Risk Of Respiratory Syncytial Virus Infection Research Articles

From The First Breath to the Golden Years: Respiratory Syncytial Virus Prevention in Infants and Older Adults

Respiratory syncytial virus (RSV) is one of the most common respiratory infections observed in primary care. Although many think of RSV as a ‘common cold’, it is a serious health threat to certain populations, including children, particularly infants who are 6 months of age or younger, those with comorbidities, and older adults. With the increasing number of options to reduce the impact of RSV infections, including morbidity and mortality, it is important to recognize that primary care clinicians must be able to identify people at risk for RSV infection, effectively educate them on the potential impact of the condition, and identify strategies to lower the risk.

Transient increased risk of influenza infection following RSV infection in South Africa: findings from the PHIRST study, South Africa, 2016–2018

BackgroundLarge-scale prevention of respiratory syncytial virus (RSV) infection may have ecological consequences for co-circulating pathogens, including influenza. We assessed if and for how long RSV infection alters the risk for subsequent influenza infection.MethodsWe analysed a prospective longitudinal cohort study conducted in South Africa between 2016 and 2018. For participating households, nasopharyngeal samples were taken twice weekly, irrespective of symptoms, across three respiratory virus seasons, and real-time polymerase chain reaction (PCR) was used to identify infection with RSV and/or influenza. We fitted an individual-level hidden Markov transmission model in order to estimate RSV and influenza infection rates and their interdependence.ResultsOf a total of 122,113 samples collected, 1265 (1.0%) were positive for influenza and 1002 (0.8%) positive for RSV, with 15 (0.01%) samples from 12 individuals positive for both influenza and RSV. We observed a 2.25-fold higher incidence of co-infection than expected if assuming infections were unrelated. We estimated that infection with influenza is 2.13 (95% CI 0.97–4.69) times more likely when already infected with, and for a week following, RSV infection, adjusted for age. This equates to 1.4% of influenza infections that may be attributable to RSV in this population. Due to the local seasonality (RSV season precedes the influenza season), we were unable to estimate changes in RSV infection risk following influenza infection.ConclusionsWe find no evidence to suggest that RSV was associated with a subsequent reduced risk of influenza infection. Instead, we observed an increased risk for influenza infection for a short period after infection. However, the impact on population-level transmission dynamics of this individual-level synergistic effect was not measurable in this setting.

Association of COVID-19 with respiratory syncytial virus (RSV) infections in children aged 0–5 years in the USA in 2022: a multicentre retrospective cohort study

ObjectiveTo investigate whether COVID-19 infection was associated with increased risk for incident respiratory syncytial virus (RSV) infections and associated diseases among young children that might have contributed to the 2022...

Reconstructing the impact of COVID-19 on the immunity gap and transmission of respiratory syncytial virus in Lombardy, Italy

Respiratory syncytial virus (RSV) is a leading cause of hospitalisation and mortality in young children globally. The social distancing measures implemented against COVID-19 in Lombardy (Italy) disrupted the typically seasonal RSV circulation during 2019-2021 and caused substantially more hospitalisations during 2021-2022. The primary aim of this study is to quantify the immunity gap-defined as the increased proportion of the population naïve to RSV infection following the relaxation of COVID-19 restrictions in Lombardy, which has been hypothesised to be a potential cause of the increased RSV burden in 2021-2022. We developed a catalytic model to reconstruct changes in the age-dependent susceptibility profile of the Lombardy population throughout the COVID-19 pandemic. The model is calibrated to routinely collected hospitalisation, syndromic, and virological surveillance data and tested for alternative assumptions on age-dependencies in the risk of RSV infection throughout the pandemic. We estimate that the proportion of the Lombardy population naïve to RSV infection increased by 60.8% (95% CrI: 55.2-65.4%) during the COVID-19 pandemic: from 1.4% (95% CrI: 1.3-1.6%) in 2018-2019 to 2.3% (95% CrI: 2.2-2.5%) before the 2021-2022 season, corresponding to an immunity gap of 0.87% (95% CrI: 0.87-0.88%). We found evidence of heterogeneity in RSV transmission by age, suggesting that the COVID-19 restrictions had variable impact on the contact patterns and risk of RSV infection across ages. We estimate a substantial increase in the population-level susceptibility to RSV in Lombardy during 2019-2021, which contributed to an increase in primary RSV infections in 2021-2022. UK Medical Research Council (MRC), UK Foreign, Commonwealth & Development Office (FCDO), EDCTP2 programme, European Union, Wellcome Trust, Royal Society, EU-MUR PNRR INF-ACT.

