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JAMA Network Open Aug 2023Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide.
IMPORTANCE
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) and infant hospitalization worldwide.
OBJECTIVE
To evaluate the characteristics and outcomes of RSV-related critical illness in US infants during peak 2022 RSV transmission.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used a public health prospective surveillance registry in 39 pediatric hospitals across 27 US states. Participants were infants admitted for 24 or more hours between October 17 and December 16, 2022, to a unit providing intensive care due to laboratory-confirmed RSV infection.
EXPOSURE
Respiratory syncytial virus.
MAIN OUTCOMES AND MEASURES
Data were captured on demographics, clinical characteristics, signs and symptoms, laboratory values, severity measures, and clinical outcomes, including receipt of noninvasive respiratory support, invasive mechanical ventilation, vasopressors or extracorporeal membrane oxygenation, and death. Mixed-effects multivariable log-binomial regression models were used to assess associations between intubation status and demographic factors, gestational age, and underlying conditions, including hospital as a random effect to account for between-site heterogeneity.
RESULTS
The first 15 to 20 consecutive eligible infants from each site were included for a target sample size of 600. Among the 600 infants, the median (IQR) age was 2.6 (1.4-6.0) months; 361 (60.2%) were male, 169 (28.9%) were born prematurely, and 487 (81.2%) had no underlying medical conditions. Primary reasons for admission included LRTI (594 infants [99.0%]) and apnea or bradycardia (77 infants [12.8%]). Overall, 143 infants (23.8%) received invasive mechanical ventilation (median [IQR], 6.0 [4.0-10.0] days). The highest level of respiratory support for nonintubated infants was high-flow nasal cannula (243 infants [40.5%]), followed by bilevel positive airway pressure (150 infants [25.0%]) and continuous positive airway pressure (52 infants [8.7%]). Infants younger than 3 months, those born prematurely (gestational age <37 weeks), or those publicly insured were at higher risk for intubation. Four infants (0.7%) received extracorporeal membrane oxygenation, and 2 died. The median (IQR) length of hospitalization for survivors was 5 (4-10) days.
CONCLUSIONS AND RELEVANCE
In this cross-sectional study, most US infants who required intensive care for RSV LRTIs were young, healthy, and born at term. These findings highlight the need for RSV preventive interventions targeting all infants to reduce the burden of severe RSV illness.
Topics: Child; Infant; Humans; Male; Female; Prospective Studies; Seasons; Cross-Sectional Studies; Hospitalization; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Intensive Care Units; Respiratory Tract Infections
PubMed: 37581884
DOI: 10.1001/jamanetworkopen.2023.28950 -
Nature Communications Apr 2024Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide....
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread.
Topics: Infant; Child; Humans; Child, Preschool; Respiratory Syncytial Virus Infections; Phylogeny; Respiratory Syncytial Virus, Human; Genomics; Respiratory Tract Infections
PubMed: 38600104
DOI: 10.1038/s41467-024-47118-6 -
Viruses Aug 2023Lower respiratory tract infections (LRIs) are a significant cause of disability-adjusted life-years (DALYs) across all age groups, especially in children under 9 years...
Lower respiratory tract infections (LRIs) are a significant cause of disability-adjusted life-years (DALYs) across all age groups, especially in children under 9 years of age, and adults over 75. The main causative agents are viruses, such as influenza and respiratory syncytial virus (RSV). Viral LRIs in adults have historically received less attention. This study investigated the incidence of RSV and influenza in adult patients admitted to a referral hospital, as well as the clinical profile of these infections. Molecular testing was conducted on nasopharyngeal samples taken from a respiratory surveillance cohort comprising adult (15-59 years) and elderly (60+ years) hospitalized patients who tested negative for SARS-CoV-2, to determine the prevalence for influenza and RSV. Influenza was found to be less frequent among the elderly. The main symptoms of RSV infections were cough, fever, dyspnea, malaise, and respiratory distress, while headache, nasal congestion, a sore throat, and myalgia were most frequent in influenza. Elderly patients with RSV were not found to have more severe illness than adults under age 60, underscoring the importance of providing the same care to adults with this viral infection.
