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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 -
Cellular and Molecular Life Sciences :... Jun 2024Neutralizing antibodies are considered a correlate of protection against severe human respiratory syncytial virus (HRSV) disease. Currently, HRSV neutralization assays...
Neutralizing antibodies are considered a correlate of protection against severe human respiratory syncytial virus (HRSV) disease. Currently, HRSV neutralization assays are performed on immortalized cell lines like Vero or A549 cells. It is known that assays on these cell lines exclusively detect neutralizing antibodies (nAbs) directed to the fusion (F) protein. For the detection of nAbs directed to the glycoprotein (G), ciliated epithelial cells expressing the cellular receptor CX3CR1 are required, but generation of primary cell cultures is expensive and labor-intensive. Here, we developed a high-throughput neutralization assay based on the interaction between clinically relevant HRSV grown on primary cells with ciliated epithelial cells, and validated this assay using a panel of infant sera. To develop the high-throughput neutralization assay, we established a culture of differentiated apical-out airway organoids (Ap-O AO). CX3CR1 expression was confirmed, and both F- and G-specific monoclonal antibodies neutralized HRSV in the Ap-O AO. In a side-by-side neutralization assay on Vero cells and Ap-O AO, neutralizing antibody levels in sera from 125 infants correlated well, although titers on Ap-O AO were consistently lower. We speculate that these lower titers might be an actual reflection of the neutralizing antibody capacity in vivo. The organoid-based neutralization assay described here holds promise for further characterization of correlates of protection against HRSV disease.
Topics: Humans; Respiratory Syncytial Virus, Human; Antibodies, Neutralizing; Organoids; Animals; Neutralization Tests; Chlorocebus aethiops; Vero Cells; Respiratory Syncytial Virus Infections; CX3C Chemokine Receptor 1; Antibodies, Viral; Viral Fusion Proteins; Infant; Epithelial Cells; Antibodies, Monoclonal
PubMed: 38884678
DOI: 10.1007/s00018-024-05307-y -
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 -
Journal of Medical Virology Jun 2024This study aimed to determine the timing patterns of the initial respiratory syncytial virus (RSV) infection and to identify the factors influencing disease severity in...
This study aimed to determine the timing patterns of the initial respiratory syncytial virus (RSV) infection and to identify the factors influencing disease severity in infants of varying health status. A retrospective study was conducted at the Affiliated Children's Hospital of Chongqing Medical University from 2012 to 2022. The timing of the first RSV infection was estimated in infants with differing health status using correlation analysis, considering their birth time. Logistic regression was utilized to identify factors influencing severe RSV infection in these infants. RSV detection primarily occurred in the winter and spring. Epidemic season and peak timing of RSV were not significantly affected by health status or the COVID-19 pandemic. A strong positive correlation was observed between the age at RSV infection and the interval from birth to the RSV peak season. Infants born during the RSV epidemic season exhibited a higher likelihood of infection within the first 2 months postbirth. In contrast, those born outside the RSV epidemic season were more susceptible to infection during the subsequent peak. Notably, infants with pre-existing health conditions contracted RSV at an earlier age compared to their healthy counterparts. Among healthy infants, severe RSV infection was associated with sex, age, and timing of infection. For infants with underlying conditions, severe RSV infection was primarily related to age and timing of infection. The initial timing of RSV infection in infants varied depending on their health status. Young age and infection timing during the RSV epidemic season were significant risk factors for severe RSV infection. These findings provide a theoretical basis for optimizing immunization strategies for infants with diverse health conditions.
Topics: Humans; Respiratory Syncytial Virus Infections; Infant; Male; Female; Retrospective Studies; Seasons; Severity of Illness Index; Infant, Newborn; Respiratory Syncytial Virus, Human; Hospitalization; Risk Factors; COVID-19; Health Status; China; Time Factors
PubMed: 38873911
DOI: 10.1002/jmv.29719 -
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 -
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 -
The Lancet. Respiratory Medicine Jul 2024
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Infant
PubMed: 38851193
DOI: 10.1016/S2213-2600(24)00184-X -
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 -
Influenza and Other Respiratory Viruses Jun 2024In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory...
Nirsevimab Effectiveness Against Cases of Respiratory Syncytial Virus Bronchiolitis Hospitalised in Paediatric Intensive Care Units in France, September 2023-January 2024.
In September 2023, France was one of the first countries that started a national immunisation campaign with nirsevimab, a new monoclonal antibody against respiratory syncytial virus (RSV). Using data from a network of paediatric intensive care units (PICUs), we aimed to estimate nirsevimab effectiveness against severe cases of RSV bronchiolitis in France. We conducted a case-control study based on the test-negative design and included 288 infants reported by 20 PICUs. We estimated nirsevimab effectiveness at 75.9% (48.5-88.7) in the main analysis and 80.6% (61.6-90.3) and 80.4% (61.7-89.9) in two sensitivity analyses. These real-world estimates confirmed the efficacy observed in clinical studies.
Topics: Humans; France; Respiratory Syncytial Virus Infections; Infant; Intensive Care Units, Pediatric; Case-Control Studies; Male; Female; Hospitalization; Respiratory Syncytial Virus, Human; Antibodies, Monoclonal, Humanized; Antiviral Agents; Bronchiolitis; Bronchiolitis, Viral; Treatment Outcome
PubMed: 38840301
DOI: 10.1111/irv.13311