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BMC Infectious Diseases Apr 2024Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the...
BACKGROUND
Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season.
METHODS
A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations.
RESULTS
Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration.
CONCLUSIONS
This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures.
Topics: Child; Humans; Infant; Child, Preschool; Respiratory Syncytial Virus, Human; Hospitalization; Seasons; Prospective Studies; Pandemics; COVID-19; Respiratory Syncytial Virus Infections; Respiratory Tract Infections; Italy; Primary Health Care
PubMed: 38605310
DOI: 10.1186/s12879-024-09229-9 -
Clinical Infectious Diseases : An... Jun 2024Respiratory syncytial virus (RSV) circulation dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt"...
BACKGROUND
Respiratory syncytial virus (RSV) circulation dropped markedly early in the COVID-19 pandemic, followed by a resurgence with heightened case counts. The "immunity debt" hypothesis proposes that the RSV-naїve pediatric population increased during the period of low transmission. However, the evidence supporting this hypothesis is limited, and the role of changing testing practices in the perceived surge has not been comprehensively evaluated.
METHODS
We conducted a multicenter, retrospective analysis of 342 530 RSV encounters and 980 546 RSV diagnostic tests occurring at 32 US pediatric hospitals in 2013-2023. We used interrupted time series analysis to estimate pandemic-associated changes in RSV patient and test volume and to quantify changes in the proportions of patients requiring hospitalization, intensive care, or mechanical ventilation. We quantified the fraction of the shifts in case counts and in the age of diagnosed patients attributable to changes in testing.
RESULTS
RSV patient volume increased 2.4-fold (95% confidence interval [CI]: 1.7, 3.5) in 2021-2023 relative to the pre-pandemic phase and was accompanied by an 18.9-fold increase (95% CI: 15.0, 23.9) in RSV test volume. Shifts in patient volume and in patient age were largely attributable to increased testing. The proportions of patients with RSV that required hospitalization, intensive care, or mechanical ventilation declined significantly across all patient age groups.
CONCLUSIONS
A surge in RSV testing, rather than in viral circulation, likely underlies the increased case counts observed in 2021-2023. These findings warrant a critical assessment of the immunity debt hypothesis and highlight the importance of considering the testing denominator when surveillance strategies are dynamic.
Topics: Humans; Respiratory Syncytial Virus Infections; COVID-19; Infant; Retrospective Studies; Child, Preschool; Female; SARS-CoV-2; Male; Child; Respiratory Syncytial Virus, Human; Hospitalization; United States; Infant, Newborn; Adolescent; Respiration, Artificial; Hospitals, Pediatric; Interrupted Time Series Analysis
PubMed: 38602423
DOI: 10.1093/cid/ciae140 -
Frontiers in Immunology 2024The human orthopneumovirus, Respiratory Syncytial Virus (RSV), is the causative agent of severe lower respiratory tract infections (LRTI) and exacerbations of chronic...
INTRODUCTION
The human orthopneumovirus, Respiratory Syncytial Virus (RSV), is the causative agent of severe lower respiratory tract infections (LRTI) and exacerbations of chronic lung diseases. In immune competent hosts, RSV productively infects highly differentiated epithelial cells, where it elicits robust anti-viral, cytokine and remodeling programs. By contrast, basal cells are relatively resistant to RSV infection, in part, because of constitutive expression of an intrinsic innate immune response (IIR) consisting of a subgroup of interferon (IFN) responsive genes. The mechanisms controlling the intrinsic IIR are not known.
METHODS
Here, we use human small airway epithelial cell hSAECs as a multipotent airway stem cell model to examine regulatory control of an intrinsic IIR pathway.
RESULTS
We find hSAECs express patterns of intrinsic IIRs, highly conserved with pluri- and multi-potent stem cells. We demonstrate a core intrinsic IIR network consisting of Bone Marrow Stromal Cell Antigen 2 (), Interferon Induced Transmembrane Protein 1 () and Toll-like receptor () expression are directly under IRF1 control. Moreover, expression of this intrinsic core is rate-limited by ambient IRF1• phospho-Ser 2 CTD RNA Polymerase II (pSer2 Pol II) complexes binding to their proximal promoters. In response to RSV infection, the abundance of IRF1 and pSer2 Pol II binding is dramatically increased, with IRF1 complexing to the BRD4 chromatin remodeling complex (CRC). Using chromatin immunoprecipitation in IRF1 KD cells, we find that the binding of BRD4 is IRF1 independent. Using a small molecule inhibitor of the BRD4 acetyl lysine binding bromodomain (BRD4i), we further find that BRD4 bromodomain interactions are required for stable BRD4 promoter binding to the intrinsic IIR core promoters, as well as for RSV-inducible pSer2 Pol II recruitment. Surprisingly, BRD4i does not disrupt IRF1-BRD4 interactions, but disrupts both RSV-induced BRD4 and IRF1 interactions with pSer2 Pol II.
