Respiratory Syncytial Virus In Young Children Research Articles

Development of innate and adaptive immunity to RSV in young children

Infection of the respiratory tract with respiratory syncytial virus (RSV) is common and occurs repeatedly throughout life with most severe disease occurring at the extremes of age: in young infants and the elderly. Effective anti-viral therapeutics are not available and therefore prevention has been the primary strategy for reducing the disease burden. Our current understanding of respiratory mucosal cell biology and the immune response within the respiratory tract is inadequate to prevent infection caused by a pathogen like RSV that does not disseminate outside of this environment. Gaps in our understanding of the activation of innate and adaptive immunity in response to RSV and the role of age upon infection also limit improvements in the design of therapeutics and vaccines for young infants. However, advancements in structural biology have improved our ability to characterize antibodies against viral proteins and in 2023 the first vaccines for those over 60 years and pregnant women became available, potentially reducing the burden of disease. This review will examine our current understanding of the critical facets of anti-RSV immune responses in infants and young children as well as highlight areas where more research is needed.

Impact of COVID-19 on viral respiratory infection epidemiology in young children: A single-center analysis.

BackgroundThe COVID-19 pandemic impacts different health aspects. Concomitant with the adoption of non-pharmaceutical interventions (NPIs) to reduce the spread of SARS-CoV-2, global surveillance studies reported a reduction in occurrence of respiratory pathogens like influenza A and B virus (IAV & IBV) and respiratory syncytial virus (RSV). We hypothesized to observe this collateral benefit on viral respiratory infection epidemiology in young children.MethodsRespiratory samples of children aged below 6 years, presenting at the outpatient clinic, emergency department, or pediatric infectious diseases department of the University Hospitals Leuven, between April 2017 and April 2021 were retrospectively analyzed. The occurrence (positivity rate), and seasonal patterns of viral respiratory infections were described. Chi-squared or Fisher's exact test (and Bonferroni correction) were used to explore differences in occurrence between 2020-2021 and previous 12-month (April to April) periods.ResultsWe included 3020 samples (453 respiratory panels, 2567 single SARS-CoV-2 PCR tests). IAV and IBV were not detected from March and January 2020, respectively. For IAV, positivity rate in 2020–2021 (0%, n = 0) was significantly different from 2018-2019 (12.4%, n = 17) (p < 0.001) and 2019-2020 (15.4%, n = 19) (p < 0.001). IBV positivity rate in 2020-2021 (0%, n = 0) was not significantly different from previous periods. RSV occurrence was significantly lower in 2020–2021 (3.2%, n = 3), compared to 2017-2018 (15.0%, n = 15) (p = 0.006), 2018–2019 (16.1%, n = 22) (p = 0.002) and 2019-2020 (22.8%, n = 28) (p < 0.001). The RSV (winter) peak was absent and presented later (March-April 2021). Positivity rate of parainfluenza virus 3 (PIV-3) was significantly higher in 2020-2021 (11.8%, n = 11) than 2017-2018 (1%, n = 1) (p = 0.002). PIV-3 was absent from April 2020 to January 2021, whereas no clear seasonal pattern was distinguished the other years. For the other viruses tested, no significant differences in occurrence were observed between 2020-2021 and previous periods. From March 2020 onwards, 20 cases (0.7%) of SARS-CoV-2 were identified.ConclusionThese findings reinforce the hypothesis of NPIs impacting the epidemiology of influenza viruses and RSV in young children. Compared to previous periods, no IAV and IBV cases were observed in the 2020-2021 study period, and the RSV peak occurred later. Since the pandemic is still ongoing, continuation of epidemiological surveillance, even on a larger scale, is indicated.

Clinical and Socioeconomic Burden of Respiratory Syncytial Virus in Iceland.

Respiratory syncytial virus (RSV), a very common pathogen, causes variable disease severity. In addition to considerable clinical burden on children, their families and healthcare facilities, RSV infections in children also carry significant direct and indirect socioeconomic burden. We analyzed data from 5 consecutive RSV seasons (2015-2020) and used virologically confirmed RSV infections and age <5 years as case definition. Clinical information was retrieved from electronic patient records. Costs were estimated by assuming an annual 30% attack rate and a combination of direct medical costs and calculations of societal costs of lost productivity. A total of 716 children younger than 5 years of age had confirmed RSV infection of which 254 needed hospitalizations, most of whom were previously healthy. The median length of admission was 3.6 days and 13 patients needed intensive care. The hospital admission incidence rate was 2.5/1000 children/year, but 9.1 for children younger than 1 years of age. The total annual cost of RSV was estimated at €4.3 million, of which 10% was direct healthcare costs. The clinical and socioeconomic disease burden of RSV in Iceland is substantial despite slightly lower hospital admission rates than other high-income countries. The prevention of RSV in young children, either through maternal or infant vaccination, has the potential to decrease both clinical and financial impact of the annual epidemics.

