Respiratory Syncytial Research Articles

Prevalence of Respiratory Syncytial Virus Among Children in Dhamar Governorate, Yemen

Respiratory syncytial virus (RSV) is a significant cause of respiratory illness in pediatric populations worldwide. This study aims to determine the prevalence of RSV among children under two years of age with respiratory tract infection in Dhamar Governorate and evaluate related risk factors. The study, conducted at various hospitals and centers in Dhamar Governorate, enrolled 130 children under two years of age with signs and symptoms of respiratory tract infection from January 2020 to December 2020. A pre-designed questionnaire was used to collect data on Sociodemographic information, symptoms, and risk factors such as age, sex, birth weight, breastfeeding, and presence of other medical conditions. Results showed that RSV was detected in 36.9% of the patients, with females being more affected than males. Most RSV-infected children were in their first eight months of life, and an association was found between the presence of smokers among family members, birth weight, breastfeeding, number of siblings, lung disorder, and family medical history, and RSV infection. Further analysis revealed significant associations between RSV infection and risk factors such as lung disorders and family medical history. Symptoms commonly exhibited by RSV-infected patients included cough, fever, wheezing, difficulty breathing, sore throat, runny nose, and blue lips. Environmental factors such as passive smoking, number of siblings, and family medical history of respiratory infections were identified as potential risk factors for RSV infection. Seasonal variations in RSV prevalence were also observed, with higher rates during certain months. In conclusion, the prevalence of RSV among children with respiratory tract infection in Dhamar Governorate is relatively high, with several risk factors influencing infection rates. Recommendations based on the study findings include considering RSV in the diagnosis and treatment of respiratory illnesses in young children, planning prevention and control programs, and providing health education to mothers to prevent RSV transmission. Keyword: Respiratory Syncytial Virus, Children, Dhamar Governorate.

Novel imported clades accelerated the RSV surge in Beijing, China, 2023-2024

ObjectivesDespite the optimisation of the zero-COVID policy in late 2022, there was a subsequent increase noted in the number of respiratory syncytial virus (RSV) cases in Northern China. In this study, we investigated and characterised the dynamics of this surge at the genomic level in Beijing, China. MethodsPatients with acute respiratory tract infections (ARTIs) were enrolled from 35 sentinel hospitals in Beijing, China. Epidemiological investigations, G gene amplification, and whole-genome sequencing were performed, followed by epidemiological analysis, imported clade detection, and mutation identification. We also combined global data to illustrate the biological and epidemiological characteristics of the emerging clades. ResultsA total of 60,423 patients with ARTIs were recruited between January 2015 and January 2024. The RSV peak observed in the winter of 2023 was the highest in the past 9 years. Two novel imported clades, A.D.5.2 and B.D.E.1, were detected for the first time in China. This surge was mainly driven by B.D.E.1, which exhibited a significantly higher proportion of older individuals both in Beijing and globally. Seven non-synonymous mutations in B.D.E.1 were found in Beijing. B.D.E.1 had more sites suffering from positive selection than its parent. ConclusionsThe novel imported clade B.D.E.1 accelerated an unprecedented RSV surge in Beijing, presenting noteworthy epidemiological and biological characteristics. Continuous RSV genome monitoring has important implications for RSV outbreak identification, genetic diversity tracking, vaccine development, and strategy implementation.

The Cumulative Variations of Respiratory Syncytial Virus Fusion Protein (F) in Ten Consecutive Years in China.

Variations in the fusion (F) protein of respiratory syncytial virus (RSV) with main antigenic sites I-V and Ø may affect the development of RSV vaccines and therapies. In the study, 30 respiratory specimens positive for RSV were randomly selected from children with acute lower respiratory infections (ALRI) in Beijing every year from 2012 to 2021 for F gene sequencing. Then, 300 F gene sequences and 508 uploaded to GenBank from China were subjected to phylogenetic analysis. The results indicated the nucleotide identities were 95.4-100% among 446 sequences of RSV A, and 96.3-100% among 362 of RSV B. The most common variant loci were N80K (100.00%) and R213S (97.76%) for site Ø, and V384I/T (98.43%) for site I among sequences of RSV A, and M152I (100.00%), I185V (100.00%), and L172Q/H (94.48%) for site V, and R202Q (99.45%) for site Ø among sequences of RSV B. N276S appears in 95.29% sequences of RSV A, while S276N and N262 I/S appear in 1.38% and 0.55% sequences of RSV B, respectively. No variation was found in all sequences at the binding sites of 14N4 and motavizumab. There were cumulative variations of the RSV F gene, especially at some binding sites of antigenic sites.

