Economic Burden of Medically Attended Respiratory Syncytial Virus Infections Among Privately Insured Children Under 5 Years of Age in the USA.

BACKGROUND: The cost of medically attended RSV LRI (lower respiratory infection) is critical in determining the economic value of new RSV immunoprophylaxes. However, most studies have focused on intermittent RSV encounters, not the episode of care that captures the entirety of RSV illness. METHODS: We created age- and condition-specific cohorts of children under 5 years of age using MarketScan® data (2015-2019). We contrasted aggregating healthcare costs over RSV-LRTI episodes to ascertaining costs based on RSV-specific encounters only. Economic burden was estimated by multiplying costs per encounter or per episode by their respective incidence rates. RESULTS: Average cost was higher per episode than per encounter regardless of settings (inpatient: $28,586 vs. $18,056 and outpatient/ED: $2099 vs. $407 for infants). Across ages, the economic burden was highest for infants and RSV-LRTI requiring inpatient care, but the burden in outpatient/ED settings was disproportionately higher than costs due to higher incidence rates (for inpatient vs. outpatient episodes: $226,403 vs. $101,269; for inpatient vs. outpatient encounters: $151,878 vs. $38,819 per 1000 infant-years). For high-risk children, cost and burden were up to 3-10 times higher, respectively. CONCLUSIONS: With a comprehensive stratification by settings and risk condition, the encounter- versus episode-based estimates provide a robust range for policymakers' economic appraisal of new RSV immunoprophylaxes.

Burden of respiratory syncytial virus, human metapneumovirus and influenza virus infections in Japanese adults in the Hospitalized Acute Respiratory Tract Infection study.

BACKGROUND: Respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and influenza virus are responsible for acute respiratory tract infections (ARTIs) in adults. We assessed the clinical burden of RSV, hMPV and influenza virus infection among Japanese adults hospitalized with ARTIs. METHODS: The Hospitalized Acute Respiratory Tract Infection (HARTI) study was a multinational, prospective cohort study in adults with ARTIs across the 2017-2019 epidemic seasons. Enrolment in Japan began in Sept 2018 and ran until Oct 2019. The clinical diagnosis of ARTI and the decision to hospitalize the patient were made according to local standard of care practices. Viral testing was performed by reverse transcription polymerase chain reaction. RESULTS: Of the 173 adults hospitalized with ARTI during this period at the Japan sites, 7 (4.0%), 9 (5.2%), and 11 (6.4%) were positive for influenza virus, RSV, and hMPV, respectively. RSV season was observed from Oct 2018 to Jan 2019, followed by influenza from Dec 2018 to Apr 2019. hMPV was detected across both the RSV and influenza seasons. Two patients with RSV and 1 patient with hMPV required ICU admission whereas none with influenza. Use of antibiotics, bronchodilators and inhaled corticosteroids was high amongst patients with RSV and hMPV at 1, 2, and 3 months' post-discharge compared with patients with influenza, with few exceptions. CONCLUSION: These findings highlight the need for a high degree of clinical suspicion for RSV and hMPV infection in adults hospitalized with ARTIs.

Respiratory Syncytial Virus: Epidemiology, Burden of Disease, and Clinical Update.

Respiratory syncytial virus (RSV) is a common viral pathogen that accounts about 33 million cases of acute lower respiratory tract infection (LRTI) worldwide in children under the age of 5 years each year. High-risk populations, particularly preterm infants, those with underlying chronic lung disease, congenital heart disease, or compromised immune systems, are afflicted most significantly. RSV infection is characterized by significant amount of mucus and submucosal edema in the respiratory tract, leading to congestion and, oftentimes, significant respiratory distress. Antigen- and PCR-based testing are used to diagnose RSV infection.

A single-center, retrospective study of hospitalized patients with lower respiratory tract infections: clinical assessment of metagenomic next-generation sequencing and identification of risk factors in patients.

INTRODUCTION: Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. METHODS: In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). RESULTS: (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis. CONCLUSION: The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.

