Respiratory Syncytial Virus Virus Research Articles

Comparison of clinical characteristics and outcomes in hospitalized adult patients infected with respiratory syncytial virus and influenza virus

Background Because patients infected with respiratory syncytial virus (RSV) have been reported to be older than patients infected with influenza virus, the more frequent incidence of complications in RSV-infected patients may be age-related. This study compared clinical characteristics and outcomes in hospitalized adults infected with RSV with findings in age- and sex-matched adults infected with influenza virus. Methods The medical records of hospitalized adult patients infected with RSV or influenza virus at two university hospitals from 2013 to 2022 were retrospectively analyzed. Virus infection was confirmed by real-time polymerase chain reaction. Each RSV-infected patient was matched by age and sex with two influenza virus-infected patients, and their clinical symptoms, laboratory parameters and hospital courses were compared. Results The study cohort consisted of 552 patients, 184 infected with RSV and 368 infected with influenza virus. Fever (71.2% vs. 79.9%, p = .022) and cough (70.1% vs. 80.4%, p = .007) were significantly less frequent in the RSV than in the influenza group, whereas white blood cell counts (9132/mm3 vs. 7616/mm3, p < .001) and C-reactive protein concentrations (10.25 vs. 8.88 mg/dL, p = .029) were significantly higher in the RSV group. The frequency of oxygen therapy was higher (60.3% vs. 48.6%, p = .010) and hospital stay was longer (8 vs. 6 days, p = .003) in RSV than in influenza virus-infected patients. Conclusions Clinical symptoms were less frequent, but disease was more severe, in hospitalized adult patients infected with RSV than in age- and sex-matched patients infected with influenza. Greater attention should be paid to diagnosing and preventing RSV infection in adults.

Epidemiology and Diagnostic Accuracy of Respiratory Pathogens in Pediatric Populations: Insights From Global Studies.

Lower respiratory tract infections (LRTIs) are the most common cause for going to the doctor's at pediatric age. Respiratory infections are still of interest because they are widespread, significantly impact public health by potentially leading to pandemics, drive antimicrobial resistance through antibiotic misuse, more often spread globally due to traveling, and benefit from ongoing advancements in diagnostics and research for better management.This paper's main aim was to offer a systematic review of the literature published over the last 10 years on the etiology of LRTIs. The search strategy was based on reviewing original articles, systematic reviews, position papers, and guidelines published in MEDLINE, EMBASE, Cochrane Library, and PubMed. The review was previously registered with PROSPERO. The final review included 27 articles that met the eligibility criteria (studies identifying the etiology of inferior respiratory infections in children, according to the WHO definition, published in the last 10 years). Statistical analysis was performed using Microsoft Excel Version 2406 (Microsoft Corporation, Redmond, Washington, USA) and SPSS Statistics V.23 (IBM Corp., Armonk, New York, USA). The total number of patients was 2,193,978. Eight articles focused on children younger than five years, and two included children under the age of two.The results revealed that Mycoplasma pneumoniae and respiratory syncytial virus (RSV) are significant respiratory pathogens with seasonal peaks and age-specific prevalence and that nasopharyngeal aspirates (NPAs) are more reliable than throat swabs for confirming infections due to their higher positive predictive value (PPV).The impact of COVID-19 interventions led to reduced infections from RSV, adenovirus, and influenza viruses, but an increase in rhinovirus post-reopening, with high co-infection rates. Co-infections are common, particularly with pathogens like human bocavirus (HBoV) and RSV, underscoring the need for comprehensive diagnostic approaches. The impact of non-pharmaceutical interventions during the COVID-19 pandemic significantly reduced the prevalence of many respiratory pathogens, except for rhinovirus, which increased post-reopening. Understanding these dynamics is crucial for managing respiratory infections, especially in pediatric populations.

