The genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus.

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.

Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

BACKGROUND: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. OBJECTIVE: We aim to describe the RSC's plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. METHODS: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA's sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA's reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. RESULTS: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC's pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. CONCLUSIONS: The RSC extended its surveillance activities to meet more but not all of the mosaic framework's objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

Rationale and protocol for a prospective cohort study of respiratory viral infections in patients admitted from emergency departments of community hospitals: Effect of respiratory Virus infection on EmeRgencY admission (EVERY) study.

INTRODUCTION: Respiratory syncytial virus (RSV) is a causative virus for the common cold worldwide and can result in hospitalisations and even death in patients with high-risk conditions and older adults. However, the relationship between RSV or other incidental respiratory infections and acute exacerbations of underlying conditions has not been well investigated. The primary objective of this study is to estimate RSV prevalence, risk factors for adverse outcomes or hospitalisation and their effect on the hospital course of patients with acute respiratory symptoms admitted from emergency departments. Furthermore, we evaluate the prevalence of other respiratory viruses associated with respiratory symptoms. METHODS AND ANALYSIS: We are conducting a multicentre prospective cohort study in Japan. We plan to enrol 3000 consecutive patients admitted from emergency departments with acute respiratory symptoms or signs from 1 July 2023 to 30 June 2024. A nasopharyngeal swab is obtained within 24 hours of admission and the prevalence of RSV and other respiratory viruses is measured using the FilmArray Respiratory 2.1 panel. Paired serum samples are collected from patients with suspected lower respiratory infections to measure RSV antibodies at admission and 30 days later. Information on patients' hospital course is retrieved from the electronic medical records at discharge, death or 30 days after admission. Furthermore, information on readmission to the hospital and all-cause mortality is collected 180 days after admission. We assess the differences in clinical outcomes between patients with RSV or other respiratory viruses and those without, adjusting for baseline characteristics. Clinical outcomes include in-hospital mortality, length of hospital stay, disease progression, laboratory tests and management of respiratory symptoms or underlying conditions. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional review boards of participating hospitals. Our study reports will be published in academic journals as well as international meetings. TRIAL REGISTRATION NUMBER: NCT05913700.

Decreased risk of non-influenza respiratory infection after influenza B virus infection in children.

Previous studies suggest that influenza virus infection may provide temporary non-specific immunity and hence lower the risk of non-influenza respiratory virus infection. In a randomized controlled trial of influenza vaccination, 1 330 children were followed-up in 2009-2011. Respiratory swabs were collected when they reported acute respiratory illness and tested against influenza and other respiratory viruses. We used Poisson regression to compare the incidence of non-influenza respiratory virus infection before and after influenza virus infection. Based on 52 children with influenza B virus infection, the incidence rate ratio (IRR) of non-influenza respiratory virus infection after influenza virus infection was 0.47 (95% confidence interval: 0.27-0.82) compared with before infection. Simulation suggested that this IRR was 0.87 if the temporary protection did not exist. We identified a decreased risk of non-influenza respiratory virus infection after influenza B virus infection in children. Further investigation is needed to determine if this decreased risk could be attributed to temporary non-specific immunity acquired from influenza virus infection.

Genetic characterization of pediatric SARI-associated human adenoviruses in eight Chinese provinces during 2017-2021.