Why do children under 5 years go to the GP in Lambeth: a cross-sectional study.

OBJECTIVES: This study identifies the most common recorded reason for attendance to primary care for children under 5 years old, including a breakdown via age, ethnicity, deprivation quintile and sex. DESIGN: Cross-sectional. SETTING: 39 of 40 general practices in Lambeth, London, UK. PARTICIPANTS: 22 189 children under 5 years who had attended primary care between the 1 April 2017 and 31 March 2020 and had not opted out of anonymous data sharing within Lambeth DataNet. OUTCOME MEASURE: The primary objective was to identify the most frequently recorded complaint in general practice for children under 5 years old. The secondary objective was to understand how presenting complaint differs by age, ethnicity, sex and deprivation level. The third objective was to create a multivariate logistic regression with frequent attendance as the outcome variable. RESULTS: Nine conditions formed over 50% of all patient interactions: the most common reason was upper respiratory tract infections (14%), followed by eczema (8%) and cough (7%). While there was some variation by ethnicity and age, these nine conditions remained dominant. Children living in the most deprived area are more likely to be frequent attenders than children living in the least deprived area (adjusted OR (AOR) 1.27 (95% CI 1.14 to 1.41)). Children of Indian (AOR 1.47 (1.04 to 2.08)), Bangladeshi (AOR 2.70 (1.95 to 3.74)) and other white (AOR 1.18 (1.04 to 1.34)) ethnicities were more likely to be frequent attenders, compared with those of white British ethnicity. CONCLUSIONS: Most reasons for attendance for children under 5 years to primary care are for acute, self-limiting conditions. Some of these could potentially be managed by increasing access to community care services, such as pharmacies. By focusing on the influence of the broader determinants of health as to why particular groups are more likely to attend, health promotion efforts have the opportunity to reduce barriers to healthcare and improve outcomes.

Electronic Health Record-Based Algorithm for Monitoring Respiratory Virus-Like Illness.

Viral respiratory illness surveillance has traditionally focused on single pathogens (e.g., influenza) and required fever to identify influenza-like illness (ILI). We developed an automated system applying both laboratory test and syndrome criteria to electronic health records from 3 practice groups in Massachusetts, USA, to monitor trends in respiratory viral-like illness (RAVIOLI) across multiple pathogens. We identified RAVIOLI syndrome using diagnosis codes associated with respiratory viral testing or positive respiratory viral assays or fever. After retrospectively applying RAVIOLI criteria to electronic health records, we observed annual winter peaks during 2015-2019, predominantly caused by influenza, followed by cyclic peaks corresponding to SARS-CoV-2 surges during 2020-2024, spikes in RSV in mid-2021 and late 2022, and recrudescent influenza in late 2022 and 2023. RAVIOLI rates were higher and fluctuations more pronounced compared with traditional ILI surveillance. RAVIOLI broadens the scope, granularity, sensitivity, and specificity of respiratory viral illness surveillance compared with traditional ILI surveillance.

Applications of Quantitative Microbial Risk Assessment to Respiratory Pathogens and Implications for Uptake in Policy: A State-of-the-Science Review.