Unmasking bocavirus: is it a co-infectious agent or an actual respiratory pathogen?

ABSTRACT Objectives Although human bocavirus (HBoV) is primarily linked to respiratory tract infections, its exact role as a respiratory pathogen remains unclear. This study aims to investigate HBoV detection rates, as well as clinical, laboratory, microbiological, and radiological characteristics, length of stay in the emergency department (ED), rate of hospitalization, and severity of illness in cases where HBoV is detected in respiratory secretions. Methods We conducted a retrospective analysis of all consecutive patients under 18 years who visited a large-volume tertiary pediatric ED from January to December 2023 and tested positive for HBoV in their respiratory viral panel (RVP). Results Among the 14,315 patients who underwent RVP testing during the study period, 591 (4%) tested positive for HBoV. After excluding those with incomplete data, 528 patients (57% male) were included in the analyses. The median age was 2.8 [1.2–4.9] years. The most common symptoms were cough (67%), fever (58%), runny nose/nasal congestion/sore throat (34%), and respiratory distress (24%). Thirty percent of the patients had a history of antibiotic use before admission. Thirteen percent of the patients had at least one chronic illness. Co-infection with HBoV occurred in 37% of the patients, with respiratory syncytial virus (RSV) being the most frequently co-detected virus (45%). Lymphopenia was documented in 12% of patients, and 36% had elevated C-reactive protein levels (median 21 [12–38] g/dl). Abnormal chest X-rays were noted in 85% of patients. The management approach included outpatient care for more than half of the patients (69%). Clinical severity was classified as high in 11% of patients (n = 60), necessitating ICU admission. Conclusion Although typically mild, HBoV infections can escalate to severe respiratory illnesses, requiring respiratory support and intensive care.

Human pathogen nucleic acids in wastewater solids from 191 wastewater treatment plants in the United States

We measured concentrations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, influenza A and B viruses, respiratory syncytial virus, human metapneumovirus, enterovirus D68, human parainfluenza types 1, 2, 3, 4a, and 4b in aggregate, norovirus genotype II, rotavirus, Candida auris, hepatitis A virus, human adenovirus, mpox virus, H5 influenza A virus, and pepper mild mottle virus nucleic acids in wastewater solids prospectively at 191 wastewater treatment plants in 40 states across the United States plus Washington DC. Measurements were made two to seven times per week from 1 January 2022 to 30 June 2024, depending on wastewater treatment plant staff availability. Measurements were made using droplet digital (reverse-transcription–) polymerase chain reaction (ddRT-PCR) following best practices for making environmental molecular biology measurements. These data can be used to better understand disease occurrence in communities contributing to the wastewater.

8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus.

Respiratory syncytial virus (RSV), along with other prominent respiratory RNA viruses such as influenza and SARS-CoV-2, significantly contributes to the global incidence of respiratory tract infections. These pathogens induce the production of reactive oxygen species (ROS), which play a crucial role in the onset and progression of respiratory diseases. However, the mechanisms by which viral RNA manages ROS-induced base oxidation remain poorly understood. Here, we reveal that 8-oxo-7,8-dihydroguanine (8-oxoGua) is not merely an incidental byproduct of ROS activity but serves as a strategic adaptation of RSV RNA to maintain genetic fidelity by hijacking the 8-oxoguanine DNA glycosylase 1 (OGG1). Through RNA immunoprecipitation and next-generation sequencing, we discovered that OGG1 binding sites are predominantly found in the RSV antigenome, especially within guanine-rich sequences. Further investigation revealed that viral ribonucleoprotein complexes specifically exploit OGG1. Importantly, inhibiting OGG1's ability to recognize 8-oxoGua significantly decreases RSV progeny production. Our results underscore the viral replication machinery's adaptation to oxidative challenges, suggesting that inhibiting OGG1's reading function could be a novel strategy for antiviral intervention.