Star-shaped flexible arm multivalent aptamers for largely improved virus binding affinity

Here we explore the click chemistry-based synthesis of high affinity multivalent aptamers and their application for virus detection. In contrast to attempts based on rigid constructs, such as aptamer-modified nanoparticles or hybridization-connected constructs, we propose highly flexible “star-shaped” multivalent aptamers to facilitate the cooperative binding to randomly distributed viral proteins on the surface of pleomorphic viruses such as the respiratory syncytial virus (RSV). Polyethylene glycols (PEGs) with 4 azide terminated flexible arms spanning from a pentaerythritol core were conjugated to aptamer strands with dibenzocyclooctyne and a fluorescent label at their, 3’ and 5’ terminus, respectively. By controlling the aptamer - PEG ratio and following electrophoretic separation all the different valency aptamer conjugates could be prepared. For proof of concept, we used an aptamer selected for the G protein of RSV. We show that significantly higher apparent affinities can be obtained by using multivalent aptamers for both the G protein and RSV virus than with the single stranded aptamer, i.e. with up to ca. 2 orders of magnitude. The inherent convenience of synthesizing fluorescently labelled multivalent aptamers leads to a versatile class of affinity ligands for sensing as demonstrated through the improved detection sensitivity of tetravalent aptamer tagged RSV by fluorescence nanoparticle tracking analysis.

Seasonal Patterns of Common Respiratory Viral Infections in Immunocompetent and Immunosuppressed Patients.

Several respiratory viruses have been shown to have seasonal patterns. The aim of our study was to evaluate and compare these patterns in immunocompetent and immunosuppressed patients for five different respiratory viruses. We performed a retrospective analysis of results for 13,591 respiratory tract samples for human metapneumovirus (HMPV), influenza virus, parainfluenza virus (PIV) and respiratory syncytial virus (RSV) in immunocompetent and immunosuppressed patients. A seasonal pattern was aligned to the data of immunocompetent patients through a logistic regression model of positive and negative test results. A narrow seasonal pattern (January to March) was documented for HMPV. Most RSV infections were detected in the winter and early spring months, from December to March, but occasional cases of RSV could be found throughout the year. The peak season for PIV-3 was during the summer months, and that for PIV-4 was mostly in autumn. A narrow seasonal pattern emerged for influenza virus as most infections were detected in the winter, in January and February. The seasonal patterns of HMPV, RSV, PIV, and influenza virus were similar for both immunocompetent and immunocompromised patients. We found no difference in the seasonality of HMPV, RSV, PIV, and influenza virus infections between immunosuppressed and immunocompetent hosts.

Assembly of respiratory syncytial virus matrix protein lattice and its coordination with fusion glycoprotein trimers

Respiratory syncytial virus (RSV) is an enveloped, filamentous, negative-strand RNA virus that causes significant respiratory illness worldwide. RSV vaccines are available, however there is still significant need for research to support the development of vaccines and therapeutics against RSV and related Mononegavirales viruses. Individual virions vary in size, with an average diameter of ~130 nm and ranging from ~500 nm to over 10 µm in length. Though the general arrangement of structural proteins in virions is known, we use cryo-electron tomography and sub-tomogram averaging to determine the molecular organization of RSV structural proteins. We show that the peripheral membrane-associated RSV matrix (M) protein is arranged in a packed helical-like lattice of M-dimers. We report that RSV F glycoprotein is frequently observed as pairs of trimers oriented in an anti-parallel conformation to support potential interactions between trimers. Our sub-tomogram averages indicate the positioning of F-trimer pairs is correlated with the underlying M lattice. These results provide insight into RSV virion organization and may aid in the development of RSV vaccines and anti-viral targets.

Cold-adapted influenza vaccine carrying three repeats of a respiratory syncytial virus (RSV) fusion glycoprotein epitope site protects BALB/c mice and cotton rats against RSV infection

Respiratory syncytial virus is the major cause of respiratory viral infections, particularly in infants, immunocompromised populations, and the elderly (over 65 years old), the prevention of RSV infection has become a priority. In this study, we generated a chimeric influenza virus, termed LAIV/RSV/HA-3F, using reverse genetics technology which contained three repeats of the RSV fusion protein neutralizing epitope site II to the N terminal in the background of the hemagglutinin (HA) gene of cold adapted influenza vaccine A/California/7/2009 ca. LAIV/RSV/HA-3F exhibited cold-adapted (ca) and attenuated (att) phenotype. BALB/c mice immunized intranasally with LAIV/RSV/HA-3F showed robust immunogenicity, inducing viral-specific antibody responses against both influenza and RSV, eliciting RSV-specific humoral, cellular and mucosal immune responses. LAIV/RSV/HA-3F also conferred protection as indicated by reduced viral titers and improved lung histopathological alterations against live RSV virus challenge. Mechanismly, single-cell RNA sequencing (scRNA-seq) and single-cell T cell antigen receptor (TCR) sequencing were employed to characterize the immune responses triggered by chimeric RSV vaccine, displaying that LAIV/RSV/HA-3F provided protection mainly via interferon-γ (IFN-γ). Moreover, we found that LAIV/RSV/HA-3F significantly inhibited viral replication in the challenged lung and protected against subsequent RSV challenge in cotton rats without causing lung disease. Taken together, our findings demonstrated that LAIV/RSV/HA-3F has potential as a promising bivalent vaccine with dual purpose candidate for the prevention of influenza and RSV, and preclinical and clinical studies warrant further investigations.

