Respiratory syncytial virus: desperately seeking solutions

Respiratory syncytial virus (RSV) infection remains a major public health problem, especially in younger children and the elderly. But several monoclonal antibodies, antivirals and vaccines, either recently launched or in development, offer new hope for RSV prevention and treatment.Copyright © 2023 Wiley Interface Ltd.

Impact of the COVID-19 pandemic on the seasonality of respiratory syncytial viral infection.

The article presents an overview of current trends in the epidemiology of respiratory syncytial viral (RSV) infection, including its seasonality, under the impact of the COVID-19 pandemic, both according to world literature and taking into account monitoring epidemiological studies conducted in the Russian Federation. A detailed description of the dynamics of RSV detection in the period 2020-2021 and the beginning of 2022 in Russia according to the results of the all-Russian epidemiological monitoring is given. Epidemiological studies in different regions of the world, including Russia, have revealed the absence of seasonal rises in the incidence of RSV infection, characteristic of previous years, in 2020 and winter-spring in 2021 under the influence of the COVID-19 pandemic. In 2021-2022, a sharp increase in the incidence and hospitalization of children was noted against the backdrop of a decrease in cases of a new coronavirus infection in all countries of the world, while the start time and duration of respiratory syncytial virus infection, typical for the prepandemic period, changed. Our previous studies have shown that in different years and in different regions of Russia, the start and end times of the epidemiological season may also not coincide, which makes it difficult to predict seasonal peaks in incidence, their duration and severity only on the basis of previously obtained data. This makes it expedient to extend the terms of passive specific prophylaxis with palivizumab for a year if there are indications for its use, including taking into account the data of epidemiological monitoring conducted in the Russian Federation.Copyright © 2022 Authors. All rights reserved.

Impact of the COVID-19 pandemic on the seasonality of respiratory syncytial viral infection

The article presents an overview of current trends in the epidemiology of respiratory syncytial viral (RSV) infection, including its seasonality, under the impact of the COVID-19 pandemic, both according to world literature and taking into account monitoring epidemiological studies conducted in the Russian Federation. A detailed description of the dynamics of RSV detection in the period 2020-2021 and the beginning of 2022 in Russia according to the results of the all-Russian epidemiological monitoring is given. Epidemiological studies in different regions of the world, including Russia, have revealed the absence of seasonal rises in the incidence of RSV infection, characteristic of previous years, in 2020 and winter-spring in 2021 under the influence of the COVID-19 pandemic. In 2021-2022, a sharp increase in the incidence and hospitalization of children was noted against the backdrop of a decrease in cases of a new coronavirus infection in all countries of the world, while the start time and duration of respiratory syncytial virus infection, typical for the prepandemic period, changed. Our previous studies have shown that in different years and in different regions of Russia, the start and end times of the epidemiological season may also not coincide, which makes it difficult to predict seasonal peaks in incidence, their duration and severity only on the basis of previously obtained data. This makes it expedient to extend the terms of passive specific prophylaxis with palivizumab for a year if there are indications for its use, including taking into account the data of epidemiological monitoring conducted in the Russian Federation. © 2022 Authors. All rights reserved.

Impact of the COVID-19 pandemic on the seasonality of respiratory syncytial viral infection.

The article presents an overview of current trends in the epidemiology of respiratory syncytial viral (RSV) infection, including its seasonality, under the impact of the COVID-19 pandemic, both according to world literature and taking into account monitoring epidemiological studies conducted in the Russian Federation. A detailed description of the dynamics of RSV detection in the period 2020-2021 and the beginning of 2022 in Russia according to the results of the all-Russian epidemiological monitoring is given. Epidemiological studies in different regions of the world, including Russia, have revealed the absence of seasonal rises in the incidence of RSV infection, characteristic of previous years, in 2020 and winter-spring in 2021 under the influence of the COVID-19 pandemic. In 2021-2022, a sharp increase in the incidence and hospitalization of children was noted against the backdrop of a decrease in cases of a new coronavirus infection in all countries of the world, while the start time and duration of respiratory syncytial virus infection, typical for the prepandemic period, changed. Our previous studies have shown that in different years and in different regions of Russia, the start and end times of the epidemiological season may also not coincide, which makes it difficult to predict seasonal peaks in incidence, their duration and severity only on the basis of previously obtained data. This makes it expedient to extend the terms of passive specific prophylaxis with palivizumab for a year if there are indications for its use, including taking into account the data of epidemiological monitoring conducted in the Russian Federation.Copyright © 2022 Authors. All rights reserved.