Limited RSV Vaccine Administration: A Case for Redesigning the Preventive Care Model

In this commentary, the authors describe existing barriers to vaccination access linked to the restriction of pharmacists’ prescribing authority, rationalize the need for more innovative care models to enhance the role of the pharmacist, and outline the framework required for health care redesign to enable nonphysicians to close gaps in preventive care. Regulatory and legal issues challenge care redesign at scale. To illustrate this scalability issue and its downstream impact on public health, real-world data from a large national pharmacy chain in the United States, CVS Pharmacy, were leveraged to examine the influence of state-by-state immunization policies on respiratory syncytial virus vaccination administration during the national rollout for adults. As a result of these policies, preventive care (e.g., vaccination administration) was limited in a vulnerable population.

RSV enhances Staphylococcus aureus bacterial growth in the lung.

Patients coinfected with respiratory syncytial virus (RSV) and bacteria have longer hospital stays, higher risk of intensive care unit admission, and worse outcomes. We describe a model of RSV line 19F/methicillin-resistant Staphylococcus aureus (MRSA) USA300 coinfection that does not impair viral clearance, but prior RSV infection enhances USA300 MRSA bacterial growth in the lung. The increased bacterial burden post-RSV correlates with reduced accumulation of neutrophils and impaired bacterial killing by alveolar macrophages. Surprisingly, reduced neutrophil accumulation is likely not explained by reductions in phagocyte-recruiting chemokines or alterations in proinflammatory cytokine production compared with mice infected with S. aureus alone. Neutrophils from RSV-infected mice retain their ability to migrate toward chemokine signals, and neutrophils from the RSV-infected lung are better able to phagocytize and kill S. aureus ex vivo on a per cell basis. In contrast, while alveolar macrophages could ingest USA300 post-RSV, intracellular bacterial killing was impaired. The RSV/S. aureus coinfected lung promotes a state of overactivation in neutrophils, demonstrated by increased production of reactive oxygen species (ROS) that can drive formation of neutrophil extracellular traps (NETs), resulting in cell death. Mice with RSV/S. aureus coinfection had increased extracellular DNA and protein in bronchoalveolar lavage fluid and histological evidence confirmed NETosis in vivo. Taken together, these data highlight that prior RSV infection can prime the overactivation of neutrophils leading to cell death that impairs neutrophil accumulation in the lung. Additionally, alveolar macrophage killing of bacteria is impaired post-RSV. Together, these defects enhance USA300 MRSA bacterial growth in the lung post-RSV.

A new RSV vaccine (mResvia) for adults ≥60 years old.

The FDA has licensed mResvia (Moderna), an mRNA respiratory syncytial virus (RSV) vaccine, for prevention of lower respiratory tract disease (LRTD) caused by RSV in adults ≥60 years old. It is the first mRNA vaccine to be licensed in the US for this indication. Two recombinant RSV vaccines, Arexvy and Abrysvo, are also available for prevention of RSV LRTD.1 Arexvy is approved for use in adults ≥50 years old.2 Abrysvo is approved for use in adults ≥60 years old and in pregnant women to prevent RSV LRTD in their infants.

Induction of neutralizing antibody responses by AAV5-based vaccine for respiratory syncytial virus in mice.