Respiratory Syncytial Virus-Associated Hospitalizations in Children

The coronavirus disease 2019 pandemic disrupted respiratory syncytial virus (RSV) seasonality resulting in early, atypical RSV seasons in 2021 and 2022, with an intense 2022 peak overwhelming many pediatric healthcare facilities. We conducted prospective surveillance for acute respiratory illness during 2016-2022 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested respiratory specimens for RSV and other respiratory viruses. We estimated annual RSV-associated hospitalization rates in children aged <5 years and compared hospitalization rates and characteristics of RSV-positive hospitalized children over 4 prepandemic seasons (2016-2020) to those hospitalized in 2021 or 2022. There was no difference in median age or age distribution between prepandemic and 2021 seasons. Median age of children hospitalized with RSV was higher in 2022 (9.6 months vs 6.0 months, P < .001). RSV-associated hospitalization rates were higher in 2021 and 2022 than the prepandemic average across age groups. Comparing 2021 to 2022, RSV-associated hospitalization rates were similar among children <2 years of age; however, children aged 24 to 59 months had significantly higher rates of RSV-associated hospitalization in 2022 (rate ratio 1.68 [95% confidence interval 1.37-2.00]). More RSV-positive hospitalized children received supplemental oxygen and there were more respiratory virus codetections in 2022 than in prepandemic seasons (P < .001 and P = .003, respectively), but there was no difference in the proportion hypoxemic, mechanically ventilated, or admitted to intensive care. The atypical 2021 and 2022 RSV seasons resulted in higher hospitalization rates with similar disease severity to prepandemic seasons.

Simultaneous detection of influenza A, B and respiratory syncytial virus in wastewater samples by one-step multiplex RT-ddPCR assay

BackgroundAfter the occurrence of the COVID-19 pandemic, detection of other disseminated respiratory viruses using highly sensitive molecular methods was declared essential for monitoring the spread of health-threatening viruses in communities. The development of multiplex molecular assays are essential for the simultaneous detection of such viruses even at low concentrations. In the present study, a highly sensitive and specific multiplex one-step droplet digital PCR (RT-ddPCR) assay was developed for the simultaneous detection and absolute quantification of influenza A (IAV), influenza B (IBV), respiratory syncytial virus (RSV), and beta-2-microglobulin transcript as an endogenous internal control (IC B2M).ResultsThe assay was first evaluated for analytical sensitivity and specificity, linearity, reproducibility, and recovery rates with excellent performance characteristics and then applied to 37 wastewater samples previously evaluated with commercially available and in-house quantitative real-time reverse transcription PCR (RT-qPCR) assays. IAV was detected in 16/37 (43%), IBV in 19/37 (51%), and RSV in 10/37 (27%) of the wastewater samples. Direct comparison of the developed assay with real-time RT-qPCR assays showed statistically significant high agreement in the detection of IAV (kappa Cohen’s correlation coefficient: 0.834, p = 0.001) and RSV (kappa: 0.773, p = 0.001) viruses between the two assays, while the results for the detection of IBV (kappa: 0.355, p = 0.27) showed good agreement without statistical significance.ConclusionsOverall, the developed one-step multiplex ddPCR assay is cost-effective, highly sensitive and specific, and can simultaneously detect three common respiratory viruses in the complex matrix of wastewater samples even at low concentrations. Due to its high sensitivity and resistance to PCR inhibitors, the developed assay could be further used as an early warning system for wastewater monitoring.

Resurgence of respiratory syncytial virus with dominance of RSV-B during the 2022-2023 season.