BACKGROUND: Respiratory tract infections are major contributors to the global disease burden. Quantitative microbial risk assessment (QMRA) holds potential as a rapidly deployable framework to understand respiratory pathogen transmission and inform policy on infection control. OBJECTIVES: The goal of this paper was to evaluate, motivate, and inform further development of the use of QMRA as a rapid tool to understand the transmission of respiratory pathogens and improve the evidence base for infection control policies. METHODS: We conducted a literature review to identify peer-reviewed studies of complete QMRA frameworks on aerosol inhalation or contact transmission of respiratory pathogens. From each of the identified studies, we extracted and summarized information on the applied exposure model approaches, dose-response models, and parameter values, including risk characterization. Finally, we reviewed linkages between model outcomes and policy. RESULTS: We identified 93 studies conducted in 16 different countries with complete QMRA frameworks for diverse respiratory pathogens, including SARS-CoV-2, Legionella spp., Staphylococcus aureus, influenza, and Bacillus anthracis. Six distinct exposure models were identified across diverse and complex transmission pathways. In 57 studies, exposure model frameworks were informed by their ability to model the efficacy of potential interventions. Among interventions, masking, ventilation, social distancing, and other environmental source controls were commonly assessed. Pathogen concentration, aerosol concentration, and partitioning coefficient were influential exposure parameters as identified by sensitivity analysis. Most (84%, n=78) studies presented policy-relevant content including a) determining disease burden to call for policy intervention, b) determining risk-based threshold values for regulations, c) informing intervention and control strategies, and d) making recommendations and suggestions for QMRA application in policy. CONCLUSIONS: We identified needs to further the development of QMRA frameworks for respiratory pathogens that prioritize appropriate aerosol exposure modeling approaches, consider trade-offs between model validity and complexity, and incorporate research that strengthens confidence in QMRA results. https://doi.org/10.1289/EHP12695.

Assessment of Illness Severity in Adults Hospitalized With Acute Respiratory Tract Infection due to Influenza, Respiratory Syncytial Virus, or Human Metapneumovirus.

BACKGROUND: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician-rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient-reported outcomes (PROs). METHODS: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ-5D-5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. RESULTS: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between-pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician-rated symptoms. CONCLUSIONS: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well-being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza.

Epidemiological and health economic implications of symptom propagation in respiratory pathogens: A mathematical modelling investigation.

BACKGROUND: Respiratory pathogens inflict a substantial burden on public health and the economy. Although the severity of symptoms caused by these pathogens can vary from asymptomatic to fatal, the factors that determine symptom severity are not fully understood. Correlations in symptoms between infector-infectee pairs, for which evidence is accumulating, can generate large-scale clusters of severe infections that could be devastating to those most at risk, whilst also conceivably leading to chains of mild or asymptomatic infections that generate widespread immunity with minimal cost to public health. Although this effect could be harnessed to amplify the impact of interventions that reduce symptom severity, the mechanistic representation of symptom propagation within mathematical and health economic modelling of respiratory diseases is understudied. METHODS AND FINDINGS: We propose a novel framework for incorporating different levels of symptom propagation into models of infectious disease transmission via a single parameter, α. Varying α tunes the model from having no symptom propagation (α = 0, as typically assumed) to one where symptoms always propagate (α = 1). For parameters corresponding to three respiratory pathogens-seasonal influenza, pandemic influenza and SARS-CoV-2-we explored how symptom propagation impacted the relative epidemiological and health-economic performance of three interventions, conceptualised as vaccines with different actions: symptom-attenuating (labelled SA), infection-blocking (IB) and infection-blocking admitting only mild breakthrough infections (IB_MB). In the absence of interventions, with fixed underlying epidemiological parameters, stronger symptom propagation increased the proportion of cases that were severe. For SA and IB_MB, interventions were more effective at reducing prevalence (all infections and severe cases) for higher strengths of symptom propagation. For IB, symptom propagation had no impact on effectiveness, and for seasonal influenza this intervention type was more effective than SA at reducing severe infections for all strengths of symptom propagation. For pandemic influenza and SARS-CoV-2, at low intervention uptake, SA was more effective than IB for all levels of symptom propagation; for high uptake, SA only became more effective under strong symptom propagation. Health economic assessments found that, for SA-type interventions, the amount one could spend on control whilst maintaining a cost-effective intervention (termed threshold unit intervention cost) was very sensitive to the strength of symptom propagation. CONCLUSIONS: Overall, the preferred intervention type depended on the combination of the strength of symptom propagation and uptake. Given the importance of determining robust public health responses, we highlight the need to gather further data on symptom propagation, with our modelling framework acting as a template for future analysis.

