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A globally implemented unified phylogenetic classification for human respiratory syncytial virus (HRSV) below the subgroup level remains elusive. We formulated global consensus of HRSV classification on the basis of the challenges and limitations of our previous proposals and the future of genomic surveillance. From a high-quality curated dataset of 1,480 HRSV-A and 1,385 HRSV-B genomes submitted to GenBank and GISAID (https://www.gisaid.org) public sequence databases through March 2023, we categorized HRSV-A/B sequences into lineages based on phylogenetic clades and amino acid markers. We defined 24 lineages within HRSV-A and 16 within HRSV-B and provided guidelines for defining prospective lineages. Our classification demonstrated robustness in its applicability to both complete and partial genomes. We envision that this unified HRSV classification proposal will strengthen HRSV molecular epidemiology on a global scale.

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.

Since its discovery in 1957, respiratory syncytial virus (RSV) has been widely recognized as a common and deadly pathogen. Although early studies focused on the impact of RSV on the health of children, more recent data show that RSV imposes a significant burden on individuals aged ≥ 70 years. RSV also substantially harms the health of individuals with cardiopulmonary diseases. Early efforts to develop an RSV vaccine were hampered by toxicity due to antibody-enhanced viral pneumonia and a lack of efficacy in vaccines that targeted the postfusion configuration of the F fusion protein, which is crucial to the pathogenesis of RSV-mediated injury. A newer wave of vaccines has targeted a stabilized prefusion F protein, generating effective neutralizing antibodies and reducing the burden of mild and severe RSV lower respiratory tract injury. This review focuses on the burden of RSV in patients with pulmonary diseases, highlights the tumultuous path from the early days of RSV vaccine development to the modern era, and offers insights into key gaps in knowledge that must be addressed to adequately protect the vulnerable population of patients with severe pulmonary diseases. RSV vaccination with bivalent RSVPreF or RSVPreF3OA, which target the stabilized prefusion F protein, can be broadly recommended to adults aged ≥ 60 years with pulmonary diseases. However, more data are needed to understand how these vaccinations affect key clinical outcomes in individuals with pulmonary disease. [ABSTRACT FROM AUTHOR]

We recently expanded the viral genomic surveillance program in Minnesota, USA, to include human respiratory syncytial virus. We performed whole-genome sequencing of 575 specimens collected at Minnesota healthcare facilities during July 2023-February 2024. Subgroups A and B differed in their genomic landscapes, and we identified 23 clusters of genetically identical genomes. [ABSTRACT FROM AUTHOR]

Introduction: We aimed to describe the risk profile of RSV infections among children aged ≤ 24 months in Valladolid from January 2010 to August 2022 and to compare them with influenza and COVID-19 controls. Methods: 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 < 30 days) and compared severity between hospitalized RSV patients vs. influenza and COVID-19 controls using multivariable logistic regression models. Results: We included 1507 patients with RSV (1274 inpatient), 32 with influenza, and 52 COVID-19 controls. Hospitalized RSV (mean age 5.3 months) and COVID-19 (4 months) were younger than influenza (9.1 months) 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. Conclusions: 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 59 months. RSV monoclonal antibody is recommended for ≤ 6 months but a third of patients were aged 6–24 months. Maternal RSV vaccination can protect their children directly from birth and indirectly through breastfeeding. [ABSTRACT FROM AUTHOR]

Introduction: Lower respiratory tract illness (LRTI) caused by respiratory syncytial virus (RSV) is common among young children in Argentina. Use of the currently available prophylactic agent is limited to children aged ≤ 2 years with selected high-risk conditions, and thus the majority of infants remain unprotected. We estimated the value-based price (VBP) of a novel RSVpreF vaccine for use among pregnant people for prevention of RSV-LRTI among infants during the first year of life. Methods: Clinical outcomes and economic costs of RSV-LRTI during infancy and expected impact of RSVpreF vaccination during pregnancy were projected using a population-based Markov-type cohort model. Model results—estimated on the basis of gestational age at birth, disease/fatality rates, and mother's vaccination status—include total numbers of RSV-LRTI cases, RSV-LRTI-related deaths, and associated costs. Base case analyses (RSVpreF vs. no vaccine) were conducted from the healthcare system perspective. Probabilistic sensitivity analyses (PSA; 1000 replications) were also conducted. Willingness-to-pay (WTP) was $10,636 per quality-adjusted life-year (QALY; i.e., 1 × 2021 gross domestic product [GDP] per capita) in base case analyses and PSA. Costs are reported in USD, estimated on the basis of the June 22, 2023 exchange rate. Results: Use of RSVpreF among 342,110 pregnant persons provided protection to 330,079 infants at birth. In total, RSVpreF prevented 3915 RSV hospitalizations, 6399 RSV cases requiring emergency department care, 6182 RSV cases requiring a physician office visit, and 67 disease-related deaths. Direct costs were projected to be reduced by $5.0 million. With 2061 QALYs gained and vaccine administration cost of $1.4 million, the VBP of RSVpreF was estimated to be $74.46 per dose. In PSA, mean VBP was $75.02 (95% confidence interval 54.24–97.30). Conclusions: RSVpreF among pregnant persons would significantly reduce the clinical and economic burden of RSV-LRTI among infants in Argentina and would be considered a cost-effective intervention up to a price of approximately $75. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory syncytial virus (RSV) incidence is known to be underestimated in adults due to its infrequent diagnostic testing and lower sensitivity of single nasal/nasopharyngeal swab PCR testing outside of the early childhood period. RSV can trigger acute cardiac events as well as cause respiratory disease. Consequently, we used a model-based study to estimate RSV-attributable hospitalization and mortality incidence among adults in Italy between 2015 and 2019. Methods: Through a database predisposed by CREA Sanità, by extracting monthly data from the Italian hospitalization collection data of the Ministry of Health and the Italian National Institute of Statistics (ISTAT) data (mortality), we estimated yearly RSV-attributable incidence of events for different cardiorespiratory outcomes. We used a quasi-Poisson regression model, which accounted for periodic and aperiodic time trends and viral activity proxies. Results: The yearly RSV-attributable cardiorespiratory hospitalization incidence increased with age and was highest among adults aged ≥ 75 years (1064–1527 cases per 100,000 person-years). Similarly, the RSV-attributable cardiorespiratory mortality rate was highest among persons aged ≥ 75 years (59–85 deaths per 100,000 person-years). Incidence rates for RSV-attributable hospitalizations and RSV-attributable mortality were on average 2–3 times higher for cardiorespiratory than respiratory disease alone. Incidence rate based on RSV-specific ICD codes only were 405–1729 times lower than modeled estimates accounting for untested events. Conclusion: RSV causes a substantial disease burden among adults in Italy and contributes to both respiratory and cardiovascular conditions. Our results emphasize the need for effective RSV prevention strategies, particularly among older adults. [ABSTRACT FROM AUTHOR]