Respiratory syncytial virus (RSV) is a common cause of upper and lower respiratory tract infections. This study aimed to explore the prevalence of respiratory syncytial virus (RSV) and other respiratory viruses in Bulgaria, characterize the genetic diversity of RSV strains, and perform amino acid sequence analyses of RSV surface and internal proteins. Clinical and epidemiological data and nasopharyngeal swabs were prospectively collected from patients with acute respiratory infections between October 2020 and May 2023. Real-time PCR for 13 respiratory viruses, whole-genome sequencing, phylogenetic, and amino acid analyses were performed. This study included three epidemic seasons (2020-2021, 2021-2022, and 2022-2023) from week 40 of the previous year to week 20 of the following year. Of the 3,047 patients examined, 1,813 (59.5%) tested positive for at least one viral respiratory pathogen. RSV was the second most detected virus (10.9%) after SARS-CoV-2 (22%). Coinfections between RSV and other respiratory viruses were detected in 68 cases, including 14 with SARS-CoV-2. After two seasons of low circulation, RSV activity increased significantly during the 2022-2023 season. The detection rates of RSV were 3.2, 6.6, and 13.7% in the first, second, and third seasons, respectively. RSV was the most common virus found in children under 5 years old with bronchiolitis (40%) and pneumonia (24.5%). RSV-B drove the 2022-2023 epidemic. Phylogenetic analysis indicated that the sequenced RSV-B strains belonged to the GB5.0.5a and GB5.0.6a genotypes. Amino acid substitutions in the surface and internal proteins, including the F protein antigenic sites were identified compared to the BA prototype strain. This study revealed a strong resurgence of RSV in the autumn of 2022 after the lifting of anti-COVID-19 measures, the leading role of RSV as a causative agent of serious respiratory illnesses in early childhood, and relatively low genetic diversity in circulating RSV strains.

Predictors of Respiratory Syncytial Virus, Influenza Virus, and Human Metapneumovirus Carriage in Children Under 5 Years With WHO-Defined Fast-Breathing Pneumonia in Pakistan.

Pneumonia is a leading cause of morbidity and mortality in children < 5 years. We describe nasopharyngeal carriage of respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus among children with fast-breathing pneumonia in Karachi, Pakistan. We performed a cross-sectional analysis of nasopharyngeal swabs from children aged 2-59 months with fast-breathing pneumonia, enrolled in the randomized trial of amoxicillin versus placebo for fast-breathing pneumonia (RETAPP) (NCT02372461) from 2014 to 2016. Swabs were collected using WHO standardized methods, processed at the Aga Khan University, Pakistan. Viral detection was performed using LUMINEX xTAG respiratory viral panel assay and logistic regression identified clinical and sociodemographic predictors. Of the 1000 children tested, 92.2% (n = 922) were positive for viral carriage. RSV, hMPV, and influenza virus were detected in 59 (6.4%), 56 (6.1%), and 58 (6.3%) children and co-infections in three samples (two RSV-hMPV and one influenza-hMPV). RSV carriage was common in infants (56%), we observed a higher occurrence of fever in children with hMPV and influenza virus (80% and 88%, respectively) and fast breathing in RSV (80%) carriage. RSV carriage was positively associated with a history of fast/difficulty breathing (aOR: 1.96, 95% CI 1.02-3.76) and low oxygen saturation (aOR: 2.52, 95% CI 1.32-4.82), hMPV carriage was positively associated with a complete vaccination status (aOR: 2.22, 95% CI 1.23-4.00) and body temperature ≥ 37.5°C (aOR: 2.34, 95% CI 1.35-4.04) whereas influenza viral carriage was associated with body temperature ≥ 37.5°C (aOR: 4.48, 95% CI 2.53-7.93). We observed a high nasopharyngeal viral carriage among children with WHO-defined fast-breathing pneumonia in Pakistan. Fever, difficulty in breathing, hypoxia and vaccination status areimportant clinical predictors for viral nonsevere community-acquired pneumonia.

Urban wastewater-based epidemiology for multi-viral pathogen surveillance in the Valencian region, Spain