Assessment of effectiveness and impact of universal prophylaxis with nirsevimab for prevention of hospitalizations due to respiratory syncytial virus in infants. The NIRSE-GAL study protocol.

Nirsevimab has been recently licensed for universal RSV prophylaxis in infants. NIRSE-GAL is a three-year population-based study initiated in Galicia in September 2023. It aims to evaluate nirsevimab effectiveness against RSV-related hospitalizations lower respiratory tract infections (LRTI), severe RSV, all-cause LRTI, and all-cause hospitalization. NIRSE-GAL also aims to estimate nirsevimab impact on primary healthcare use in the short and mid-term, children's wheezing and asthma, and medical prescriptions for RSV. The immunization campaigns will be scheduled based on the expected start week for the RSV season and will last the whole season. Immunization will be offered to: i) infants born during the campaign (seasonal), ii) infants < 6 months at the start of the campaign (catch-up), and iii) infants with high-risk factors, aged 6-24 months at the start of the campaign (high-risk). The follow-up period will start: i) the immunization date for all immunized infants, ii) the start of the campaign, for the non-immunized catch-up or high-risk groups, or iii) the birthdate for the non-immunized seasonal group. Infants will be followed up until outcome occurrence, death, or end of study. Nirsevimab effectiveness will be estimated using Poisson and Cox regression models. Sensitivity and stratified analyses will be undertaken. The number of averted cases and the number needed to immunize will be estimated. Immunization failure and nirsevimab safety will be monitored. NIRSE-GAL was approved by the ethics committee of Galicia (CEIC 2023-377) and registered in ClinicalTrials.gov (ID: NCT06180993). Findings will be mainly shared via peer-reviewed publications and scientific conferences.

Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study.

Respiratory viral infections (RVIs) are common reasons for healthcare consultations. The inpatient management of RVIs consumes significant resources. From 2009 to 2014, we assessed the costs of RVI management in 4776 hospitalized children aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by detailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU ('non-ICU') versus management requiring ICU care ('ICU') added up to EUR 2767.14 (non-ICU) vs. EUR 29,941.71 (ICU) for influenza, EUR 2713.14 (non-ICU) vs. EUR 16,951.06 (ICU) for RSV infections, and EUR 2767.33 (non-ICU) vs. EUR 14,394.02 (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all eight RVIs studied: influenza, RSV, hRV, adenovirus (hAdV), metapneumovirus (hMPV), parainfluenza virus (hPIV), bocavirus (hBoV), and seasonal coronavirus (hCoV) infections. ICU costs for influenza, however, exceeded all other RVIs. At the time of the study, influenza was the only RVI with antiviral treatment options available for children, but only 9.8% of influenza patients (non-ICU) and 1.5% of ICU patients with influenza received antivirals; only 2.9% were vaccinated. Future studies should investigate the economic impact of treatment and prevention of influenza, COVID-19, and RSV post vaccine introduction.

Assessment and clinical utility of metagenomic next-generation sequencing for suspected lower respiratory tract infections.

OBJECTIVES: This study aims to compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) to traditional diagnostic methods in patients with lower respiratory tract infections (LRTIs), elucidate the etiological spectrum of these infections, and explore the impact of mNGS on guiding antimicrobial therapy. METHODS: We retrospectively analyzed data from 128 patients admitted to the Respiratory Department of Anqing 116 Hospital between July 2022 and July 2023. All patients had undergone both mNGS and conventional microbiological techniques (CMT) for LRTI diagnosis. We assessed the diagnostic performance of these methods and examined the influence of mNGS on antimicrobial decision-making. RESULTS: Overall, mNGS demonstrated superior sensitivity (96.8%) and accuracy (96.8%) compared to CMT. For Mycobacterium tuberculosis detection, the accuracy and sensitivity of mNGS was 88.8% and 77.6%, which was lower than the 94.7% sensitivity of the T-spot test and the 79.6% sensitivity of CMT. In fungal pathogen detection, mNGS showed excellent sensitivity (90.5%), specificity (86.7%), and accuracy (88.0%). Bacteria were the predominant pathogens detected (75.34%), with Mycobacterium tuberculosis (41.74%), Streptococcus pneumoniae (21.74%), and Haemophilus influenzae (16.52%) being most prevalent. Bacterial infections were most common (62.10%), followed by fungal and mixed infections (17.74%). Of the 118 patients whose treatment regimens were adjusted based on mNGS results, 102 (86.5%) improved, 7 (5.9%) did not respond favorably, and follow-up was lost for 9 patients (7.6%). CONCLUSIONS: mNGS offers rapid and precise pathogen detection for patients with suspected LRTIs and shows considerable promise in diagnosing Mycobacterium tuberculosis and fungal infections. By broadening the pathogen spectrum and identifying polymicrobial infections, mNGS can significantly inform and refine antibiotic therapy.

