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American Journal of Transplantation :... Jun 2024In 2023, the Food and Drug Administration approved 2 recombinant subunit respiratory syncytial virus (RSV) vaccines based on prefusion RSV F glycoproteins for the... (Review)
Review
In 2023, the Food and Drug Administration approved 2 recombinant subunit respiratory syncytial virus (RSV) vaccines based on prefusion RSV F glycoproteins for the prevention of RSV-associated lower respiratory tract disease. These vaccines were subsequently recommended for individuals ≥60 years of age using shared clinical decision-making by the Center for Disease Control and Prevention's Advisory Committee on Immunization Practices. The development, deployment, and uptake of respiratory virus vaccines are of particular importance for solid organ recipients who are at higher risk of infectious complications and poor clinical outcomes, including from RSV-associated lower respiratory tract disease, compared to patients without immunocompromise. This review aims to summarize what is currently known about the burden of RSV disease in solid organ transplantation, to describe the currently available tools to mitigate the risk, and to highlight considerations regarding the implementation of these vaccines before and after transplantation. We also explore areas of unmet need for organ transplant recipients including questions of RSV vaccine effectiveness and safety, inequities in disease and vaccine access based on race and socioeconomic status, and expansion of coverage to immunocompromised individuals below the age of 60 years.
Topics: Humans; Respiratory Syncytial Virus Infections; Organ Transplantation; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Immunocompromised Host
PubMed: 38341028
DOI: 10.1016/j.ajt.2024.02.003 -
The Journal of Infectious Diseases Nov 2023Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar increase occurs in children and quantified underascertainment associated with diagnostic testing.
METHODS
We searched databases for studies involving RSV detection in persons <18 years using ≥2 specimen types or tests. We assessed study quality using a validated checklist. We pooled detection rates by specimen and diagnostic tests and quantified performance.
RESULTS
We included 157 studies. Added testing of additional specimens to NP aspirate (NPA), NPS, and/or nasal swab (NS) RT-PCR resulted in statistically nonsignificant increases in RSV detection. Adding paired serology testing increased RSV detection by 10%, NS by 8%, oropharyngeal swabs by 5%, and NPS by 1%. Compared to RT-PCR, direct fluorescence antibody tests, viral culture, and rapid antigen tests were 87%, 76%, and 74% sensitive, respectively (pooled specificities all ≥98%). Pooled sensitivity of multiplex versus singleplex RT-PCR was 96%.
CONCLUSIONS
RT-PCR was the most sensitive pediatric RSV diagnostic test. Adding multiple specimens did not substantially increase RSV detection, but even small proportional increases could result in meaningful changes in burden estimates. The synergistic effect of adding multiple specimens should be evaluated.
Topics: Adult; Child; Humans; Respiratory Syncytial Virus Infections; Sensitivity and Specificity; Respiratory Syncytial Virus, Human; Viruses; Diagnostic Techniques and Procedures; Nasopharynx; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 37285396
DOI: 10.1093/infdis/jiad185 -
Signal Transduction and Targeted Therapy Aug 2023Respiratory syncytial virus (RSV) is a nonsegmented, negative strand RNA virus that has caused severe lower respiratory tract infections of high mortality rates in...
Respiratory syncytial virus (RSV) is a nonsegmented, negative strand RNA virus that has caused severe lower respiratory tract infections of high mortality rates in infants and the elderly, yet no effective vaccine or antiviral therapy is available. The RSV genome encodes the nucleoprotein (N) that forms helical assembly to encapsulate and protect the RNA genome from degradation, and to serve as a template for transcription and replication. Previous crystal structure revealed a decameric ring architecture of N in complex with the cellular RNA (N-RNA) of 70 nucleotides (70-nt), whereas cryo-ET reconstruction revealed a low-resolution left-handed filament, in which the crystal monomer structure was docked with the helical symmetry applied to simulate a nucleocapsid-like assembly of RSV. However, the molecular details of RSV nucleocapsid assembly remain unknown, which continue to limit our complete understanding of the critical interactions involved in the nucleocapsid and antiviral development that may target this essential process during the viral life cycle. Here we resolve the near-atomic cryo-EM structure of RSV N-RNA that represents roughly one turn of the helical assembly that unveils critical interaction interfaces of RSV nucleocapsid and may facilitate development of RSV antiviral therapy.