Wastewater-based epidemiology (WBE) has lately arised as a promising tool for monitoring and tracking viral pathogens in communities. In this study, we analysed WBE's role as a multi-pathogen surveillance strategy to detect the presence of several viral illness causative agents. Thus, an epidemiological study was conducted from October 2021 to February 2023 to estimate the weekly levels of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), Respiratory Syncytial virus (RSV), and Influenza A virus (IAV) in influent wastewater samples (n = 69). In parallel, a one-year study (October 2021 to October 2022) was performed to assess the presence of pathogenic human enteric viruses. Besides, monitoring of proposed viral fecal contamination indicators crAssphage and Pepper mild mottle virus (PMMoV) was also assessed, along with plaque counting of somatic coliphages. Genetic material of rotavirus (RV), human astrovirus (HAStV), and norovirus genogroup I (GI) and GII was found in almost all samples, while hepatitis A and E viruses (HAV and HEV) only tested positive in 3.77 % and 22.64 % of the samples, respectively. No seasonal patterns were overall found for enteric viruses, although RVs had a peak prevalence in the winter months. All samples tested positive for SARS-CoV-2 RNA, with a mean concentration of 5.43 log genome copies per liter (log GC/L). The tracking of the circulating SARS-CoV-2 variants of concern (VOCs) was performed by both duplex RT-qPCR and next generation sequencing (NGS). Both techniques reliably showed how the dominant VOC transitioned from Delta to Omicron during two weeks in Spain in December 2021. RSV and IAV viruses peaked in winter months with mean concentrations 6.40 and 4.10 log GC/L, respectively. Moreover, the three selected respiratory viruses strongly correlated with reported clinical data when normalised by wastewater physico-chemical parameters and presented weaker correlations when normalising sewage concentration levels with crAssphage or somatic coliphages titers. Finally, predictive models were generated for each respiratory virus, confirming high reliability on WBE data as an early-warning system and communities illness monitoring system. Overall, this study presents WBE as an optimal tool for multi-pathogen tracking reflecting viral circulation and diseases trends within a selected area, its value as a multi-pathogen early-warning tool stands out due to its public health interest.

Influenza-like illness surveillance may underestimate the incidence of respiratory syncytial virus in adult outpatients

Although respiratory syncytial virus (RSV) is a leading cause of acute respiratory infections (ARIs), it is unclear which of the case definitions that prompt swab collection predicts RSV best. We aimed to profile RSV-positive adults and to identify possible RSV case definitions. This individual-based pooled analysis was based on influenza-like illness (ILI) surveillance conducted among Italian outpatient adults. All samples were tested for influenza, RSV and other respiratory viruses. RSV was detected in 5.2% of the 1240 ILI adults tested. The prevalence of fever/feverishness was significantly lower (83.3%) in individuals positive for RSV and those negative for both viruses (79.4%) than in influenza-positive subjects (96.2%). Conversely, 98.3% of RSV-positive adults reported cough. Compared with subjects who tested negative, the adjusted relative risk ratio of cough in RSV-positive subjects was much higher than in influenza-positive subjects (6.89 vs 2.79). Using ARI with cough as the RSV case definition increased specificity. As fever/feverishness is more common among influenza than RSV cases, ILI-based surveillance may underestimate RSV incidence in adult outpatients. While broad ARI definitions are useful for routine RSV surveillance, their low specificity may hamper vaccine effectiveness studies. The use of further ARI qualifiers like cough increases specificity.

What are the environmental factors that affect respiratory viral pathogen transmission and outcomes? A scoping review of the published literature

IntroductionRespiratory viral pathogens are a major cause of morbidity and mortality, and there is a need to understand how to prevent their transmission.MethodsWe performed a scoping review to assess the amount and scope of published research literature on environmental factors, including meteorological factors and pollution, that affect the transmission of respiratory viral pathogens. We used Joanna Briggs Institute methodology for conducting a scoping review. We searched the electronic databases: MEDLINE, Register of Controlled Trials (Cochrane CENTRAL), TRIP database, WHO Covid-19 Database, Global Index Medicus, LitCovid, medRxiv, and Google Scholar. We included studies on environmental exposures and transmission of respiratory viruses (including but not restricted to: influenza, respiratory syncytial virus (RSV), human coronaviruses, viral pneumonia).ResultsThe searches identified 880 studies for screening; after screening we included 481 studies, including 395 primary studies and 86 reviews. Data were extracted by one reviewer (ES) and independently checked by a second reviewer for accuracy (AP). All primary studies were observational, mostly using an ecological design; 2/395 primary studies were prospective cohorts. Among the primary studies, 241/395 were on SARS-CoV-2/COVID-19; 95 focussed on influenza; the remaining 59 reported on RSV, other coronaviruses, and other respiratory viruses. Exposures were most commonly temperature (306 primary studies) and humidity (201 primary studies); other commonly reported exposures were air pollution, wind speed, precipitation, season, and UV radiation. It was frequently reported, but not consistently, that temperature, humidity and air pollution were positively correlated with COVID-19 cases/deaths; for influenza, season/seasonality was commonly reported to be associated with cases/deaths.DiscussionThe majority of studies reported on SARS-CoV-2/COVID-19 and were of ecological design. Few prospective cohort studies have been done for any respiratory virus and environmental exposures. Understanding the role of environmental factors on transmission is limited by the lack of prospective cohort studies to inform decision making.Systematic Review Registrationhttps://osf.io/ntdjx/, identifier: 10.17605/OSF.IO/NTDJX.

