Respiratory Syncytial Research Articles

Respiratory syncytial virus prevention is finally here: An overview of safety.

A number of respiratory syncytial virus (RSV) prevention products have recently been approved in Australia. These products focus on highest risk groups, aiming to prevent RSV disease in young infants and older adults. While not currently included in the National Immunisation Program (NIP), an RSV vaccine (Arexvy, GlaxoSmithKline [GSK]) isavailable privately for adults ≥60 years, and some Australian jurisdictions have commenced RSV monoclonal antibody (nirsevimab) programs for infants in 2024. This article summarises safety data regarding RSV prevention products approved in Australia, including vaccines for adults ≥60 years, maternal vaccines and monoclonal antibodies for infants. Clinical trial data found these products were largely well tolerated, with most local and systemic reactions being mild-moderate and short-lived. Proportions of serious adverse events were low. While very rare, potential safety signals being further assessed include risk of preterm birth following the maternal vaccine (Abrysvo, Pfizer) and Guillain-Barré syndrome (GBS) following RSV vaccines in older adults (Abrysvo and Arexvy). Close monitoring of these adverse events of special interest via post-licensure surveillance is underway.

Impact of respiratory syncytial virus infection among patients with hematological cancer in the era of post-coronavirus pandemic.

400 Background: Two vaccine is recently approved for elderly patient with compromised immunity. Despite the recommendation by Center for Disease Control and Prevention (CDC), RSV vaccination is remains low among patient with hematological malignancy, when compare to influenza vaccination. Thus, we conducted an observational study to estimate the impact of RSV infection among patients with hematological malignancy. Methods: We conducted a population-based retrospective cohort utilized the TritNetx dataset, which consist of patients across 63 U.S. healthcare organization. This study included patient who had respiratory viral infection after a diagnosis of hematological malignancy during 6/1/2022 - 4/1/2022. Hematological malignancy was identified using ICD-10 codes. CPT code and ICD-10 code were used to identify diagnosis of respiratory viral infection after respiratory pathogen panel testing. Patient who was diagnosed with RSV, influenza or COVID-19 were paired based on the following variable, including demographics, body mass index, comorbidities, and anti-neoplastic therapy. Hazard ratio (HR) was estimated by Cox proportional hazard regression models and log-rank test. Risk ratio (RR) was calculated by logistic regression. Results: A total of 6,088 patients with hematological malignancy contracted RSV, influenza or COVID during the observation period. When compare to influenza, patients with RSV infection were associate with high healthcare utilization, including emergency visit (HR: 1.20, 95% CI:[1.00-1.41]), and hospitalization (HR: 1.29, 95% CI:[1.06-1.57]). RSV infection was also resulted in higher acuity including viral pneumonia (HR: 15.42, 95% CI:[9.26-25.68]), use of antibiotics (HR: 1.54, 95% CI:[1.28-1.86]), renal replacement therapy (HR: 2.09, 95% CI:[1.10-3.96]), and acute respiratory failure (HR: 1.54, 95% CI:[1.14-2.07]). When compare to COVID-19, RSV infection showed similar trend including more frequent emergency visit (HR: 1.30, 95% CI:[1.10-1.54]), and high risk of developing viral pneumonia (HR 23.48, 95% CI: [12.79-43.09]). Interestingly, the intubation rate, 28 days all-cause mortality and 90 days all-cause mortality were similar between the three cohort. Conclusions: RSV infection was associated with higher rate of pneumonia and healthcare utilization. RSV vaccination should be considered to prevent RSV-associated morbidity among patients with hematological malignancy.

RSV Neutralizing Antibodies Following Nirsevimab and Palivizumab Dosing.

