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Biomedicines Oct 2022Human metapneumovirus (HMPV) and human respiratory virus (HRSV) are two leading causes of acute respiratory tract infection in young children. While there is no licensed...
Human metapneumovirus (HMPV) and human respiratory virus (HRSV) are two leading causes of acute respiratory tract infection in young children. While there is no licensed drug against HMPV, the monoclonal antibody (mAb) Palivizumab is approved against HRSV for prophylaxis use only. Novel therapeutics against both viruses are therefore needed. Here, we describe the identification of human mAbs targeting these viruses by using flow cytometry-based cell sorting. One hundred and two antibodies were initially identified from flow cytometry-based cell sorting as binding to the fusion protein from HRSV, HMPV or both. Of those, 95 were successfully produced in plants, purified and characterized for binding activity by ELISA and neutralization assays as well as by inhibition of virus replication in mice. Twenty-two highly reactive mAbs targeting either HRSV or HMPV were isolated. Of these, three mAbs inhibited replication in vivo of a single virus while one mAb could reduce both HRSV and HMPV titers in the lung. Overall, this study identifies several human mAbs with virus-specific therapeutic potential and a unique mAb with inhibitory activities against both HRSV and HMPV.
PubMed: 36289776
DOI: 10.3390/biomedicines10102516 -
Journal of Clinical Immunology Jan 2023Due to the absence of curative treatments for inborn errors of immunity (IEI), children born with IEI require long-term follow-up for disease manifestations and related...
BACKGROUND
Due to the absence of curative treatments for inborn errors of immunity (IEI), children born with IEI require long-term follow-up for disease manifestations and related complications that occur over the lifespan. Effective transition from pediatric to adult services is known to significantly improve adherence to treatment and long-term outcomes. It is currently not known what transition services are available for young people with IEI in Europe.
OBJECTIVE
To understand the prevalence and practice of transition services in Europe for young people with IEI, encompassing both primary immunodeficiencies (PID) and systemic autoinflammatory disorders (AID).
METHODS
A survey was generated by the European Reference Network on immunodeficiency, autoinflammatory, and autoimmune diseases Transition Working Group and electronically circulated, through professional networks, to pediatric centers across Europe looking after children with IEI.
RESULTS
Seventy-six responses were received from 52 centers, in 45 cities across 17 different countries. All services transitioned patients to adult services, mainly to specialist PID or AID centers, typically transferring up to ten patients to adult care each year. The transition process started at a median age of 16-18 years with transfer to the adult center occurring at a median age of 18-20 years. 75% of PID and 68% of AID centers held at least one joint appointment with pediatric and adult services prior to the transfer of care. Approximately 75% of PID and AID services reported having a defined transition process, but few centers reported national disease-specific transition guidelines to refer to.
CONCLUSIONS
Transition services for children with IEI in Europe are available in many countries but lack standardized guidelines to promote best practice.
Topics: Adult; Humans; Child; Adolescent; Young Adult; Europe; Immunologic Deficiency Syndromes; Autoimmune Diseases; Prevalence; Hereditary Autoinflammatory Diseases
PubMed: 36222999
DOI: 10.1007/s10875-022-01345-y -
Revista Brasileira de Enfermagem 2022to analyze the occurrence of respiratory complications over the first year of life in preterm infants who did not receive palivizumab monoclonal antibodies.
OBJECTIVES
to analyze the occurrence of respiratory complications over the first year of life in preterm infants who did not receive palivizumab monoclonal antibodies.
METHODS
analytical retrospective cohort study with preterm infants born between 2012 and 2016 in Uberlândia, state of Minas Gerais, Brazil. Data collection occurred from January to November 2018, by consulting hospital and primary healthcare medical records. Data were processed with the Poisson regression model, with p<0.05.
RESULTS
of a total of 5,213 preterm births, 504 (9.7%) met the inclusion criteria. The preterm infants in this subset were assisted 2,899 times in primary care, which resulted in 1,098 (37.5%) medical diagnoses, of which 803 (78.5%) involved the respiratory tract. Preterm babies fed on formula milk at hospital discharge had more diagnoses of respiratory diseases. Maternal age (p=0.039), respiratory diagnosis at hospital discharge (p=0.028), and number of sporadic appointments (p<0.001) showed a significant association with bronchiolitis; number of sporadic appointments showed a significant association with occurrence of respiratory diseases; and breastfeeding had a protective effect against the development of bronchiolitis.