Respiratory Syncytial Virus (RSV) is a significant cause of respiratory illnesses worldwide, particularly in infants and elderly individuals. Despite the burden RSV imposes, effective preventive measures are limited. The research application of adeno-associated virus (AAV) in vaccine platforms has been expanding, and its potential in prevention and treatment has garnered much attention. In this study, we explored the potential application of a recombinant adeno-associated virus 5 (rAAV5) vector-based RSV vaccine, focusing on the expression of the pre-fusion (Pre-F) protein structure. Through intramuscular immunization in mice. The immunogenicity of the vaccine was evaluated in Balb/c mice immunized intramuscularly and intranasal, respectively. The rAAV5-RSV-Fm vaccine demonstrated positive humoral and induced antibody titers against RSV strains A and B for up to 120 days post-immunization. Notably, intranasal administration also elicited protective antibodies. Characterization studies confirmed the ability of the vac-cine to express the Pre-F protein and its superior immunogenicity compared to that of full-length F protein. These findings underscore the potential application of rAAV5 vector platforms in RSV vaccine development and further investigation into their protective efficacy is warranted.

Healthcare resource utilisation and costs in infants with confirmed respiratory syncytial virus infections: a national population cohort study

BackgroundRespiratory syncytial virus (RSV) is the leading cause of severe respiratory infections in infants worldwide, significantly affecting their health and contributing to the global healthcare burden. We aimed to examine healthcare resource utilisation patterns and costs for infants under one year old with confirmed RSV infection across subgroups of different gestational ages and health conditions and the cost implications of RSV infections over time, thereby demonstrating the economic burden of the disease.MethodsThis retrospective cohort study utilised nationwide claims data from the Korea Health Insurance Review and Assessment Service for infants under one year of age with confirmed RSV infection in the first year of life from January 2017 to April 2022. The infants were stratified into three subgroups based on their gestational age and health status: unhealthy preterm, healthy preterm, and full-term infants. A descriptive analysis was conducted to estimate healthcare utilization by type of resource and costs related to the treatment of RSV.ResultsOut of 93,585 RSV infections identified, 31,206 patients met the inclusion criteria; these included 963 unhealthy preterm, 1,768 healthy preterm and 28,475 full-term infants. In our study, 76.3% of the infants with confirmed RSV infection required intensive care, including hospitalisation and more critical interventions such as intensive care unit (ICU) or mechanical ventilation (MV). The total average cost of RSV management was notably higher for unhealthy preterm infants ($ 6,325; 95% confidence interval (CI): $ 5,484-7,165) than for healthy preterm ($ 1,134; 95% CI: $ 1,006 − 1,261) and full-term infants ($ 606; 95% CI: 583–630). Our findings confirmed a significant epidemiological and economic burden, with infants at greater risk–shorter gestational age and poorer health conditions. Furthermore, we observed a marked increase in the total average cost of RSV management during COVID-19, reflecting the complex interplay between RSV and pandemic-related healthcare dynamics.ConclusionOur findings provide evidence for the significant economic burden of RSV infection among infants, with considerable disparities based on gestational age and health status subgroups. However, RSV prevention policies should also recognise that healthy preterm or full-term infants who receive intensive care face a significant disease burden.

Recombinant RSV G protein vaccine induces enhanced respiratory disease via IL-13 and mucin overproduction

The G protein expressed on the surface of respiratory syncytial virus (RSV) is important for adhesion to host cells and as a vaccine target antigen. The corresponding vaccines can effectively eliminate RSV. However, they exacerbate pulmonary immunopathology including eosinophilic infiltration in the lungs after an RSV challenge in animal models, raising concerns about enhanced respiratory disease (ERD); thus, approaches that mitigate these effects are urgently needed. Herein, we aimed to examine the mechanisms of G protein vaccine-induced ERD in mice, using recombinant G protein as a vaccine antigen. After the RSV challenge, G protein-vaccinated mice exhibited lung weight gain, lung tissue damage, and increased infiltration of eosinophils, neutrophils, and CD4+ T cells into the lungs. We set lung weight gain as the endpoint for ERD and examined the impact of each infiltrating cell on lung weight gain. We observed that CD4+ T cells, but not eosinophils or neutrophils, that infiltrate the lungs are responsible for lung weight gain. In addition, T helper 2 cell-mediated IL-13 induced mucin hypersecretion and lung weight gain. Mucin hypersecretion may contribute to weight gain in the lungs. In conclusion, our results indicate a novel mechanism of G protein vaccine-induced ERD via IL-13 and mucin hypersecretion, which could lead to the development of safe G protein vaccines and the elucidation of the causes of ERD associated with other vaccines.