Background and Objective: Understanding the seasonal behaviours of respiratory viruses is crucial for preventing infections. We evaluated the seasonality of respiratory viruses using time‐series analyses. Methods: This study analysed prospectively collected nationwide surveillance data on eight respiratory viruses, gathered from the Korean Influenza and Respiratory Surveillance System. The data were collected on a weekly basis by 52 nationwide primary healthcare institutions between 2015 and 2019. We performed Spearman correlation analyses, similarity analyses via dynamic time warping (DTW) and seasonality analyses using seasonal autoregressive integrated moving average (SARIMA). Results: The prevalence of rhinovirus (RV, 23.6%–31.4%), adenovirus (AdV, 9.2%–16.6%), human coronavirus (HCoV, 3.0%–6.6%), respiratory syncytial virus (RSV, 11.7%–20.1%), influenza virus (IFV, 11.7%–21.5%), parainfluenza virus (PIV, 9.2%–12.6%), human metapneumovirus (HMPV, 5.6%–6.9%) and human bocavirus (HBoV, 5.0%–6.4%) were derived. Most of them exhibited a high positive correlation in Spearman analyses. In DTW analyses, all virus data from 2015 to 2019, except AdV, exhibited good alignments. In SARIMA, AdV and RV did not show seasonality. Other viruses showed 12‐month seasonality. We describe the viruses as winter viruses (HCoV, RSV and IFV), spring/summer viruses (PIV, HBoV), a spring virus (HMPV) and all‐year viruses with peak incidences during school periods (RV and AdV). Conclusion: This is the first study to comprehensively analyse the seasonal behaviours of the eight most common respiratory viruses using nationwide, prospectively collected, sentinel surveillance data. [ABSTRACT FROM AUTHOR]

Aim: To explore whether children in specialist care with COVID-19 have increased post-discharge health care use when compared with children in specialist care with 1) respiratory syncytial virus (RSV) infection, and 2) other respiratory tract infections (RTIs). Methods: In 34,214 children aged 1 month to 5 years who were registered as having one or more hospital visit (outpatient or inpatient) with a diagnosis of COVID-19 (N = 128), RSV infection (N = 4,009), or other RTIs (N = 34,458) from 2017 to 2021, we used a difference-in-differences study design to investigate individual all-cause primary and specialist health care use from 12 weeks prior to 12 weeks after the hospital visit, stratified by infants (1 to 11 months) and children (1 to 5 years). Results: We found a slight increase in primary health care use in the first 4 weeks after the hospital visit for infants with COVID-19 when compared with infants with RSV infection (6 per 10,000; 95% CI [2, 13], a 0.52% relative increase). For infants diagnosed with COVID-19, we found a similar post-visit increase in inpatients when compared with infants with RSV infection, which lasted for 12 weeks. Conclusions: Our findings imply a slightly increased health care use among infants after a hospital visit for COVID-19 than among infants with other RTIs, the potential etiological mechanisms of which deserve future clinical research. Severe COVID-19 in young children will not represent any markedly increased burden on the health services. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is responsible for outbreaks of bronchiolitis, bronchitis, and pneumonia and is effective and lethal in children under five years old. Current RSV detection methods are expensive, time-consuming, and require highly skilled personnel. Therefore, we developed a cost-effective impedimetric immunosensor for the detection of RSV based on a pencil graphite electrode (PGE) modified with a polymeric film derived from 3-amino phenylacetic acid. The current responses in the potassium ferricyanide and methylene blue solutions suggest the presence of unchanged carboxylic acid groups in the polymer. With a similar number of electrons involved in the first step of the reaction and electron/proton ratio to those proposed for aniline, a mechanism for electropolymerization was proposed. The immunosensor was assembled by activating the carboxyl groups via an EDC/NHS nucleophilic substitution reaction with the amino groups present in the anti-RSV monoclonal antibody (mAb). The detection was performed using electrochemical impedance spectroscopy, and the data were evaluated using equivalent circuits. The charge transfer resistance values increased as PGE was modified in the following order: PGE < PGE/polymer < PGE/polymer/mAb < PGE/polymer/mAb/virus. 100 ng of mAb was used, and the immobilization times for mAb and blocker were 3 h and 50 min, respectively. The response time for RSV immobilization was 30 min. The limit of detection was 22.54 PFU mL−1, and the limit of quantification was 75.12 PFU mL−1, with a linear range from 50 – 2000 PFU mL−1, demonstrating that the proposed immunosensor is a viable alternative for the detection of RSV. [ABSTRACT FROM AUTHOR]

This retrospective study aims to analyze the baseline characteristics and factors associated with poor outcomes in patients with necrotizing enterocolitis (NEC) complicating respiratory syncytial virus (RSV) infection. Using the Virtual Pediatric Systems data registry, patients under 2 years admitted to the pediatric intensive care unit (PICU) were screened. Patients with documented RSV infection and NEC, intestinal perforation, noninfectious gastroenteritis/colitis, or pneumatosis intestinalis occurring around the timing of RSV bronchiolitis diagnosis were included. Out of the screened patients, 41 were analyzed. Most patients (93%) were aged 30 days to 2 years, one-third had baseline anatomical cardiac defects, and 20% history of prematurity. Median PICU length of stay was 11.7 days. Seven patients died before hospital discharge. While not statistically significant, nonsurvivors tended to exhibit higher PRISM-3 scores, more acidemia, and lower systolic blood pressure. These findings emphasize the need for cautious assessment of gastrointestinal symptoms in critically ill patients with RSV infection. [ABSTRACT FROM AUTHOR]

Acute respiratory infections are the leading cause of death and illness in children under 5 years old and represent a significant burden in older adults. Primarily caused by viruses infecting the lower respiratory tract, symptoms include cough, congestion, and low‐grade fever, potentially leading to bronchiolitis and pneumonia. Messenger ribonucleic acid (mRNA)‐based vaccines are biopharmaceutical formulations that employ mRNA molecules to induce specific immune responses, facilitating the expression of viral or bacterial antigens and promoting immunization against infectious diseases. Notably, this technology had significant relevance during the COVID‐19 pandemic, as these formulations helped to limit SARS‐CoV‐2 virus infections, hospitalizations, and deaths. Importantly, mRNA vaccines promise to be implemented as new alternatives for fighting other respiratory viruses, such as influenza, human respiratory syncytial virus, and human metapneumovirus. This review article analyzes mRNA‐based vaccines' main contributions, perspectives, challenges, and implications against respiratory viruses. [ABSTRACT FROM AUTHOR]