Home Immunization with Palivizumab-A Randomized Pilot Study Describing Safety Aspects and Parents’ Preferences

Among prematurely born infants and newborns with chronic conditions, a respiratory syncytial virus (RSV) infection may cause (re-)admission and later respiratory complications. Therapeutic protection is possible with monthly injections of a specific monoclonal antibody, palivizumab, during RSV season. Standard care is giving up to five injections in clinic-based settings. Immunization at home could be an alternative to standard care for vulnerable infants to reduce the number of revisits and associated risk of RSV infection. The aim of this randomized pilot trial was to evaluate safety aspects and explore parents' preferences of home versus hospital immunization with palivizumab during one RSV season. Immediate adverse events (AEs) were observed and registered by a pediatric specialist nurse. Late-onset AEs were reported by parents. Parents' perceptions were collected through a questionnaire and analyzed using content analysis. The study population consisted of 43 infants in 38 families. No immediate AEs occurred. Three late-onset AEs were reported in two infants in the intervention group. Three categories emerged in the content analysis: (1) protect and watch over the infant, (2) optimal health and well-being for the whole family, and (3) avoid suffering for the infant. The study results show that home immunization with palivizumab is feasible if safety aspects are considered and that parental involvement in the choice of place for immunization after a neonatal intensive care experience can be important.

Air quality, meteorological variability and pediatric respiratory syncytial virus infections in Singapore

Respiratory syncytial virus (RSV) is an important cause of respiratory illness among children. While studies have focused on the air-quality and climate dependence of RSV infections, few have been undertaken in South-East Asia where the burden of respiratory illness is among the highest across the globe. This study aimed to determine the relationships between climatic factors and air quality with RSV infections among children in Singapore. We obtained all laboratory-confirmed reports of RSV infections in children below 5 years old from the largest public hospital specializing in pediatric healthcare in Singapore. We assessed the independent cumulative effects of air quality and meteorological factors on RSV infection risk using the Distributed Lag Non-Linear Model (DLNM) framework in negative binomial models adjusted for long-term trend, seasonality and changes in the diagnostic systems. We included 15,715 laboratory-confirmed RSV reports from 2009 to 2019. Daily maximum temperature exhibited a complex, non-linear association with RSV infections. Absolute humidity (Relative Risk, 90th percentile [RR90th percentile]: 1.170, 95% CI: [1.102, 1.242]) was positively associated with RSV risk. Higher levels of particulate matter of aerodynamic diameter of less than (i) 2.5 µm (PM2.5), (ii) 10 µm (PM10), carbon monoxide (CO) and sulfur dioxide (SO2) were associated with lower RSV infection risk. RSV infections exhibited both annual and within-year seasonality. Our findings suggest that falls in ambient temperature and rises in absolute humidity exacerbated pediatric RSV infection risk while increases in air pollutant concentrations were associated with lowered infection risk. These meteorological factors, together with the predictable seasonality of RSV infections, can inform the timing of mitigation measures aimed at reducing transmission.

Epidemiological Features, Risk Factors, and Disease Burden of Respiratory Viruses among Hospitalized Children with Acute Respiratory Tract Infections in Xiamen, China.

Well-established surveillance and monitoring systems for respiratory viruses need to be improved, and epidemiological data on respiratory viruses in China are scarce. This study aimed to investigate the epidemiological characteristics of respiratory viruses among hospitalized children aged ≤2 years with acute respiratory tract infections (ARTIs) in Xiamen, China, from October 2014 to September 2017. The clinical records of 7,248 children hospitalized for ARTIs were retrospectively analyzed. Respiratory syncytial virus (RSV) (22.3%) was the most common virus among hospitalized children aged ≤2 years, followed by parainfluenza (5.0%), adenovirus (3.5%), and influenza (1.7%). RSV-infected children had a higher disease burden, including a higher intensive care unit (ICU) admission rate (12.7%) and higher hospital charges ($635.36). Particularly, infants aged <6 months had the highest risk of RSV infection (odds ratio = 2.4; 95% CI, 1.9-2.9) and a higher ICU admission rate (12.1% vs. 4.5%, 4.6%) and hospital cost ($923.3 vs. $785.5, $811.7) than the other age groups. Therefore, infants aged 0-6 months, particularly premature infants and children with congenital diseases, should receive more attention. There is an urgent need to develop effective immunization strategies to protect these infants during the first 6 months of life and in the RSV season.