RSV Disease Burden in Primary Care in Italy: A Multi-Region Pediatric Study, Winter Season 2022-2023.

INTRODUCTION: Human respiratory syncytial virus (RSV) is one of the most frequent causes of respiratory infections in children under 5 years of age, but its socioeconomic impact and burden in primary care settings is still little studied. METHODS: During the 2022/2023 winter season, 55 pediatricians from five Italian regions participated in our community-based study. They collected a nasal swab for RSV molecular test from 650 patients under the age of 5 with acute respiratory infections (ARIs) and performed a baseline questionnaire. The clinical and socioeconomic burden of RSV disease in primary care was evaluated by two follow-up questionnaires completed by the parents of positive children on Days 14 and 30. RESULTS: RSV laboratory-confirmed cases were 37.8% of the total recruited ARI cases, with RSV subtype B accounting for the majority (65.4%) of RSV-positive swabs. RSV-positive children were younger than RSV-negative ones (median 12.5 vs. 16.5 months). The mean duration of symptoms for all children infected by RSV was 11.47 ± 6.27 days. We did not observe substantial differences in clinical severity between the two RSV subtypes, but RSV-A positive patients required more additional pediatric examinations than RSV-B cases. The socioeconomic impact of RSV infection was considerable, causing 53% of children to be absent from school, 46% of parents to lose working days, and 25% of families to incur extra costs. CONCLUSIONS: Our findings describe a baseline of the RSV disease burden in primary care in Italy before the introduction of upcoming immunization strategies.

Value-based comparison of ambulatory children with respiratory diseases in an emergency department and a walk-in clinic: a retrospective cohort study in Québec, Canada.

OBJECTIVE: To compare health outcomes and costs given in the emergency department (ED) and walk-in clinics for ambulatory children presenting with acute respiratory diseases. DESIGN: A retrospective cohort study. SETTING: This study was conducted from April 2016 to March 2017 in one ED and one walk-in clinic. The ED is a paediatric tertiary care centre, and the clinic has access to lab tests and X-rays. PARTICIPANTS: Inclusion criteria were children: (1) aged from 2 to 17 years old and (2) discharged home with a diagnosis of upper respiratory tract infection (URTI), pneumonia or acute asthma. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of patients returning to any ED or clinic within 3 and 7 days of the index visit. The secondary outcome measures were the mean cost of care estimated using time-driven activity-based costing and the incidence of antibiotic prescription for URTI patients. RESULTS: We included 532 children seen in the ED and 201 seen in the walk-in clinic. The incidence of return visits at 3 and 7 days was 20.7% and 27.3% in the ED vs 6.5% and 11.4% in the clinic (adjusted relative risk at 3 days (aRR) (95% CI) 3.17 (1.77 to 5.66) and aRR at 7 days 2.24 (1.46 to 3.44)). The mean cost (95% CI) of care (CAD) at the index visit was $C96.68 (92.62 to 100.74) in the ED vs $C48.82 (45.47 to 52.16) in the clinic (mean difference (95% CI): 46.15 (41.29 to 51.02)). Antibiotic prescription for URTI was less common in the ED than in the clinic (1.5% vs 16.4%; aRR 0.10 (95% CI 0.03 to 0.32)). CONCLUSIONS: The incidence of return visits and cost of care were significantly higher in the ED, while antibiotic use for URTI was more frequent in the walk-in clinic. These data may help determine which setting offers the highest value to ambulatory children with acute respiratory conditions.

