Respiratory Syncytial Virus Infection Research Articles

Effects of nonpharmaceutical interventions during COVID-19 pandemic on pediatric asthma exacerbations and viral infections

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in March 2020 led to the implementation of nonpharmaceutical interventions (NPIs) to curb its spread. Studies have shown that adult asthma exacerbations and viral infections decreased during NPI use. However, few studies have shown the effects of NPIs on pediatric asthma exacerbations and infections during and after the pandemic. This study aimed to understand the impact of NPIs on asthma exacerbations and viral respiratory infections in pediatric patients at our institution from March 2018 to December 2022. The medical record numbers of children with asthma exacerbations seen at our institution between March 2018 and December 2022 were analyzed. Subjects were categorized on the basis of timing of their exacerbation in relation to NPI enforcement. We used the results from clinical testing with the BioFire Respiratory Panel (BRP) to detect up to 22 respiratory pathogens and then correlated these results with asthma exacerbation severity. There were 5,758 asthma exacerbations recorded, with a 50% decline in average weekly exacerbations during NPI enforcement. Of the 70,682 BRP tests performed, 87% returned a positive result for at least 1 pathogen. Several viruses (respiratory syncytial virus, parainfluenza, and influenza) had a decrease in positivity rate with NPIs, whereas rhinovirus/enterovirus positivity rates were unchanged throughout the pandemic. Asthma exacerbations with a positive BRP result required higher clinical levels of care during the admission. NPIs were associated with significantly reduced numbers of asthma exacerbations and respiratory viral infections. The post-NPI period saw a return to prepandemic levels of asthma exacerbations and an unusual surge in respiratory syncytial virus infections, emphasizing the need for continuous monitoring and adaptive strategies in the postpandemic landscape.

The severity of respiratory syncytial virus infection in children during the SARS-CoV-2/COVID-19 pandemic: A nationwide study of 11,915 cases in Germany.

Respiratory syncytial virus (RSV) infection is a major cause of childhood hospitalization. The COVID-19 pandemic has disrupted the usual seasonal pattern of RSV, resulting in high activity during the off-season. This study aims to evaluate the effects of the pandemic on the severity of RSV infections. Data from 11,915 children hospitalized due to RSV infection between 2016 and 2022 were analyzed. The hospitalized patients were categorized into two groups, from January2016 to February 2020 (PreCoV19 group) and from March 2020 to December 2022 (CoV19 group). The hospitalization duration, intensive care unit (ICU) admissions, length of stay at ICU, mechanical ventilation requirement and duration, Elixhauser comorbidity index scores, and in-hospital mortality were analyzed. Children in the PreCoV19 group had a mean age of 0.4 ± 0.7, whereas those in the CoV19 group had a mean age of 0.6 ± 1.0 years. Children during the pandemic had significantly shorter hospital stays (4.3 ± 2.6 days) compared to children of the pre-pandemic period (4.9 ± 3.3 days). Although ICU admission rates did not change, the duration of ICU stays decreased in the CoV19 group. Moreover, the in-hospital mortality did not differ between the groups. A multivariable analysis showed that younger age, regardless of the pandemic period, was associated with prolonged hospital stays, higher ICU admission rates, and an increased requirement for mechanical ventilation. Our findings highlight significant changes of the clinical characteristics of RSV infections during the pandemic, with implications for clinical management and public health strategies.

Impact of Child Respiratory Syncytial Virus-Confirmed Infections on Caregivers in Japan: A Web-Based Survey.

Background/Objectives: Despite being the leading cause of acute lower respiratory tract infections in infants, the impact of respiratory syncytial virus (RSV) on the caregivers of infected children remains largely unexplored. This study is the first in Japan to examine the psychological, social, and economic burdens on caregivers of infants infected with RSV. Methods: An online questionnaire survey was used to understand the circumstances surrounding RSV infection and the psychological, social, and economic burdens on caregivers. Equal numbers of infants aged either <6 or ≥6 months were enrolled. Results: A total of 606 caregivers were included in the final analysis. Notably, 36.1% of the infants were hospitalized. Most caregivers (91.4%) felt anxious about their infants' RSV infection, and more than half (55.8%) answered that their anxiety interfered with their daily lives. Caregivers whose daily routines were disrupted due to concerns about RSV infection were more likely to hospitalize infants, particularly for extended stays. Infection significantly affected family dynamics, hindering normal daily activities and escalating stress, which in turn led to conflicts and arguments among family members (30.4%). Regarding the financial burden, most caregivers incurred medical expenses (34.2%). Additionally, 76.9% of caregivers expressed interest in the hypothetical RSV vaccination. Conclusions: In Japan, caregivers of infants with RSV experience had significant psychological burden regardless of whether the treatment is outpatient or inpatient. In addition, a non-negligible proportion of caregivers suffer from societal and economic burdens. This study lays the groundwork for all stakeholders to fully comprehend the comprehensive disease burden of child RSV infections.