Reducing the Burden of Respiratory Syncytial Virus Across the Lifespan

Abstract Respiratory syncytial virus (RSV) is a common cause of respiratory infections, which often involve mild, upper respiratory illness, but can cause severe morbidity and mortality across the lifespan. Respiratory syncytial virus is the leading cause of infant hospitalization in the United States and of bronchiolitis and pneumonia in children younger than 1 year of age. Before the COVID-19 pandemic, among adults, RSV ranked second only to influenza as a cause of medically significant respiratory illnesses. The economic burden of RSV is substantial, with estimated annual costs for RSV-related hospitalizations exceeding $3 billion in young children and adults. Despite this burden, RSV remains an underappreciated public health concern. Diagnosis of RSV infection is limited by the absence of accurate, rapid, cost-effective, point-of-care tests for adults. In addition, there are currently no RSV vaccines or treatments approved for use across the lifespan. Strategies to reduce the burden of RSV infections may include: (1) increase RSV awareness and education, (2) strengthen RSV public health surveillance and related policies, and (3) increase support for RSV research and innovation. Surveillance systems are needed to understand the true burden of RSV in at-risk populations. The need for improved diagnostic tests and RSV prevention and treatment options remains great. Appropriate use of interventions will rely on raising awareness among health care professionals about the broad clinical spectrum and impact of RSV infection. Using these strategies can reduce the burden of RSV in communities, with a focus on protecting children and older adults who are at greatest risk for RSV infection.

Respiratory syncytial virus in pediatric influenza-like illness cases in Lombardy, Northern Italy, during seven consecutive winter seasons (from 2014-2015 to 2020-2021).

IntroductionRespiratory syncytial virus (RSV) is the major cause of lower respiratory tract illness in young children and can also cause influenza‐like illness (ILI). Here we investigated the epidemiological features of RSV infection in pediatric ILI cases in Lombardy (a region in Northern Italy accounting nearly 10 million inhabitants) from 2014–2015 to 2020–2021 winter seasons.Material and MethodsData for this study were retrieved and statistically analyzed from the database of virological influenza surveillance of the regional reference laboratory for Lombardy within the Italian influenza surveillance network (InfluNet).ResultsRSV accounted for nearly 19% of pediatric ILI with a risk of infection nearly two‐fold greater than that of individuals ≥15 years. RSV positivity rate increased to 28% considering 0–5 years old children. Although in children ≤5 years the risk of infection from influenza viruses resulted nearly two‐fold higher than the risk of RSV infection, the age group 4–6 months and 7–12 months showed a five‐fold greater risk of infection from RSV than from influenza. Children ≤5 years of age with pre‐existing underlying health conditions had a nearly five‐fold greater risk of getting RSV infection than otherwise healthy 0–5 years old children. RSV was identified in ILI cases <15 years of age in all considered winter seasons except in the 2020–2021 season.DiscussionSentinel surveillance of ILI allowed us to identify groups at higher risk of RSV and influenza infection and to define the start, duration, timing, and intensity of the RSV and influenza community circulation. This surveillance approach can be implemented to assess the RSV circulation and impact in a real‐time manner.

Assessment of surveillance predictors for suspected respiratory syncytial virus, influenza and Streptococcus pneumoniae infections in children aged

The lack of rapid, sensitive and affordable diagnostic tests that can distinguish a wide variety of respiratory pathogens at the point of care is an obstacle to the rapid implementation of control measures following events and epidemics. In addition, the absence of a standardized case definition to differentiate putative aetiologies is a challenge to assessing the burden of disease. This study aimed to identify the clinical spectrum of respiratory pathogens commonly associated with respiratory tract infections in the context of disease surveillance. Data obtained from prospective hospital-based severe acute respiratory infection surveillance among children aged <5 years from November 2010 to July 2013 were used in this study. Intercostal recession and dyspnoea were predictive of respiratory syncytial virus (RSV) infection, whereas headache and chills were more often observed during influenza A infection. Male patients were at a higher risk for RSV infection than female patients. Productive cough, chills, sweating and weight loss were significantly associated with Streptococcus pneumoniae infection. The presence of fever did not necessarily indicate RSV infection. Combined with other examinations, this study shows the value of including the syndromic approach in the panel of diagnostic criteria for rapid identification of the risk of infectious diseases in areas where laboratory diagnostics are challenging. Given the current situation with coronavirus disease 2019, this approach may help decision makers to implement appropriate control measures.