Topics: Aged; Infant; Humans; Respiratory Syncytial Viruses; Cryoelectron Microscopy; Nucleocapsid; Antiviral Agents; RNA
PubMed: 37607909
DOI: 10.1038/s41392-023-01602-5 -
Revista Espanola de Quimioterapia :... Jun 2024The properties of the main surface proteins and the viral cycle of the respiratory syncytial virus (RSV) make it an attractive pathogen from the perspective of... (Review)
Review
The properties of the main surface proteins and the viral cycle of the respiratory syncytial virus (RSV) make it an attractive pathogen from the perspective of microbiology. The virus gets its name from the manner it infects cells, which enables it to produce syncytia, which allow the virus' genetic material to move across cells without having to release viral offspring to the cellular exterior, reducing immune system identification. This causes a disease with a high impact in both children and adults over 60, which has sparked the development of several preventive interventions based on vaccines and monoclonal antibodies for both age groups. The epidemiological characteristics of this virus, which circulates in epidemics throughout the coldest months of the year and exhibits a marked genetic and antigenic drift due to its high mutation capability, must be taken into consideration while using these preventive methods. The most important microbiological and epidemiological elements of RSV are covered in this study, along with how they have affected the creation of preventive medications and their use in the future.
Topics: Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Vaccines
PubMed: 38515332
DOI: 10.37201/req/006.2024 -
Pediatric Allergy and Immunology :... Mar 2024Wheezing is the cardinal symptom of asthma; its presence early in life, mostly caused by viral infections, is a major risk factor for the establishment of persistent or... (Review)
Review
Wheezing is the cardinal symptom of asthma; its presence early in life, mostly caused by viral infections, is a major risk factor for the establishment of persistent or recurrent disease. Early-life wheezing and asthma exacerbations are triggered by common respiratory viruses, mainly rhinoviruses (RV), and to a lesser extent, respiratory syncytial virus, parainfluenza, human metapneumovirus, coronaviruses, adenoviruses, influenza, and bocavirus. The excess presence of bacteria, several of which are part of the microbiome, has also been identified in association with wheezing and acute asthma exacerbations, including haemophilus influenza, streptococcus pneumoniae, moraxella catarrhalis, mycoplasma pneumoniae, and chlamydophila pneumonia. While it is not clear when asthma starts, its characteristics develop over time. Airway remodeling already appears between the ages of 1 and 3 years of age even prior to the presence of atopic inflammation or an asthma diagnosis. The role of genetic defect or variations hampering the airway epithelium in response to environmental stimuli and severe disease morbidity are now considered as major determinants for early structural changes. Repeated viral infections can induce and perpetuate airway hyperresponsiveness. Allergic sensitization, that often precedes infection-induced wheezing, shifts inflammation toward type-2, while common respiratory infections themselves promote type-2 inflammation. Nevertheless, most children who wheeze with viral infections during infancy and during preschool years do not develop persistent asthma. Multiple factors, including illness severity, viral etiology, allergic sensitization, and the exposome, are associated with disease persistence. Here, we summarize current knowledge and developments in infection epidemiology of asthma in children, describing the known impact of each individual agent and mechanisms of transition from recurrent wheeze to asthma.
Topics: Child; Child, Preschool; Humans; Infant; Influenza, Human; Respiratory Sounds; Asthma; Bacteria; Respiratory Syncytial Viruses; Inflammation
PubMed: 38445451
DOI: 10.1111/pai.14098 -
International Journal of Infectious... Oct 2023Understanding the global patterns of respiratory syncytial virus (RSV) is crucial for developing effective prevention and control strategies.