While respiratory syncytial virus (RSV) is one of the most common pathogens in adults admitted to the ICU due to respiratory diseases, no reports regarding the occurrence rate of RSV infections in adults in Japan during the COVID-19 pandemic exist. We conducted this retrospective study to examine the exact occurrence rate of RSV infections in adults. We reviewed all patients (≥18 years) with any respiratory symptoms who received quantitative polymerase chain reaction (PCR) using nasopharyngeal samples for respiratory viruses by GeneLEAD at the Aichi Medical University Hospital between November 2022 and November 2023. A total of 541 adult patients who underwent PCR test were enrolled in this study. RSV was identified in 18 cases (3.3 %); 8 (1.5 %) upper and 10 (1.8 %) lower respiratory tract infections. Influenza A and SARS-CoV-2 were found in 10 (1.8 %) and 61 (11.3 %), respectively. Patients with RSV infections and COVID-19 had more comorbidities than those with Influenza virus infections. As for RSV-associated with lower respiratory tract infection cases, 10 developed acute respiratory failure, resulting in 1 fatal case due to pneumonia and 1 died of septic shock due to ileus. The 30-, 90-day mortality rates were 1 (6 %) and 2 (11 %) respectively. About 3 % of adults had RSV infections during the COVID-19 pandemic. The outcomes of RSV infections in adults were similar to those by COVID-19. Those with comorbidities should have a preventive method against RSV infections, the same as for COVID-19. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory syncytial virus (RSV) causes acute respiratory tract infection (ARTI) and reinfects adults throughout life, posing a risk for hospitalization in older adults (>60 years) with frailty and comorbidities. Methods: To investigate serum and mucosal antibodies for protection against RSV infections, baseline serum samples were compared for RSV-pre- and -postfusion (F) binding, and RSV-A2 neutralizing IgG antibodies between symptomatic RSV-ARTI (N = 30), non-RSV (RSV negative) ARTI (N = 386), and no ARTI (N = 338). Mucosal RSV-pre-F IgA and IgG levels, as well as serum RSV-G IgG antibodies, were analyzed to determine their association with protection from symptomatic RSV-ARTI in a subset study. Results: Using a receiver operating characteristic (ROC) analysis, we established thresholds of 1.4- to 1.6-fold change (FC) for RSV-pre-F and -post-F, and RSV-A2 neutralizing IgG antibodies, respectively, enabling the identification of asymptomatic RSV cases with high sensitivity and specificity (>80% and >90%, respectively). As a result, serum RSV-pre-F, RSV-G IgG, and mucosal pre-F binding IgA antibodies showed correlations with protection against symptomatic RSV infection. RSV-pre-F IgG antibodies were correlated with protection from RSV infections irrespective of the symptoms. Discussion: This study provides insights into antibody-mediated protection for symptomatic RSV infection in a community-dwelling older-adult population and establishes a threshold to identify asymptomatic RSV infection using a datadriven approach. [ABSTRACT FROM AUTHOR]

The pathology of respiratory syncytial virus (RSV) infection remains unclear. An unbalanced immune response to RSV infection can lead to immunopathology, causing airway damage and impaired exchange of oxygen and carbon dioxide between the air and the bloodstream. We aimed to evaluate the association of the expression of inflammatory and antiviral genes in peripheral blood with severe hypoxemia in children with RSV infection seen in the hospital emergency room. We conducted a cross-sectional study on 121 RSV-infected children seen in hospital emergency rooms between 2015 and 2023. Total RNA was extracted from whole blood samples, and gene expression (IL-6, TNFa, CXCL8, ISG15, IFIT1, RIGI, IFNb, CCL5, and CXCL10) was quantified using quantitative RT-PCR. The outcome variable was having severe hypoxemia (SpO2 ≤ 90%). The association analysis was performed using a volcano plot, adjusted logistic regression, and orthogonal partial least squares discriminant analysis (OPLSDA). We found that 26 of 121 children had severe hypoxemia (SpO2 ≤ 90%). CXCL8 was overexpressed [fold changes (FC) > 2; q-value < 0.05], and ISG15, IFIT1, RIGI, IFNb, CCL5, and CXCL10 were underexpressed (FC <0.5; q-value <0.05) in children with severe hypoxemia. These associations were ratified using adjusted logistic regression. The OPLS-DA showed that the gene expressions of CXCL8, ISG15, IFIT1, RIGI, and CXCL10 had values of variable importance in projection (VIP) ≥1, being the most relevant features. In conclusion, an imbalance favoring inflammation over antiviral defense may contribute to the pathogenesis of severe hypoxemia in RSV-infected children. These findings provide valuable insights into the pathology of RSV infection. [ABSTRACT FROM AUTHOR]

Background: Human respiratory syncytial virus (HRSV) is worldwide one of the leading causes of acute respiratory tract infections in young children and the elderly population. Two distinct subtypes of HRSV (A and B) and a multitude of genotypes have been described. The laboratory of Clinical and Epidemiological Virology (KU Leuven/University Hospitals Leuven) has a long-standing history of HRSV surveillance in Belgium. Methods: In this study, the seasonal circulation of HRSV in Belgium was monitored during 8 consecutive seasons prior to the SARS-CoV-2 pandemic (2011–2012 until 2018–2019). By use of a multiplex quantitative real time PCR panel, 27,386 respiratory samples were tested for HRSV. Further subtyping and sequencing of the HRSV positive samples was performed by PCR and Sanger sequencing. The prevalence and positivity rate were estimated in 4 distinct age groups and the circulating strains of each subtype were situated in a global context and in reference to the described genotypes in literature. Results: HRSV circulated in Belgium in a yearly re-occurring pattern during the winter months and both HRSV subtypes co-circulated simultaneously. All HRSV-B strains contained the 60 nt duplication in the HVR2 region of the G gene. Strains of subtype HRSV-A with a 72 nt duplication in the HVR2 region were first observed during the 2011–2012 season and replaced all other circulating strains from 2014 to 2015 onwards. [ABSTRACT FROM AUTHOR]

Key points Viral infections lead to a greater than twofold increased risk of developing chronic rhinosinusitis within 1 year. Viral infections lead to a greater than twofold increased risk of developing chronic rhinosinusitis within 1 year. Recurrent viral infections pose a greater risk of chronic rhinosinusitis than single episodes. [ABSTRACT FROM AUTHOR]