Human adenovirus (HAdV) is a significant viral pathogen causing severe acute respiratory infections (SARIs) in children. To improve the understanding of type distribution and viral genetic characterization of HAdV in severe cases, this study enrolled 3404 pediatric SARI cases from eight provinces of China spanning 2017-2021, resulting in the acquisition of 112 HAdV strains. HAdV-type identification, based on three target genes (penton base, hexon, and fiber), confirmed the diversity of HAdV types in SARI cases. Twelve types were identified, including species B (HAdV-3, 7, 55), species C (HAdV-1, 2, 6, 89, 108, P89H5F5, Px1/Ps3H1F1, Px1/Ps3H5F5), and E (HAdV-4). Among these, HAdV-3 exhibited the highest detection rate (44.6%), followed by HAdV-7 (19.6%), HAdV-1 (12.5%), and HAdV-108 (9.8%). All HAdV-3, 7, 55, 4 in this study belonged to dominant lineages circulating worldwide, and the sequences of the three genes demonstrated significant conservation and stability. Concerning HAdV-C, excluding the novel type Px1/Ps3H1F1 found in this study, the other seven types were detected both in China and abroad, with HAdV-1 and HAdV-108 considered the two main types of HAdV-C prevalent in China. Two recombinant strains, including P89H5F5 and Px1/Ps3H1F1, could cause SARI as a single pathogen, warranting close monitoring and investigation for potential public health implications. In conclusion, 5 years of SARI surveillance in China provided crucial insights into HAdV-associated respiratory infections among hospitalized pediatric patients.

The impact of non-pharmaceutical interventions on community non-SARS-CoV-2 respiratory infections in preschool children.

BACKGROUND: Effects of non-pharmaceutical interventions during the pandemic were mainly studied for severe outcomes. Among children, most of the burden of respiratory infections is related to infections which are not medically attended. The perspective on infections in the community setting is necessary to understand the effects of the pandemic on non-pharmaceutical interventions. METHODS: In the unique prospective LoewenKIDS cohort study, we compared the true monthly incidence of self-reported acute respiratory infections (ARI) in about 350 participants (aged 3-4 years old) between October 2019 to March 2020 (pre-pandemic period) and October 2020 to March 2021 (pandemic period). Parents reported children's symptoms using a diary. Parents were asked to take a nasal swab of their child during all respiratory symptoms. We analysed 718 swabs using Multiplex PCR for 25 common respiratory viruses and bacteria. RESULTS: During the pre-pandemic period, on average 44.6% (95% CI: 39.5-49.8%) of children acquired at least one ARI per month compared to 19.9% (95% CI: 11.1-28.7%) during the pandemic period (Incidence Rate Ratio = 0.47; 95% CI: 0.41-0.54). The detection of influenza virus decreased absolute by 96%, respiratory syncytial virus by 65%, metapneumovirus by 95%, parainfluenza virus by 100%, human enterovirus by 96% and human bocavirus by 70% when comparing the pre-pandemic to the pandemic period. However, rhinoviruses were nearly unaffected by NPI. Co-detection (detection of more than one virus in a single symptomatic swab) was common in the pre-pandemic period (222 of 390 samples with viral detection; 56.9%) and substantially less common during the pandemic period (46 of 216 samples; 21.3%). CONCLUSION: Non-pharmaceutical interventions strongly reduced the incidence of all respiratory infections in preschool children but did not affect rhinovirus.

Multiplex PCR in Diagnosing Respiratory Tract Infections in Hospitalized Children.

OBJECTIVES: To elaborate the utility of multiplex quantitative polymerase chain reaction (multiplex qPCR) for the accurate diagnosis of severe respiratory tract infections (RTIs) in hospitalized children. METHODS: In two separate periods during 2022, 76 respiratory specimens (combined throat/nasopharyngeal swabs) were submitted for multiplex qPCR regarding 26 respiratory pathogens. The specimens were obtained from children with severe RTIs hospitalized in the Institute for Respiratory Diseases in Children, Skopje. RESULTS: Multiplex qPCR detected at least one respiratory pathogen in all examined specimens (76/76), with 83% (63/76) rate of co-infections. Considering that positive results are only the ones with Ct value below 28, the rates of detected pathogens and co-infections decrease to 75% and 22%, respectively. The most commonly detected pathogens during the spring period were Parainfluenza type 3 (PIV3) followed by Adenovirus (AdV) and Respiratory syncytial virus type B (RSVB) with frequency rate of 23%, 19% and 19%, respectively. During the autumn period, the most common were RSVB and Streptococcus pneumoniae with frequency rate of 31% and 17%, respectively. CONCLUSION: Multiplex qPCR is a powerful tool for diagnosing RTIs. Semi-quantification of the viral load by reporting Ct values added higher level of evidence for accurate diagnosis. Seasonal detection of the examined viruses was notable with higher prevalence of PIV3 in spring and RSVB in autumn period.