CONCLUSIONS
We conclude that the IRF1 functions in two modes- in absence of infection, ambient IRF1 mediates constitutive expression of the intrinsic IIR, whereas in response to RSV infection, the BRD4 CRC independently activates pSer2 Pol II to mediates robust expression of the intrinsic IIR. These data provide insight into molecular control of anti-viral defenses of airway basal cells.
Topics: Humans; Antiviral Agents; Bromodomain Containing Proteins; Cell Cycle Proteins; Immunity, Innate; Nuclear Proteins; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; RNA Polymerase II; Transcription Factors
PubMed: 38601157
DOI: 10.3389/fimmu.2024.1366235 -
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 -
PloS One 2024Respiratory syncytial virus (RSV) is the leading viral cause of bronchiolitis and pneumonia in infants and toddlers, but there currently is no licensed pediatric...
Mutations in the F protein of the live-attenuated respiratory syncytial virus vaccine candidate ΔNS2/Δ1313/I1314L increase the stability of infectivity and content of prefusion F protein.
Respiratory syncytial virus (RSV) is the leading viral cause of bronchiolitis and pneumonia in infants and toddlers, but there currently is no licensed pediatric vaccine. A leading vaccine candidate that has been evaluated for intranasal immunization in a recently completed phase 1/2 clinical trial is an attenuated version of RSV strain A2 called RSV/ΔNS2/Δ1313/I1314L (hereafter called ΔNS2). ΔNS2 is attenuated by deletion of the interferon antagonist NS2 gene and introduction into the L polymerase protein gene of a codon deletion (Δ1313) that confers temperature-sensitivity and is stabilized by a missense mutation (I1314L). Previously, introduction of four amino acid changes derived from a second RSV strain "line 19" (I79M, K191R, T357K, N371Y) into the F protein of strain A2 increased the stability of infectivity and the proportion of F protein in the highly immunogenic pre-fusion (pre-F) conformation. In the present study, these four "line 19" assignments were introduced into the ΔNS2 candidate, creating ΔNS2-L19F-4M. During in vitro growth in Vero cells, ΔNS2-L19F-4M had growth kinetics and peak titer similar to the ΔNS2 parent. ΔNS2-L19F-4M exhibited an enhanced proportion of pre-F protein, with a ratio of pre-F/total F that was 4.5- to 5.0-fold higher than that of the ΔNS2 parent. The stability of infectivity during incubation at 4°C, 25°C, 32°C and 37°C was greater for ΔNS2-L19F-4M; for example, after 28 days at 32°C, its titer was 100-fold greater than ΔNS2. ΔNS2-L19F-4M exhibited similar levels of replication in human airway epithelial (HAE) cells as ΔNS2. The four "line 19" F mutations were genetically stable during 10 rounds of serial passage in Vero cells. In African green monkeys, ΔNS2-L19F-4M and ΔNS2 had similar growth kinetics, peak titer, and immunogenicity. These results suggest that ΔNS2-L19F-4M is an improved live attenuated vaccine candidate whose enhanced stability may simplify its manufacture, storage and distribution, which merits further evaluation in a clinical trial in humans.
Topics: Animals; Humans; Chlorocebus aethiops; Child; Respiratory Syncytial Virus Vaccines; Vero Cells; Antibodies, Viral; Viral Fusion Proteins; Respiratory Syncytial Virus, Human; Antibodies, Neutralizing; Mutation, Missense; Respiratory Syncytial Virus Infections
PubMed: 38593167
DOI: 10.1371/journal.pone.0301773 -
Italian Journal of Pediatrics Apr 2024Respiratory Syncytial Virus (RSV) is responsible for the majority of acute lower respiratory infections in infants and can affect also older age groups. Restrictions...
