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Anales de Pediatria Oct 2023Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain. (Review)
Review
INTRODUCTION
Nirsevimab, a monoclonal antibody for the prevention of disease caused by respiratory syncytial virus (RSV), has recently been approved for use in Europe and Spain.
OBJECTIVES
To provide recommendations for the administration of nirsevimab for prevention of RSV disease.
METHODS
The approach chosen to develop these recommendations involved a critical review of the literature and the use of the Delphi and GRADE methods. An expert group was formed. The group engaged in three rounds to define the questions, express support or opposition, grade recommendations and establish the agreement or disagreement with the conclusions.
RESULTS
In the general neonatal population, routine administration of nirsevimab is recommended to reduce the frequency of illness and hospitalisation for bronchiolitis and RSV lower respiratory tract infection. Nirsevimab is recommended for all infants born in high-incidence RSV season and infants aged less than 6 months at the season onset. In infants born preterm between 29 and 35 weeks of gestation, with haemodynamically significant heart disease or with chronic lung disease, routine administration of nirsevimab is recommended to reduce the incidence of disease and hospitalisation due to bronchiolitis and RSV lower respiratory tract infection. In patients in whom palivizumab is currently indicated, its substitution by nirsevimab is recommended to reduce the burden of bronchiolitis.
CONCLUSIONS
Routine administration of nirsevimab to all infants aged less than 6 months born during the RSV season or aged less than 6 months at the start of the winter season is recommended to reduce the burden of disease and the frequency of hospitalization due to bronchiolitis.
Topics: Infant, Newborn; Infant; Humans; Child; Antiviral Agents; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Communicable Diseases; Respiratory Tract Infections; Bronchiolitis
PubMed: 37743207
DOI: 10.1016/j.anpede.2023.09.006 -
Journal of the Pediatric Infectious... Aug 2023In children with congenital heart disease and/or chronic lung disease entering their second respiratory syncytial virus (RSV) season, 200 mg nirsevimab had a similar...
In children with congenital heart disease and/or chronic lung disease entering their second respiratory syncytial virus (RSV) season, 200 mg nirsevimab had a similar safety profile to that of palivizumab and resulted in nirsevimab serum exposures associated with efficacy in healthy infants, supporting efficacy in this population at risk of severe RSV disease.
Topics: Infant; Child; Humans; Antibodies, Monoclonal; Antiviral Agents; Seasons; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Lung Diseases
PubMed: 37466917
DOI: 10.1093/jpids/piad052 -
Clinical Transplantation Sep 2019These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management...
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation review the diagnosis, prevention, and management of RNA respiratory viral infections in the pre- and post-transplant period. Viruses reviewed include influenza, respiratory syncytial virus (RSV), parainfluenza, rhinovirus, human metapneumovirus (hMPV), and coronavirus. Diagnosis is by nucleic acid testing due to improved sensitivity, specificity, broad range of detection of viral pathogens, automatization, and turnaround time. Respiratory viral infections may be associated with acute rejection and chronic lung allograft dysfunction in lung transplant recipients. The cornerstone of influenza prevention is annual vaccination and in some cases antiviral prophylaxis. Treatment with neuraminidase inhibitors and other antivirals is reviewed. Prevention of RSV is limited to prophylaxis with palivizumab in select children. Therapy of RSV upper or lower tract disease is controversial but may include oral or aerosolized ribavirin in some populations. There are no approved vaccines or licensed antivirals for parainfluenza, rhinovirus, hMPV, and coronavirus. Potential management strategies for these viruses are given. Future studies should include prospective trials using contemporary molecular diagnostics to understand the true epidemiology, clinical spectrum, and long-term consequences of respiratory viruses as well as to define preventative and therapeutic measures.
Topics: Anti-Infective Agents; Humans; Organ Transplantation; Practice Guidelines as Topic; RNA Viruses; Respiratory Tract Infections; Societies, Medical; Transplant Recipients
PubMed: 30817023
DOI: 10.1111/ctr.13511 -
The Journal of Infectious Diseases Aug 2022Respiratory syncytial virus (RSV) is associated with substantial morbidity in the United States, especially among infants. Nirsevimab, an investigational long-acting...
BACKGROUND
Respiratory syncytial virus (RSV) is associated with substantial morbidity in the United States, especially among infants. Nirsevimab, an investigational long-acting monoclonal antibody, was evaluated as an immunoprophylactic strategy for infants in their first RSV season and for its potential impact on RSV-associated, medically attended lower respiratory tract illness (RSV-MALRTI) and associated costs.
METHODS
A static decision-analytic model of the US birth cohort during its first RSV season was developed to estimate nirsevimab's impact on RSV-related health events and costs; model inputs included US-specific costs and epidemiological data. Modelled RSV-related outcomes included primary care and emergency room visits, hospitalizations including intensive care unit admission and mechanical ventilations, and RSV-related mortality.