Global burden and trends of respiratory syncytial virus infection across different age groups from 1990 to 2019: A systematic analysis of the Global Burden of Disease 2019 Study.
OBJECTIVE
Understanding the global patterns of respiratory syncytial virus (RSV) is crucial for developing effective prevention and control strategies.
METHODS
Data on RSV-related burden were extracted from the Global Burden of Disease 2019. Joinpoint regression models were used to assess the global temporal trends of RSV and further stratified analyses were conducted according to the Socio-demographic Index (SDI), which is a composite measure of income, education, and total fertility. Age-period-cohort model was used to evaluate age, period, and cohort effects.
RESULTS
In 2019, the global age-standardized rate of mortality (ASMR) and disability-adjusted life years (ASR-DALYs) of RSV were 4.79/100,000 (95% uncertainty interval [95% UI]: 1.82/100,000-9.32/100,000) and 218.34/100,000 (95% UI: 92.06/100,000-376.80/100,000), respectively. The burden of RSV was higher in men than women. The highest ASMR (10.26/100,000, 3.80/100,000-20.16/100,000) and ASR-DALYs (478.71/100,000, 202.40/100,000-840.85/100,000) were reported in low-SDI region. Although mortality and DALYs rates in all age groups declined globally, the pace of decline was not uniform across age groups. Mortality rate in the elderly over 70 years surpassed that in children under 5 years in 2019.
CONCLUSION
This study highlights the need for targeted interventions to reduce the burden of RSV, particularly in low-SDI region, and among the elderly over 70 years.
Topics: Male; Child; Humans; Female; Child, Preschool; Aged; Quality-Adjusted Life Years; Global Burden of Disease; Respiratory Syncytial Virus Infections; Socioeconomic Factors; Income; Respiratory Syncytial Virus, Human; Global Health
PubMed: 37567553
DOI: 10.1016/j.ijid.2023.08.008 -
Antiviral Research Jan 2024Human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LRTI) in young children and elderly people worldwide. Recent... (Review)
Review
Human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LRTI) in young children and elderly people worldwide. Recent significant progress in our understanding of the structure and function of RSV proteins has led to the discovery of several clinical candidates targeting RSV fusion and replication. These include both the development of novel small molecule interventions and the isolation of potent monoclonal antibodies. In this review, we summarize the state-of-the-art of RSV drug discovery, with a focus on the characteristics of the candidates that reached the clinical stage of development. We also discuss the lessons learned from failed and discontinued clinical developments and highlight the challenges that remain for development of RSV therapies.
Topics: Child; Humans; Aged; Child, Preschool; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Antibodies, Monoclonal; Respiratory Tract Infections; Respiratory Syncytial Virus Vaccines; Viral Fusion Proteins; Antibodies, Viral; Antibodies, Neutralizing
PubMed: 38160942
DOI: 10.1016/j.antiviral.2023.105791 -
Microbiology Spectrum Aug 2023Respiratory viruses may interfere with each other and affect the epidemic trend of the virus. However, the understanding of the interactions between respiratory viruses...