1013. Predicting RSV Efficacy for MK-1654 in Temperate and Tropical Climates using MBMA and Clinical Trial Simulation to Account for Seasonal Differences in RSV Force-of-Infection

Abstract Background MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody under development to prevent RSV infection in infants. A model-based meta-analysis (MBMA) describing the relationship between RSV serum neutralizing activity (SNA) and clinically relevant endpoints (e.g. incidence rates) in humans, including lower respiratory tract infection (LRI) in infants, was presented previously. This model accounted for variable exposure to RSV over the course of the season through a force-of-infection (FOI) function modulating the overall risk of RSV infection over time. The objective of the current work was to determine whether variations in regional seasonality would impact the efficacy of a clinical trial evaluating MK-1654. Methods A FOI function to describe the degree of RSV exposure as a function of time was created by fitting epidemiological data to a Gaussian function added to a constant baseline value. Clinical trial simulations were conducted using the MBMA to predict seasonal incidence rates (IR) of RSV medically attended lower-respiratory tract infection (MALRI) and efficacies for a range of MK-1654 doses in both temperate and tropical regions. Results Epidemiological data was well captured by the FOI function. Clinical trial simulations indicated that seasonal IRs of RSV were sensitive to differences in the FOI represented by temperate and tropical regions; however, there was no substantial impact on efficacies across MK-1654 dose levels. Consistent with predictions for a temperate climate, MK-1654, when administered at the start of the RSV season in a region with a tropical climate, was also predicted to maintain high efficacy ( &amp;gt; 75%) for the prevention of RSV MALRI for 150 days. Conclusion Simulations indicated that while FOI is a substantial driver of overall RSV incidence rates, MK-1654 efficacy in a late-stage clinical trial is likely to be high, regardless of regional variations in RSV. Disclosures Nele Plock, PhD, Certara (Employee, Shareholder)Merck &amp; Co., Inc. (Independent Contractor) Jos Lommerse, PhD, Certara (Employee, Shareholder)Merck &amp; Co., Inc. (Independent Contractor) Brian M. Maas, PharmD, Merck &amp; Co., Inc. (Employee, Shareholder) Jingxian Chen, PhD, Merck &amp; Co., Inc. (Employee, Shareholder) Francesco Bellanti, PhD, Certara (Employee, Shareholder)Merck &amp; Co., Inc. (Independent Contractor) Li Qin, PhD, Certara (Employee, Shareholder)Merck &amp; Co., Inc. (Independent Contractor) Han Witjes, PhD, Certara (Employee, Shareholder)Merck &amp; Co., Inc. (Independent Contractor) Philippe Pierrillas, PhD, Certara (Employee, Shareholder)Merck &amp; Co., Inc. (Independent Contractor) Radha Railkar, PhD, Merck &amp; Co., Inc. (Employee, Shareholder) Antonios O. Aliprantis, MD, PhD, Merck &amp; Co., Inc. (Employee, Shareholder) Kalpit A. Vora, PhD, Merck &amp; Co., Inc. (Employee, Shareholder) Wei Gao, PhD, Merck &amp; Co., Inc. (Employee, Shareholder) Luzelena Caro, PhD, Merck &amp; Co., Inc. (Employee, Shareholder) S. Y. Amy Cheung, PhD, Certara (Employee, Shareholder) Jeffrey R. Sachs, PhD, Merck &amp; Co., Inc. (Employee, Shareholder)

Palivizumab for preventing severe respiratory syncytial virus (RSV) infection in children.