BACKGROUND
Respiratory Syncytial Virus (RSV) is responsible for the majority of acute lower respiratory infections in infants and can affect also older age groups. Restrictions linked to the emergence of the SARS-CoV-2 pandemic and their subsequent lifting caused a change in the dynamics of RSV circulation. It is therefore fundamental to monitor RSV seasonal trends and to be able to predict its seasonal peak to be prepared to the next RSV epidemics.
METHODS
We performed a retrospective descriptive study on laboratory-confirmed RSV infections from Bambino Gesù Children's Hospital in Rome from 1st January 2018 to 31st December 2022. Data on RSV-positive respiratory samples (n = 3,536) and RSV-confirmed hospitalizations (n = 1,895) on patients aged 0-18 years were analyzed. In addition to this, a SARIMA (Seasonal AutoRegressive Integrated Moving Average) forecasting model was developed to predict the next peak of RSV.
RESULTS
Findings show that, after the 2020 SARS-CoV-2 pandemic season, where RSV circulation was almost absent, RSV infections presented with an increased and anticipated peak compared to pre-pandemic seasons. While mostly targeting infants below 1 year of age, there was a proportional increase in RSV infections and hospitalizations in older age groups in the post-pandemic period. A forecasting model built using RSV weekly data from 2018 to 2022 predicted the RSV peaks of 2023, showing a reasonable level of accuracy (MAPE 33%). Additional analysis indicated that the peak of RSV cases is expected to be reached after 4-5 weeks from case doubling.
CONCLUSION
Our study provides epidemiological evidence on the dynamics of RSV circulation before and after the COVID-19 pandemic. Our findings highlight the potential of combining surveillance and forecasting to promote preparedness for the next RSV epidemics.
Topics: Infant; Child; Humans; Aged; Respiratory Syncytial Virus Infections; Seasons; Retrospective Studies; Pandemics; Hospitals, Pediatric; Respiratory Syncytial Virus, Human; Italy
PubMed: 38589886
DOI: 10.1186/s13052-024-01624-x -
Scientific Reports Apr 2024The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are...
The human respiratory syncytial virus (hRSV) and the human metapneumovirus (hMPV) are important human respiratory pathogens from the Pneumoviridae family. Both are responsible for severe respiratory tract infections in infants, young children, elderly individuals, adults with chronic medical conditions, and immunocompromised patients. Despite their large impact on human health, vaccines for hRSV were only recently introduced, and only limited treatment options exist. Here we show that Ginkgolic acid (GA), a natural compound from the extract of Ginkgo biloba, with known antiviral properties for several viruses, efficiently inhibits these viruses' infectivity and spread in cultures in a dose-dependent manner. We demonstrate that the drug specifically affects the entry step during the early stages on the viruses' life cycle with no effect on post-entry and late stage events, including viral gene transcription, genome replication, assembly and particles release. We provide evidence that GA acts as an efficient antiviral for members of the Pneumoviridae family and has the potential to be used to treat acute infections.
Topics: Child; Adult; Infant; Humans; Child, Preschool; Aged; Paramyxoviridae Infections; Metapneumovirus; Respiratory Tract Infections; Respiratory Syncytial Virus, Human; Virus Diseases; Respiratory Syncytial Virus Infections; Antiviral Agents; Salicylates
PubMed: 38589437
DOI: 10.1038/s41598-024-58032-8 -
The Journal of Infection May 2024This study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023.
OBJECTIVES
This study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023.
METHODS
Respiratory specimens from patients with RTI suspicion at Hospital Universitari Vall d'Hebron were collected from October 2013 to May 2023 for laboratory-confirmation of respiratory viruses. Next-generation sequencing was performed in randomly-selected samples with Illumina technology. Phylogenetic analyses of whole genome sequences were performed with BEAST v1.10.4. Signals of selection and evolutionary pressures were inferred by population dynamics and evolutionary analyses. Mutations in major surface proteins were genetic and structurally characterised, emphasizing those within antigenic epitopes.
RESULTS
Analyzing 139,625 samples, 5.3% were HRSV-positive (3008 HRSV-A, 3882 HRSV-B, 56 HRSV-A and -B, and 495 unsubtyped HRSV), with a higher prevalence observed in the paediatric population. Pandemic-related shifts in seasonal patterns returned to normal in 2022-2023. A total of 198 whole-genome sequences were obtained for HRSV-A (6.6% of the HRSV-A positive samples) belonging to GA2.3.5 lineage. For HRSV-B, 167 samples were sequenced (4.3% of the HRSV-B positive samples), belonging to GB5.0.2, GB5.0.4a and GB5.0.5a. HRSV-B exhibited a higher evolution rate. Post-SARS-CoV-2 pandemic, both subtypes showed increased evolutionary rates and decreased effective population size initially, followed by a sharp increase. Analyses indicated negative selective pressure on HRSV. Mutations in antigenic epitopes, including S276N and M274I in palivizumab-targeted site II, and I206M, Q209R, and S211N in nirsevimab-targeted site Ø, were identified.