Characterization of Respiratory Viruses in Patients with Acute Respiratory Infection in the City of Barranquilla during the SARS-CoV-2/COVID-19 Pandemic.

Introduction: Severe acute respiratory infection (SARI) is mainly caused by viral pathogens, with a high prevalence in high-risk populations such as infants and older adults. Coinfections by different viruses are frequent and, in some cases, associated with severe disease outcomes. Purpose: The main purpose of this study was to identify respiratory viruses circulating in Barranquilla during the peaks of the COVID-19 pandemic and estimate the prevalence of viral coinfections in samples from individuals with different degrees of respiratory infection. Methods: We received 5083 samples between epidemiological weeks 33-42 of 2021 submitted by the District Health Laboratory of Barranquilla and four local healthcare institutions during COVID-19 surveillance. Among them, we analyzed 101 samples from individuals presenting with influenza-like illness (ILI). Eighteen respiratory viruses, including SARS-CoV-2, were evaluated via qRT-PCR using nasal swabs or nasopharyngeal aspirate samples. Results: Of the 101 study individuals, 56 were male and 45 were female (55.5% and 44.5%, respectively); 25.7% of individuals were infected with at least one of the evaluated viruses. Respiratory syncytial virus (RSV) and human rhinovirus (HRV) were the two most frequently detected viruses (30.7% and 15.4% of total positives, respectively). Coinfections with two or more respiratory viruses accounted for 42% of the total positive cases. Discussion: Our findings indicate the presence of different respiratory viruses in swab or nasopharyngeal aspirate samples from individuals with ILI, including coinfections. These results reveal the circulation of several respiratory viruses in the city of Barranquilla, confirming their importance as potential causes of SARI in Colombia and the need for their active surveillance.

Respiratory Syncytial Virus Risk Profile in Hospitalized Infants and Comparison with Influenza and COVID-19 Controls in Valladolid, Spain, 2010-2022.

We aimed to describe the risk profile of RSV infections among children aged ≤ 24months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls. We conducted a retrospective cohort study of all laboratory-confirmed RSV, influenza, and COVID-19 infections. We analyzed risk factors for RSV hospitalization and severity (length-of-stay ≥ 8 days, intensive-care-unit admission, in-hospital death or readmission < 30days) and compared severity between hospitalized RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. We included 1507 patients with RSV (1274 inpatient), 32 with influenza, and 52 COVID-19 controls. Hospitalized RSV (mean age 5.3months) and COVID-19 (4months) were younger than influenza (9.1months) patients. Sixteen percent of patients had RSV within the first month of life. Most infants did not have comorbidities (74% RSV, 56% influenza, and 69% COVID-19). Forty-one percent of patients with RSV and influenza were coinfected vs. 27% COVID-19 (p = 0.04). Among RSV, hospitalization risk factors were prematurity (adjusted OR 3.11 [95% CI 1.66, 4.44]) and coinfection (2.03 [1.45, 2.85]). Risks for higher severity were maternal smoking (1.89 [1.07, 3.33]), prematurity (2.31 [1.59, 3.34]), chronic lung disease (2.20 [1.06, 4.58]), neurodevelopmental condition (4.28 [2.10, 8.73]), and coinfection (2.67 [2.09, 3.40]). Breastfeeding was protective against hospitalization (0.87 [0.80, 0.95]) and severity (0.81 [0.74, 0.88]), while complete vaccination schedule was protective against severity (0.51 [0.27, 0.97]). RSV had 2.47 (1.03, 5.96) higher risk of experiencing any severe outcome compared to influenza and did not show significant differences vs. COVID-19. RSV hospitalizations were more frequent and severe than influenza, while severity was comparable to the early pandemic COVID-19. Currently, both influenza and COVID-19 vaccines are included in the maternal and childhood Spanish immunization schedule between the ages of 6 and 59months. RSV monoclonal antibody is recommended for ≤ 6months but a third of patients were aged 6-24months. Maternal RSV vaccination can protect their children directly from birth and indirectly through breastfeeding.