Respiratory viruses are the leading cause of lower respiratory tract infection (LRTI) and hospitalisation in infants and young children. Respiratory syncytial virus (RSV) is the main infectious agent in this population.Palivizumab is administered intramuscularly every month during five months in the first RSV season to prevent serious RSV LRTI in children.Given its high cost, it is essential to know if palivizumab continues to be effective in preventing severe RSV disease in children. To assess the effects of palivizumab for preventing severe RSV infection in children. We searched CENTRAL, MEDLINE, threeotherdatabases and two trialsregistersto 14 October 2021,together with reference checking, citation searching and contact with study authors to identify additional studies. We searched Embase to October 2020, as we did not have access to this database for 2021. We included randomised controlled trials (RCTs), including cluster-RCTs,comparing palivizumabgiven at a dose of 15 mg/kg once a month (maximum five doses) with placebo, no intervention or standard care in children 0 to 24 months of agefrom both genders, regardless ofRSV infection history. DATA COLLECTION AND ANALYSIS: We used Cochrane's Screen4Me workflow to help assess the search results.Two review authors screened studies for selection, assessed risk of bias and extracted data.We used standard Cochrane methods.We used GRADE to assess the certainty of the evidence.The primary outcomes were hospitalisation due to RSV infection, all-cause mortality and adverse events. Secondary outcomes were hospitalisation due to respiratory-related illness, length of hospital stay,RSV infection, number of wheezing days, days of supplemental oxygen, intensive care unit length of stay and mechanical ventilation days. We included five studies with a total of 3343 participants.All studies were parallel RCTs, assessing the effects of 15 mg/kg of palivizumabevery month up to five months compared to placebo or no intervention in an outpatient setting, although one study also included hospitalised infants. Most of the included studies were conducted in children with a high risk of RSV infection due to comorbidities like bronchopulmonary dysplasia and congenital heart disease. The risk of bias of outcomes across all studies was similar and predominately low. Palivizumabreduceshospitalisation due to RSV infectionat two years' follow-up (risk ratio (RR) 0.44, 95% confidence interval (CI) 0.30 to 0.64;5 studies, 3343 participants; high certainty evidence). Based on 98 hospitalisations per 1000 participants in the placebo group, this corresponds to 43 (29 to 62) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in mortalityat two years' follow-up (RR 0.69, 95% CI 0.42 to 1.15;5 studies, 3343 participants;moderate certainty evidence). Based on 23 deaths per 1000 participants in the placebo group, this corresponds to 16 (10 to 27) per 1000 participants in the palivizumab group. Palivizumab probably results in little to no difference in adverse events at 150 days' follow-up (RR 1.09, 95% CI 0.85 to 1.39;3 studies, 2831 participants;moderate certainty evidence). Based on 84 cases per 1000 participants in the placebo group, this corresponds to 91 (71 to 117) per 1000 participants in the palivizumab group. Palivizumab probably results in a slight reductionin hospitalisation due to respiratory-related illness at two years' follow-up (RR 0.78, 95% CI 0.62 to 0.97;5 studies, 3343participants; moderate certainty evidence). Palivizumabmay result in a large reductionin RSV infection at two years' follow-up (RR 0.33, 95% CI 0.20 to 0.55;3 studies, 554participants;low certainty evidence). Based on 195 cases of RSV infection per 1000 participants in the placebo group, this corresponds to 64 (39 to 107) per 1000 participants in the palivizumab group. Palivizumab also reduces thenumber of wheezing days at one year's follow-up (RR 0.39, 95% CI 0.35 to 0.44;1 study, 429 participants; high certainty evidence). The available evidence suggests that prophylaxis with palivizumabreduceshospitalisation due to RSV infection and results in little to no difference in mortality oradverse events. Moreover, palivizumabresults in a slight reductionin hospitalisation due to respiratory-related illness and may result in a large reductionin RSV infections. Palivizumabalso reduces thenumber of wheezing days. These results may be applicable to children with a high risk of RSV infection due to comorbidities. Further research is needed to establish the effect of palivizumabon children with other comorbidities known as risk factors for severe RSV disease (e.g. immune deficiencies) and other social determinants of the disease, including children living in low- and middle-income countries, tropical regions, childrenlacking breastfeeding, living inpoverty, or members of families in overcrowded situations.

Respiratory syncytial virus in young children: community cohort study integrating serological surveys, questionnaire and electronic health records, Born in Bradford cohort, England, 2008 to 2013.