Introduction: In Brazil, few studies were performed regarding the co-detection of respiratory viruses in hospitalized patients. In this way, the study aimed to describe the epidemiological profile of hospitalized patients due to influenza virus infection that presented co-detection with another respiratory virus. Methods: The epidemiological analysis was made by collecting data from Open-Data-SUS. The study comprised patients infected by the influenza A or B virus with positive co-detection of another respiratory virus, such as adenovirus, bocavirus, metapneumovirus, parainfluenza virus (types 1, 2, 3, and 4), rhinovirus, and respiratory syncytial virus (RSV). The markers [gender, age, clinical signs and symptoms, comorbidities, need for intensive care unit (ICU) treatment, and need for ventilatory support] were associated with the chance of death. The data was collected during the first three years of the coronavirus disease (COVID)-19 pandemic--from December 19, 2019, to April 06, 2023. Results: A total of 477 patients were included, among them, the influenza A virus was detected in 400 (83.9%) cases. The co-detection occurred, respectively, for RSV (53.0%), rhinovirus (14.0%), adenovirus (13.4%), parainfluenza virus type 1 (10.7%), parainfluenza virus type 3 (5.2%), metapneumovirus (3.8%), parainfluenza virus type 2 (3.6%), bocavirus (3.4%), and parainfluenza virus type 4 (1.5%). The co-detection rate was higher in the male sex (50.7%), age between 0-12 years of age (65.8%), and white individuals (61.8%). The most common clinical symptoms were cough (90.6%), dyspnea (78.8%), and fever (78.6%). A total of 167 (35.0%) people had at least one comorbidity, mainly cardiopathy (14.3%), asthma (8.4%), and diabetes mellitus (7.3%). The need for ICU treatment occurred in 147 (30.8%) cases, with most of them needing ventilatory support (66.8%), mainly non-invasive ones (57.2%). A total of 33 (6.9%) patients died and the main predictors of death were bocavirus infection (OR = 14.78 [95%CI = 2.84-76.98]), metapneumovirus infection (OR = 8.50 [95%CI = 1.86-38.78]), race (other races vs. white people) (OR = 3.67 [95%CI = 1.39-9.74]), cardiopathy (OR = 3.48 [95%CI = 1.13-10.71]), and need for ICU treatment (OR = 7.64 [95%CI = 2.44-23.92]). Conclusion: Co-detection between the influenza virus and other respiratory viruses occurred, mainly with RSV, rhinovirus, and adenovirus being more common in men, white people, and in the juvenile phase. Co-detection of influenza virus with bocavirus and metapneumovirus was associated with an increased chance of death. Other factors such as race, cardiopathy, and the need for an ICU were also associated with a higher chance of death. [ABSTRACT FROM AUTHOR]

Introduction: 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. Methods: 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. Results: The rAAV5-RSV-Fm vaccine demonstrated positive humoral and induced antibody titers against RSV strains A and B for up to 120 days postimmunization. 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. Conclusion: These findings underscore the potential application of rAAV5 vector platforms in RSV vaccine development and further investigation into their protective efficacy is warranted. [ABSTRACT FROM AUTHOR]

Respiratory infections are a leading cause of death in developing countries. Infants and young children are especially susceptible to disease because they lack immunity, whereas adults who have acquired immunity can be infected asymptomatically. Great ape species, all of which are endangered, are similarly susceptible to respiratory illnesses caused by human respiratory pathogens. We obtained 432 nasopharyngeal swab samples (127 from adults and 305 from children) in a cross‐sectional study that took place between February and October 2022 at four sites in Western Uganda (Budongo Central Forest Reserve, Bulindi Town Council, Bwindi Impenetrable National Park, and Kibale National Park) where the participants live in communities where interaction with apes is frequent. Prior research at Kibale has shown that locally circulating human respiratory pathogens have led to multiple lethal outbreaks in wild eastern chimpanzees (Pan troglodytes schweinfurthii). We used a multiplex PCR panel to characterize respiratory pathogens, with the goal of assessing whether respiratory illnesses in the chimpanzees of Budongo and Bulindi and the mountain gorillas (Gorilla beringei beringei) of Bwindi might have originated in local children and been introduced to the apes via asymptomatic adult carriers. The prevalence of respiratory pathogens was twice as high in Bwindi (44.0%) as it was in Budongo (24.0%) and Bulindi (20.8%), while the prevalence was intermediate at Kibale (34.4%). Rates of respiratory pathogen detection were higher but statistically indistinguishable in children compared to adults at Budongo and Bulindi, and children were 15.0 times more likely than adults to have positive detections at Kibale. At Bwindi, however, the pattern was reversed, with adults 2.6 times more likely than children to have positive detections. Rhinovirus, metapneumovirus, human parainfluenza virus 3, respiratory syncytial virus, and coronavirus OC43, all of which have been identified as causative agents of respiratory disease outbreaks in great ape populations across sub‐Saharan Africa, accounted for three quarters (73.6%) of detected pathogens. Our data support the idea that human respiratory pathogens that can infect great apes occur at high frequencies in human populations in Western Uganda that live close to and interact with wild apes that have suffered from lethal outbreaks caused by these same pathogens. Reducing respiratory infections in local children, thereby reducing both carriage of those infections into the forest by people and ape exposure to these pathogens when they enter human spaces, should decrease the risk of respiratory disease outbreaks in apes. [ABSTRACT FROM AUTHOR]

This research comprehensively investigates the epidemiological features and pathogen profile of acute respiratory infections (ARI) in Shihezi City, Xinjiang. A pivotal aspect of this study is the construction of a Bayes discriminant function for principal pathogen infections. This innovative methodology aims to furnish a robust scientific basis for the prevention and clinical management of ARI, potentially guiding more effective strategies in both public health and clinical settings. We compiled and examined data from January 2020 to June 2023, pertaining to patients admitted with acute respiratory infections at the First Affiliated Hospital of Shihezi University. This investigation focused on discerning patterns in epidemiology and pathogen etiology. Among 2110 cases of acute respiratory infections (ARI), 1736 underwent pathogenetic testing. Of these, 595 cases tested positive for at least one pathogen, marking a positivity rate of 34.27%. Viral detections, at a rate of 27.47%, were notably higher than bacterial detections, which stood at 6.51%. The most prevalent viruses identified were Human respiratory syncytial virus (hRSV), Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2), and Human adenovirus (HAdV), while the dominant bacterial pathogens included Klebsiella pneumoniae, Haemophilus influenzae, and Staphylococcus aureus. Co‐infections were observed in 76 cases, accounting for 12.77% of positive diagnoses, predominantly involving hRSV in conjunction with other pathogens. In cases of acute bronchiolitis, hRSV was the most frequent pathogen, contributing to 23.10% of such cases. Similarly, in severe pneumonia cases, SARS‐CoV‐2 was predominant, accounting for 25.4% of these infections. The group with bacterial positivity exhibited elevated levels of C‐reactive protein (CRP, 19.17 mg/L) and neutrophilic granulocyte percentage (NE%, 54.7%). The Bayes discriminant function demonstrated an initial validation accuracy of 74.9% and a cross‐validation accuracy of 63.7%. The study underscores that hRSV, SARS‐CoV‐2, and HAdV are the primary pathogens in acute respiratory infections in the Shihezi region. Pathogen susceptibility exhibits variation across different age groups, with a higher pathogen detection rate in children compared to adults. The Bayes discriminant function shows significant promise in the classification and diagnosis of major pathogenic infections. [ABSTRACT FROM AUTHOR]