Respiratory pathogenic microbial infections: a narrative review.

Respiratory infectious diseases have long been recognised as a substantial global healthcare burden and are one of the leading causes of death worldwide, particularly in vulnerable individuals. In the post COVID-19 era, there has been a surge in the prevalence of influenza virus A and other multiple known viruses causing cold compared with during the same period in the previous three years, which coincided with countries easing COVID-19 restrictions worldwide. This article aims to review community-acquired respiratory illnesses covering a broad spectrum of viruses, bacteria, and atypical microorganisms and focuses on the cluster prevalence of multiple known respiratory pathogens in China, thereby providing effective prevention and control measures.

Pre-COVID-19-pandemic RSV epidemiology and clinical burden in pediatric primary care in Italy: a comparative analysis across two regions for the 2019/2020 season.

BACKGROUND: Respiratory syncytial virus (RSV) infection in children under 5 years have a significant clinical burden, also in primary care settings. This study investigates the epidemiology and burden of RSV in Italian children during the 2019/20 pre-pandemic winter season. METHODS: A prospective cohort study was conducted in two Italian regions. Children with Acute Respiratory Infection (ARI) visiting pediatricians were eligible. Nasopharyngeal swabs were collected and analyzed via multiplex PCR for RSV detection. A follow-up questionnaire after 14 days assessed disease burden, encompassing healthcare utilization and illness duration. Statistical analyses, including regression models, explored associations between variables such as RSV subtype and regional variations. RESULTS: Of 293 children with ARI, 41% (119) tested positive for RSV. Median illness duration for RSV-positive cases was 7 days; 6% required hospitalization (median stay: 7 days). Medication was prescribed to 95% (110/116) of RSV cases, with 31% (34/116) receiving antibiotics. RSV subtype B and regional factors predicted increased healthcare utilization. Children with shortness of breath experienced a 36% longer illness duration. CONCLUSIONS: This study highlights a significant clinical burden and healthcare utilization associated with RSV in pre-pandemic Italian primary care settings. Identified predictors, including RSV subtype and symptomatology, indicate the need for targeted interventions and resource allocation strategies. RSV epidemiology can guide public health strategies for the implementation of preventive measures.

Exploring viral aetiology in upper respiratory tract infections: insights from metagenomic next-generation sequencing in Swiss outpatients before and during the SARS-CoV-2 pandemic.

AIMS OF THE STUDY: Upper respiratory tract infections are among the most common reasons for primary care consultations. They are diagnosed predominantly based on clinical assessment. Here, we investigated the benefit of viral metagenomic next-generation sequencing (mNGS) in an outpatient setting. METHODS: This prospective cross-sectional study included immunocompetent patients with acute upper respiratory tract infections. General practitioners collected pharyngeal swabs and demographic and clinical data. Specimens were analysed using viral mNGS and conventional tests. RESULTS: Two hundred seventy-seven patients were recruited by 21 general practitioners between 10/2019 and 12/2020, of which 91% had a suspected viral aetiology. For 138 patients (49.8%), mNGS identified one or more respiratory viruses. The mNGS showed a high overall agreement with conventional routine diagnostic tests. Rhinoviruses were the most frequently detected respiratory viruses (20.2% of patients). Viral mNGS reflected the influenza wave in early 2020 and the SARS-CoV-2 pandemic outbreak in Switzerland in March 2020. Notably, rhinoviruses continued to circulate despite non-pharmaceutical hygiene measures. CONCLUSIONS: Viral mNGS allowed the initial diagnosis to be retrospectively re-evaluated. Assuming reduced turnaround times, mNGS has the potential to directly guide the treatment of upper respiratory tract infections. On an epidemiological level, our study highlights the utility of mNGS in respiratory infection surveillance, allowing early detection of epidemics and providing information crucial for prevention.