BackgroundBronchiolitis caused by respiratory syncytial virus (RSV) is a major cause of mortality and morbidity in infants.AimTo describe RSV epidemiology in children in the community in a high-income setting.MethodsWe used stored blood samples from the United Kingdom Born in Bradford cohort study that had been collected at birth, age 1 and 2 years old, tested for IgG RSV postfusion F antibody and linked to questionnaires and primary and hospital care records. We used finite mixture models to classify children as RSV infected/not infected according to their antibody concentrations at age 1 and 2 years. We assessed risk factors for primary RSV infection at each age using Poisson regression models.ResultsThe study cohort included 700 children with cord blood samples; 490 had additional blood samples taken at both ages 1 and 2 years old. Of these 490 children, 258 (53%; 95% confidence interval (CI): 48–57%) were first infected with RSV at age 1, 99 of whom (38%; 95% CI: 33–43%) had been in contact with healthcare during peak RSV season (November–January). Having older siblings, birth in October–June and attending formal childcare were associated with risk of RSV infection in infancy. By age 2, a further 164 of 490 children (33%; 95% CI: 29–38%) had been infected.ConclusionOver half of children experienced RSV infection in infancy, a further one third had evidence of primary RSV infection by age 2, and one in seven remained seronegative by their second birthday. These findings will inform future analyses to assess the cost-effectiveness of RSV vaccination programmes in high-income settings.

Seroepidemiology of respiratory syncytial virus infection in rural and semi-rural areas of the Littoral region of Cameroon

BackgroundThe respiratory syncytial virus (RSV) has been established as a leading cause of acute lower respiratory illness (ALRI) in infants and children. In 2015, the global disease burden (GBD) study estimated that the overall RSV-ALRI mortality could be as high as 118,200, with most death occurring in low- and middle-incomes countries (LMIC). This study aimed to assess the burden of RSV infection among children less than 2 years with acute respiratory infections (ARI) in the Littoral region of Cameroon.MethodsWe carried out a cross-sectional study in seven health centres in the Littoral region of Cameroon. Venous blood was collected using serum separation tubes from eligible children who visited these health centres with acute respiratory infections. ELISA (Enzyme-linked immunosorbent assay) testing was used to assess the seroprevalence of anti-IgM RSV for the total population and by selected demographic and health parameters and potential risk factors.ResultsThe overall RSV-associated ARI seroprevalence was 33% (95%CI:23.6–42.3; 33/100 children). The only demographic factor significantly associated with RSV acquisition was age of 6 months and below (odds ratio: 7.54 (2.62, 23.36); p = 0.000). Children who were clinically diagnosed to be concomitantly infected with malaria had a lower risk of RSV infection (odds ratio: 0.38 (0.14, 0.95; P = 0.03).ConclusionsThe RSV burden is high among children less than 2 years with ARI in the Littoral region of Cameroon. There is a need for an effective public health RSV surveillance system with standard laboratory techniques and equipment to better understand the RSV disease age-specific incidence, seasonality, risk factors and RSV burden among patients in communities in Cameroon.

Palivizumab Prophylaxis among Infants at Increased Risk of Hospitalization due to Respiratory Syncytial Virus Infection in UAE: A Hospital-Based Study.

Background Respiratory syncytial virus (RSV) represents a significant public health burden and the leading cause of lower respiratory tract infections globally, and it is the major cause of hospitalization during the winter. We aimed to evaluate the effectiveness of palivizumab prophylaxis to reduce the hospitalization in children at high risk of RSV infection. Methods We performed a retrospective observational single-arm hospital-based study including five RSV seasons (September to March) from 2012 to 2017. We retrospectively included premature infants born at less than 35 weeks of gestation with chronic lungs disease or hemodynamic significant congenital heart disease for palivizumab prophylaxis against RSV infection according to the criteria presented. Results A total of 925 children were enrolled in the study over the five RSV seasons. Of them, 410 (44.3%) infants born at <32 weeks of gestation and 515 (55.6%) infants born at 32–35 weeks of gestation with mean (±SD) birth weight of 1104.8 ± 402.85 and 1842.5 ± 377.5, respectively. The compliance with the course of palivizumab was reported in 841 (90.9%) children. Of them, about 75 (8.9%) hospitalized children were reported, and 17 (2.02%) RSV positive children were detected. Hospitalization due to RSV infection was decreased from 9.23% in the 2012-2013 season to 0.67% in the 2016-2017 season. Conclusion This study demonstrated that palivizumab prophylaxis in children at high risk of developing RSV infection was effective in reducing the risk of hospitalization with a high compliance rate over the five RSV seasons.