Epidemiological characteristics of human respiratory syncytial virus infection in febrile respiratory syndrome cases in China from 2010 to 2020

Objective: To analyze the epidemiological characteristics of human respiratory syncytial virus (HRSV) in cases of febrile respiratory syndrome in China from 2010 to 2020. Methods: Based on the sub-project of the National Science and Technology Major Project for Infectious Disease Prevention and Control "Infectious Disease Monitoring Technology Platform", active monitoring of febrile respiratory syndrome cases was conducted in sentinel hospitals in 31 provinces across China (excluding Hong Kong, Macau, and Chinese Taiwan) from January 2010 to December 2020, resulting in the inclusion of 191 441 cases. Clinical specimens of monitored cases were screened for HRSV nucleic acid, and the differences in HRSV detection rates among different age groups, regions, and time periods were analyzed using the χ2 test/Fisher exact probability method. Results: Among the 191 441 cases of febrile respiratory syndrome in China from 2010 to 2020, the age group M (Q1, Q3) was 9 (2, 40) years old, with 83 773 cases (43.8%) in the <5 years old group. There were 113 660 males, with a male-to-female ratio of 1.5∶1.0. There were as many as 105 508 cases (55.2%) of scattered children and preschool children. About 70 565 cases (36.9%) lived in the northern region. There were 13 858 HRSV positive cases, with a total positive rate of 7.2%. The positive rate of HRSV detection in the northern population was 5.7% (4 004/70 565), which was lower than that in the southern population (8.2%, 9 854/120 876), and the difference was statistically significant (χ2=407.4, P<0.001). HRSV was detected in all age groups, with the highest positive rate of 23.9% in the <6 months age group. The month with the highest positive rate was December, and autumn and winter were the main epidemic seasons. Both northern and southern HRSV subtypes were mainly infected with type A, with a low proportion of mixed infections of type A and type B. Conclusion: HRSV is a common pathogen causing respiratory infections in children from 2010 to 2020. It can be detected throughout the year and shows the main peak of prevalence in autumn and winter. The HRSV strain is mainly classified as a type A infection.

The cost of care for children hospitalized with respiratory syncytial virus (RSV) associated lower respiratory infection in Kenya

BackgroundRespiratory syncytial virus (RSV) is one of the main causes of hospitalization for lower respiratory tract infection in children under five years of age globally. Maternal vaccines and monoclonal antibodies for RSV prevention among infants are approved for use in high income countries. However, data are limited on the economic burden of RSV disease from low- and middle-income countries (LMIC) to inform decision making on prioritization and introduction of such interventions. This study aimed to estimate household and health system costs associated with childhood RSV in Kenya.MethodsA structured questionnaire was administered to caregivers of children aged < 5 years admitted to referral hospitals in Kilifi (coastal Kenya) and Siaya (western Kenya) with symptoms of acute lower respiratory tract infection (LRTI) during the 2019–2021 RSV seasons. These children had been enrolled in ongoing in-patient surveillance for respiratory viruses. Household expenditures on direct and indirect medical costs were collected 10 days prior to, during, and two weeks post hospitalization. Aggregated health system costs were acquired from the hospital administration and were included to calculate the cost per episode of hospitalized RSV illness.ResultsWe enrolled a total of 241 and 184 participants from Kilifi and Siaya hospitals, respectively. Out of these, 79 (32.9%) in Kilifi and 21(11.4%) in Siaya, tested positive for RSV infection. The total (health system and household) mean costs per episode of severe RSV illness was USD 329 (95% confidence interval (95% CI): 251–408 ) in Kilifi and USD 527 (95% CI: 405– 649) in Siaya. Household costs were USD 67 (95% CI: 54–80) and USD 172 (95% CI: 131– 214) in Kilifi and Siaya, respectively. Mean direct medical costs to the household during hospitalization were USD 11 (95% CI: 10–12) and USD 67 (95% CI: 51–83) among Kilifi and Siaya participants, respectively. Observed costs were lower in Kilifi due to differences in healthcare administration.ConclusionsRSV-associated disease among young children leads to a substantial economic burden to both families and the health system in Kenya. This burden may differ between Counties in Kenya and similar multi-site studies are advised to support cost-effectiveness analyses.