Population-based Influenza and Respiratory Syncytial Virus Hospitalizations and In-hospital Mortality Rates Among Mexican Children Less Than Five Years of Age.

Population-based information regarding the impact of respiratory syncytial virus (RSV) and influenza on hospital admissions and mortality is scant for many countries. Prospective testing of RSV and influenza virus was undertaken in patients <5 years old admitted to hospital with acute respiratory infection (ARI) between July, 2014 and June, 2015, and mortality rates for children living in 3 municipalities in the state of San Luis Potosí were calculated. During the 12-month study period, 790 children living in these municipalities were admitted with ARI. RSV was detected in 245 (31%) and influenza in 47 (5.9%). History of preterm birth was recorded for 112 children on admission. For children <5 years old, ARI-, RSV- and influenza-associated admission rates were 23.2, 7.2 and 1.4 (per 1000 population), respectively. The corresponding admission rates per 1000 infants <1 year old were 78, 25.2 and 4.4. Preterm infant admission rates were 2 times higher than those of term infants. Six children died; RSV was detected in 4 (66.6%) of the deceased, while no deaths were associated with influenza. ARI and RSV in-hospital mortality rates for children <5 years were 0.18 and 0.12 per 1000 population. ARI and RSV mortality rates in preterm infants were 7 and 14 times higher than in term infants, respectively. RSV was associated with both high admission and in-hospital mortality rates in children <5 years old. Specific interventions, such as active or passive immunization, to prevent RSV infections are required to reduce ARI-associated infant mortality.

Respiratory Syncytial Virus-Associated Hospitalizations Among Children

Respiratory syncytial virus (RSV) is the leading cause of hospitalization in US infants. Accurate estimates of severe RSV disease inform policy decisions for RSV prevention. We conducted prospective surveillance for children <5 years old with acute respiratory illness from 2016 to 2020 at 7 pediatric hospitals. We interviewed parents, reviewed medical records, and tested midturbinate nasal ± throat swabs by reverse transcription polymerase chain reaction for RSV and other respiratory viruses. We describe characteristics of children hospitalized with RSV, risk factors for ICU admission, and estimate RSV-associated hospitalization rates. Among 13 524 acute respiratory illness inpatients <5 years old, 4243 (31.4%) were RSV-positive; 2751 (64.8%) of RSV-positive children had no underlying condition or history of prematurity. The average annual RSV-associated hospitalization rate was 4.0 (95% confidence interval [CI]: 3.8-4.1) per 1000 children <5 years, was highest among children 0 to 2 months old (23.8 [95% CI: 22.5-25.2] per 1000) and decreased with increasing age. Higher RSV-associated hospitalization rates were found in premature versus term children (rate ratio = 1.95 [95% CI: 1.76-2.11]). Risk factors for ICU admission among RSV-positive inpatients included: age 0 to 2 and 3 to 5 months (adjusted odds ratio [aOR] = 1.97 [95% CI: 1.54-2.52] and aOR = 1.56 [95% CI: 1.18-2.06], respectively, compared with 24-59 months), prematurity (aOR = 1.32 [95% CI: 1.08-1.60]) and comorbid conditions (aOR = 1.35 [95% CI: 1.10-1.66]). Younger infants and premature children experienced the highest rates of RSV-associated hospitalization and had increased risk of ICU admission. RSV prevention products are needed to reduce RSV-associated morbidity in young infants.

RSV Neutralizing Antibodies in Dried Blood.