RSVpredict: An Online Tool to Calculate the Likelihood of Respiratory Syncytial Virus Infection in Children Hospitalized With Acute Respiratory Disease.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection in young children. Early detection of RSV infection can avoid unnecessary diagnostic and therapeutic intervention and is required to prevent the nosocomial spread of RSV infection in pediatric hospitals. We developed a web tool to calculate the probability of RSV infection in children hospitalized with acute respiratory tract infection (ARTI) (RSVpredict). During winter seasons 2014/2015 to 2017/2018, 1545 children hospitalized with clinical symptoms of ARTI at the University Hospital Heidelberg/Germany were prospectively included. Medical information was reported on a standardized data sheet, and nasopharyngeal swabs were obtained for multiplex real-time polymerase chain reaction analyses. We applied logistic regression to develop a prediction model and developed a web-based application to predict the individual probability of RSV infection. Duration of clinical symptoms ≥2 days on admission, calendar month of admission, admission for lower respiratory tract infection, the presence of cough and rale and younger age were associated with RSV infection (P < 0.05). Those data were included in the prediction model (RSVpredict, https://web.imbi.uni-heidelberg.de/rsv/). RSVpredict is a web-based application to calculate the risk of RSV infection in children hospitalized with ARTI. The prediction model is based on easily accessible clinical symptoms and predicts the individual probability of RSV infection risk immediately. Pediatricians might use the RSVpredict to take informed decisions on further diagnostic and therapeutic intervention, including targeted RSV testing in children with relevant RSV infection risk.

Informing randomized clinical trials of respiratory syncytial virus vaccination during pregnancy to prevent recurrent childhood wheezing: A sample size analysis

BackgroundEarly RSV illness is associated with wheeze-associated disorders in childhood. Candidate respiratory syncytial virus (RSV) vaccines may prevent acute RSV illness in infants. We investigated the feasibility of maternal RSV vaccine trials to demonstrate reductions in recurrent childhood wheezing in general paediatric populations. MethodsWe calculated vaccine trial effect sizes that depended on vaccine efficacy, allocation ratio, rate of early severe RSV illness, risk of recurrent wheezing at age 3, and increased risk of RSV infection on recurrent wheezing. Model inputs came from systematic reviews and meta-analyses. For each combination of inputs, we estimated the sample size required to detect the effect of vaccination on recurrent wheezing. ResultsThere were 81 scenarios with 1:1 allocation ratio. Risk ratios between vaccination and recurrent wheezing ranged from 0.9 to 1.0 for 70% of the scenarios. Among the 57 more plausible scenarios, the lowest sample size required to detect significant reductions in recurrent wheezing was 6196 mother-infant pairs per trial arm; however, 75% and 47% of plausible scenarios required >31,060 and >100,000 mother-infant pairs per trial arm, respectively. Studies with asthma endpoints at age 5 will likely need to be larger. DiscussionClinical efficacy trials of candidate maternal RSV vaccines undertaken for licensure are unlikely to demonstrate an effect on recurrent wheezing illness due to the large sample sizes likely needed to demonstrate a significant effect. Further efforts are needed to plan for alternative study designs to estimate the impact of maternal RSV vaccine programs on recurrent childhood wheezing in general populations.

Transplacental transfer of maternal respiratory syncytial virus (RSV) antibody and protection against RSV disease in infants in rural Nepal

BackgroundRespiratory syncytial virus (RSV) is the most important viral cause of pneumonia in children. RSV-specific antibody (ab) protects infants from disease, and may be increased by a potential strategy of maternal RSV vaccination. ObjectivesTo describe the effect of RSV antibody on RSV infection risk in infants in a resource-limited setting. Study designIn a prospective study in Nepal, women were enrolled during pregnancy and maternal and infant cord blood were collected at birth. Weekly surveillance for respiratory illness was performed from birth to 180days. Nasal swabs were tested for RSV by PCR and serum was tested using an RSV antibody microneutralization assay. Antibody concentrations at time of RSV infection were estimated based on a decay rate of 0.026 log2/day. ResultsCord:maternal RSV antibody transfer ratio was 1.03 (0.88–1.19), with RSV antibody concentration of log2 11.3 and log2 11.7 in 310 paired maternal and infant samples, respectively. Cord blood RSV antibody was log2 12.1 versus 11.6 in those with or without RSV infection (P=0.86). Among infants with RSV infection, estimated RSV antibody concentration at time of infection did not differ in infants with upper (n=8; log2 10.7) versus lower respiratory tract infection (n=21; log2 9.8; P=0.37). Cord blood RSV antibody concentrations did not correlate with age at primary RSV infection (R=0.11; P=0.57). ConclusionsTransplacental transfer of RSV antibody from mother to the fetus was highly efficient in mother-infant pairs in rural Nepal, though higher antibody concentrations were not protective against earlier or more severe RSV infection in infants.