Cocirculation and coinfection of multiple respiratory viruses during autumn and winter seasons of 2023 in Beijing, China: A retrospective study.

China experienced severe epidemics of multiple respiratory pathogens in 2023 after lifting "Zero-COVID" policy. The present study aims to investigate the changing circulation and infection patterns of respiratory pathogens in 2023. The 160 436 laboratory results of influenza virus and respiratory syncytial virus (RSV) from February 2020 to December 2023, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from June 2020 to December 2023, Mycoplasma pneumoniae, adenovirus, and human rhinovirus from January 2023 to December 2023 were analyzed. We observed the alternating epidemics of SARS-CoV-2 and influenza A virus (IAV), as well as the out-of-season epidemic of RSV during the spring and summer of 2023. Cocirculation of multiple respiratory pathogens was observed during the autumn and winter of 2023. The susceptible age range of RSV in this winter epidemic (10.5, interquartile range [IQR]: 5-30) was significantly higher than previously (4, IQR: 3-34). The coinfection rate of IAV and RSV in this winter epidemic (0.695%) was significantly higher than that of the last cocirculation period (0.027%) (p < 0.001). Similar trend was also found in the coinfection of IAV and SARS-CoV-2. The present study observed the cocirculation of multiple respiratory pathogens, changing age range of susceptible population, and increasing coinfection rates during the autumn and winter of 2023, in Beijing, China.

Prevalence and genetic diversity of human rhinovirus among patients with acute respiratory infections in China, 2012-2021.

To understand the prevalence of rhinovirus (RV) among acute respiratory infection (ARI) patients, 10-year ARI surveillance in multiple provinces of China were conducted during 2012-2021. Of 15 645 ARI patients, 1180 (7.54%) were confirmed to have RV infection and 820 (69.49%) were children under 5 years of age. RV typing was performed on the 527 VP1 gene sequences, and species A, B, and C accounted for 73.24%, 4.93%, and 21.82%, respectively. Although no significant difference in the proportions of age groups or disease severity was found between RV species, RV-C was more frequently detected in children under 5 years of age, RV-A was more frequently detected in elderly individuals (≥60), and the proportions of pneumonia in RV-A and RV-C patients were higher than those in RV-B patients. The epidemic peak of RV-A was earlier than that of RV-C. A total of 57 types of RV-A, 13 types of RV-B, and 35 types of RV-C were identified in RV-infected patients, and two uncertain RV types were also detected. The findings showed a few differences in epidemiological and clinical features between RV species in ARI patients, and RV-A and RV-C were more prevalent than RV-B.

Effect of housing construction material on childhood acute respiratory infection: a hospital based case control study in Bangladesh.

Despite several studies conducted to investigate housing factors, the effects of housing construction materials on childhood ARI symptoms in Bangladesh remain unclear. Hence, the study aimed to measure such a correlation among children under the age of five. A hospital-based case-control study was conducted, involving 221 cases and 221 controls from January to April 2023. Bivariate and multivariate binary logistic regression was performed to measure the degree of correlation between housing construction materials and childhood ARI symptoms. Households composed of natural floor materials had 2.7 times (95% confidence interval 1.27-5.57) and households composed of natural roof materials had 1.8 times (95% confidence interval 1.01-3.11) higher adjusted odds of having under-five children with ARI symptoms than household composed of the finished floor and finished roof materials respectively. Households with natural wall type were found protective against ARI symptoms with adjusted indoor air pollution determinants. The study indicates that poor housing construction materials are associated with an increased risk of developing ARI symptoms among under-five children in Bangladesh. National policy regarding replacing poor housing materials with concrete, increasing livelihood opportunities, and behavioral strategies programs encouraging to choice of quality housing construction materials could eliminate a fraction of the ARI burden.

Risk Factors for Severe COVID-19 Among Children and Adolescents Enrolled in Acute Respiratory Infection Sentinel Surveillance in South Africa, 2020-2022.