The key correlate of protection of respiratory syncytial virus (RSV) vaccines and monoclonal antibodies (mAbs) is virus neutralization, measured via sera obtained through venipuncture. Dried blood obtained with a finger prick can simplify acquisition, processing, storage, and transport in trials and thereby reduce costs. In this study, we validate an assay to measure RSV neutralization in dried capillary blood. Functional antibodies were compared between matched serum and dried blood samples from a phase 1 trial with RSM01, an investigational anti-RSV prefusion F mAb. Hep-2 cells were infected with a serial dilution of sample-virus mixture by using RSV-A2-mKate to determine the half-maximal inhibitory concentration. Stability of dried blood was evaluated over time and during temperature stress. Functional antibodies in dried blood were highly correlated with serum (R2 = 0.98, P < .0001). The precision of the assay for dried blood was similar to serum. The function of mAb remained stable for 9 months at room temperature and frozen dried blood samples. We demonstrated the feasibility of measuring RSV neutralization using dried blood as a patient-centered solution that may replace serology testing in trials against RSV or other viruses, such as influenza and SARS-CoV-2. Clinical Trials Registration. NCT05118386 (ClinicalTrials.gov).

Incidence and causative agent distribution of viral-induced paediatric asthma exacerbations under strict infection control measures: a single-centre retrospective study in Japan

BackgroundThe prevalence of respiratory viruses in children changed under strict infection control measures during the coronavirus disease 2019 (COVID-19) outbreak. In this study, we investigated the frequency of viral detection in the nasopharynx of paediatric patients with asthma exacerbations requiring hospitalization during the COVID-19 pandemic, as well as the distribution of causative viruses.MethodsWe included paediatric patients admitted for asthma exacerbations between November 2020 and December 2022 at a single centre in Kobe, Japan. Demographic, clinical, and laboratory data were collected from their medical records and using additional questionnaires. All patients enrolled in this study met the diagnostic criteria for asthma exacerbations outlined in the Japanese Pediatric Guideline for the Treatment and Management of Bronchial Asthma 2020. Statistical differences were calculated using univariate analyses (chi-square or Mann‒Whitney U test).ResultsWe enrolled 203 children hospitalized for asthma attacks and collected nasopharyngeal samples from 189 patients. The median patient age was 3.0 years. Asthma severity was classified as mild (4.0%), moderate (82.3%), or severe (13.8%). The proportion of viral respiratory infections was 95.2% (180/189). The rate of patients with multiple viral infections was 20.6% (39/189). The most frequently detected pathogens were rhinovirus and enterovirus (RV/EV) at 69.3% (131/189), allowing for duplicate detection, followed by respiratory syncytial virus (RSV) at 28.6% (54/189). We also detected RV/EV almost every month compared to RSV and other viruses. In addition, RV/EV-positive patients were significantly older (p = 0.033), exhibited higher WBC counts (p < 0.001) and higher Eos counts (p < 0.001), had elevated total IgE levels (p < 0.001) and house dust mite-specific IgE levels (p = 0.019), had a shorter duration of hospitalization (p < 0.001), and had a shorter duration of oxygen therapy (p < 0.001). In patients positive for RV/EV, the use of ICSs significantly reduced the severity of the condition (p < 0.001).ConclusionEven under strict infection control measures, respiratory viruses were detected in the nasopharynx of almost all paediatric patients who had asthma exacerbations requiring hospitalization.

Molecular epidemiology and characteristics of respiratory syncytial virus among hospitalized children in Guangzhou, China

BackgroundHuman respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection and hospitalization, especially in children. Highly mutagenic nature and antigenic diversity enable the RSV to successfully survive in human population. We conducted a molecular epidemiological study during 2017–2021 to investigate the prevalence and genetic characteristics of RSV.MethodsA total of 6499 nasopharyngeal (NP) swabs were collected from hospitalized children at Department of Pediatrics, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, Guangdong, China. All NP swab specimens were preliminary screened for common respiratory viruses and then tested for RSV using specific PCR assays. Partial G genes of RSV were amplified for phylogenetic analysis and genetic characterization.ResultsThe overall detection rate for common respiratory viruses was 16.12% (1048/6499). Among those, 405 specimens (6.20%, 405/6499) were found positive for RSV. The monthly distribution of RSV and other respiratory viruses was variable, and the highest incidence was recorded in Autumn and Winter. Based on the sequencing of hypervariable region of G gene, 93 RSV sequences were sub-grouped into RSV-A (56, 60.2%) and RSV-B (37, 39.8%). There was no coinfection of RSV-A and RSV-B in the tested samples. Phylogenetic analysis revealed that RSV-A and RSV-B strains belonged to ON1 and BA9 genotypes respectively, indicating predominance of these genotypes in Guangzhou. Several substitutions were observed which may likely change the antigenicity and pathogenicity of RSV. Multiple glycosylation sites were noticed, demonstrating high selection pressure on these genotypes.ConclusionThis study illustrated useful information about epidemiology, genetic characteristics, and circulating genotypes of RSV in Guangzhou China. Regular monitoring of the circulating strains of RSV in different parts of China could assist in the development of more effective vaccines and preventive measures.