Respiratory viruses may interfere with each other and affect the epidemic trend of the virus. However, the understanding of the interactions between respiratory viruses at the population level is still very limited. We here conducted a prospective laboratory-based etiological study by enrolling 14,426 patients suffered from acute respiratory infection (ARI) in Beijing, China during 2005 to 2015. All 18 respiratory viruses were simultaneously tested for each nasal and throat swabs collected from enrolled patients using molecular tests. The virus correlations were quantitatively evaluated, and the respiratory viruses could be divided into two panels according to the positive and negative correlations. One included influenza viruses (IFVs) A, B, and respiratory syncytial virus (RSV), while the other included human parainfluenza viruses (HPIVs) 1/3, 2/4, adenovirus (Adv), human metapneumovirus (hMPV), and enterovirus (including rhinovirus, named picoRNA), α and β human coronaviruses (HCoVs). The viruses were positive-correlated in each panel, while negative-correlated between panels. After adjusting the confounding factors by vector autoregressive model, positive interaction between IFV-A and RSV and negative interaction between IFV-A and picoRNA are still be observed. The asynchronous interference of IFV-A significantly delayed the peak of β human coronaviruses epidemic. The binary property of the respiratory virus interactions provides new insights into the viral epidemic dynamics in human population, facilitating the development of infectious disease control and prevention strategies. Systematic quantitative assessment of the interactions between different respiratory viruses is pivotal for the prevention of infectious diseases and the development of vaccine strategies. Our data showed stable interactions among respiratory viruses at human population level, which are season irrelevant. Respiratory viruses could be divided into two panels according to their positive and negative correlations. One included influenza virus and respiratory syncytial virus, while the other included other common respiratory viruses. It showed negative correlations between the two panels. The asynchronous interference between influenza virus and β human coronaviruses significantly delayed the peak of β human coronaviruses epidemic. The binary property of the viruses indicated transient immunity induced by one kind of virus would play role on subsequent infection, which provides important data for the development of epidemic surveillance strategies.
Topics: Humans; Infant; Prospective Studies; Viruses; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Orthomyxoviridae
PubMed: 37378522
DOI: 10.1128/spectrum.00019-23 -
Pediatrics Mar 2024The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and...
The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The ACIP met October 25 to 26, 2023, to discuss meningococcal vaccines, mpox vaccines, respiratory syncytial virus (RSV) vaccines, influenza vaccines, coronavirus disease 2019 (COVID-19) vaccines, and the combined pediatric and adult immunization schedules for 2024. The ACIP also held special meetings on September 12 and September 22 to discuss COVID-19 2023-2024 vaccine recommendations and RSV immunization in pregnant women. This update summarizes the proceedings of these meetings that are most relevant to the pediatric population. Major updates for pediatric clinicians include recommendations for XBB monovalent COVID-19 immunization for the 2023-2024 respiratory season, the recently licensed pentavalent meningococcal conjugate vaccine and mpox vaccination in high-risk young adults, and discussion regarding the parallel strategies of protection against RSV disease in infants via maternal immunization during pregnancy or direct prophylaxis of infants with nirsevimab.
Topics: Infant; Young Adult; Child; Humans; Female; Pregnancy; Meningococcal Vaccines; Influenza, Human; Advisory Committees; Respiratory Syncytial Viruses; COVID-19; Immunization; Neisseria meningitidis
PubMed: 38095041
DOI: 10.1542/peds.2023-064990 -
Journal of Medical Virology Feb 2024With the approval of the first vaccines against respiratory syncytial virus (RSV) and a novel RSV-neutralizing antibody, 2023 has been perceived as a game-changing year... (Review)
Review
With the approval of the first vaccines against respiratory syncytial virus (RSV) and a novel RSV-neutralizing antibody, 2023 has been perceived as a game-changing year in preventing severe outcomes of RSV infections in infants and the elderly. However, the costs of these pharmaceuticals are high, while RSV disproportionately impacts populations of low-to-middle-income regions, which may continue to suffer from a lack of pharmaceutical measures for RSV prevention under health and socioeconomic disparities. This paper presents an overview of the characteristics, clinical results, and approval status of various RSV vaccines and anti-RSV antibodies. It posits that wealthy nations cannot monopolize RSV immunoprophylaxis and should work jointly to make it available to lower-income countries. An approach toward RSV immunoprophylaxis equity based on five points is offered: (1) integration of RSV vaccines and antibodies into the existing global humanitarian distribution systems, (2) using affordable RSV vaccine pricing models, (3) enforcing equity as a part of national and global public health strategy, (4) implementing equitable allocation frameworks for RSV immunoprophylaxis, and (5) promoting local manufacturing. Such a plan needs to be put into action as soon as possible to avoid delays in serving the populations with the highest needs related to RSV burden.
Topics: Infant; Humans; Aged; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Immunization; Antibodies, Viral
PubMed: 38305000
DOI: 10.1002/jmv.29453