Respiratory syncytial virus hospitalization outcomes and costs of full-term and preterm infants.

Objective:Infection with respiratory syncytial virus (RSV), which causes lower respiratory tract infections, is the leading cause of hospitalization among children <1 year old in the United States. Risk factors for RSV hospitalization include premature birth and younger chronologic age, along with several comorbid conditions. However, in terms of RSV hospitalization costs, premature infants are rarely studied separately from full-term infants. The objective of this study is to describe the cost and severity of RSV hospitalizations among preterm and full-term infants without chronic lung disease or other high-risk conditions.Study Design:This analysis used Truven Health Market Scan Multi-State Medicaid and Commercial Claims and Encounters databases, which contain a combined 4 million births from 2003 to 2013. Infants with comorbid conditions associated with increased risk for RSV infection were excluded. Infants were classified as preterm (<29, 29−30, 31−32, 33−34 and 35−36 weeks' gestational age (wGA)) or full term based on diagnostic coding. Health-care claims during the first year of life were evaluated for RSV hospitalizations, defined as inpatient claims with a diagnosis code for RSV in any position. Costs of RSV hospitalizations were captured and reported in 2014 USD. Inpatient claims for RSV hospitalizations were evaluated for the presence of codes indicating admission to the intensive care unit (ICU), use of mechanical ventilation (MV) and length of stay. These three measures were used to describe hospital severity. Chronologic age at the time of RSV hospitalization was also captured. Data were summarized and no statistical comparisons were conducted.Results:There were 1 683 188 infants insured through Medicaid and 1 663 832 infants insured through commercial plans born from 1 July 2003 to 30 June 2013. Of those, 10.8 and 8.8% in each database, respectively, were born prematurely. There were 29 967 Medicaid-insured infants and 16 310 commercially insured infants with an RSV hospitalization during their first year of life. Mean first-year RSV hospitalization costs were higher for preterm infants, ranging from $8324 and $10 570 for full-term infants to $15 839 and $19 931 for preterm infants 33–34 wGA, and to $39 354 and $40 813 for preterm infants <29 wGA, among Medicaid-insured and commercially insured infants, respectively. RSV hospitalizations also tended to be more severe among preterm infants, with longer lengths of stay, a higher proportion of infants admitted to the intensive care unit (ICU) and increased use of MV compared with full-term infants. Mean costs of RSV hospitalizations with a PICU admission ranged from approximately $35 000 to $89 000. In both Medicaid and commercial groups, costs were greater for infants hospitalized at <90 days of age compared with older infants.Conclusions:Infants who were born prematurely and those hospitalized at <90 days of age have more costly and more severe RSV hospitalizations during the first year of life. These findings demonstrate important differences in the costs and severity of first-year RSV hospitalizations of premature and full-term infants. These differences are likely to be obscured in combined analysis, in which full-term infants predominate. Clinical guidelines and health-care policies relating to RSV would benefit from the availability of data obtained from separate analyses of these two infant subgroups.

Haze is a risk factor contributing to the rapid spread of respiratory syncytial virus in children.

This study investigated whether respiratory syncytial virus (RSV) infection in children was associated with ambient temperature and air pollutants in Hangzhou, China. A distributed lag non-linear model (DLNM) was used to estimate the effects of daily meteorological data and air pollutants on the incidence of RSV infection among children. A total of 3650 childhood RSV infection cases were included in the study. The highest air pollutant concentrations were in January to May and October to December during the year. The yearly RSV-positive rate was 10.0% among children with an average age of 4.3months. The highest RSV-positive rate occurred among patients 0 to 3months old. Children under 6.5months old accounted for 80% of the total patients infected by RSV. A negative correlation was found between ambient temperature and RSV infection, and it was strongest with minimum ambient temperature (r=-0.804, P<0.001). There was a positive correlation between the infection rate and the particulate matter (PM) 2.5 (r=0.446, P<0.001), PM10 (r=0.397, P<0.001), SO2 (r=0.389, P<0.001), NO2 (r=0.365, P<0.001) and CO (r=0.532, P<0.001). The current study suggested that temperature was an important factor associated with RSV infection among children in Hangzhou. Air pollutants significantly increased the risk of RSV infection with dosage, lag and cumulative effects.