Air pollution and upper respiratory diseases: an examination among medically insured populations in Wuhan, China.

Multiple evidence has supported that air pollution exposure has detrimental effects on the cardiovascular and respiratory systems. However, most investigations focus on the general population, with limited research conducted on medically insured populations. To address this gap, the current research was designed to examine the acute effects of inhalable particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), ground-level ozone (O3), and sulfur dioxide (SO2) on the incidence of upper respiratory tract infections (URTI), utilizing medical insurance data in Wuhan, China. Data on URTI were collected from the China Medical Insurance Basic Database for Wuhan covering the period from 2014 to 2018, while air pollutant data was gathered from ten national monitoring stations situated in Wuhan city. Statistical analysis was performed using generalized additive models for quasi-Poisson distribution with a log link function. The analysis indicated that except for ozone, higher exposure to four other pollutants (NO2, SO2, PM2.5, and PM10) were significantly linked to an elevated risk of URTI, particularly during the previous 0-3 days and previous 0-4 days. Additionally, NO2 and SO2 were found to be positively linked with laryngitis. Furthermore, the effects of air pollutants on the risk of URTI were more pronounced during cold seasons than hot seasons. Notably, females and the employed population were more susceptible to infection than males and non-employed individuals. Our findings gave solid proof of the link between ambient air pollution exposure and the risk of URTI in medically insured populations.

Race and Antibiotic Use for Children Hospitalized With Acute Respiratory Infections.

We sought to evaluate whether children hospitalized with acute respiratory infections experienced differences in antibiotic use by race and ethnicity. We found that likelihood of broad-spectrum antibiotic receipt differed across racial and ethnic groups. Future work should confirm this finding, evaluate causes, and ensure equitable antibiotic use.

A robust, scalable, and cost-efficient approach to whole genome sequencing of RSV directly from clinical samples.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections causing significant morbidity and mortality among children and the elderly; two RSV vaccines and a monoclonal antibody have recently been approved. Thus, there is an increasing need for a detailed and continuous genomic surveillance of RSV circulating in resource-rich and resource-limited settings worldwide. However, robust, cost-effective methods for whole genome sequencing of RSV from clinical samples that are amenable to high-throughput are still scarce. We developed Next-RSV-SEQ, an experimental and computational pipeline to generate whole genome sequences of historic and current RSV genotypes by in-solution hybridization capture-based next generation sequencing. We optimized this workflow by automating library preparation and pooling libraries prior to enrichment in order to reduce hands-on time and cost, thereby augmenting scalability. Next-RSV-SEQ yielded near-complete to complete genome sequences for 98% of specimens with Cp values ≤31, at median on-target reads >93%, and mean coverage depths between ~1,000 and >5,000, depending on viral load. Whole genomes were successfully recovered from samples with viral loads as low as 230 copies per microliter RNA. We demonstrate that the method can be expanded to other respiratory viruses like parainfluenza virus and human metapneumovirus. Next-RSV-SEQ produces high-quality RSV genomes directly from culture isolates and, more importantly, clinical specimens of all genotypes in circulation. It is cost-efficient, scalable, and can be extended to other respiratory viruses, thereby opening new perspectives for a future effective and broad genomic surveillance of respiratory viruses. IMPORTANCE: Respiratory syncytial virus (RSV) is a leading cause of severe acute respiratory tract infections in children and the elderly, and its prevention has become an increasing priority. Recently, vaccines and a long-acting monoclonal antibody to protect effectively against severe disease have been approved for the first time. Hence, there is an urgent need for genomic surveillance of RSV at the global scale to monitor virus evolution, especially with an eye toward immune evasion. However, robust, cost-effective methods for RSV whole genome sequencing that are suitable for high-throughput of clinical samples are currently scarce. Therefore, we have developed Next-RSV-SEQ, an experimental and computational pipeline that produces reliably high-quality RSV genomes directly from clinical specimens and isolates.