Evaluation of a standardised protocol to measure the disease burden of respiratory syncytial virus infection in young children in primary care

BackgroundA better understanding of the burden of respiratory syncytial virus (RSV) infections in primary care is needed for policymakers to make informed decisions regarding new preventive measures and treatments. The aim of this study was to develop and evaluate a protocol for the standardised measurement of the disease burden of RSV infection in primary care in children aged < 5 years.MethodsThe standardised protocol was evaluated in Italy and the Netherlands during the 2019/20 winter. Children aged < 5 years who consulted their primary care physician, met the WHO acute respiratory infections (ARI) case definition, and had a laboratory confirmed positive test for RSV (RT-PCR) were included. RSV symptoms were collected at the time of swabbing. Health care use, duration of symptoms and socio-economic impact was measured 14 days after swabbing. Health related Quality of life (HRQoL) was measured using the parent-proxy report of the PedsQL™4.0 generic core scales (2–4 years) and PedsQL™4.0 infant scales (0–2 years) 30 days after swabbing. The standardised protocol was evaluated in terms of the feasibility of patient recruitment, data collection procedures and whether parents understood the questions.ResultsChildren were recruited via a network of paediatricians in Italy and a sentinel influenza surveillance network of general practitioners in the Netherlands. In Italy and the Netherlands, 293 and 152 children were swabbed respectively, 119 and 32 tested RSV positive; for 119 and 12 children the Day-14 questionnaire was completed and for 116 and 11 the Day-30 questionnaire. In Italy, 33% of the children had persistent symptoms after 14 days and in the Netherlands this figure was 67%. Parents had no problems completing questions concerning health care use, duration of symptoms and socio-economic impact, however, they had some difficulties scoring the HRQoL of their young children.ConclusionRSV symptoms are common after 14 days, and therefore, measuring disease burden outcomes like health care use, duration of symptoms, and socio-economic impact is also recommended at Day-30. The standardised protocol is suitable to measure the clinical and socio-economic disease burden of RSV in young children in primary care.

Respiratory Syncytial Virus Disease Severity in Young Children.

Respiratory syncytial virus (RSV) is the leading cause of acute respiratory infections (ARIs) in hospitalized children. Although prematurity and underlying medical conditions are known risk factors, most of these children are healthy, and factors including RSV load and subgroups may contribute to severity. Therefore, we aimed to evaluate the role of RSV in ARI severity and determine factors associated with increased RSV-ARI severity in young children. Children aged <5 years with fever and/or ARI symptoms were recruited from the emergency department (ED) or inpatient settings at Vanderbilt Children's Hospital. Nasal and/or throat swabs were tested using quantitative reverse-transcription polymerase chain reaction for common respiratory viruses, including RSV. A severity score was calculated for RSV-positive children. From November 2015 through July 2016, 898 participants were enrolled, and 681 (76%) had at least 1 virus detected, with 191 (28%) testing positive for RSV. RSV-positive children were more likely to be hospitalized, require intensive care unit admission, and receive oxygen compared with children positive for other viruses. Higher viral load, White race, younger age, and higher severity score were independently associated with hospitalization in RSV-positive children. No differences in disease severity were noted between RSV A and RSV B. RSV was associated with increased ARI severity in young children enrolled from the ED and inpatient settings, but no differences in disease severity were noted between RSV A and RSV B. These findings emphasize the need for antiviral therapy and/or preventive measures such as vaccines against RSV in young children.

Multicenter evaluation of BD Veritor System and RSV K-SeT for rapid detection of respiratory syncytial virus in a diagnostic laboratory setting

The recently introduced BD Veritor System RSV laboratory kit (Becton Dickinson, Sparks, MD, USA) with automatic reading was evaluated and compared with the RSV K-SeT (Coris BioConcept, Gembloux, Belgium) for the detection of respiratory syncytial virus (RSV) using 248 nasopharyngeal aspirates of children younger than 6years old with respiratory tract infection. Compared to reverse transcriptase polymerase chain reaction as gold standard, both tests had an identical sensitivity of 78.1% and a specificity of 96.8% and 95.8% for the BD Veritor System and RSV K-SeT, respectively. Both antigen tests can be used to reliably confirm RSV in young children. However, a negative result does not definitively exclude the presence of RSV.

Safety and Immunogenicity of a Live Attenuated RSV Vaccine in Healthy RSV-Seronegative Children 5 to 24 Months of Age

Despite substantial morbidity associated with respiratory syncytial virus (RSV) infection, there is no licensed vaccine. MEDI-559 is a live attenuated intranasal vaccine candidate being developed for prevention of lower respiratory illness due to RSV in young children. This randomized, placebo-controlled study evaluated safety of MEDI-559 in healthy, RSV-seronegative children. MEDI-559 or placebo was administered on 3 occasions, 2 months apart. Primary safety was based on solicited symptoms (SSs) and adverse events (AEs) collected for 28 days after each dose. Nasal wash samples were collected 3 times after each dose (days 7-10, 12-18, 28-34) and at sick visits. Serum was collected for measuring antibody immune responses to RSV prior to first vaccination and 28 days post final dose. Long-term safety was monitored for 365 days from first dose. SSs were mild and frequent (MEDI-559 84%; placebo 91%); most common SSs were runny/stuffy nose, cough, and irritability/fussiness. AEs occurred in 67% MEDI-559 and 57% placebo recipients: most common AE was upper respiratory tract infection (MEDI-559 35%; placebo 23%). Higher incidence of medically attended lower respiratory illness within 28 days after dosing occurred in the MEDI-559 arm compared to placebo (none associated with vaccine virus shedding). There was no evidence of enhanced RSV disease. Vaccine virus was detected only in MEDI-559 recipients; shedding occurred in 56%subjects, primarily post dose 1. A functional immune response was observed in 59% and 9% MEDI-559 and placebo recipients, respectively, by an RSV microneutralization assay. Vaccine take, assessed by proportion that shed vaccine-type virus or had a seroresponse against RSV, was seen in 95% MEDI-559 subjects. MEDI-559 is therefore biologically active and immunogenic in this seronegative pediatric population. Although the frequency of SSs and AEs was not considered clinically significant, the increase in medically attended lower respiratory illnesses in the vaccine group warrants expanded safety studies.Trial RegistrationClinicalTrials.gov NCT00767416