Data describing respiratory syncytial virus (RSV) neutralizing antibody (nAb) levels for nirsevimab, a recently approved, extended half-life, anti-RSV fusion protein (F protein) monoclonal antibody, relative to the previous standard of care, palivizumab, have not been reported. The MEDLEY trial was a randomized, palivizumab-controlled, phase 2/3 study of nirsevimab during 2 RSV seasons (season 1 and 2) in infants born preterm (≤35 weeks' gestational age; dosed season 1 only) or with congenital heart disease or chronic lung disease of prematurity (dosed seasons 1 and 2). Participants were randomly assigned to receive a single dose of nirsevimab followed by 4 monthly placebo doses, or 5 once-monthly doses of palivizumab. Anti-RSV fusion protein serology (ie, levels of prefusion [pre-F]/postfusion [post-F] conformation antibodies), nirsevimab and palivizumab serum concentrations, and RSV nAbs were measured in participant samples collected at baseline (pre-dose) and days 31, 151, and 361. Serologic data were similar in seasons 1 and 2. Nirsevimab predominately conferred pre-F antibodies, whereas palivizumab conferred pre-F and post-F antibodies. Nirsevimab and palivizumab serum concentrations were highly correlated with nAb levels in both seasons. In season 1, the nAb levels in nirsevimab recipients were highest in day 31 samples and gradually declined but remained 17-fold above baseline at day 361. nAb levels in palivizumab recipients increased incrementally with monthly doses to day 151. nAb levels followed similar patterns in season 2. nAb levels were ∼10-fold higher with nirsevimab compared with palivizumab across both seasons. Nirsevimab prophylaxis confers ∼10-fold higher and more sustained RSV nAb levels relative to palivizumab.

Epidemiological Characteristics of Upper Respiratory Tract Pathogens in Children in Guangdong, China.

Researches on the epidemiology of various respiratory pathogens at multiple testing points in the pediatric population are limited, and these are crucial for the prevention of respiratory tract infections in children. We obtained 1788 upper respiratory tract swabs from children exhibiting symptoms of respiratory infection (notably fever with a body temperature exceeding 38.5°C) across five hospitals in Guangdong between November 2020 and June 2022. We used the multiplex probe amplification (MPA) PCR testing to identify 11 respiratory viruses and subsequently analyzed the prevalence characteristics of these pathogens among febrile children in hospitals. The overall detection rate of the pathogens was 58.1% (1039/1788). Human rhinovirus (HRV) exhibited the highest detection rate at 19.0% (339/1788), succeeded by human parainfluenza virus (HPIV), human adenovirus (HAdV), and respiratory syncytial virus (RSV). The positivity and coinfection rates were higher in children aged 5 years and below compared to those above 5 years. Moreover, a distinct pathogen spectrum was observed across different age groups. Hospitalized patients demonstrated a significantly higher positivity and coinfection rate compared to outpatients. During COVID-2019, RSV appeared a counter-seasonal trend. Respiratory viral infections in children display distinct characteristics concerning age, hospitalization status, and seasonality. Children under the age of 5 and minor patients admitted to hospitals at least be tested for RSV, HRV, HPIV, and HAdV. The epidemiological patterns of RSV in the post-epidemic period require ongoing surveillance.

Infant-derived human nasal organoids exhibit relatively increased susceptibility, epithelial responses, and cytotoxicity during RSV infection

BackgroundRespiratory syncytial virus (RSV) causes significant morbidity and mortality, especially in young children. Why RSV infection in children is more severe compared to healthy adults is not fully understood. MethodsWe used ex-vivo human nasal organoid platforms from infants and adults to investigate the underlying mechanism of this disease disparity at the initial site of RSV replication, the nasal epithelium. ResultsInfant-derived human nasal organoid-air liquid interface (HNO-ALIs) lines were more susceptible to early RSV replication. Moreover, infant-derived HNO-ALIs elicited a statistically significant greater overall cytokine response, enhanced mucous production, and greater cellular damage compared to their adult counterparts. Furthermore, the adult cytokine response was associated with a superior regulatory cytokine response, which could explain less cellular damage than in infant lines. ConclusionsOur data highlights substantial differences in how infant and adult upper respiratory tract epithelium responds to RSV infection at the cellular level. These differences in epithelial cellular response can lead to impaired mucociliary clearance, a more dysregulated innate immune response predisposing infants to more severe RSV infection compared to adults.