Global disease burden of and risk factors for acute lower respiratory infections caused by respiratory syncytial virus in preterm infants and young children in 2019: a systematic review and meta-analysis of aggregated and individual participant data.

BACKGROUND: Infants and young children born prematurely are at high risk of severe acute lower respiratory infection (ALRI) caused by respiratory syncytial virus (RSV). In this study, we aimed to assess the global disease burden of and risk factors for RSV-associated ALRI in infants and young children born before 37 weeks of gestation. METHODS: We conducted a systematic review and meta-analysis of aggregated data from studies published between Jan 1, 1995, and Dec 31, 2021, identified from MEDLINE, Embase, and Global Health, and individual participant data shared by the Respiratory Virus Global Epidemiology Network on respiratory infectious diseases. We estimated RSV-associated ALRI incidence in community, hospital admission, in-hospital mortality, and overall mortality among children younger than 2 years born prematurely. We conducted two-stage random-effects meta-regression analyses accounting for chronological age groups, gestational age bands (early preterm, <32 weeks gestational age [wGA], and late preterm, 32 to <37 wGA), and changes over 5-year intervals from 2000 to 2019. Using individual participant data, we assessed perinatal, sociodemographic, and household factors, and underlying medical conditions for RSV-associated ALRI incidence, hospital admission, and three severity outcome groups (longer hospital stay [>4 days], use of supplemental oxygen and mechanical ventilation, or intensive care unit admission) by estimating pooled odds ratios (ORs) through a two-stage meta-analysis (multivariate logistic regression and random-effects meta-analysis). This study is registered with PROSPERO, CRD42021269742. FINDINGS: We included 47 studies from the literature and 17 studies with individual participant-level data contributed by the participating investigators. We estimated that, in 2019, 1 650 000 (95% uncertainty range [UR] 1 350 000-1 990 000) RSV-associated ALRI episodes, 533 000 (385 000-730 000) RSV-associated hospital admissions, 3050 (1080-8620) RSV-associated in-hospital deaths, and 26 760 (11 190-46 240) RSV-attributable deaths occurred in preterm infants worldwide. Among early preterm infants, the RSV-associated ALRI incidence rate and hospitalisation rate were significantly higher (rate ratio [RR] ranging from 1·69 to 3·87 across different age groups and outcomes) than for all infants born at any gestational age. In the second year of life, early preterm infants and young children had a similar incidence rate but still a significantly higher hospitalisation rate (RR 2·26 [95% UR 1·27-3·98]) compared with all infants and young children. Although late preterm infants had RSV-associated ALRI incidence rates similar to that of all infants younger than 1 year, they had higher RSV-associated ALRI hospitalisation rate in the first 6 months (RR 1·93 [1·11-3·26]). Overall, preterm infants accounted for 25% (95% UR 16-37) of RSV-associated ALRI hospitalisations in all infants of any gestational age. RSV-associated ALRI in-hospital case fatality ratio in preterm infants was similar to all infants. The factors identified to be associated with RSV-associated ALRI incidence were mainly perinatal and sociodemographic characteristics, and factors associated with severe outcomes from infection were mainly underlying medical conditions including congenital heart disease, tracheostomy, bronchopulmonary dysplasia, chronic lung disease, or Down syndrome (with ORs ranging from 1·40 to 4·23). INTERPRETATION: Preterm infants face a disproportionately high burden of RSV-associated disease, accounting for 25% of RSV hospitalisation burden. Early preterm infants have a substantial RSV hospitalisation burden persisting into the second year of life. Preventive products for RSV can have a substantial public health impact by preventing RSV-associated ALRI and severe outcomes from infection in preterm infants. FUNDING: EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe.