafarnib dose-dependently reduced the replication of RSV in BALB/c mice. Collectively, lonafarnib could be a potential fusion inhibitor for RSV infection.
Topics: Humans; Respiratory Syncytial Virus Infections; Pyridines; Mice; Animals; Respiratory Syncytial Virus, Human; Viral Fusion Proteins; Farnesyltranstransferase; Antiviral Agents; Piperidines; Mice, Inbred BALB C; Protein Conformation; Dibenzocycloheptenes
PubMed: 38853183
DOI: 10.1038/s41392-024-01858-5 -
Human Vaccines & Immunotherapeutics Dec 2024A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups...
A maternal vaccine and long-acting monoclonal antibody (mAb) were recently approved to protect infants against respiratory syncytial virus (RSV). We identified subgroups of pregnant people with different preferences for RSV preventives and respondent characteristics associated with subgroup membership. An online survey, including a discrete choice experiment (DCE), was conducted among US pregnant people. RSV preventive attributes included effectiveness, duration of protection during RSV season, injection recipient/timing, preventive type (vaccine or mAb), and type of visit required to receive injection. In DCE choice tasks, pregnant people selected between two hypothetical preventive profiles with varying attribute-levels and a no-preventive option. Logistic regression, including latent class analysis (LCA), was used to analyze the data. Of 992 pregnant people (mean age: 30.0 years), 60.3% were expecting their second/later birth. LCA identified three preference subgroups: 'Effectiveness' (preventive choice mostly driven by increases in effectiveness; 51.4% class membership probability), 'Season' (preventive choice mostly driven by improvement in duration of protection during the RSV season; 39.2% class membership probability), and 'No Preventive' (frequently chose no-preventive option; 9.4% class membership probability). 'Effectiveness' and 'Season' preferred maternal vaccine over mAb; mAb was preferred by 'No Preventive.' Perceiving RSV as serious for infants, higher health literacy, and lower household income were associated with 'Effectiveness.' Perceiving RSV as serious for pregnant people was associated with 'Season.' Perceiving RSV to not be serious for pregnant people and not being employed were associated with 'No Preventive.' Subgroups of pregnant people vary in preferences for RSV preventives. Most pregnant people preferred a maternal vaccine, although some may be more willing to accept alternative preventive options.
Topics: Humans; Female; Pregnancy; Respiratory Syncytial Virus Infections; United States; Adult; Respiratory Syncytial Virus Vaccines; Latent Class Analysis; Young Adult; Respiratory Syncytial Virus, Human; Infant; Surveys and Questionnaires; Patient Preference; Vaccination; Pregnant Women; Antibodies, Monoclonal; Adolescent
PubMed: 38847198
DOI: 10.1080/21645515.2024.2358566