Inno4Vac Workshop Report Part 2: RSV-Controlled Human Infection Model (CHIM) Strain Selection and Immune Assays for RSV CHIM Studies, November 2021, MHRA, UK.

Controlled human infection models (CHIMs) are a critical tool for the understanding of infectious disease progression, characterising immune responses to infection and rapid assessment of vaccines or drug treatments. There is increasing interest in using CHIMs for vaccine development and an obvious need for widely available and fit-for-purpose challenge agents. Inno4Vac is a large European consortium working towards accelerating and de-risking the development of new vaccines, including development of CHIMs for influenza, respiratory syncytial virus and Clostridium difficile. This report (in two parts) summarises a workshop held at the MHRA in 2021, focused on how to select CHIM candidate strains of influenza and respiratory syncytial virus (RSV) based on desirable virus characteristics and which immune assays would provide relevant information for assessing pre-existing and post-infection immune responses and defining correlates of protection. This manuscript (part 2) summarises presentations and discussions centred around RSV CHIMs and immune assays (an additional manuscript summarises influenza CHIM and immune assays: Inno4Vac workshop report Part 1: Controlled human influenza virus infection model (CHIVIM) strain selection and immune assays for CHIVIM studies, November 2021, MHRA, UK).

Correlation between Viral Wastewater Concentration and Respiratory Tests, Oregon, USA.

We evaluated the association between wastewater concentration and weekly percent positivity of patient testing for SARS-CoV-2, influenza, and respiratory syncytial virus in Oregon, USA. We found strong, positive correlations for SARS-CoV-2 (ρ=0.84, p<0.001), influenza (ρ=0.73, p<0.001) and respiratory syncytial virus (ρ=0.69, p<0.001).

Q &amp; A: Coding for Immunization Against Respiratory Syncytial Virus

The season for increased risk of respiratory syncytial virus (RSV) infection in the United States begins in October and continues through March. This means many practices are beginning to immunize infants against RSV for the 2024–2025 season. This article reviews coding for administration of the monoclonal antibody product, nirsevimab (RSV-mAb; brand name Beyfortus). This article answers questions on correct coding for immunization against RSV infection, including the following: What is the diagnosis code for RSV-mAb administration?What codes are reported for the RSV-mAb product?What codes are reported for RSV-mAb administration?How is administration of the 200-mg dose reported?Are evaluation and management (E/M) services reported separately?What are other billing and coding considerations for RSV-mAb?

Seasonality and Co-Detection of Respiratory Viral Infections Among Hospitalised Patients Admitted With Acute Respiratory Illness-Valencia Region, Spain, 2010-2021.

Respiratory viruses are known to represent a high burden in winter, yet the seasonality of many viruses remains poorly understood. Better knowledge of co-circulation and interaction between viruses is critical to prevention and management. We use > 10-year active surveillance in the Valencia Region to assess seasonality and co-circulation. Over 2010-2021, samples from patients hospitalised for acute respiratory illness were analysed using multiplex real-time PCR to test for 9 viruses: influenza, respiratory syncytial virus (RSV), parainfluenza virus (PIV), rhino/enteroviruses (HRV/ENV), metapneumovirus (MPV), bocavirus, adenovirus, SARS-CoV-2 and non-SARS coronaviruses (HCoV). Winter seasonal patterns of incidence were examined. Instances of co-detection of multiple viruses in a sample were analysed and compared with expected values under a crude model of independent circulation. Most viruses exhibited consistent patterns between years. Specifically, RSV and influenza seasons were clearly defined, peaking in December-February, as did HCoV and SARS-CoV-2. MPV, PIV and HRV/ENV showed less clear seasonality, with circulation outside the observed period. All viruses circulated in January, suggesting any pair had opportunity for co-infection. Multiple viruses were found in 4% of patients, with more common co-detection in children under 5 (9%) than older ages. Influenza co-detection was generally observed infrequently relative to expectation, while RSV co-detections were more common, particularly among young children. We identify characteristic patterns of viruses associated with acute respiratory hospitalisation during winter. Simultaneous circulation permits extensive co-detection of viruses, particularly in young children. However, virus combinations appear to differ in their rates of co-detection, meriting further study.

