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Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infection in young children and the second leading cause of infant death worldwide. While global circulation has been extensively studied for respiratory viruses such as seasonal influenza, and more recently also in great detail for SARS-CoV-2, a lack of global multi-annual sampling of complete RSV genomes limits our understanding of RSV molecular epidemiology. Here, we capitalise on the genomic surveillance by the INFORM-RSV study and apply phylodynamic approaches to uncover how selection and neutral epidemiological processes shape RSV diversity. Using complete viral genome sequences, we show similar patterns of site-specific diversifying selection among RSVA and RSVB and recover the imprint of non-neutral epidemic processes on their genealogies. Using a phylogeographic approach, we provide evidence for air travel governing the global patterns of RSVA and RSVB spread, which results in a considerable degree of phylogenetic mixing across countries. Our findings highlight the potential of systematic global RSV genomic surveillance for transforming our understanding of global RSV spread. This study on respiratory syncytial virus (RSV) reveals global genomic gaps. Using INFORM-RSV data, it uncovers selection’s impact on RSVA and RSVB diversity. Analysing full genomes, it highlights non-neutral epidemic processes. The research emphasises air travel’s influence on global spread, underscoring the need for comprehensive RSV genomic surveillance.

BackgroundRespiratory syncytial virus (RSV) is the most common cause of hospitalisation for lower respiratory tract infection (LRTI) in children. RSV LRTI during early childhood may increase susceptibility to recurrent wheezing and asthma.Research questionThe aim of this study was to describe the pulmonary sequelae at 1 and 2 years of age following RSV LRTI hospitalisation during the first year of life in term infants.Study design and methodsA longitudinal case–control study was undertaken from April 2016 to December 2019. Cases constituted children hospitalised with PCR-confirmed RSV LRTI during infancy and controls were children not previously hospitalised with LRTI. A questionnaire detailing environmental and medical history, as well as a modified International Study of Asthma and Allergies (ISAAC) questionnaire, was administered, and pulmonary function testing, including oscillometry, tidal breath flow-volume loops and multiple breath wash-out, was performed, at one and two years of age.ResultsOne (n=308) and two-year-old (n=214) cases were more likely than one (n=292) and two-year-old (n=209) controls to have experienced clinical pulmonary symptoms, including wheezing ((55% vs 24%; p<0.001) and (61% vs 16%; p<0.001)), received treatment for wheezing ((17 vs 8%; p<0.001) and (51 vs 6%; p<0.001)) and had any admissions for wheezing ((31 vs 6%; p<0.001) and (46 vs 1.4%; p<0.001)) or any LRTI ((24 vs 2%; p<0.001) and (32 vs 1.4%; p<0.001)), after the initial RSV hospitalisation. RSV LRTI during infancy was associated with an increase in airway resistance by two years (22.46 vs 20.76 hPa.s.l-1 (p=0.022)), along with a decrease in compliance at both one (−4.61 vs −3.09 hPa.s/l (p<0.001)) and two years (−0.99 vs 0.33 hPa.s/l1 (p<0.001)). There was an increased work of breathing at one year, but this was no longer present at two years.InterpretationRSV LRTI during infancy in cases was associated with more clinical and pulmonary function sequelae through to two years of age.