RESULTS
Under current standard of care, RSV caused 529 915 RSV-MALRTIs and 47 281 hospitalizations annually, representing $1.2 billion (2021 US dollars [USD]) in costs. Universal immunization of all infants with nirsevimab is expected to reduce 290 174 RSV-MALRTI, 24 986 hospitalizations, and expenditures of $612 million 2021 USD.
CONCLUSIONS
An all-infant immunization strategy with nirsevimab could substantially reduce the health and economic burden for US infants during their first RSV season. While this reduction is driven by term infants, all infants, including palivizumab-eligible and preterm infants, would benefit from this strategy.
Topics: Antibodies, Monoclonal, Humanized; Humans; Immunization; Infant; Infant, Newborn; Infant, Premature; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Seasons; United States
PubMed: 35968866
DOI: 10.1093/infdis/jiac216 -
Vaccines Nov 2023Respiratory syncytial virus (RSV) is a well-known infant pathogen transmitted mainly by droplets. It is a leading cause of upper respiratory tract infections in... (Review)
Review
Respiratory syncytial virus (RSV) is a well-known infant pathogen transmitted mainly by droplets. It is a leading cause of upper respiratory tract infections in children, usually with a mild course of illness. RSV has also been a threat to older people, especially those with underlying medical conditions. For a long time, prevention was limited to passive immunoprophylaxis with palivizumab for high-risk infants. There was a strong need to find other treatment or prevention methods against RSV infections. In addition, after the coronavirus disease 2019 (COVID-19) pandemic, some significant changes in RSV epidemiology have been observed. Researchers noticed the shift in RSV seasonality and age distribution and the increased number of cases in older infants and adults. All of these made the need to find other medical options even stronger. Fortunately, two protein-based vaccines against RSV have successfully passed all phases of clinical trials and have been approved for use by adults and older people. One of them is also approved for infants from birth to 6 months of age (after maternal immunisation during pregnancy) and for pregnant women between 24 and 36 weeks of pregnancy. Also, a new passive immunisation option named nirsevimab (a highly potent monoclonal antibody with a long half-life) is now available for the paediatric group. In this review, we will discuss the previous and current RSV prevention methods in the light of structural discoveries of RSV antigens.
PubMed: 38140201
DOI: 10.3390/vaccines11121797 -
Molecules (Basel, Switzerland) Jan 2024Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals.... (Review)
Review
Respiratory syncytial virus (RSV) is a significant viral pathogen that causes respiratory infections in infants, the elderly, and immunocompromised individuals. RSV-related illnesses impose a substantial economic burden worldwide annually. The molecular structure, function, and in vivo interaction mechanisms of RSV have received more comprehensive attention in recent times, and significant progress has been made in developing inhibitors targeting various stages of the RSV replication cycle. These include fusion inhibitors, RSV polymerase inhibitors, and nucleoprotein inhibitors, as well as FDA-approved RSV prophylactic drugs palivizumab and nirsevimab. The research community is hopeful that these developments might provide easier access to knowledge and might spark new ideas for research programs.
Topics: Humans; Infant; Aged; Antiviral Agents; Palivizumab; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Anti-Retroviral Agents
PubMed: 38338343
DOI: 10.3390/molecules29030598 -
JAMA Network Open Jun 2024Respiratory syncytial virus (RSV) transmission was disrupted worldwide following the COVID-19 pandemic, and further study is required to better understand these changes.
IMPORTANCE
Respiratory syncytial virus (RSV) transmission was disrupted worldwide following the COVID-19 pandemic, and further study is required to better understand these changes.
OBJECTIVE
To compare observed and expected RSV hospital and intensive care unit (ICU) admission rates and characteristics of admitted children during the 2021-2022 and 2022-2023 seasons.
DESIGN, SETTING, AND PARTICIPANTS
A population-based cohort study of all children aged younger than 5 years in Ontario, Canada, July 1, 2017, through March 31, 2023, was conducted.
EXPOSURES
Individual and neighborhood-level sociodemographic and clinical characteristics were identified from administrative data, including age, palivizumab eligibility, complex medical conditions, rurality, and living in a marginalized neighborhood.
MAIN OUTCOMES AND MEASURES
The main outcome was RSV-associated hospitalization. Secondary outcomes included ICU admissions, mechanical ventilation, extracorporeal membrane oxygenation, and in-hospital death. Poisson generalized estimating equations were used to model weekly age- and sex-specific hospitalization rates and estimate expected rates in the postpandemic era; adjusted rate ratios (RRs) and 95% CIs are reported.
RESULTS
This cohort study included approximately 700 000 children per study year. Compared with prepandemic years (2017-2018, 2018-2019, and 2019-2020), the 2021-2022 RSV season peaked slightly earlier, but overall admission rates were comparable (289.1 vs 281.4-334.6 per 100 000, or approximately 2000 admissions). The 2022-2023 season peaked a month earlier and resulted in more than twice as many hospitalizations (770.0 per 100 000; n = 4977 admissions). The proportion of children admitted to an ICU in 2022-2023 (13.9%) was slightly higher than prepandemic (9.6%-11.4%); however, the population-based rate was triple the prepandemic levels (106.9 vs 27.6-36.6 per 100 000 children in Ontario). With the exception of palivizumab-eligible children, all sociodemographic and health status characteristics were associated with lower-than-expected RSV hospitalization rates in 2021-2022. In contrast, older age of patients was associated with higher-than-expected rates in 2022-2023 (ie, 24-59 months: RR, 1.90; 95% CI, 1.35-2.66).