BACKGROUND: Identifying children at risk for severe COVID-19 disease from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may guide future mitigation interventions. Using sentinel surveillance data, we aimed to identify risk factors for SARS-CoV-2-associated hospitalisation among patients aged ≤ 18 years with respiratory illness. METHODS: From April 2020 to March 2022, patients meeting study case definitions were enrolled at four outpatient influenza-like illness (ILI) and five inpatient severe respiratory infection (SRI) surveillance sites and tested for SARS-CoV-2 infection using polymerase chain reaction (PCR). Each ILI clinic shared a catchment area with its corresponding SRI hospital. Potential risk factors for SARS-CoV-2-associated hospitalisation were analysed using multivariable logistic regression by comparing inpatient versus outpatient SARS-CoV-2 cases. RESULTS: Of 4688 participants aged ≤ 18 years, 4556 (97%) with complete PCR and HIV data were included in the analysis. Among patients with ILI and SRI, 92/1145 (8%) and 154/3411 (5%) tested SARS-CoV-2 positive, respectively. Compared to outpatients, hospitalised SARS-CoV-2 cases were associated with age < 6 months ([adjusted odds ratio (aOR) 8.0, 95% confidence interval (CI) 2.7-24.0] versus 1-4 years); underlying medical condition other than HIV [aOR 5.8, 95% CI 2.3-14.6]; laboratory-confirmed Omicron BA.1/BA.2 or Delta variant ([aOR 4.9, 95% CI 1.7-14.2] or [aOR 2.8, 95% CI 1.1-7.3] compared to ancestral SARS-CoV-2); and respiratory syncytial virus coinfection [aOR 6.2, 95% CI 1.0-38.5]. CONCLUSION: Aligning with previous research, we identified age < 6 months or having an underlying condition as risk factors for SARS-CoV-2-associated SRI hospitalisation and demonstrated the potential of sentinel surveillance to monitor COVID-19 in children.

The incidence of upper respiratory infections in children is related to the concentration of vanadium in indoor dust aggregates.

Background: It has been reported that the disease-initiated and disease-mediated effects of aerosol pollutants can be related to concentration, site of deposition, duration of exposure, as well as the specific chemical composition of pollutants. Objectives: To investigate the microelemental composition of dust aggregates in primary schools of Vilnius and determine trace elements related to acute upper respiratory infections among 6-to 11-year-old children. Methods: Microelemental analysis of aerosol pollution was performed using dust samples collected in the classrooms of 11 primary schools in Vilnius from 2016 to 2020. Sites included areas of its natural accumulation behind the radiator heaters and from the surface of high cupboards. The concentrations of heavy metals (Pb, W, Sb, Sn, Zr, Zn, Cu, Ni, Mn, Cr, V, and As) in dust samples were analyzed using a SPECTRO XEPOS spectrometer. The annual incidence rates of respiratory diseases in children of each school were calculated based on data from medical records. Results: The mean annual incidence of physician-diagnosed acute upper respiratory infections (J00-J06 according to ICD-10A) among younger school-age children was between 25.1 and 71.3% per school. A significant correlation was found between vanadium concentration and the number of episodes of acute upper respiratory infections during each study year from 2016 to 2020. The lowest was r = 0.67 (p = 0.024), and the highest was r = 0.82 (p = 0.002). The concentration of vanadium in the samples of dust aggregates varied from 12.7 to 52.1 parts per million (ppm). No significant correlations between the other trace elements and the incidence of upper respiratory infections were found, which could be caused by a small number of study schools and relatively low concentrations of other heavy metals found in the samples of indoor dust aggregates. Conclusion: A significant and replicable correlation was found between the concentration of vanadium in the samples of natural dust aggregates collected in primary schools and the incidence of acute upper respiratory infections in children. Monitoring the concentration of heavy metals in the indoor environment can be an important instrument for the prevention and control of respiratory morbidity in children.

Parental engagement in research on paediatric lower respiratory tract infections in Indonesia.