Diagnosis of pneumonia remains challenging. Digitally recorded and remote human classified lung sounds may offer benefits beyond conventional auscultation, but it is unclear whether classifications differ between the two approaches. We evaluated concordance between digital and conventional auscultation. We collected digitally recorded lung sounds, conventional auscultation classifications and clinical measures and samples from children with pneumonia (cases) in low-income and middle-income countries. Physicians remotely classified recordings as crackles, wheeze or uninterpretable. Conventional and digital auscultation concordance was evaluated among 383 pneumonia cases with concurrently (within 2 hours) collected conventional and digital auscultation classifications using prevalence-adjusted bias-adjusted kappa (PABAK). Using an expanded set of 737 cases that also incorporated the non-concurrently collected assessments, we evaluated whether associations between auscultation classifications and clinical or aetiological findings differed between conventional or digital auscultation using χ tests and logistic regression adjusted for age, sex and site. Conventional and digital auscultation concordance was moderate for classifying crackles and/or wheeze versus neither crackles nor wheeze (PABAK=0.50), and fair for crackles-only versus not crackles-only (PABAK=0.30) and any wheeze versus no wheeze (PABAK=0.27). Crackles were more common on conventional auscultation, whereas wheeze was more frequent on digital auscultation. Compared with neither crackles nor wheeze, crackles-only on both conventional and digital auscultation was associated with abnormal chest radiographs (adjusted OR (aOR)=1.53, 95% CI 0.99 to 2.36; aOR=2.09, 95% CI 1.19 to 3.68, respectively); any wheeze was inversely associated with C-reactive protein >40 mg/L using conventional auscultation (aOR=0.50, 95% CI 0.27 to 0.92) and with very severe pneumonia using digital auscultation (aOR=0.67, 95% CI 0.46 to 0.97). Crackles-only on digital auscultation was associated with mortality compared with any wheeze (aOR=2.70, 95% CI 1.12 to 6.25). Conventional auscultation and remotely-classified digital auscultation displayed moderate concordance for presence/absence of wheeze and crackles among cases. Conventional and digital auscultation may provide different classification patterns, but wheeze was associated with decreased clinical severity on both.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in children, and is associated with long-term pulmonary sequelae for up to 30 years after infection. The mainstay of RSV management is supportive therapy such as supplemental oxygen. Palivizumab (Synagis™–AstraZeneca), a monoclonal antibody targeting the RSV F protein site II, has been licensed for the prevention of RSV in high-risk groups since 1998. There has been recent promising progress in preventative strategies that include vaccines and long-acting, high-potency monoclonal antibodies. Nirsevimab (Beyfortus™–AstraZeneca/Sanofi), a monoclonal antibody with an extended half-life, has recently been registered in the European Union and granted licensure by the US Food and Drug Administration. Furthermore, a pre-fusion sub-unit protein vaccine has been granted licensure for pregnant women, aimed at protecting their young infants, following established safety and efficacy in clinical trials (Abrysvo™–Pfizer). Also, multiple novel antiviral therapeutic options are in early phase clinical trials. The next few years have the potential to change the landscape of LRTI through improvements in the prevention and management of RSV LRTI. Here, we discuss these new approaches, current research, and clinical trials in novel therapeutics, monoclonal antibodies, and vaccines against RSV infection in infants and children.

Respiratory syncytial virus (RSV) is the most common cause of lower respiratory tract infection (LRTI) in children, causing approximately 3.6 million hospitalizations per year, and has been associated with long-term pulmonary sequelae for up to 30 years after infection, yet preventative strategies and active treatment options remain elusive. The associated morbidity and healthcare related costs could be decreased substantially with the development of these much-needed medications. After an initial false start in the development of an RSV vaccine, gradual progress is now being made with the development of multiple vaccine candidates using numerous different mechanisms of action. Furthermore, nirsevimab, a new monoclonal antibody for the prevention of RSV, has recently been registered in the European Union. New novel treatments for RSV infection are also in the pipeline, which would provide the clinician with much needed ammunition in the management of the acute disease. The next few years have the potential to change the landscape of LRTI forever through the prevention and management of RSV LRTI and thereby decrease the mortality and morbidity associated with it. In this review, we discuss these new approaches, current research, and clinical trials in monoclonal antibody and vaccine development against RSV.

Introduction: Foreign body aspiration is a common and often serious problem in paediatric patients. Approximately 80% of paediatric foreign body aspiration episodes occur in children younger than 3 years. Almost 90% of aspirated foreign bodies are non-radiodense and therefore not seen on radiographs. Clinical presentation may be subtle and can become a diagnostic dilemma, particularly if there is no witnessed aspiration. Aim: An educational poster on a radiological approach to aspirated non-radiodense foreign bodies. Methods: We present serial chest radiographs of bronchoscopically confirmed non-radiodense foreign bodies. Conclusion: Knowledge about the different radiological features suspicious for foreign body aspiration is essential and can guide appropriate intervention including bronchoscopic retrieval, which may prevent permanent pulmonary sequelae.