Pathogen distribution and infection patterns in pediatric severe pneumonia: A targeted next-generation sequencing study

ObjectiveSevere pneumonia in children represents a significant clinical challenge due to its high incidence and associated mortality. This study aimed to assess the distribution of pathogens and patterns of infection in pediatric patients with severe pneumonia. MethodsThis study included 110 pediatric patients diagnosed with severe pneumonia, who were admitted to Guangxi Maternal and Child Health Hospital between July 2021 and November 2023. Pathogen-targeted next-generation sequencing (tNGS) was employed to identify respiratory pathogens in these cases. ResultsPathogens were detected in 109 out of 110 cases, yielding a positive detection rate of 99.09%. Among these cases, 25 (22.72%) involved single-pathogen infections, while 84 (76.36%) were characterized by mixed infections. The infection pattern in children with severe pneumonia was relatively common with bacterial-viral coinfection (28.2%, 31/110). A total of 39 pathogens were identified from the 110 children with severe pneumonia, with the top three pathogens being Mycoplasma pneumoniae (30.91%, 34/110), Human Respiratory Syncytial Virus Type A (26.36%, 29/110), and Human Herpesvirus (18.18%, 20/110). Notably, 38.2% (13/34) of the cases were found to have macrolide-resistant Mycoplasma pneumoniae (MRMP). Additionally, 40% (44/110) of the children required admission to the intensive care unit (ICU). ConclusionThe application of tNGS demonstrates significant utility in the detection of pathogens in pediatric patients with severe pneumonia. The predominant pathogens identified in this study are Mycoplasma pneumoniae, Human Respiratory Syncytial Virus, and Human Herpesvirus. Furthermore, mixed infections involving multiple pathogens were observed in 76.36% of the cases, and a substantial proportion (40%) of these patients necessitated intensive care.

The Potential of mRNA Vaccines to Fight Against Viruses.

Vaccines have always been a critical tool in preventing infectious diseases. However, the development of traditional vaccines often takes a long time and may struggle to address the challenge of rapidly mutating viruses. The emergence of mRNA technology has brought revolutionary changes to vaccine development, particularly in rapidly responding to the threat of emerging viruses. The global promotion of mRNA vaccines against severe acute respiratory syndrome coronavirus 2 has demonstrated the importance of mRNA technology. Also, mRNA vaccines targeting viruses such as influenza, respiratory syncytial virus, and Ebola are under development. These vaccines have shown promising preventive effects and safety profiles in clinical trials, although the duration of immune protection is still under evaluation. However, the development of mRNA vaccines also faces many challenges, such as stability, efficacy, and individual differences in immune response. Researchers adopt various strategies to address these challenges. Anyway, mRNA vaccines have shown enormous potential in combating viral diseases. With further development and technological maturity, mRNA vaccines are expected to have a profound impact on public health and vaccine equity. This review discussed the potential of mRNA vaccines to fight against viruses, current progress in clinical trials, challenges faced, and future prospects, providing a comprehensive scientific basis and reference for future research.

Respiratory Syncytial Virus and United States Pediatric Intensive Care Utilization—A New Era?

Respiratory Syncytial Virus and United States Pediatric Intensive Care Utilization—A New Era?

Changes in the Antimicrobial Resistance and Bacterial Epidemiology of Moraxella catarrhalis from Pediatric Community-Acquired Pneumonia Patients During the COVID-19 Pandemic: A 5-Year Study at a Tertiary Hospital of Southwest China.