BACKGROUND: Lower respiratory tract infections (LRTIs) in children are a major concern in Indonesia as it is the leading cause of morbidity and mortality. Therefore, research on LRTIs is crucial to improve children's health. However, clinical research in children is challenging due to parental concerns. This study aims to understand parental considerations for taking part in clinical studies on LRTI in the Indonesian context. METHODS: A cross-sectional study using a validated online questionnaire was conducted from November 2021 to March 2022. This study included parents from two public elementary schools and two private primary schools in Semarang, Indonesia. A total of 1236 responses were analysed. RESULTS: There was a significant association between educational attainment and willingness to participate in general health and LRTI-related research requiring specimen collection; respondents with an advanced educational level were more likely to refuse participation in research. A similar pattern was observed among respondents with smaller families and younger children against participation in LRTI research. Most respondents who indicated not to participate explained that they did not perceive the necessity to take part and expressed their concerns about endangering their child's health as a consequence of the specimen collection. Most respondents expected a personal benefit and prioritized access to the study results for their child. CONCLUSION: Parents' educational background and family composition are important determinants of parental engagement in research on LRTI in Indonesia. Notably, parents with a lower educational level, having large families, and older children were more inclined to participate. The emphasis on concerns about potential harm and personal benefit underscores the need for a targeted communication strategy.

Epidemiology and diagnosis technologies of human metapneumovirus in China: a mini review.

Human metapneumovirus (HMPV) is a newly identified pathogen causing acute respiratory tract infections in young infants worldwide. Since the initial document of HMPV infection in China in 2003, Chinese scientists have made lots of efforts to prevent and control this disease, including developing diagnosis methods, vaccines and antiviral agents against HMPV, as well as conducting epidemiological investigations. However, effective vaccines or special antiviral agents against HMPV are currently not approved, thus developing early diagnosis methods and knowing its epidemiological characteristics will be beneficial for HMPV control. Here, we summarized current research focused on the epidemiological characteristics of HMPV in China and its available detection methods, which will be beneficial to increase the public awareness and disease control in the future.

Respiratory syncytial virus-associated hospitalizations among children: an Italian retrospective observational study.

BACKGROUND: Respiratory syncytial virus (RSV), a single-stranded RNA virus, is a leading cause of hospitalization in infants, especially ≤ 2 months of life. In the light new immunization strategies adoption, we described epidemiological and clinical characteristics of RSV-associated hospitalizations in pediatric and neonatal intensive care units of the Policlinico Foggia Hospital, Apulia Region, Italy. METHODS: Hospitalized children with a laboratory-confirmed RSV infection from 2011 to 2023 were retrospectively evaluated. Clinical information was collected from Hospital Discharge Registry in the period 2011-2020. The proportion of the hospitalization for acute respiratory infections (ARIs) associated to RSV was calculated and the hospitalization cost was analyzed by using the diagnosis-related group reimbursement rate. The anticipated impact of immunization either with monoclonal antibodies or maternal immunization on the number of hospitalizations was estimated. All analyses and quality assessment were performed using STATA/SE15.0. RESULTS: A total of 1,005 RSV-cases were included in the study, of which 86.3% occurred between December-March. In the period 2011-2020, 832 RSV-cases were matched with the corresponding hospital admissions; 75.2% were aged < 1 year (49.6% 0-2 months). Bronchiolitis was the most frequent admission diagnosis occurring in 63.3% of patients; 25% of children were affected by a very severe RSV-disease. Younger age ≤ 2 months (OR:14.8, 95%CI:8.30-26.31, p = 0.000), higher length-of-hospital-stay (OR:1.01, 95%CI:1.0-1.02, p = 0.030) and history of prematurity (OR:4.4, 95%CI:1.57-12.11, p = 0.005) were associated with a higher disease severity. RSV caused 48.9% of ARIs among children < 1 year. The mean cost of an RSV-associated hospitalization was 3,036 euros/year, with the higher cost in the 0-2 months age group (4,225 euros/year). Immunization programs with nirsevimab could prevent 51.4 RSV hospitalizations/year and 18.1 very severe RSV disease/year in infants < 1 year of age. RSV vaccine could prevent 46.1 of hospitalizations/year caused by RSV within 180 days after birth. CONCLUSIONS: Our study contributes to outlining the baseline profile of RSV-associated hospitalizations among Italian children by providing epidemiological/clinical/economic estimates. While awaiting new recommendations on immunization, healthcare-workers should persist in implementing public health measures and appropriate case management to control RSV seasonal epidemics. Strengthened laboratory RSV surveillance is needed to inform the implementation of the new immunization strategies.