Background: Pulmonary underdevelopment is categorised into three groups: pulmonary agenesis, pulmonary aplasia and pulmonary hypoplasia. Pulmonary agenesis is the complete absence of the lung parenchyma, bronchus and lung vasculature. Pulmonary aplasia is characterised by the absence of the lung parenchyma and pulmonary vasculature; however, there is a rudimentary blind-ending bronchus present. Pulmonary hypoplasia is defined by the presence of a bronchus and rudimentary lung parenchyma with a reduction in number and size of airways, alveoli and pulmonary vasculature. Objective: This is an educational poster in the form of a quiz to identify and differentiate the type of pulmonary underdevelopment according to imaging features, associations and aetiology. Method: Radiological images of patients with pulmonary underdevelopment, who presented to the Paediatric Department of Chris Hani Baragwanath Academic Hospital, were selected. Conclusion: It is reported that up to 50% of patients with pulmonary agenesis and pulmonary aplasia have at least one other systemic congenital abnormality. Secondary pulmonary hypoplasia is more common than primary pulmonary hypoplasia and the aetiology is often evident on the imaging series. Radiological imaging is essential in differentiating the type of pulmonary underdevelopment.

Non-pharmaceutical interventions affected the circulation of and illness due to endemic respiratory pathogens during the COVID-19 pandemic. We investigated the incidence of admissions to hospital for overall and specific pathogen-associated lower respiratory tract infection (LRTI) during the COVID-19 pandemic compared with incidence in the pre-pandemic period. In this observational study, we analysed surveillance data for children younger than 5 years from two public hospitals in Soweto, South Africa, for all-cause LRTI, respiratory syncytial virus (RSV), influenza, human metapneumovirus, and Bordetella pertussis from Jan 1, 2015 to Dec 31, 2022. Data were obtained from an electronic database that includes information for all admissions to the general paediatric wards at the two hospitals, automatically identified by a computer program. We excluded children admitted to hospital with incidental SARS-CoV-2 infection or COVID-19 without LRTI diagnosis. Incidence during COVID-19 pandemic years (2020, 2021, and 2022) were compared with pre-pandemic rates (2015–19). Overall, there were 42 068 all-cause hospital admissions, including 18 303 all-cause LRTI hospital admissions, from Jan 1, 2015, to Dec 31, 2022, 17 822 (42·4%) of whom were female, 23 893 (57·0%) were male, and 353 (0·8%) had missing data. All-cause LRTI incidence risk ratio (IRR) was 30% lower in 2020 (IRR 0·70, 95% CI 0·67–0·74) and 13% lower in 2021 (0·87, 0·83–0·91), but 16% higher in 2022 (1·16, 1·11–1·21) compared with the pre-pandemic period. Furthermore, compared with the pre-pandemic period, incidence of RSV-associated LRTI (0·52, 0·45–0·58), influenza-associated LRTI (0·05, 0·02–0·11), and pulmonary tuberculosis (0·52, 0·41–0·65) were lower in 2020, with similar trends observed for human-metapneumovirus-associated LRTI, pertussis, and invasive pneumococcal disease (IPD). Compared with the pre-pandemic period, by 2022, RSV-associated LRTI incidence was similar (1·04, 0·95–1·14) and influenza-associated LRTI showed a non-significant increase (1·14, 0·92–1·39), whereas incidence remained lower for tuberculosis (0·79, 0·65–0·94) and IPD (0·51, 0·24–0·99). In 2022, the incidence of COVID-19-associated LRTI hospital admission (65 per 100 000 children younger than 5 years) was lower than pre-pandemic RSV-associated LRTI (0·23, 0·19–0·27) but higher than pre-pandemic influenza-associated LRTI (1·19, 0·97–1·45), although the difference was not significant. All-cause LRTI death in 2022 (57 per 100 000 children younger than 5 years) was 28% higher than in the pre-pandemic period (1·28, 1·03–1·58). The higher incidence of all-cause LRTI admissions to hospital in 2022 compared with the pre-pandemic period is partly due to ongoing COVID-19 admission to hospital, and could worsen if other endemic respiratory pathogens revert to pre-pandemic incidence. Interventions, including the introduction of vaccines for people who are pregnant that aim to prevent RSV and possibly COVID-19 in young children, are warranted. The Bill & Melinda Gates Foundation.