Examining intra-host genetic variation of RSV by short read high-throughput sequencing.

Every viral infection entails an evolving population of viral genomes. High-throughput sequencing technologies can be used to characterize such populations, but to date there are few published examples of such work. In addition, mixed sequencing data are sometimes used to infer properties of infecting genomes without discriminating between genome-derived reads and reads from the much more abundant, in the case of a typical active viral infection, transcripts. Here we apply capture probe-based short read high-throughput sequencing to nasal wash samples taken from a previously described group of adult hematopoietic cell transplant (HCT) recipients naturally infected with respiratory syncytial virus (RSV). We separately analyzed reads from genomes and transcripts for the levels and distribution of genetic variation by calculating per position Shannon entropies. Our analysis reveals a low level of genetic variation within the RSV infections analyzed here, but with interesting differences between genomes and transcripts in 1) average per sample Shannon entropies; 2) the genomic distribution of variation 'hotspots'; and 3) the genomic distribution of hotspots encoding alternative amino acids. In all, our results suggest the importance of separately analyzing reads from genomes and transcripts when interpreting high-throughput sequencing data for insight into intra-host viral genome replication, expression, and evolution.

Respiratory Syncytial Virus Infections in Pediatric Intensive Care: Association of Sociodemographic Data and Clinical Outcomes with Viral and Bacterial Co-infections.

The aim of the study was to evaluate respiratory syncytial virus (RSV) infections in cases followed in the pediatric intensive care unit (PICU). The study was designed as a prospective cohort in 6 PICUs. There were 3 groups: only RSV (+), RSV (v+) who were positive for another viral agent(s) in addition to RSV, and RSV (b+) who were positive for a bacterial agent(s) in addition to RSV. A total of 119 cases were included in the study, 67 (56.3%) of whom were male. The RSV (+) group had a lower pH compared to the other groups and a higher rate of acute bronc hiolitis/bronchitis diagnoses compared to the RSV (v+) group. The RSV (v+) group had higher bicarbonate levels, higher creatinine levels, longer hospital stays, and higher Pediatric Risk of Mortality-3 scores (PRISM-3) compared to the RSV (+) group. Cases with RSV (b+) were younger and also had lower body weight compared to the other groups. Furthermore, the RSV (b+) group had higher C-reactive protein and Procalcitonin (PCT) levels and higher rates of High Flow Nasal Cannula-Oxygen Therapy (HFNC-OT) use. Multiple linear regression analysis revealed that PRISM-3 score, PCT levels, Pediatric Acute Respiratory Distress Syndrome diagnoses, inhaled steroid use, chronic illness status, and heart rate on admission were associated with the length of stay in the PICU. High flow nasal cannula-oxygen therapy continues to be the most frequently preferred respiratory support method in RSV infections. Viral infections accompanying RSV can increase the severity of the disease.

Changes in the epidemiological patterns of respiratory syncytial virus and human metapneumovirus infection among pediatric patients and their correlation with severe cases: a long-term retrospective study.

We aim to investigate the prevalence of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) among pediatric patients with acute respiratory tract illness (ARTI) in southern China both pre- and post-COVID-19 pandemic, as well as identify associated risk factors for severe infections. The study conducted a real-time PCR analysis on hospitalized children with ARTI from 2012 to 2023, specifically targeting RSV, hMPV, and other respiratory pathogens. Additionally, demographic data was collected during this analysis. The prevalence of RSV occurs triennially, and likewise, the temporal pattern of hMPV outbreaks mirrors that of RSV. The peak infection rates of RSV and hMPV occurred during and following the implementation of COVID-19 epidemic prevention and control measures. The incidence of RSV infection exhibited bimodal peaks in 2022, while hMPV demonstrated seasonal peaks during the spring, fall, and winter periods post-COVID-19 pandemic. After the COVID-19 outbreak, there has been an upward trend in the proportion of female patients and patients aged one year and older presenting with ARTI, RSV infections, and hMPV infections. Infant (OR = 4.767, 95%CI: [3.888-5.846], p < 0.0001), presence of co-infection (OR = 0.540, 95%CI: [0.404-0.722], p < 0.0001), and existence of comorbidities (OR = 1.582, 95%CI: [1.285-1.949], p < 0.0001) was the risk ratio for the severity of RSV infection. Children infected with hMPV under the age of 1 year (OR = 0.322, 95%CI: [0.180 - 0.575], p < 0.0001), as well as those with comorbidities (OR = 8.809, 95%CI: [4.493 - 17.272], p < 0.0001), have a higher risk of developing severe illness. The changing epidemiological patterns have the potential to lead to widespread severe outbreaks among children, particularly those with underlying medical conditions who may experience more severe symptoms. Conducting surveillance for pneumoviridae viruses in children is an imperative measure to establish a robust foundation for future epidemic prevention and treatment strategies.

Association of SNP-SNP interactions of surfactant protein genes with severity of respiratory syncytial virus infection in children.

The severity of respiratory syncytial virus (RSV) may be linked to host genetic susceptibility. Surfactant protein (SP) genetic variants have been associated with RSV severity, but the impact of single-nucleotide polymorphism (SNP)-SNP interactions remains unexplored. Therefore, we used a novel statistical model to investigate the association of SNP-SNP interactions of SFTP genes with RSV severity in two- and three-interaction models. We analyzed available genotype and clinical data from prospectively enrolled 405 children diagnosed with RSV, categorizing them into moderate or severe RSV groups. Using Wang's statistical model, we studied significant associations of SNP-SNP interactions with RSV severity in a case-control design. We observed, first, association of three interactions with increased risk of severe RSV in a two-SNP model. One intragenic interaction was between SNPs of SFTPA2, and the other two were intergenic, involving SNPs of hydrophilic and hydrophobic SPs alone. We also observed, second, association of 22 interactions with RSV severity in a three-SNP model. Among these, 20 were unique, with 12 and 10 interactions associated with increased or decreased risk of RSV severity, respectively, and included at least one SNP of either SFTPA1 or SFTPA2. All interactions were intergenic except one, among SNPs of SFTPA1. The remaining interactions were either among SNPs of hydrophilic SPs alone (n = 8) or among SNPs of both hydrophilic or hydrophobic SPs (n = 11). Our findings indicate that SNPs of all SFTPs may contribute to genetic susceptibility to RSV severity. However, the predominant involvement of SFTPA1 and/or SFTPA2 SNPs in these interactions underscores their significance in RSV severity.NEW & NOTEWORTHY Although surfactant protein (SP) genetic variants are associated with respiratory syncytial virus (RSV) severity, the impact of single-nucleotide polymorphism (SNP)-SNP interactions of SP genes remained unexplored. Using advanced statistical models, we uncovered 22 SNP-SNP interactions associated with RSV severity, with notable involvement of SFTPA1 and SFTPA2 SNPs. This highlights the comprehensive role of all SPs in genetic susceptibility to RSV severity, shedding light on potential avenues for targeted interventions.

Burden of Respiratory Syncytial Virus (RSV) Infection Among Adults in Nursing and Care Homes: A Systematic Review.

Older adults in nursing and care homes (NCHs) are vulnerable to severe respiratory syncytial virus (RSV) infection, hospitalization, and death. This study aimed to gather data on RSV disease among older adults in NCHs and identify reported risk factors for RSV hospitalization and case fatality. The study protocol was registered in PROSPERO (CRD42022371908). We searched MEDLINE, EMBASE, and Global Health databases to identify articles published between 2000 and 2023. Observational and experimental studies conducted among older adults in NCHs requiring assistive care and reporting RSV illness were included and relevant data were extracted. Of 18,690 studies screened, 32 were selected for full-text review, and 20 were included. Overall, the number of NCH residents ranged from 42 to 1459 with a mean age between 67.6 and 85 years. Attack rates ranged from 6.7% to 47.6% and annual incidence ranged from 0.5% to 14%. Case fatality rates ranged from 7.7% to 23.1%. We found similar annual incidence rates of RSV-positive acute respiratory infection (ARI) of 4582 (95% CI: 3259-6264) and 4785 (95% CI: 2258-10,141) per 100,000 reported in two studies. Annual incidence rate of RSV-positive lower respiratory tract infection was 3040 (95% CI: 1986-4454) cases per 100,000 adults. Annual RSV-ARI hospital admission rates were between 600 (95% CI: 190-10,000) and 1104 (95% CI: 350-1930) per 100,000 person-years. Among all RSV disease cases, commonly reported chronic medical conditions included chronic obstructive pulmonary disease (COPD), heart failure, ischemic heart disease, coronary artery disease, hypertension, diabetes, kidney dysfunction, cerebrovascular accident, malignancies, dementia, and those with a Charlson comorbidity score > 6.5. Data on RSV infection among NCH residents are limited and largely heterogeneous but document a high risk of illness, frequent hospitalization, and high mortality. Preventive interventions, such as vaccination, should be considered for this high-risk population. Nationally representative epidemiologic studies and NCH-based viral pathogen surveillance could more precisely assess the burden on NCH residents.

Systematic Review of the Efficacy and Safety of RSV-Specific Monoclonal Antibodies and Antivirals in Development.

Respiratory syncytial virus (RSV) is a leading cause of acute respiratory infection amongst all ages, causing a significant global health burden. Preventative and therapeutic options for RSV infection have long been under development, and recently, several widely-publicised vaccines targeting older adult and maternal populations have become available. Promising monoclonal antibody (mAb) and antiviral (AV) therapies are also progressing in clinical trials, with the prophylactic mAb nirsevimab recently approved for clinical use in infant populations. A systematic review on current progress in this area is lacking. We performed a systematic literature search (PubMed, Embase, Web of Science, ClinicalTrials.gov, EudraCT, ANZCTR-searched Nov 29th, 2023) to identify studies on all RSV-specific mAbs and AV therapies that has undergone human clinical trials since year 2000. Data extraction focused on outcomes related to the therapeutic efficacy and safety of the intervention on trial, and all studies were graded against the OCEBM Levels of Evidence Table. Results from 59 studies were extracted, covering efficacy and safety data on six mAbs (motavizumab, motavizumab-YTE, nirsevimab, ALX-0171, suptavumab, clesrovimab) and 12 AV therapies (ALN-RSV01, RSV604, presatovir, MDT-637, lumicitabine, IFN-α1b, rilematovir, enzaplatovir, AK0529, sisunatovir, PC786, EDP-938). Of the mAbs reviewed, nirsevimab and clesrovimab hold considerable promise. The timeline for RSV-specific AV availability is less advanced, although EDP-938 and AK0529 have reported promising phase 2 efficacy and safety data. Moving forward, passive immunisation and treatment options for RSV infection will play a significant role in reducing the health burden of RSV, complementing recent advancements in vaccine development. TRIAL REGISTRATION: PROSPERO registration: CRD42022376633.

Adult Respiratory Syncytial Virus Infection: Defining Incidence, Risk Factors for Hospitalization, and Poor Outcomes, a Regional Cohort Study, 2016-2022.

Respiratory syncytial virus (RSV) is a significant cause of illness in adults, especially older adults and those with underlying conditions. This study aimed to assess the incidence of RSV hospitalizations in adults and identify risk factors for hospitalization and poor outcomes. A retrospective cohort study was conducted using data from two hospitals in southern Israel from 2016-2022. We calculated incidence rates of RSV and influenza hospitalizations. Risk factors for hospitalization were analyzed using Poisson regression. We evaluated poor outcomes (death, ICU admission, or mechanical ventilation) among RSV-hospitalized patients. The median annual incidence of RSV hospitalization was 28.2/100,000 population, increasing with age to 199/100,000 in those ≥75 years. Significant risk factors for RSV hospitalization included pulmonary diseases (RR 4.2, 95% CI 3.4-5.2), cardiovascular diseases (RR 3.3, 95% CI 2.6-4.2), and chronic renal failure (RR 2.9, 95% CI 2.3-3.7). Among hospitalized RSV patients, 13.9% had poor outcomes. Renal failure (RR 1.81, 95% CI 1.23-2.66), neutropenia (RR 2.53, 95% CI 1.19-5.35), neutrophilia (RR 1.66, 95% CI 1.81-2.34), and lymphopenia (RR 2.03, 95% CI 1.37-3.0) were associated with poor outcomes. RSV causes a substantial burden of hospitalizations in adults, particularly among older adults and those with comorbidities. Identifying high-risk groups can help target prevention and treatment strategies, including vaccination.

Analysis of the epidemic characteristics of common respiratory pathogens infection in children in a 3A special hospital

ObjectiveTo analyze the epidemic characteristics of common respiratory tract infection pathogens in children with respiratory tract infection, and provide scientific basis for the prevention and control of respiratory tract infection.MethodsA retrospective collection of clinical data was conducted on 11,538 children with respiratory tract infections at Luoyang Maternal and Child Health Hospital from December 2022 to November 2023. The types of respiratory tract infections, including upper and lower respiratory tract infections, as well as five respiratory pathogens: influenza A virus (influenza A), influenza B virus (influenza B virus, adenovirus (ADV), respiratory syncytial virus (RSV), and Mycoplasma pneumoniae (MP) infections, were analyzed and compared for different genders, ages, temperatures, and air quality in different months; And the changes of five pathogens in children with respiratory tract infections of different disease severity.ResultsFrom December 2022 to November 2023, a total of 11,538 children with respiratory infections were included in the analysis, including 6436 males and 5102 females, with an age of 4.92 ± 2.03 years. The proportion of upper respiratory tract infections is as high as 72.17%, and lower respiratory tract infections account for 27.83%. Among them, 2387 were positive for Flu A antigen, with a positive rate of 20.69%, 51 cases were positive for Flu B antigen, and the positive rate was 0.4%, 1296 cases were positive for adv antigen, with a positive rate of 11.23%, 868 cases were positive for RSV antigen, with a positive rate of 7.52%, 2481 cases were positive for MP IgM antibody or MP antigen, and the positive rate was 21.50%. Flu B in male children The infection rate of ADV and MP was higher than that of female children (p < 0.05); Among children in different age groups, the older the age, the older the Flu A The higher the infection rate of MP (p < 0.05), the higher the positive rate of RSV in children with younger age (p < 0.05). The positive rate of ADV in children aged 3–6 years and > 6 years was higher than that in children aged 0–3 years (p < 0.05); Flu A and MP are popular throughout the year, and the positive rate peaks during the period of temperature rise and air quality decline from February to March, and during the period of temperature drop and air quality index rise from August to November, The positive rate of RSV peaked after the turning point of temperature rise from March to April. The infection rate was higher during the period of sharp decline in air quality from March to May and sharp decline in temperature in November, The positive rate of ADV was higher at the turning point of temperature rise from February to March, and then the infection rate decreased. During the period of sharp temperature drop from August to November, the positive rate increased sharply, and the peak of infection occurred; As the disease worsens, The positive rates of Flu A, Flu B, RSV, MP and combined infection with more than two pathogens were all increased (p < 0.05).ConclusionAfter the new coronavirus epidemic in 2022, Flu A and MP have the highest infection rate of respiratory pathogens in children, showing a peak growth in general, with epidemic characteristics changing with environmental temperature, air quality and seasons. The main disease type is upper respiratory tract infection, MP and adv infections were mainly in male children, Flu A, MP and ADV infections are more common in older children, RSV infection was more common in younger children; Flu A, Flu B, RSV and MP infection and the co infection of more than two pathogens may more easily lead to the occurrence of severe pneumonia.