Topics: Child; Aged; Adult; Humans; Middle Aged; Respiratory Syncytial Virus Infections; Neglected Diseases; Influenza, Human; COVID-19; SARS-CoV-2; Respiratory Syncytial Virus, Human
PubMed: 37766255
DOI: 10.3390/v15091848 -
Cellular Immunology 2024Infection of the respiratory tract with respiratory syncytial virus (RSV) is common and occurs repeatedly throughout life with most severe disease occurring at the... (Review)
Review
Infection of the respiratory tract with respiratory syncytial virus (RSV) is common and occurs repeatedly throughout life with most severe disease occurring at the extremes of age: in young infants and the elderly. Effective anti-viral therapeutics are not available and therefore prevention has been the primary strategy for reducing the disease burden. Our current understanding of respiratory mucosal cell biology and the immune response within the respiratory tract is inadequate to prevent infection caused by a pathogen like RSV that does not disseminate outside of this environment. Gaps in our understanding of the activation of innate and adaptive immunity in response to RSV and the role of age upon infection also limit improvements in the design of therapeutics and vaccines for young infants. However, advancements in structural biology have improved our ability to characterize antibodies against viral proteins and in 2023 the first vaccines for those over 60 years and pregnant women became available, potentially reducing the burden of disease. This review will examine our current understanding of the critical facets of anti-RSV immune responses in infants and young children as well as highlight areas where more research is needed.
Topics: Humans; Respiratory Syncytial Virus Infections; Adaptive Immunity; Immunity, Innate; Infant; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Child, Preschool; Antibodies, Viral; Female; Respiratory Syncytial Viruses
PubMed: 38615612
DOI: 10.1016/j.cellimm.2024.104824 -
The Pediatric Infectious Disease Journal Dec 2023We analyzed the frequency, clinical impact and severity of respiratory syncytial virus (RSV) and SARS-CoV-2 coinfections in a single pediatric center between March 2020...
We analyzed the frequency, clinical impact and severity of respiratory syncytial virus (RSV) and SARS-CoV-2 coinfections in a single pediatric center between March 2020 and January 2023. Compared to single RSV infections, RSV/SARS-CoV-2 coinfections were uncommon (2.1%), occurred more frequently during circulation of omicron, and were associated with increased disease severity as defined by longer hospitalization and increased need for high-flow nasal cannula.
Topics: Infant; Child; Humans; Child, Preschool; SARS-CoV-2; Coinfection; Clinical Relevance; COVID-19; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Hospitalization
PubMed: 37670468
DOI: 10.1097/INF.0000000000004080 -
Antiviral Research May 2024Despite the availability of effective preventative vaccines and potent small-molecule antiviral drugs, effective non-toxic prophylactic and therapeutic measures are... (Review)
Review
Despite the availability of effective preventative vaccines and potent small-molecule antiviral drugs, effective non-toxic prophylactic and therapeutic measures are still lacking for many viruses. The use of monoclonal and polyclonal antibodies in an antiviral context could fill this gap and provide effective virus-specific medical interventions. In order to develop these therapeutic antibodies, preclinical animal models are of utmost importance. Due to the variability in viral pathogenesis, immunity and overall characteristics, the most representative animal model for human viral infection differs between virus species. Therefore, throughout the years researchers sought to find the ideal preclinical animal model for each virus. The most used animal models in preclinical research include rodents (mice, ferrets, …) and non-human primates (macaques, chimpanzee, ….). Currently, antibodies are tested for antiviral efficacy against a variety of viruses including different hepatitis viruses, human immunodeficiency virus (HIV), influenza viruses, respiratory syncytial virus (RSV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and rabies virus. This review provides an overview of the current knowledge about the preclinical animal models that are used for the evaluation of therapeutic antibodies for the abovementioned viruses.
Topics: Animals; Mice; Ferrets; Antibodies, Viral; Respiratory Syncytial Virus, Human; SARS-CoV-2; Disease Models, Animal; Antiviral Agents
PubMed: 38548022
DOI: 10.1016/j.antiviral.2024.105843 -
The Lancet. Digital Health Nov 2023Novel immunisation methods against respiratory syncytial virus (RSV) are emerging, but knowledge of risk factors for severe RSV disease is insufficient for optimal...
BACKGROUND
Novel immunisation methods against respiratory syncytial virus (RSV) are emerging, but knowledge of risk factors for severe RSV disease is insufficient for optimal targeting of interventions against them. Our aims were to identify predictors for RSV hospital admission from registry-based data and to develop and validate a clinical prediction model to guide RSV immunoprophylaxis for infants younger than 1 year.