Nirsevimab is an extended half-life monoclonal antibody to the respiratory syncytial virus (RSV) fusion protein that has been developed to protect infants for an entire RSV season. Previous studies have shown that the nirsevimab binding site is highly conserved. However, investigations of the geotemporal evolution of potential escape variants in recent (ie, 2015–2021) RSV seasons have been minimal. Here, we examine prospective RSV surveillance data to assess the geotemporal prevalence of RSV A and B, and functionally characterise the effect of the nirsevimab binding-site substitutions identified between 2015 and 2021. We assessed the geotemporal prevalence of RSV A and B and nirsevimab binding-site conservation between 2015 and 2021 from three prospective RSV molecular surveillance studies (the US-based OUTSMART-RSV, the global INFORM-RSV, and a pilot study in South Africa). Nirsevimab binding-site substitutions were assessed in an RSV microneutralisation susceptibility assay. We contextualised our findings by assessing fusion-protein sequence diversity from 1956 to 2021 relative to other respiratory-virus envelope glycoproteins using RSV fusion protein sequences published in NCBI GenBank. We identified 5675 RSV A and RSV B fusion protein sequences (2875 RSV A and 2800 RSV B) from the three surveillance studies (2015–2021). Nearly all (25 [100%] of 25 positions of RSV A fusion proteins and 22 [88%] of 25 positions of RSV B fusion proteins) amino acids within the nirsevimab binding site remained highly conserved between 2015 and 2021. A highly prevalent (ie, >40·0% of all sequences) nirsevimab binding-site Ile206Met:Gln209Arg RSV B polymorphism arose between 2016 and 2021. Nirsevimab neutralised a diverse set of recombinant RSV viruses, including new variants containing binding-site substitutions. RSV B variants with reduced susceptibility to nirsevimab neutralisation were detected at low frequencies (ie, prevalence <1·0%) between 2015 and 2021. We used 3626 RSV fusion-protein sequences published in NCBI GenBank between 1956 and 2021 (2024 RSV and 1602 RSV B) to show that the RSV fusion protein had lower genetic diversity than influenza haemagglutinin and SARS-CoV-2 spike proteins. The nirsevimab binding site was highly conserved between 1956 and 2021. Nirsevimab escape variants were rare and have not increased over time. AstraZeneca and Sanofi.

Respiratory Syncytial Virus (RSV) is the commonest cause of lower respiratory tract infection (LRTI) and hospitalization for LRTI in children. RSV LRTI during early childhood may increase susceptibility to recurrent wheezing and asthma. The objective of this study was to determine the pulmonary sequelae at one and two years of age following RSV LRTI hospitalization in term infants.A longitudinal case-control study was undertaken in Johannesburg from April 2016 to December 2019. Cases constituted infants previously hospitalized with PCR-confirmed RSV LRTI; and controls were well infants not previously hospitalized with LRTI. A questionnaire detailing environmental and medical history, as well as a modified ISAAC questionnaire, was administered, and pulmonary function testing, including forced oscillation technique, tidal breath flow-volume loops, and multiple breath wash-out, was performed, at one and two years of age.One (n=308) and two-year-old (n=214) cases were more likely than one (n=292) and two-yearold (n=209) controls to have experienced clinical pulmonary symptoms, including wheezing or whistling in the chest, received treatment for wheezing or whistling in the chest, and had any admissions for wheezing or whistling in the chest or any chest infection, after the initial RSV LRTI during infancy.Pulmonary function testing reported that RSV LRTI during infancy led to an increase in airway resistance by two years, along with a decrease in compliance at both one and two years. There was an increased work of breathing at one year, but this was no longer present at two years. The expiratory time was decreased, while the expiratory flow parameters, as well as the time to peak expiratory flow to total expiratory time ratio were increased. FRC and LCI were abnormal at one year but had returned to normal at two years.This study described the first set of pulmonary function indices in healthy one and two-year-old black African children from a LMIC.Children hospitalized with RSV LRTI during infancy had more clinical and pulmonary function sequelae through to two years of age when compared to healthy controls. Whether prevention of RSV LRTI during early infancy would reduce the risk for subsequent pulmonary sequelae warrants further investigation.