Respiratory syncytial virus infection among children younger than 2 years admitted to a paediatric intensive care unit with extended severe acute respiratory infection in ten Gavi-eligible countries: the RSV GOLD—ICU Network study

Patient-level data on life-threatening respiratory syncytial virus (RSV) infection in children in low-income and lower-middle-income countries (LMICs) are scarce, and this scarcity might limit demand for RSV interventions in LMICs who rely on support from Gavi, the Vaccine Alliance. We aimed to describe the characteristics of RSV-positive children younger than 2 years who were admitted to paediatric intensive care units (PICUs) with extended severe acute respiratory infection (eSARI) in Gavi-eligible countries. The RSV GOLD-ICU Network study is a 2-year prospective, multicountry, observational study of children younger than 2 years admitted to a PICU with eSARI. The study was conducted at 12 referral hospitals in Bolivia, Cameroon, The Gambia, Ghana, Haiti, Mozambique, Nepal, Nigeria, Sudan, and Tanzania. For comparison with a high-income country, patients were also included from two referral hospitals in the Netherlands. Children were eligible for inclusion if they were aged between 4 days and 2 years, admitted to a PICU, and met the WHO eSARI definition. RSV infection was confirmed within 72 h of PICU admission via a molecular point-of-care test at LMIC study sites and via a PCR test at the Dutch study sites. Clinical data were extracted from admission charts of patients; underlying conditions that were identified at admission were classified as comorbidities. Socioeconomic and demographic data were collected via a written, structured, parental questionnaire. Between April 28, 2021, and Sept 30, 2023, we included 2118 children who were admitted to a PICU with eSARI in the ten participating countries. 614 (29·0%; range 23·0-38·2) of 2118 children tested positive for RSV and 608 were included in descriptive analyses as six medical files were lost at one study site and data could not be retrieved. Among all 608 children infected with RSV, 379 (62%) were male and 229 (38%) were female. Median age at testing was 3·0 months (IQR 1·3-7·7). 30 (5%) of 608 children died from RSV infection. RSV fatality occurred at seven of ten participating LMIC study sites and was highest in Tanzania (seven [27%] of 26 children). Median age at testing of children who died with RSV infection was 1·8 months (IQR 1·1-4·2). To our knowledge, this is the first prospective, multicountry study reporting data from children admitted to a PICU with life-threatening RSV infection in Gavi-eligible countries. As there is no access to intensive care for most children in LMICs, RSV prevention is urgently needed. Bill & Melinda Gates Foundation. For the Arabic, Portuguese, Hausa and Nepali translations of the abstract see Supplementary Materials section.

Increased risk of bacterial pneumonia before and after respiratory syncytial virus infection in young children.

The burden of respiratory disease is great among children. This study aimed to examine the temporal relationship between hospitalisation for respiratory syncytial virus (RSV) and bacterial pneumonia. A Swedish population-based cohort was created by combining data from the Swedish Medical Birth Register, the National Inpatient Register, the Cause of Death Register, the Total Population Register, and the Longitudinal Integration Database for Health Insurance and Labour Market Studies. Children born between 1998 and 2015 were included and followed for 2 years. We examined the temporal relationship between RSV hospitalisation and bacterial pneumonia using piecewise exponential models. The final cohort comprised 1 641 747 children, 48.5% were females. There were 23 632 RSV and 4722 bacterial pneumonia hospitalisations, with mean age of 137.8 and 424.2 days, respectively. RSV hospitalisation was associated with bacterial pneumonia with an adjusted incidence rate ratio (aIRR) of 3.18. The risk was highest in the first month after RSV hospitalisation, aIRR 11.19. The risk of bacterial pneumonia was elevated for 4 months after RSV hospitalisation and before RSV hospitalisation. We found an increased risk for bacterial pneumonia hospitalisation in children hospitalised for RSV both before and after RSV hospitalisation, indicating a bidirectional relationship.

Next - generation sequencing whole genome respiratory syncytial virus in North Viet Nam, 2017 – 2020

Human Respiratory Syncytial Virus (RSV) infections pose a significant risk to both children and adults worldwide. 95% of children have been affected by RSV at least one time before 2 years old. This study aims to develop and apply a high-throughput sequencing strategy to sequence Vietnamese RSV whole genomes directly from clinical specimens in North Vietnam, 2017 - 2020. 38 clinical RSV-A and 43 clinical RSV-B samples were used to extract RNA, then converted to cDNA and PCR with specific primer sets. Next-generation sequencer with Illumina platform and analysis data by CLC Genomics Workbench. In silico analysis and laboratory testing revealed that the primer sets worked well and successfully amplified the whole genome of RSV. The nucleotide positions of gene start and gene end, as well as the substitutions in amino acid in each gene were determined. This protocol is simple to set up, easily scalable in sample preparation, and suitable for analysis. This reseach is the first public method of whole genome RSV sequencing and the most updated data of molecular RSV genome after 2015 in Viet Nam.