Respiratory pathogen infections are seasonally prevalent and are likely to cause co-infections or serial infections during peak periods of infection. Since they often cause similar symptoms, simultaneous and on-site detection of respiratory pathogens is essential for accurate diagnosis and efficient treatment of these infectious diseases. However, molecular diagnostic techniques for multiple pathogens in this field are lacking. Herein, we developed a microfluidic LAMP and real-time fluorescence assay for rapid detection of multiple respiratory pathogens using a ten-channel microfluidic chip with pathogen primers pre-embedded in the chip reaction well. The microfluidic chip provided a closed reaction environment, effectively preventing aerosol contamination and improving the accuracy of the detection results. Its corresponding detection instrument could automatically collect and display the fluorescence curve in real time, which was more conducive to the interpretation of results. The results showed that the developed method could specifically recognize the nucleic acid of influenza A(H1N1), Mycoplasma pneumoniae, respiratory syncytial virus type A, and SARS-CoV-2 with low detection limits of 104 copies per mL or 103 copies per mL. The test results on clinical samples demonstrated that the developed method has high sensitivity (92.00%) and high specificity (100.00%) and even has the capability to differentiate mixed-infection samples. With simple operation and high detection efficiency, the present portable and simultaneous detection assay could significantly improve the efficiency of on-site detection of respiratory infectious diseases and promote the accurate treatment, efficient prevention and control of the diseases. [ABSTRACT FROM AUTHOR]

Background: In addition to the persistence of SARS-CoV-2 infections, those with Influenza A/B and RSV have reappeared in 2022/23. To compare the development of prevalence, clinical outcomes and risk factors, we analysed data of the season 2023/24 from the same region/hospital as for 2022/23. Methods: Patients covering the whole age range with a positive polymerase chain reaction (PCR) test for SARS-CoV-2, Influenza A/B, RSV were included from the internal, neurological and paediatric units of the RoMed hospital Rosenheim, Germany/Bavaria, from August 1st 2023 to 29th February 2024. Results: Of 932 patients included, 912 showed single infections with SARS-CoV-2, Influenza A or RSV (47.9% female, median age 68.0 years; 52.9% SARS-CoV-2, 23.2% Influenza A, 21.8% RSV). Co-infections (2.0%) and Influenza B (0.1%) were negligible. In patients of age ≥ 18 years (n = 628, 68.5% SARS-CoV-2, 26.0% Influenza A, 5.6% RSV), patients with Influenza A were younger compared to SARS-CoV-2 (p < 0.001), with RSV similar to SARS-CoV-2. Heart failure and asthma were the most prevalent comorbidities for RSV, immunosuppression for Influenza A. Admission to Intensive Care Unit (ICU) occurred in 111 patients (17.0% of SARS-CoV-2, 17.2% Influenza A, 28.6% RSV), and 59 patients died (8.8% SARS-CoV-2, 8.6% Influenza A, 20.0% RSV). Low-flow oxygen supplementation and non-invasive ventilation (NIV) were most frequent for RSV (68.6% and 20.0%, respectively), oxygen demand upon admission for Influenza A (39.3%), without differences in high-flow oxygen supply or length of hospital stay. Among patients aged < 18 years (n = 284, 21.4% SARS-CoV-2, 18.0% Influenza A, 57.1% RSV), 15 were admitted to ICU (4.8% SARS-CoV-2, 3.8% Influenza A, 6.0% RSV); none of them died. Oxygen supply via high-flow, low-flow or upon admission was highest for RSV (23.8%, 70.2%, 21.4%, respectively), as well as the length of hospital stay. Conclusion: Between 8/2023 to 2/2024, a large population of patients hospitalized due to respiratory tract infection, showed relative contributions of SARS-CoV-2, Influenza A or RSV similar to those in 2022/23. The findings underline that in both, adults and children, RSV posed a relatively higher clinical risk than Influenza A and SARS-CoV-2, though absolute numbers remained highest for SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71–85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52–92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48–85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70–83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023–24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. The Centers for Disease Control and Prevention. [ABSTRACT FROM AUTHOR]

AbstractRespiratory syncytial virus (RSV) is a widespread viral infection that causes millions of high-risk illnesses annually. Medicinal herbs such as ginseng root, echinacea purpurea, and radix astragali have a positive effect on antiviral activity by preventing viral adhesion, syncytial development, inhibiting viral internalization, relieving respiratory inflammation, strengthening the immune system, and stimulating the release of interferons. The potential benefits of natural products in terms of lower costs, better patient outcomes, and fewer adverse effects are discussed. This review examines the current evidence on the prevention and control of RSV with natural ingredients and the challenges and opportunities in clinical practice. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Severe respiratory syncytial virus (RSV) infection during early life has been linked to gut dysbiosis, which correlates with increased disease severity and a higher risk of developing asthma later in life. However, the impact of such early-life RSV infections on intestinal immunity in adulthood remains unclear. Herein, we show that RSV infection in 3-week-old mice induced persistent differential natural killer (NK) and T cell profiles within the lungs and gastrointestinal (GI) lymphoid tissues (GALT) in adulthood. Notably, male mice exhibited more pronounced RSV-induced changes in immune cell populations in both the lungs and GALT, while female mice displayed greater resilience. Importantly, early-life RSV infection was associated with the chronic downregulation of CD69-expressing T lymphocytes, particularly T regulatory cells in Peyer's patches, which could have a significant impact on T cell functionality and immune tolerance. We propose that RSV infection in early life is a trigger for the breakdown in immune tolerance at mucosal surfaces, with potential implications for airways allergic disease, food allergies, and other GI inflammatory diseases. [ABSTRACT FROM AUTHOR]

Background The adjuvanted respiratory syncytial virus (RSV) prefusion F protein–based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50–59 years without or with increased risk for RSV disease due to specific chronic medical conditions. Methods This observer-blind, phase 3, noninferiority trial included adults aged 50–59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50–59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. Results The exposed population included 1152 participants aged 50–59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50–59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. Conclusions RSVPreF3 OA was immunologically noninferior in 50–59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50–59-year-olds was consistent with that in ≥60-year-olds. Clinical Trial Registration ClinicalTrials.gov : NCT05590403. [ABSTRACT FROM AUTHOR]