CONCLUSIONS AND RELEVANCE
There were notable differences in RSV epidemiologic characteristics in Ontario following the COVID-19 pandemic. It is not yet clear whether and how long atypical RSV epidemics may persist. Clinicians and program planners should consider the potential for ongoing impacts to health care capacity and RSV immunization programs.
Topics: Humans; Respiratory Syncytial Virus Infections; Hospitalization; Infant; Male; Female; Child, Preschool; Ontario; COVID-19; SARS-CoV-2; Intensive Care Units; Cohort Studies; Infant, Newborn; Respiration, Artificial; Pandemics; Palivizumab
PubMed: 38861259
DOI: 10.1001/jamanetworkopen.2024.16077 -
Reviews in Medical Virology May 2022Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking... (Review)
Review
Respiratory syncytial virus (RSV) is a major health problem. A better understanding of the geographical and temporal dynamics of RSV circulation will assist in tracking resistance against therapeutics currently under development. Since 2015, the field of RSV molecular epidemiology has evolved rapidly with around 20-30 published articles per year. The objective of this systematic review is to identify knowledge gaps in recent RSV genetic literature to guide global molecular epidemiology research. We included 78 studies published between 2015 and 2020 describing 12,998 RSV sequences of which 8,233 (63%) have been uploaded to GenBank. Seventeen (22%) studies were performed in low- and middle-income countries (LMICs), and seven (9%) studies sequenced whole-genomes. Although most reported polymorphisms for monoclonal antibodies in clinical development (nirsevimab, MK-1654) have not been tested for resistance in neutralisation essays, known resistance was detected at low levels for the nirsevimab and palivizumab binding site. High resistance was found for the suptavumab binding site. We present the first literature review of an enormous amount of RSV genetic data. The need for global monitoring of RSV molecular epidemiology becomes increasingly important in evaluating the effectiveness of monoclonal antibody candidates as they reach their final stages of clinical development. We have identified the following three knowledge gaps: whole-genome data to study global RSV evolution, data from LMICs and data from global surveillance programs.
Topics: Antibodies, Monoclonal; Antiviral Agents; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34543489
DOI: 10.1002/rmv.2284 -
Journal of Proteins and Proteomics 2022Viral infections are progressively becoming a global health burden, as witnessed in the ongoing COVID-19 pandemic. Respiratory Syncytial Virus (RSV) is another highly...
UNLABELLED
Viral infections are progressively becoming a global health burden, as witnessed in the ongoing COVID-19 pandemic. Respiratory Syncytial Virus (RSV) is another highly contagious negative-sense RNA virus that causes lower respiratory tract infections and high mortality in infants. Palivizumab (Synagis) is the only humanized monoclonal antibody (mAb) approved by the FDA against RSV. The virus neutralization efficacy often depends on the nature and abundance of the glycoforms in therapeutic mAbs. Therefore, a thorough estimation of their PTM profile, especially glycosylation, is relevant. Here, we describe the intact and released glycan analysis of palivizumab (Synagis) using HILIC chromatography and mass spectrometry. We detected five glycoforms (Man5/G0FB, G0F/G1F, G1F/G1F, G0FB/G0FB, and G2F/G2F) in deconvoluted MS spectra of intact glycosylated palivizumab. The mapping of the peptide and glycopeptides using LC-ESI-MS led to the detection of associated PTMs and the direct identification of a glycopeptide, GlcNAcMan. EEQYNSTYR, derived from the heavy chain of palivizumab.Release glycan analysis using UHPLC-HILIC revealed a typical glycan profile consisting of major glycans, G0F (33.94%), G1F (35.50%), G2F (17.24%) also reported previously and minor G1F' (5.81%), Man5 (3.96%) and G0FB (2.26%) forms with the superior resolution of isomeric G1F/G1F'. Next, we provide the first experimental evidence of Neu5Gc in the commercial palivizumab formulation using DMB labelling. The estimated monosaccharide composition was consistent with previous studies. The findings of the study highlight the efficiency of the release glycan method in providing a correct measure of the total palivizumab glycan pool compared to the intact glycoprotein/glycopeptide approach. The UHPLC-RPLC/HILIC and MS combinations provide a more comprehensive glycoprofile assessment due to the parallel use of fluorescent labels for the analysis of the release of -glycan, sialic acid, and monosaccharide composition. This approach is suitable for quick quality testing and market surveillance of therapeutic mAbs. Alongside a well-perceived need for cost-effective immunoprophylaxis and the ongoing fast-paced development of next-generation variants of palivizumab, such as MEDI8897, the study reiterates glycosylation as a critical parameter that needs monitoring for drug characterization and quality control.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s42485-022-00086-1.
PubMed: 35572846
DOI: 10.1007/s42485-022-00086-1