CONCLUSIONS
preterm infants who did not receive palivizumab showed a high percentage of respiratory diseases, and breastfeeding helped protect them against bronchiolitis. It is recommended that these preterm babies be monitored in primary health care.
Topics: Antibodies, Monoclonal; Antiviral Agents; Bronchiolitis; Cohort Studies; Female; Hospitalization; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Palivizumab; Respiration Disorders; Retrospective Studies
PubMed: 36197428
DOI: 10.1590/0034-7167-2021-0362 -
Vaccine Oct 2022Respiratory syncytial virus (RSV) remains a leading cause of medically-attended acute respiratory infection in infants and children. With multiple preventative...
BACKGROUND
Respiratory syncytial virus (RSV) remains a leading cause of medically-attended acute respiratory infection in infants and children. With multiple preventative interventions under development, accurate estimates of health care resource utilization are essential for policy decision making.
METHODS
We developed a literature-based decision-tree model that estimated annual medically-attended RSV (MA-RSV) lower respiratory tract infection (LRTI) and non-LRTI episodes in the US for all infants and for high-risk toddlers. The model accounted for the gestational age and birth-month of infants, and the seasonal variation in RSV incidence. The impact of no prophylaxis, palivizumab, maternal vaccine, and long-acting monoclonal antibody (mAb) interventions was estimated.
RESULTS
We estimated 1.23 million (range: 0.96 million-1.40 million) annual MA-RSV LRTI/non-LRTI episodes comprised of 1.19 million (range: 0.93 million-1.36 million) emergency department (ED) and outpatient visits, and 39,040 (range: 32,726-45,851) hospitalizations. Outpatient and ED visits were comprised of 586,034 (range: 430,595-718,868) LRTIs and 608,733 (range: 495,705-644,658) non-LRTIs. The long-acting mAb intervention resulted in the greatest number of averted outpatient and ED episodes (310,997 [53%] LRTIs; 284,305 [47%] non-LRTIs) and hospitalizations (21,845 [56%]). Full-term infants constitute the highest proportion of episodes across all interventions.
CONCLUSIONS
MA-RSV disease is substantial in infants and high-risk toddlers. Long-acting mAbs are most effective at reducing the number of MA-RSV LRTI/non-LRTI episodes, and the only intervention that prevents disease in older infants (≥6 months old).
Topics: Aged; Antibodies, Monoclonal; Antiviral Agents; Child, Preschool; Hospitalization; Humans; Infant; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; United States
PubMed: 36096968
DOI: 10.1016/j.vaccine.2022.08.011 -
Journal of Paediatrics and Child Health Oct 2022Globally, respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in young children, and the association between severe RSV disease and... (Review)
Review
Globally, respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in young children, and the association between severe RSV disease and later recurrent wheeze and asthma is well established. Whilst a causal link between RSV and wheeze/asthma is not yet proven, immunological evidence suggests skewing towards a Th2-type response, and dampening of IFN-γ antiviral immunity during RSV infection underpins airway hyper-reactivity in a subset of susceptible children after RSV infection. Age at primary RSV infection, viral co-infection and genetic influences may act as effect-modifiers. Despite the significant morbidity and mortality burden of RSV disease in children, there is currently no licensed vaccine. Recent advancements in RSV preventatives, including long-acting monoclonal antibodies and maternal vaccinations, show significant promise and we are on the cusp of a new era in RSV prevention. However, the potential impact of RSV preventatives on subsequent wheeze and asthma remains unclear. The ongoing COVID-19 pandemic and associated public health measures have disrupted the usual seasonality of RSV. Whilst this has posed challenges for health-care services it has also enhanced our understanding of RSV transmission. The near absence of RSV cases during the first year of the pandemic in the context of strict public health measures has provided a rare opportunity to study the impact of delayed age of primary RSV infection on asthma prevalence. In this review, we summarise current understanding of the association between RSV, recurrent wheeze and asthma with a focus on pathophysiology, preventative strategies and future research priorities.
Topics: Antibodies, Monoclonal; Antiviral Agents; Asthma; COVID-19; Child; Child, Preschool; Humans; Infant; Pandemics; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Virus Diseases
PubMed: 36073299
DOI: 10.1111/jpc.16197 -
The Journal of Infectious Diseases Aug 2022The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized.
BACKGROUND
The burden and health care utilization (HCU) of respiratory syncytial virus (RSV) in US infants aged <1 year across health care settings are not well characterized.