This study aimed to assess the impact of the COVID-19 pandemic on Moraxella catarrhalis infections in pediatric patients hospitalized with community-acquired pneumonia (CAP). The epidemiological features and antimicrobial resistance (AMR) patterns of M. catarrhalis were compared between the pre-pandemic period (2018-2019) and during the pandemic (2020-2022). The results revealed a marked increase in the positivity rate of M. catarrhalis in 2020 and 2021 compared with the pre-pandemic years. The median age of the patients increased significantly in 2021 and 2022, while the proportion of male patients decreased substantially from 2019 to 2021. In addition, there were notable changes in the co-infections of Haemophilus influenzae, parainfluenza virus, and respiratory syncytial virus during the COVID-19 pandemic. The AMR profile of M. catarrhalis also changed significantly, showing increased resistance to ampicillin, but decreased resistance to trimethoprim-sulfamethoxazole and ofloxacin, and a lower proportion of multidrug-resistant isolates. Notably, ampicillin resistance increased among β-lactamase-producing isolates. Before the pandemic, the number and detection rate of isolates, along with resistance to ampicillin and trimethoprim-sulfamethoxazole, were seasonally distributed, peaking in autumn and winter. However, coinciding with local COVID-19 outbreaks, these indices sharply fell in February 2020, and the number of isolates did not recover during the autumn and winter of 2022. These findings indicate that the COVID-19 pandemic has significantly altered the infection landscape of M. catarrhalis in pediatric CAP patients, as evidenced by shifts in the detection rate, demographic characteristics, respiratory co-infections, AMR profiles, and seasonal patterns.

Circulating respiratory viruses including SARS-CoV-2 during 2021-2022 season in Tunisia: Epidemiological and dynamic changes

BackgroundChanging patterns in community respiratory virus activity were reported in different geographical locations during the COVID-19 pandemic. In this study, we aimed to assess the prevalence of circulating respiratory viruses, including SARS-CoV-2, during the season 2021-2022 in Tunisia. MethodsWe retrospectively enrolled 328 nasopharyngeal samples received at the Triage Center of Habib Bourguiba Hospital from patients with acute respiratory symptoms during September 2021-May 2022. All samples were screened for both SARS-CoV-2 and common respiratory viruses. This latter detection was performed using end-point multiplex RT-PCRs, Real-Time PCR, and AllplexTM Respiratory Panel 1 kit (Seegene) for Influenza Virus A (IFVA) and Respiratory Syncytial Virus (RSV) subtyping. ResultsAmong included patients, at least one viral pathogen was identified in 118 (35.9%) patients. The detection rate of SARS-CoV-2 was 21.6%. A low viral coinfection rate was observed (3.3%). The most prevalent pathogen among non-SARS-CoV-2 viruses was Enterovirus/Rhinovirus (HEV/HRV) (59.6%) followed by IFVA (15.3%) and Adenoviruses (ADV) (11.5%). Only IFVA H3N2 was found to circulate during the study period. A negative virus interaction was eventually induced by SARS-CoV-2, as it was shown by lower levels of activity of non-SARS-CoV-2 viruses (not exceeding 17.7%) while infections due to pandemic Omicron variants of concern became widespread. ConclusionsThis study highlights the relative return of community IFVA circulation during the 2021-2022 season in Tunisia. A negative viral interaction between SARS-CoV-2 and other respiratory viruses is highly suggested, which explains, in addition to the easing of COVID-19 restriction measures, the epidemiological changes in non-SARS-CoV-2 viruses circulation.

Spectrum of respiratory viruses identified from SARS-CoV-2-negative human respiratory tract specimens in Watansoppeng, Indonesia.

Respiratory infections account for millions of hospital admissions worldwide. The aetiology of respiratory infections can be attributed to a diverse range of pathogens including viruses, bacteria and fungi. SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)-negative specimens from Wattansoppeng city, South Sulawesi, were analysed to study the spectrum of respiratory viruses. Samples were screened for influenza virus, enterovirus, Paramyxoviridae, Nipah virus, Coronaviridae and Pneumoviridae. Of 210 specimens, 19 were positive for respiratory syncytial virus (RSV)-A, RSV-B, human parainfluenza virus type 1 (HPIV-1), HPIV-2, human rhinovirus (HRV)-A, HRV-B, HRV-C, human metapneumovirus (HMPV), influenza A virus (IAV) and coxsackievirus A6 (CV-A6). Influenza virus was of seasonal H3N2 subtype. The HMPVs were of genotypes B1 and A2a, while one RSV-A was of the ON-1 genotype. The viruses mostly affected children with unknown severity.