Antibiotic Overuse in Pediatric Patients Hospitalized with RSV, COVID-19, and Influenza

Abstract Background Children hospitalized with viral respiratory tract infections (RTIs) are often treated with antibiotics due to concern for bacterial co-infection, although most do not have concurrent bacterial infections. This practice leads to unnecessary antibiotic treatment, which can lead to development of resistant bacteria and adverse events. The extent of antibiotic overuse in hospitalized children with community-onset viral RTI has not been well-quantified in recent years and may have worsened during the COVID-19 pandemic. The objectives of this study were to quantify and compare the extent of antibiotic overtreatment and to determine predictors of antibiotic use post-COVID-19 pandemic in children hospitalized with RSV, COVID-19, and influenza. Methods We performed a single center retrospective study evaluating percentages of antibiotic use and bacterial co-infection among children and adolescents aged &amp;lt;19 years old, hospitalized with respiratory syncytial virus (RSV), influenza, or SARS-CoV-2 between April 2020 and May 2023. Bacterial infection was defined as growth of bacteria from any specimen source, including blood, urine, pleural fluid, cerebrospinal fluid, and respiratory secretions, excluding common contaminants like coagulase-negative Staphylococci. Predictors of antibiotic treatment were determined using multivariable logistic regression. Results During the study period 1,718 patients were included (1022 with RSV, 188 with influenza, 535 with COVID-19). RSV patients were younger and more likely to be in the ICU than influenza or COVID-19 patients. The overall proportion of patients with culture-confirmed bacterial co-infection was low at 8% and did not differ greatly by virus type (8% for influenza, 6.9% for RSV, 10.3% for COVID-19, p=0.03). The proportion of children receiving antibiotics was higher for influenza than for other viruses (60.6% for influenza, 41.2% for RSV, and 48.6% for COVID-19, p &amp;lt; 0.001). Among patients with the lowest severity of illness (with normal inflammatory markers [PCT &amp;lt;0.5 ug/mL or CRP &amp;lt;50 mg/L] and not admitted to the ICU), 7.3% had a culture-confirmed bacterial infection while 48.1% received antibiotics. Independent predictors for receiving antibiotics were elevated inflammatory markers (C-reactive protein or procalcitonin), having &amp;gt;3 comorbidities, mechanical ventilation, and influenza diagnosis. Conclusion In children hospitalized with community-onset viral RTIs, antibiotic treatment is substantially higher than the burden of culture-confirmed bacterial infection, suggesting antibiotic overuse. Antibiotic use was greater for patients with influenza than for those with RSV or COVID-19. Antibiotic overuse was estimated to occur in over 40% of patients with low severity of illness. Stewardship programs can use this data to design interventions to promote more judicious antibiotic use. Figure 1. Rates of bacterial co-infection and antibiotic utilization among patients hospitalized with influenza, RSV, and COVID. Blue, percentage of patients who had a culture-confirmed bacterial infection; orange, percentage of patients who received any antibiotics; green, percentage of patients who received &amp;gt;3 days of antibiotics.

Evaluating the Effectiveness of Nirsevimab in Reducing Pediatric RSV Hospitalizations in Spain.