Background Data on the true prevalence of respiratory syncytial virus (RSV) among medically attended acute respiratory illnesses (MAARI) has been limited by the lack of regular clinical testing of mild to moderate illnesses. Here we present a prospective evaluation of the epidemiology of RSV-associated MAARI across age groups and multimorbidity status over 3 seasons, which is informative in light of the recommendations for shared decision making for vaccination in older adults. Methods Ambulatory patients ≥6 months of age meeting a common MAARI case definition were prospectively enrolled in the Michigan Ford Influenza Vaccine Effectiveness (MFIVE) study, a subsite of the US Influenza Vaccine Effectiveness Network. All participants were tested by nasal-throat swab for RSV and influenza, including subtype, independently from clinician-directed testing. Participant illness characteristics and calculated multimorbidity-weighted index (MWI) were collected by in-person survey and electronic medical record review. Results Over 3 surveillance seasons (fall 2017 to spring 2020), 9.9% (n = 441) of 4442 participants had RSV detected. RSV-associated MAARI was more prevalent than influenza for participants 6 months to 4 years of age. Adults with RSV-MAARI had higher median MWI scores overall compared to influenza-MAARI and controls with neither virus (1.62, 0.40, and 0.64, respectively). Conclusions RSV is a significant, underrecognized cause of MAARI in both children and adults presenting for ambulatory care. Multimorbidity is an important contributor to RSV-associated MAARI in outpatient adults, providing information to support shared clinical decision making for vaccination. [ABSTRACT FROM AUTHOR]

Background The outbreak of the COVID-19 pandemic has had a profound impact on the circulation of seasonal respiratory viruses. This study aimed to compare the outcomes of SARS-CoV-2 and seasonal viruses in adults hospitalized with severe acute respiratory infection during the COVID-19 pandemic. Methods This population-based cohort study included patients aged >18 years hospitalized for severe acute respiratory infection in Brazil between February 2020 and February 2023. The primary outcome was in-hospital mortality. A competing risk analysis was used to account for competing events. Results In total, 2 159 171 patients were included in the study. SARS-CoV-2 was the predominant virus (98.7%). Among patients testing positive, the cumulative incidence of in-hospital mortality was 33.1% for SARS-CoV-2, 31.5% for adenovirus, 21.0% for respiratory syncytial virus, 18.7% for influenza, and 18.6% for other viruses. SARS-CoV-2 accounted for 99.3% of the deaths. Older age, male sex, comorbidities, hospitalization in the northern region, and oxygen saturation <95% were the common risk factors for death among all viruses. Conclusions In this large cohort study, individuals infected with SARS-CoV-2 or adenovirus had the highest risk of mortality. Irrespective of the virus type, older age, male sex, comorbidities, hospitalization in vulnerable regions, and low oxygen saturation were associated with an increased risk of fatality. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) causes severe infections in infants, immunocompromised or elderly individuals resulting in annual epidemics of respiratory disease. Currently, limited clinical surveillance and the lack of predictable seasonal dynamics limit the public health response. Wastewater-based epidemiology (WBE) has recently been used globally as a key metric in determining prevalence of severe acute respiratory syndrome coronavirus 2 in the community, but its application to other respiratory viruses is limited. In this study, we present an integrated genomic WBE approach, applying reverse-transcription quantitative polymerase chain reaction and partial G-gene sequencing to track RSV levels and variants in the community. We report increasing detection of RSV in wastewater concomitant with increasing numbers of positive clinical cases. Analysis of wastewater-derived RSV sequences permitted identification of distinct circulating lineages within and between seasons. Altogether, our genomic WBE platform has the potential to complement ongoing global surveillance and aid the management of RSV by informing the timely deployment of pharmaceutical and nonpharmaceutical interventions. [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) causes substantial respiratory disease. Bivalent RSV prefusion F (RSVpreF) vaccine is licensed in ≥60-year-olds. RSVpreF was well tolerated and immunogenic in a phase 1/2 study. We evaluated antibody persistence after initial vaccination and safety and immunogenicity after revaccination from this study. Methods Healthy adults were randomized to receive initial vaccination and revaccination 12 months later with either placebo or RSVpreF (240 µg with or without aluminum hydroxide). RSV-A and RSV-B geometric mean neutralizing titers (GMTs) were measured through 12 months after both vaccinations. Tolerability and safety were assessed. Results There were 263 participants revaccinated (18–49 years old, n = 134; 65–85 years old, n = 129). Among 18- to 49-year-olds and 65- to 85-year-olds, geometric mean fold rises (GMFRs) for both RSV subgroups (RSV-A, RSV-B) 1 month after initial RSVpreF vaccination were 13.3 to 20.4 and 8.9 to 15.5, respectively, as compared with levels before initial vaccination; corresponding GMFRs 12 months after initial vaccination were 4.1 to 5.0 and 2.6 to 4.1. GMFRs 1 month after revaccination vs levels before revaccination were 1.4 to 2.3 and 1.4 to 2.2 for 18- to 49-year-olds and 65- to 85-year-olds. Peak GMTs after revaccination were lower than those after initial vaccination. GMTs 12 months after initial vaccination and revaccination were similar, with GMFRs ranging from 0.7 to 1.6. No safety signals occurred. Conclusions RSVpreF revaccination was immunogenic and well tolerated among adults. Clinical Trials Registration. NCT03529773 (ClinicalTrials.gov). [ABSTRACT FROM AUTHOR]

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. Author summary: Respiratory tract infections caused by RSV present a significant public health concern, especially affecting infants and the elderly. Effective antiviral strategies are urgently needed against this non-segmented, negative-sense RNA virus of the Pneumoviridae family. Our research reveals how RSV maintains replication fitness despite oxidative damage, a common exacerbator of respiratory conditions. We have identified a mechanism where RSV preserves its genome integrity under oxidative stress using the DNA repair enzyme OGG1. This enzyme ensures that the viral RNA accurately pairs 8-oxoGua with cytosine, crucial for maintaining the fidelity of the viral genome. Targeting the interplay between OGG1 and RSV RNA offers a promising approach for developing novel antiviral treatments, potentially countering the virus's evolutionary adaptations. [ABSTRACT FROM AUTHOR]

Rationale: Respiratory syncytial virus (RSV) is a common global respiratory virus that is increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults that has acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions. Objectives: This prospective study aimed to establish the frequency of outpatient-managed RSV-related exacerbations of COPD in two well-characterized patient cohorts using a combination of diagnostic methods. Methods: Participants were recruited at specialist clinics in London, United Kingdom, and Groningen, the Netherlands, beginning in 2017 and observed for three consecutive RSV seasons, during exacerbations, and at least twice yearly. RSV infections were detected by RT-PCR and serologic testing. Measurements and Main Results: A total of 377 patients with COPD attended 1,999 clinic visits and reported 310 exacerbations. There were 27 RSV-related exacerbations (8.7% of the total); of these, seven were detected only by PCR, 16 only by serology, and four by both methods. Increases in RSV-specific Nucleoprotein antibody were as sensitive as those in the antibody to Pre-Fusion or Post-Fusion for serodiagnosis of RSV-related exacerbations. Conclusions: RSV is associated with 8.7% of outpatient-managed COPD exacerbations in this study. Antibodies to RSV Nucleoprotein may have diagnostic value and are potentially important in a vaccinated population. The introduction of vaccines that prevent RSV is expected to benefit patients with COPD. [ABSTRACT FROM AUTHOR]