DISCUSSION
Particularly in the context of the large-scale use in 2023-2024 season of nirsevimab, continuous epidemiological and genomic surveillance is crucial.
Topics: Humans; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Phylogeny; Child, Preschool; Child; Male; Infant; Evolution, Molecular; Female; Genome, Viral; Middle Aged; Spain; Adolescent; Adult; Genetic Variation; Antibodies, Monoclonal; Aged; Young Adult; Mutation; Whole Genome Sequencing; Antibodies, Viral; Prevalence; High-Throughput Nucleotide Sequencing; Infant, Newborn
PubMed: 38588960
DOI: 10.1016/j.jinf.2024.106153 -
Journal of Virological Methods Jun 2024Advances in high-throughput sequencing (HTS) technologies and reductions in sequencing costs have revolutionised the study of genomics and molecular biology by making...
BACKGROUND
Advances in high-throughput sequencing (HTS) technologies and reductions in sequencing costs have revolutionised the study of genomics and molecular biology by making whole-genome sequencing (WGS) accessible to many laboratories. However, the analysis of WGS data requires significant computational effort, which is the major drawback in implementing WGS as a routine laboratory technique.
OBJECTIVE
Automated pipelines have been developed to overcome this issue, but they do not exist for all organisms. This is the case for human respiratory syncytial virus (RSV), which is a leading cause of lower respiratory tract infections in infants, the elderly, and immunocompromised adults.
RESULTS
We present RSV-GenoScan, a fast and easy-to-use pipeline for WGS analysis of RSV generated by HTS on Illumina or Nanopore platforms. RSV-GenoScan automates the WGS analysis steps directly from the raw sequence data. The pipeline filters the sequence data, maps the reads to the RSV reference genomes, generates a consensus sequence, identifies the RSV subgroup, and lists amino acid mutations, insertions and deletions in the F and G viral genes. This enables the rapid identification of mutations in these coding genes that are known to confer resistance to monoclonal antibodies.
AVAILABILITY
RSV-GenoScan is freely available at https://github.com/AlexandreD-bio/RSV-GenoScan.
Topics: Respiratory Syncytial Virus, Human; Humans; Genome, Viral; Respiratory Syncytial Virus Infections; Whole Genome Sequencing; High-Throughput Nucleotide Sequencing; Computational Biology; Mutation
PubMed: 38588779
DOI: 10.1016/j.jviromet.2024.114938 -
Andes Pediatrica : Revista Chilena de... Feb 2024During the winter of 2023, Chile faced a complex situation related to the respiratory syncytial virus (RSV). After experiencing a decline in RSV circulation during the...
During the winter of 2023, Chile faced a complex situation related to the respiratory syncytial virus (RSV). After experiencing a decline in RSV circulation during the years of the SARS-CoV-2 pandemic, a late outbreak was observed in the spring of 2022 and an early onset of the outbreak in 2023, with a significant increase in the number of serious cases. The ineffectiveness of strategic planning and risk communication contributed to the complexity of the situation. To avoid the above next winter, measures such as active surveillance, unification of definitions for acute respiratory infections, identification of RSV variants, public education about infections and advance preparation regarding hospital beds and health personnel are suggested. The importance of immunization and intersectoral collaboration to acquire new preventive alternatives is highlighted, as well as the need for early communication about the importance of immunization and identification of high-risk groups, improvement in training of medical personnel and strategic planning of the Ministry of Health. seeking a proactive and collaborative approach to address the complex RSV situation in future winters. The Chilean Immunization Advisory Committee has already carried out an analysis and recommendation on a new prevention alternative. This working group will support any decision of the Ministry of Health in public policies that attempt a change in the paradigm of control of this disease for the health of the children of our country.
Topics: Child; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Immunization; Vaccination; Respiratory Tract Infections
PubMed: 38587340
DOI: 10.32641/andespediatr.v95i1.5055