Etiology of placental insufficiency in women in the second trimester of gestation during the epidemic of influenza A(H3N2) and pandemic influenza(H1N1)pdm

Aim. To study the etiology of placental insufficiency in women in the second trimester of gestation during the influenza A(H3N2) epidemic and the A(H1N1)pdm pandemic.Materials and methods. In 1865 patients in the second trimester of pregnancy, uncomplicated and complicated by exacerbation of chronic ENT pathology leading to the development of placental insufficiency, using laboratory methods in the blood, nasal epithelium and biological fluids, pathogens of monoand mixed infections (influenza A(H1N1)pdm), A(H3N2), influenza B, parainfluenza type 1-3, adenovirus, respiratory syncytial virus (RS), cytomegalovirus (CMV), herpes simplex virus type 1 and type 2 (HSV-1,2 type), candida infection (Candida albicans), chlamydia (Chlamydia trachomatis), mycoplasmosis (Mycoplasma hominis) and ureaplasmosis (Ureaplasma urealyticum) were detected. The first group consisted of 873 women with placental insufficiency diagnosed during the influenza A(H3N2) epidemic, the second group consisted of 890 patients with placental insufficiency diagnosed during circulation of the influenza A(H1N1)pdm in the population. The control group were 42 women without ENT diseases and placental insufficiency caused by monoand mixed viral infections during influenza A(H3N2) and 60 women with similar somatic, infectious and obstetric status, examined during pandemic influenza A(H1N1)pdm.Results. With the development of placental insufficiency in women of the second group, compared with the first one, mono-influenza B and parainfluenza types 1-3 are diagnosed less frequently, as well as a combination of influenza A(H1N1) pdm and influenza B; influenza A(H1N1)pdm and parainfluenza types 1-3; influenza A(H1N1)pdm and RS virus; CMV and Chlamydia trachomatis; Mycoplasma hominis and Ureaplasma urealyticum; HSV-1,2 type, Candida albicans and Chlamydia trachomatis; as well as HSV-1,2 type, Candida albicans and Ureaplasma urealyticum. At the same time, exacerbations of mono-CMV, mono-HSV-1,2 type and Candida albicans are more common, as well as combinations of CMV+HSV-1,2 type; CMV+Candida albicans; CMV+Ureaplasma urealyticum; and CMV+Mycoplasma hominis; CMV+HSV-1,2 type+Candida albicans.Conclusion. In the etiology of placental insufficiency in acute diseases of the ENT organs in women in the second trimester of gestation against the background of circulation of the A(H1N1)pdm influenza in the population, compared with placental dysfunction in pregnant women with a similar ENT pathology during the influenza A(H3N2) epidemic, there is an increase in the proportion of monocytomegalovirus, herpesvirus and candida infections, as well as mixed cytomegalovirus infection, the reactivation of which may be due to more pronounced virusinduced immunosuppression and hormonal status disorders, leading to local dysbiosis.

FREQUENCY OF BRONCHIOLITIS IN INFANTS TREATED AT THE CHILDREN'S DISEASE CLINIC, BANJALUKA IN THE 2022/2023 SEASON

haracteristics of infants with bronchiolitis diagnosed in the Banja Luka Children's Hospital in the 2022/2023 season. Methods: Prospectivelly – retrospectively we analyzed data from medical records. Results: In the period from November 2022 to the end of February 2023, Children’s Diseases Clinic in Banja Luka treated 81 infants with bronchiolitis. Out of 81 infants, 19 had a proven respiratory syncytial virus (RSV). Infant boys were more affected than grils. We treated the most children in January. The median age for infants was two months old. Conclusion: Infection with RSV virus complicates the clinical state and prolongs the duration of treatment. The therapeutic approach is individual and depends on the severity of the clinical characteristics. Given that it is an infection that can be prevented by the use of Palivizumab, we believe that there is a justified extension of the indications for its use as a mandatory vaccine in the Republic of Srpska.