METHODS
We systematically reviewed studies of RSV and bronchiolitis published 2000-2021 (data years, 1979-2020). Outcomes included RSV hospitalization (RSVH)/bronchiolitis hospitalization rates, emergency department (ED)/outpatient (OP) visit rates, and intensive care unit (ICU) admissions or mechanical ventilation (MV) use among RSV-/bronchiolitis-hospitalized infants. Study quality was determined using standard tools.
RESULTS
We identified 141 good-/fair-quality studies. Five national studies reported annual average RSVH rates (range, 11.6 per 1000 per year among infants aged 6-11 months in 2006 to 50.1 per 1000 per year among infants aged 0-2 months in 1997). Two national studies provided RSVH rates by primary diagnosis for the entire study period (range, 22.0-22.7 per 1000 in 1997-1999 and 1997-2000, respectively). No national ED/OP data were available. Among 11 nonnational studies, RSVH rates varied due to differences in time, populations (eg, prematurity), and locations. One national study reported that RSVH infants with high-risk comorbidities had 5-times more MV use compared to non-high-risk infants in 1997-2012.
CONCLUSIONS
Substantial data variability was observed. Nationally representative studies are needed to elucidate RSV burden and HCU.
Topics: Bronchiolitis; Humans; Infant; Infant, Newborn; Infant, Premature; Palivizumab; Patient Acceptance of Health Care; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; United States
PubMed: 35968876
DOI: 10.1093/infdis/jiac201 -
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 -
BMC Public Health Aug 2022The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is...
BACKGROUND
The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan.
METHODS
The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred.
RESULTS
A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020.
CONCLUSIONS
Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.
Topics: Antiviral Agents; Child; Hospitalization; Humans; Infant; Japan; Palivizumab; Respiratory Syncytial Virus Infections; Retrospective Studies; Search Engine
PubMed: 35945532
DOI: 10.1186/s12889-022-13899-y -
Frontiers in Pediatrics 2022Preterm infants are at risk of lower respiratory tract infections (LRTI), including Respiratory Syncytial Virus (RSV) associated bronchiolitis, for which palivizumab...
INTRODUCTION
Preterm infants are at risk of lower respiratory tract infections (LRTI), including Respiratory Syncytial Virus (RSV) associated bronchiolitis, for which palivizumab prophylaxis can be proposed. Our aim was to determine risk factors of very severe RSV disease in children born before 34 weeks of gestation.
METHODS
Among 2,101 infants born before 34 weeks of gestation in 3 maternity wards between 2012 and 2017, the laboratory confirmed RSV-infected patients requiring hospitalization before 12 months of corrected age were retrospectively included. We collected data about the neonatal period, the palivizumab prophylaxis and the hospitalization for a RSV-related LRTI. LRTI was considered as very severe (VS-LRTI) when patients required invasive or non-invasive positive pressure ventilation.
RESULTS
Among 86 included patients, 31 met the criteria of VS-LRTI. The VS-LRTI patients had a higher birth gestational age and weight but less heart disease and bronchopulmonary dysplasia. They received palivizumab prophylaxis less frequently than the other patients but the difference was not significant. At the onset of infection, VS-LRTI patients had a younger corrected age for prematurity and presented more frequently with apnea, bradycardia, life-threatening event, hemodynamic failure, hypercapnia. Using logistic regression, the main factor associated with VS-LRTI was a younger corrected age for prematurity at the onset of infection [Odd ratio for each month of corrected age = 0.77 (0.62; 0.93), = 0.012].
CONCLUSION
Infants at the highest risk of VS-LRTI were infants with a younger corrected age for prematurity. Therefore, a better targeting of infants requiring palivizumab prophylaxis and early interventions at hospital discharge could limit VS-LRTI in these infants.
PubMed: 35874569
DOI: 10.3389/fped.2022.884120 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jun 2022Since the palivizumab for respiratory syncytial virus was approved in 1998, therapeutic antibodies against infectious diseases have been widely used in clinical... (Review)
Review
Since the palivizumab for respiratory syncytial virus was approved in 1998, therapeutic antibodies against infectious diseases have been widely used in clinical treatment. Since the outbreak of COVID-19, plenty of neutralizing antibodies were developed and transferred into clinical trials, holding enormous promise for the treatment of COVID-19 under the context of emergency use authorization. This review summarizes the clinical progress of these drugs, in order to provide a reference for the research and development of neutralizing antibody drugs for the future.
Topics: Antibodies, Neutralizing; Antibodies, Viral; COVID-19; Humans; Neutralization Tests; SARS-CoV-2
PubMed: 35786461
DOI: 10.13345/j.cjb.220118