Highly sensitive airborne virus monitoring is critical for preventing and containing epidemics. However, the detection of airborne viruses at ultra-low concentrations remains challenging due to the lack of ultra-sensitive methods and easy-to-deployment equipment. Here, we present an integrated microfluidic cartridge that can accurately detect SARS-COV-2, Influenza A, B, and respiratory syncytial virus with a sensitivity of 10 copies/mL. When integrated with a high-flow aerosol sampler, our microdevice can achieve a sub-single-copy spatial resolution of 0.83 copies/m3 for airborne virus surveillance with an air flow rate of 400 L/min and a sampling time of 30 minutes. We then designed a series of virus-in-aerosols monitoring systems (RIAMs), including versions of a multi-site sampling RIAMs (M-RIAMs), a stationary real-time RIAMs (S-RIAMs), and a roaming real-time RIAMs (R-RIAMs) for different application scenarios. Using M-RIAMs, we performed a comprehensive evaluation of 210 environmental samples from COVID-19 patient wards, including 30 aerosol samples. The highest positive detection rate of aerosol samples (60%) proved the aerosol-based SARS-CoV-2 monitoring represents an effective method for spatial risk assessment. The detection of 78 aerosol samples in real-world settings via S-RIAMs confirmed its reliability for ultra-sensitive and continuous airborne virus monitoring. Therefore, RIAMs shows the potential as an effective solution for mitigating the risk of airborne virus transmission. Effective surveillance of respiratory virus particles in air requires highly sensitive tools that can produce timely and accurate results. Here, the authors develop a device for detection of four respiratory viruses in air with high spatial viral resolution and test it in different settings. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) infects nearly all children by 2 years of age and is a leading cause of pediatric hospitalizations. A subset of children with RSV infection (RSV+ children) develop respiratory failure requiring intensive care, but immune mechanisms distinguishing severe pediatric RSV infection are not fully elucidated. Natural killer (NK) cells are key innate immune effectors of viral host defense. In this study of 47 critically ill RSV+ children, we coupled NK cell immunophenotype and cytotoxic function with clinical parameters to identify an NK cell immune signature of severe pediatric RSV disease. Airway NK cells were increased in intubated RSV+ children with severe hypoxemia and prolonged duration of mechanical ventilation and were correlated with clinical severity scores. Peripheral blood NK cells were decreased in RSV+ patients and had altered activating receptor expression, with increased expression of CD69 and decreased expression of NKG2D. Ex vivo, circulating NK cells from RSV+ patients exhibited functional impairment characterized by decreased cytotoxicity as well as aberrant immune synapse assembly and lytic granule trafficking. NK cell frequency and phenotype correlated with clinical measures that defined disease severity. These findings implicate a role for NK cells in mediating RSV immunopathology and suggest that an altered NK cell immunophenotype is associated with severe RSV disease in young children. Editor's summary: Nearly all children are infected with respiratory syncytial virus (RSV) by 2 years of age. Although most children only develop mild symptoms, some can develop severe diseases requiring hospitalization. To better understand the potential drivers of severe disease, Reilly et al. analyzed airway and peripheral blood immune cells from pediatric patients infected with RSV requiring hospitalization. The authors found that natural killer (NK) cells were increased in the airways of children with severe RSV. A corresponding decrease was observed in peripheral blood NK cells. Moreover, the NK cells exhibited an altered phenotype and were less effective at killing target cells ex vivo. These data suggest that these NK cells may be drivers of RSV immunopathology. —Courtney Malo [ABSTRACT FROM AUTHOR]

Objective: To investigate the epidemiological characteristics and infections of respiratory syncytial virus (RSV) and influenza viruses in hospitalized elderly patients with respiratory tract infections in Suzhou City, China, and to compare the differences in clinical characteristics and economic burden associated with these two infections. Methods: In this prospective study, pathogenetic testing and clinical data for hospitalized patients aged 60 years and older with respiratory tract infections were collected in five hospitals through stratified cluster sampling from December 2023 to May 2024. Comparative study on epidemic characteristics, clinical features and costs of cases who infected RSV alone and influenza alone were conducted. Results: Among 1,894 cases included, the RSV positivity rate was 5.91% during the 2023–2024 winter-spring season, while the influenza positivity rate was 9.61%. RSV-B was the predominant subtype of RSV, and influenza A (primarily H3N2) was the dominant strain among the influenza-positive cases. Compared with cases infected influenza virus alone, those infected RSV alone had lower occurrence frequency of fever (18.8% vs. 35.7%, P = 0.004), higher occurrence frequency of complications of lower respiratory tract infections (70.8% vs. 54.8%, P = 0.011), higher direct medical costs ($996.2 vs. $841.1, P = 0.017) and total costs ($1019.7 vs. $888.1, P = 0.036). RSV single infection is more common in female cases (P = 0.007) and diabetic cases (P = 0.007) than influenza virus single infection. Conclusions: During the winter and spring months, RSV is the second most common pathogen after influenza virus among older adults hospitalized for respiratory infections in Suzhou, China. Patients infected RSV are more likely to develop complications with lower respiratory tract infections and have higher medical costs than the influenza. RSV infection in the elderly should be emphasized, especially in female patients and diabetic patients. [ABSTRACT FROM AUTHOR]

Background: Identifying risk factors for respiratory syncytial virus (RSV)–associated severe acute respiratory illness (SARI) will assist with targeting vaccine interventions. Methods: Using surveillance data from South Africa (2012–2018), we compared the characteristics of individuals with RSV-associated influenza-like illness (ILI) (reference group) to those with RSV-associated SARI to describe factors associated with SARI using a multivariable analysis. Results: RSV was detected in 6% (483/7792) of ILI cases and 15% (844/5672) of SARI cases. Factors associated with SARI in children included age < 2 months, compared to age 2–4 years (adjusted odds ratio (aOR) 54.4; 95% confidence interval (CI) 23.5–125.8), malnutrition (aOR 1.9; 95% CI 1.2–3.2), prematurity (aOR 2.4; 95% CI 1.3–4.6) and living with HIV (LWH) (aOR 22.5; 95% CI 2.9–174.3). In individuals ≥ 5 years, factors associated with SARI included age ≥ 65 years compared to age 5–24 years (aOR 10.7; 95% CI 1.1–107.5), symptom duration ≥ 5 days (aOR 2.7; 95% CI 1.1–6.3), underlying illness (aOR 2.7; 95% CI 1.5–26.1) and LWH (aOR 16.8, 95% CI: 4.8–58.2). Conclusion: Individuals at the extremes of age and those with identified risk factors might benefit most from RSV prevention interventions. Clinical trial number: Not applicable, this is not a clinical trial. [ABSTRACT FROM AUTHOR]