METHODS
In this model development and validation study, we studied all infants born in Finland between June 1, 1997, and May 31, 2020, and in Sweden between June 1, 2006, and May 31, 2020, along with the data for their parents and siblings. Infants were excluded if they died or were admitted to hospital for RSV within the first 7 days of life. The outcome was hospital admission due to RSV bronchiolitis during the first year of life. The Finnish study population was divided into a development dataset (born between June 1, 1997, and May 31, 2017) and a temporal hold-out validation dataset (born between June 1, 2017, and May 31, 2020). The development dataset was used for predictor discovery and selection in which we screened 1511 candidate predictors from the infants', parents', and siblings' data, and developed a logistic regression model with the 16 most important predictors. This model was then validated using the Finnish hold-out validation dataset and the Swedish dataset.
FINDINGS
In total, there were 1 124 561 infants in the Finnish development dataset, 130 352 infants in the Finnish hold-out validation dataset, and 1 459 472 infants in the Swedish dataset. In addition to known predictors such as severe congenital heart defects (adjusted odds ratio 2·89, 95% CI 2·28-3·65), we confirmed some less established predictors for RSV hospital admission, most notably oesophageal malformations (3·11, 1·86-5·19) and lower complexity congenital heart defects (1·43, 1·25-1·63). The prediction model's C-statistic was 0·766 (95% CI 0·742-0·789) in Finnish data and 0·737 (0·710-0·762) in Swedish validation data. The infants in the highest decile of predicted RSV hospital admission probability had 4·5 times higher observed risk compared with others. Calibration varied according to epidemic intensity. The model's performance was similar to a machine learning (XGboost) model using all 1511 candidate predictors (C-statistic in Finland 0·771, 95% CI 0·754-0·788). The prediction model showed clinical utility in decision curve analysis and in hypothetical number needed to treat calculations for immunisation, and its C-statistic was similar across different strata of parental income.
INTERPRETATION
The identified predictors and the prediction model can be used in guiding RSV immunoprophylaxis in infants, or as a basis for further immunoprophylaxis targeting tools.
FUNDING
Sigrid Jusélius Foundation, European Research Council, Pediatric Research Foundation, and Academy of Finland.
Topics: Infant; Child; Humans; Respiratory Syncytial Virus Infections; Models, Statistical; Prognosis; Respiratory Syncytial Viruses; Risk Factors; Heart Defects, Congenital
PubMed: 37890904
DOI: 10.1016/S2589-7500(23)00175-9 -
Current Opinion in Pediatrics Apr 2024Respiratory syncytial virus (RSV) is a ubiquitous virus and the leading cause of pediatric hospitalization in the United States. Prevention strategies are key for... (Review)
Review
PURPOSE OF REVIEW
Respiratory syncytial virus (RSV) is a ubiquitous virus and the leading cause of pediatric hospitalization in the United States. Prevention strategies are key for reducing the burden of RSV. Several new agents aimed at preventing RSV in infants and children were FDA-approved in 2023, and many more are in the development pipeline. This review highlights new developments in RSV prevention in pediatric patients and the important safety considerations for clinical trials.
RECENT FINDINGS
Two new preventive therapies were FDA approved in 2023; a maternal vaccine (Abrysvo) and a mAb (Beyfortus) have both demonstrated reduction in medically attended lower respiratory tract infections in infants and children. Evaluation of ongoing clinical trials demonstrates that the field is expanding further to include direct immunization of infants and children utilizing a variety of delivery modalities. While these developments present the optimistic prospect of RSV prevention in a range of ages, acute and long-term risks must be carefully evaluated.
SUMMARY
Prevention of RSV is more accessible than ever, but careful consideration must be given to risks associated with new and developing prevention strategies. Rigor of clinical trials including longitudinal outcomes of agents in development and postmarketing surveillance of newly approved therapies will be of paramount importance to ensure long-term safety of new RSV prevention strategies.
Topics: Infant; Humans; Child; United States; Respiratory Syncytial Viruses; Respiratory Syncytial Virus Infections; Hospitalization; Immunization; Viral Vaccines; Respiratory Syncytial Virus Vaccines
PubMed: 38299987
DOI: 10.1097/MOP.0000000000001336 -
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