Impact of normalized COVID-19 prevention and control measures on lower respiratory tract infection pathogenesis in hospitalized children.

Objective: This study aimed to investigate the epidemiological characteristics of common pathogens contributing to childhood lower respiratory tract infections (LRTIs) in Xiangtan City, Hunan Province before and during the coronavirus disease 2019 (COVID-19) pandemic. Methods: A total of 11,891 enrolled patients, aged 1 month to 14 years, diagnosed with LRTIs and admitted to Xiangtan Central Hospital from January 2018 to December 2021 were retrospectively reviewed in this study. Specifically, the epidemiological characteristics of these pathogens before and during the COVID-19 pandemic were analyzed. Results: There was a significant decrease in the number of children hospitalized with LRTIs during the COVID-19 pandemic (2020-2021) compared to data from 2018 to 2019 (before the COVID-19 pandemic). Of these cases, 60.01% (7,136/11,891) were male and 39.99% (4,755/11,891) were female. 78.9% (9,381/11,891) cases occurred in children under 4 years of age. The average pathogen detection rate among 11,891 hospitalized LRTIs children was 62.19% (7,395/11,891), with the average pathogen detection rate of 60.33% (4,635/7,682) and 65.57% (2,670/4,209) before and during COVID-19 pandemic, respectively. The detection rates of adenovirus (ADV), bordetella pertussis (BP) and moraxella catarrhalis (M. catarrhalis) decreased dramatically, while the detection rates of influenza viruses (IFV), parainfluenza viruses (PIV), respiratory syncytial virus (RSV), haemophilus influenzae (H. influenzae), streptococcus pneumoniae (S. pneumoniae), and staphylococcus aureus (S. aureus) increased significantly during the COVID-19 pandemic. Overall, RSV, mycoplasma pneumoniae (MP), H. influenzae, and IFV were the major pathogens causing LRTIs in hospitalized children before and during the COVID-19 pandemic. Conclusion: Public health interventions for COVID-19 prevention are beneficial to reduce the incidence of LRTIs in children by limiting the prevalence of ADV, MP, BP, and M. catarrhalis, but which have limited restrictive effects on other common LRTIs-associated pathogens. Collectively, the data in this study comprehensively investigated the effects of COVID-19 pandemic on the epidemiological characteristics of respiratory pathogens, which will be beneficial for improving early preventive measures.

No association between disease severity and respiratory syncytial virus subtypes RSV-A and RSV-B in hospitalized young children in Norway.

OBJECTIVE: There is conflicting evidence whether subtypes of Respiratory syncytial virus have different seasonality or are differentially associated with clinical severity. We aimed to explore the associations between disease severity and RSV subtypes RSV-A and RSV-B and to describe the circulation of RSV subtypes pattern by season and age. METHODS: Active prospective hospital surveillance for RSV-A and RSV-B in children <59 months of age was conducted during 2015-2018. All febrile children 12-59 months of age were enrolled, whereas children <12 months were eligible if presenting with fever or respiratory symptoms. Risk factors and upper and lower respiratory tract infection was identified by linkage to national registry data and analyzed using penalized maximum likelihood logistic regression. RESULTS: Both RSV-A and B were found to co-circulate throughout all three study seasons, and no clear seasonal pattern was identified. Likewise, we found no association between sex or measures of severity with RSV-A or RSV-B. There was significantly more RSV-A than RSV-B among children with comorbidities. CONCLUSIONS: No association was found between disease severity or sex and RSV subtypes RSV-A and RSV-B in hospitalized young children in Norway.