Background: Respiratory Syncytial Virus (RSV) is an important pathogen causing acute respiratory illnesses in adults. RSV infection can lead to severe outcomes, including hospitalizations and even death. Despite the increased recognition of the burden in older adults, immediate post-discharge care needs among adults hospitalized with RSV are not well characterized and have not been compared to other serious medical conditions (such as influenza, acute myocardial infarction (MI), and stroke) for which there have been long-standing disease prevention efforts. Objectives: This study aims to describe the immediate post-discharge care needs among adults hospitalized with RSV in the United States and descriptively compare it to those hospitalized with influenza, acute MI, or stroke. Design: Retrospective observational cohort study. Patients: Adults aged ≥ 18 years, hospitalized with a primary diagnosis of RSV, influenza, acute MI, or stroke from January 01, 2016, to December 31, 2019, were identified from the Premier Healthcare Database using the International Classification of Diseases (ICD-10) codes. Main measures: Immediate post-discharge care was categorized into three different levels of care based on the discharge dispositions. Descriptive analyses were performed. Key results: In total, 3,629 RSV, 303,577 influenza, 388,682 acute MI, and 416,750 stroke hospitalizations were identified, the majority occurred among patients aged ≥ 65 years. Professional home care needs were the highest for RSV hospitalizations (19.1%), followed by influenza (17.7%), stroke (15.4%), and acute MI (9.8%). Additionally, institutional care needs immediately following discharge were similar for RSV, influenza, and acute MI hospitalizations (14.2%, 15.8%, and 14.1%, respectively). Conclusions: Immediate post-discharge care needs among adults hospitalized with RSV, especially in older adults, can be considerable and comparable to influenza and acute MI discharges. With recently approved RSV vaccines, efforts to increase vaccination in older adults are needed to prevent RSV and associated healthcare consequences. [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: 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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Background: 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. Methods: 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. Results: 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. Conclusions: There were cumulative variations of the RSV F gene, especially at some binding sites of antigenic sites. [ABSTRACT FROM AUTHOR]

Aim: Respiratory viruses significantly impact public health, contributing to high morbidity and mortality rates in both children and adults. This study evaluates the distribution and incidence of respiratory tract viruses in our hospital from 2019 to 2022, focusing on changes post-COVID-19 pandemic. Material and Methods: Utilizing molecular methods, we analyzed nasopharyngeal swabs with the FTD Respiratory Pathogens 21 kit and the QIAStat Dx Respiratory Panel kit at Istanbul Faculty of Medicine. A total of 1186 viruses were detected in 2488 samples (47.6% of the total) examined with the FTD Respiratory Pathogens 21 kit between 2019 and 2022. Results: It was determined that the detection rates were 52.8% in 2019, 44.3% in 2020, 50.0% in 2021, and 40.0% in 2022. Notable changes in prevalence were observed for pandemic influenza A (IAV-H1N1pdm2009), parainfluenza virus (PIV)-3, rhinovirus (RV), and respiratory syncytial virus (RSV)-A/B (p < 0.05). RV consistently showed the highest detection rates across all years (17.6% to 7.9%). Additionally, 1276 viruses were detected in 1496 samples using the QIAStat DX kit, with 91.3% positivity in 2021 and 78.6% in 2022, highlighting the kit's effectiveness in rapid diagnosis. Conclusions: This study enhances understanding of respiratory virus epidemiology during and after the pandemic, emphasizing the need for ongoing surveillance and strategic public health measures to address the evolving landscape of respiratory infections. [ABSTRACT FROM AUTHOR]

Viral respiratory diseases place a heavy burden on the healthcare system, with children making up a significant portion of related hospitalizations. While comorbidities increase the risk of complications and poor outcomes, many hospitalized children lack clear risk factors. As new vaccines for respiratory viral diseases emerge, this study examined pediatric respiratory hospitalizations, focusing on viral etiology, complication rates, and the impact of comorbidities to guide future policy. Data were analyzed from eight pre-COVID influenza seasons (2011/2012–2018/2019) involving patients under 18 years hospitalized with respiratory complaints across 4–10 hospitals in Valencia, Spain. Respiratory specimens were tested for eight viral targets using multiplex real-time reverse-transcription polymerase chain reaction. Demographics, clinical outcomes, discharge diagnoses, and laboratory results were examined. Among the hospitalized children, 26% had at least one comorbidity. These children had higher rates of pneumonia, asthma exacerbation, and pneumothorax, and were twice as likely to require ICU admission, though mechanical ventilation and length of stay were similar to those without comorbidities. Respiratory syncytial virus (RSV) was the most common virus detected (23.1%), followed by rhinovirus/enterovirus (9.5%) and influenza (7.2%). Viral codetection decreased with age, occurring in 4.6% of cases. Comorbidities increase the risk of complications in pediatric respiratory illnesses, however, healthcare utilization is driven largely by otherwise healthy children. Pediatric viral vaccines could reduce this burden and should be further evaluated. [ABSTRACT FROM AUTHOR]

The respiratory syncytial virus (RSV) matrix (M) protein plays an important role in infection as it can interact with viral components as well as the host cell actin microfilaments. The M-actin interaction may play a role in facilitating the transportation of virion components to the apical surface, where RSV is released. We show that M protein's association with actin is facilitated by palladin, an actin-binding protein. Cells were infected with RSV or transfected to express full-length M as a green fluorescent protein (GFP)-tagged protein, followed by removal of nuclear and cytosolic proteins to enrich for cytoskeleton and its associated proteins. M protein was present in inclusion bodies tethered to microfilaments in infected cells. In transfected cells, GFP-M was presented close to microfilaments, without association, suggesting the possible involvement of an additional protein in this interaction. As palladin can bind to proteins that also bind actin, we investigated its interaction with M. Cells were co-transfected to express GFP-M and palladin as an mCherry fluorescenttagged protein, followed by cytoskeleton enrichment. M and palladin were observed to colocalize towards microfilaments, suggesting that palladin is involved in the M-actin interaction. In co-immunoprecipitation studies, M was found to associate with two isoforms of palladin, of 140 and 37 kDa. Interestingly, siRNA downregulation of palladin resulted in reduced titer of released RSV, while cell associated RSV titer increased, suggesting a role for palladin in virus release. Together, our data show that the M-actin interaction mediated by palladin is important for RSV budding and release. [ABSTRACT FROM AUTHOR]

Objective: 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. Methods: 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. Results: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]