Chiral Intranasal Nanovaccines as Antivirals for Respiratory Syncytial Virus.

This study aimed to develop an intranasal nanovaccine by combining chiral nanoparticles with the RSV pre-fusion protein (RSV protein) to create L-nanovaccine (L-Vac). The results showed that L-NPs increased antigen attachment in the nasal cavity by 3.83 times and prolonged its retention time to 72h. In vivo experimental data demonstrated that the intranasal immunization with L-Vac induced a 4.86-fold increase in secretory immunoglobulin A (sIgA) secretion in the upper respiratory tract, a 1.85-fold increase in the lower respiratory tract, and a 20.61-fold increase in RSV-specific immunoglobin G (IgG) titer levels in serum, compared with the commercial Alum Vac, while the neutralizing activity against the RSV authentic virus is 1.66-fold higher. The mechanistic investigation revealed that L-Vac activated the tumor necrosis factor (TNF) signaling pathway in nasal epithelial cells (NECs), in turn increasing the expression levels of interleukin-6 (IL-6) and C-C motif chemokine ligand 20 (CCL20) by 1.67-fold and 3.46-fold, respectively, through the downstream nuclear factor kappa-B (NF-κB) signaling pathway. Meanwhile, CCL20 recruited dendritic cells (DCs) and L-Vac activated the Toll-like receptor signaling pathway in DCs, promoting IL-6 expression and DCs maturation, and boosted sIgA production and T-cell responses. The findings suggested that L- Vac may serve as a candidate for the development of intranasal medicine against various types of respiratory infections.

Risk factors for poor outcome in adult patients with respiratory syncytial virus infection evaluated at the emergency department.

Respiratory syncytial virus-associated acute respiratory infection (RSV-ARI) constitutes an emerging cause of morbidity in the adult population. The present retrospective study was aimed at identifying factors predictive of poor outcome that may be assessed at the first evaluation in the Emergency Department (ED). We included 275 adult patients with laboratory-confirmed RSV-ARI that required hospital admission from the ED between January 2018 and December 2019. Poor outcome (composite of progression to high-flow oxygen therapy, non-invasive or invasive mechanical ventilation, or intensive care unit admission, and/or 30-day all-cause mortality) occurred in 31 patients (11.2%). Immunosuppression was present in 59 patients (21.5%). Although bacterial co-infection was rare, antibiotic therapy was commonly initiated. Ribavirin was administered in 10 patients. Cognitive impairment (odds ratio [OR]: 2.452; 95% confidence interval [CI]: 0.990-6.072), concurrent oral anticoagulation (OR: 3.099; 95 CI: 1.287-7.464) and a pulse oximetry oxygen saturation to fraction of inspired oxygen ratio (SpO2/FiO2) ratio <382 at ED admission (OR: 3.013; 95 CI: 1.306-6.950) were independent risk factors for poor outcome, whereas influenza vaccination in the current season was protective (OR: 0.324; 95% CI: 0.138-0.763). Various factors easily available at the ED are useful for early risk stratification in adult patients with RSV-ARI.

S1048 Respiratory Syncytial Virus Vaccine is Associated With Better Outcomes in Inflammatory Bowel Disease Patients over 60 Years Old: A US Propensity-Matched Study

S1048 Respiratory Syncytial Virus Vaccine is Associated With Better Outcomes in Inflammatory Bowel Disease Patients over 60 Years Old: A US Propensity-Matched Study

S1897 Liver Cirrhosis and its Impact on Clinical Outcomes in Adult Respiratory Syncytial Virus Pneumonia: A Retrospective Analysis of the National Inpatient Sample

S1897 Liver Cirrhosis and its Impact on Clinical Outcomes in Adult Respiratory Syncytial Virus Pneumonia: A Retrospective Analysis of the National Inpatient Sample

Molecular surveillance in the nirsevimab era: lessons from respiratory syncytial virus breakthrough infections

Molecular surveillance in the nirsevimab era: lessons from respiratory syncytial virus breakthrough infections