Background/Objectives: Respiratory syncytial virus (RSV) is a major cause of hospitalization in infants. Nirsevimab has demonstrated to be a promising tool for preventing severe RSV disease. Although clinical trials have demonstrated the efficacy of Nirsevimab in preventing severe RSV disease, evidence regarding its performance in real-world clinical settings is still limited due to its recent introduction. This study aims to fill this knowledge gap by evaluating the impact of Nirsevimab in a cohort of infants and determining its effectiveness in reducing the burden of RSV disease. Methods: A retrospective study of RSV hospitalizations was conducted in children under six months of age, between 1 October and 31 March, across four seasons: pre-COVID (2018-2019), COVID (2019-2020), post-COVID pre-Nirsevimab (2022-2023), and Nirsevimab season (2023-2024). Results: Nirsevimab demonstrated significant efficacy in reducing RSV-related hospitalizations in infants under six months of age. During the 2023/2024 season, following the introduction of Nirsevimab, there was a substantial reduction in RSV-related lower respiratory tract infection (LRTI) hospitalizations. Among infants under 3 months of age, hospitalizations decreased by 79.3% (IRR: 0.21, 95% CI: 0.12-0.34). In infants aged 3 to 6 months, there was a 66.9% reduction (IRR: 0.33, 95% CI: 0.15-0.64). Additionally, Nirsevimab decreased the severity of RSV cases with LRTI who required the support of equipment for sanitary use, further reducing overall healthcare burden. Conclusions: These results underscore Nirsevimab's vital role in preventing severe RSV infections and hospitalizations, especially among the most vulnerable infants, positioning it as a critical advancement in pediatric respiratory care.

Update to: Study Pre-protocol for "BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study".

In 2021 we launched the BronchStart study, which collected information on 17,899 presentations in children with serious respiratory tract infections following the release of lockdown restrictions. Our study informed the Joint Committee on Vaccination and Immunisation's decision to recommend the introduction maternal respiratory syncytial virus (RSV) vaccination, which was introduced in the United Kingdom in August/September 2024. We modified our original protocol to conduct a United Kingdom-wide assessment of maternal vaccination against RSV. We will conduct a multi-centre study, utilising the PERUKI network used in the original BronchStart study, to assess the effectiveness of maternal vaccination using a test-negative study design. We will gather detailed clinical information on children admitted with bronchiolitis in the post-RSV vaccination era, and understand possible reasons for incomplete vaccine uptake.

Viral epitope profiling of hematopoietic cell transplant recipients with respiratory syncytial virus upper respiratory tract and lower respiratory tract infections

Abstract Background The pre-fusion conformation of the F glycoprotein of respiratory syncytial virus (RSVpreF) has been the target of recent respiratory syncytial virus (RSV) therapies, including monoclonal antibodies for immunocompetent children and vaccines for the elderly. However, the utility of targeted therapies against RSVpreF is unknown in pediatric or adult hematopoietic cell transplant (HCT) recipients, and there are limited natural history studies characterizing humoral immune responses after RSV infection in HCT recipients. We utilized VirScan, a novel high-throughput profiling of antiviral antibody epitopes, to identify differences in global RSV-related epitope hits after an RSV infection. Methods We evaluated adult and pediatric allogeneic HCT recipients who acquired RSV from 12/2011 to 12/2019. Patients were categorized into 3 groups: upper respiratory tract infections (URTI) only, those who progressed from URTI to lower respiratory tract infections (progressors) and lower respiratory tract infections (LRTI) at diagnosis, and tested at baseline prior to infection (pre-RSV), at RSV URTI or LRTI diagnosis (RSV diagnosis), at LRTI progression (LRTI), 4-6 weeks after infection (Response 1) and &amp;gt;8 weeks after infection (Response 2), depending on sample availability. We interrogated the viral antibody repertoire using a serosurvey (VirScan) that detects immunoglobulin G responses to 206 viruses. VirScan metrics evaluated included: (1) number of RSV epitope hits, (2) log10 of the maximum RSV epitope binding signal (EBS), analogous to an antibody titer for each epitope, and (3) geometric mean of all RSV EBS. Kruskal-Wallis tests were used to compare groups for each VirScan metric at the different time points. Results A total of 129 samples from 39 patients were analyzed; 24 with URTI only, 8 progressors, and 7 with LRTI at diagnosis. At each time point, VirScan metrics were similar among the 3 patient groups (Table 1). Though patterns of VirScan metrics following RSV diagnosis varied by patient, most showed a modest increase in values (Figure 1). Conclusion In this preliminary study, we utilized the power of VirScan, a comprehensive serologic profiling tool of the entire human virome, to characterize RSV specific antibody changes after RSV infection in allogeneic HCT recipients. There were no differences in global RSV VirScan metrics between the 3 groups, suggesting that antibodies may not be the primary driver of viral infection attenuation in this population. Future analyses will focus on differences in individual epitope acquisition, including RSVpreF, between the 3 groups, and investigate possible interactions with humoral responses to other viruses. Figure 1. Longitudinal RSV VirScan metrics for each patient separated by 3 groups (top row: RSV URTI only; middle row: progressors from URTI to LRTI; bottom row: LRTI at diagnosis). Each line is an individual patient. The different panels show the changes in RSV related epitope hits (A), the log10 maximum epitope binding signal (EBS) among RSV epitopes (B), and the geometric mean of all the RSV related EBS (C). Open circles represent time points prior to RSV diagnosis, filled circles represent time points just prior to, on or after URTI, and asterisks represent time points just prior to, on, or after LRTI.

Cycles of susceptibility: Immunity debt explains altered infectious disease dynamics post -pandemic.

The concept of immunity debt is a phenomenon resulting from the suppression of endemic pathogens during the COVID-19 pandemic due to non-pharmaceutical interventions (NPIs). The reduced circulation of various pathogens during the pandemic, particularly respiratory syncytial virus (RSV), altered typical infectious disease dynamics by reducing levels of population immunity usually acquired through exposure to infection. This concept is demonstrated through post-pandemic resurgence of diseases such as RSV and Group A Streptococcus, and highlights the interplay between reduced pathogen exposure and increased susceptibility in populations. The complexities and non-linear dynamics of seasonal transmission are observed in differences in pathogen resurgence across regions. These issues highlight the importance of comprehensive disease surveillance and public health strategies in mitigating these long-term epidemiological impacts.

Distribution and seasonality of viral respiratory infections in pediatric oncologic patients in a tropical country

Abstract Background Comprehension of the distribution and seasonality viral respiratory infections pediatric oncologic patients in tropical localities remains poor. Due to lack mandatory report of all viruses and limitations in access to molecular biology techniques there is currently few data published on this topic. We report the distribution and seasonality of pediatric viral respiratory infections at a tertiary care oncological hospital in Guayaquil, Ecuador. Methods The laboratory database with results of real time PCR panel (Biofire® respiratory panel 2.1) from January to December 2021 was reviewed to collect the relative frequency and seasonality of identifiable viral infections in pediatric (ages &amp;lt; 18 years) patients. The frequency of infection according to sample characteristics including sex and age was compared using chi square test with a significance of 0.05. The frequency of detection was organized per month within the year. Percentage of coinfections was also determined. Results Out of 217 included PCR results, 143 (65.8%) tested positive for detectable viral organisms. Mean age was 7.3 years SD 4.8 years. The infection frequency for girl samples was higher than that of boy samples, X2 (1, N=217) = 4.16, p 0.041. The relation between age groups and the frequency of infection was not statistically significant X2 (2, N=217) = 5.24, p 0.073. The most prevalent viruses included Rhinovirus/Enterovirus 53 cases (relative frequency 37.0%), Parainfluenza virus 3 42 cases (relative frequency 29.3%) and Respiratory syncytial virus 19 cases (relative frequency 13.2%). Rhinovirus/Enterovirus, Paramyxovirus and Adenovirus respiratory infections occurred throughout the year while other respiratory viruses including Coronaviruses showed a higher detection rate during the rainy season (December – April). A total of 13 (5.9%) patients were coinfected with two up to four viruses. The most common combination was Parainfluenza virus 3 with Rhinovirus/Enterovirus. No bacterial targets were detected. Conclusion Larger and more complex studies are necessary to understand the burden of viral respiratory infections in pediatric oncological patients. In Ecuador, detection was higher in girls and school aged children. Rhinovirus/Enterovirus, Paramyxovirus and Adenovirus were present all year long while seasonality was common for other viruses following dry/rainy season pattern in the region. More understanding of seasonality will aim for preventive measures during more difficult months and to distribute resources accordingly. Figure 1. Seasonality of respiratory viral infections.