RSV and rhinovirus increase pneumococcal carriage acquisition and density, whereas nasal inflammation is associated with bacterial shedding

Epidemiological studies report the impact of co-infection with pneumococcus and respiratory viruses upon disease rates and outcomes, but their effect on pneumococcal carriage acquisition and bacterial load is scarcely described. Here, we assess this by combining natural viral infection with controlled human pneumococcal infection in 581 healthy adults screened for upper respiratory tract viral infection before intranasal pneumococcal challenge. Across all adults, respiratory syncytial virus (RSV) and rhinovirus asymptomatic infection confer a substantial increase in secondary infection with pneumococcus. RSV also has a major impact on pneumococcal density up to 9days post challenge. We also study rates and kinetics of bacterial shedding through the nose and oral route in a subset. High levels of pneumococcal colonization density and nasal inflammation are strongly correlated with increased odds of nasal shedding as opposed to cough shedding. Protection against respiratory viral infections and control of pneumococcal density may contribute to preventing pneumococcal disease and reducing bacterial spread.

Epidemiological trends in respiratory pathogens infections among children post-COVID-19: A cross-sectional study

ObjectiveThe aim of this study was to investigate the epidemiological trend of respiratory pathogens infections among children after the Coronavirus Disease 2019 (COVID-19) pandemic. MethodsThis study enrolled 575,373 children who came to our hospital for relevant respiratory pathogen antigen/antibody testing due to respiratory symptoms such as fever and cough. The demographic and laboratory data, including age, gender, testing time, and influenza A virus (IAV), influenza B virus (IBV), respiratory syncytial virus (RSV), adenovirus (ADV), and Mycoplasma pneumonia (MP) results, were collected from electronic medical records. SPSS (version 21.0) and GraphPad Prism 9 software were used for statistical analysis and figure creation. Results79,746 children tested positive for IAV IgM, and 3196 children tested positive for IBV IgM, with an overall positive rate of 28.5 % for IAV and 1.1 % for IBV. IAV infections peaked at 21,502 cases in March 2023. 80,699 children underwent RSV IgM testing from April to October 2023, with 5726 (7.1 %) testing positive. The apex of RSV infections occurred in May 2023, with 2140 cases. Regarding ADV, 100,460 children underwent testing from April to October 2023, with 1981 (11.9 %) testing positive. The pinnacle of ADV infections reached 4546 cases in November 2023. Concerning MP, 474,913 children underwent MP testing, with 73,833 (15.5 %) testing positive. The zenith of MP infections occurred in November 2023, with 25,291 cases. Further analysis revealed that the outbreaks of these pathogens are occurring earlier than in previous years. Additionally, our data showed that children aged >3 years accounted for 79.6 %, 87.8 %, 88.6 %, and 77.8 % of the total IAV‐positive, IBV‐positive, ADV-positive, and MP-positive children, respectively. Conversely, RSV primarily infected children <6 years. ConclusionVarious respiratory pathogens showed an epidemic trend in children among children post-COVID-19. These results indicated that we should pay timely attention to the epidemiological trends and characteristics of respiratory pathogens in children after the COVID-19 pandemic and provide relevant information for society and clinical practice.

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.

A new mechanism of respiratory syncytial virus entry inhibition by small-molecule to overcome K394R-associated resistance.

Respiratory syncytial virus (RSV) infection is a major public health concern, and many small-molecule candidates targeting the viral fusion (F) protein are associated with a considerable risk of inducing drug-resistant mutations. This study investigated virological features of the K394R variant, a mutant strain conferring resistance to multiple RSV fusion inhibitors. Our results demonstrated that the K394R variant is highly fusogenic in cell cultures and more pathogenic than the parental strain in mice. The small-molecule inhibitor CL-A3-7 substantially reduced in vitro and in vivo infections of both wild-type RSV and the K394R variant by blocking the interaction of viral F protein with its cellular receptor, showing a new mechanism of action for small-molecules to inhibit RSV infection and overcome K394R-associated resistance.