The Human Nose Organoid Respiratory Virus Model: an Ex Vivo Human Challenge Model To Study Respiratory Syncytial Virus (RSV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Pathogenesis and Evaluate Therapeutics.

There is an unmet need for preclinical models to understand the pathogenesis of human respiratory viruses and predict responsiveness to immunotherapies. Airway organoids can serve as an ex vivo human airway model to study respiratory viral pathogenesis; however, they rely on invasive techniques to obtain patient samples. Here, we report a noninvasive technique to generate human nose organoids (HNOs) as an alternative to biopsy-derived organoids. We made air-liquid interface (ALI) cultures from HNOs and assessed infection with two major human respiratory viruses, respiratory syncytial virus (RSV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infected HNO-ALI cultures recapitulate aspects of RSV and SARS-CoV-2 infection, including viral shedding, ciliary damage, innate immune responses, and mucus hypersecretion. Next, we evaluated the feasibility of the HNO-ALI respiratory virus model system to test the efficacy of palivizumab to prevent RSV infection. Palivizumab was administered in the basolateral compartment (circulation), while viral infection occurred in the apical ciliated cells (airways), simulating the events in infants. In our model, palivizumab effectively prevented RSV infection in a concentration-dependent manner. Thus, the HNO-ALI model can serve as an alternative to lung organoids to study respiratory viruses and test therapeutics. IMPORTANCE Preclinical models that recapitulate aspects of human airway disease are essential for the advancement of novel therapeutics and vaccines. Here, we report a versatile airway organoid model, the human nose organoid (HNO), that recapitulates the complex interactions between the host and virus. HNOs are obtained using noninvasive procedures and show divergent responses to SARS-CoV-2 and RSV infection. SARS-CoV-2 induces severe damage to cilia and the epithelium, no interferon-λ response, and minimal mucus secretion. In striking contrast, RSV induces hypersecretion of mucus and a profound interferon-λ response with ciliary damage. We also demonstrated the usefulness of our ex vivo HNO model of RSV infection to test the efficacy of palivizumab, an FDA-approved monoclonal antibody to prevent severe RSV disease in high-risk infants. Our study reports a breakthrough in both the development of a novel nose organoid model and in our understanding of the host cellular response to RSV and SARS-CoV-2 infection.

Resurgence of Respiratory Syncytial Virus in Children: An Out-of-Season Epidemic in Portugal.

INTRODUCTION: An out-of-season increase in respiratory syncytial virus (RSV) incidence was observed in Portugal from June 2021 onwards, revealing a continuing surge in cases throughout 2021/2022 autumn/winter. We aimed to describe this out-of-season epidemic and define its epidemic period, by analysing RSV incidence from week 40 of 2020 (2020-W40) to week 18 of 2022 (2022-W18). MATERIAL AND METHODS: Surveillance data on weekly RSV laboratory confirmed cases, in Portugal, was used to monitor RSV incidence using CUSUM test methodology for count data. RESULTS: In 2021-W23, the CUSUM score identified a significant increase in the risk of RSV. By that time, the percentage of RSV positive tests rose from 1% in 2021-W22 (3/265) to 6% in 2021-W23 (18/298). Despite a sharp decrease in RSV incidence on 2021-W33 and on 2022-W02, the CUSUM score stayed over the limit up to 2022-W07, indicating that the RSV activity remained at an epidemic level. Distinct peaks of RSV cases were observed between 2021-W30 and 2021-W32 (average of 77 RSV cases per week) and between 2021-W39 and 2021-W41 (average of 79 RSV cases per week) with positivity rates around 60%. CONCLUSION: An out-of-season RSV epidemic was identified, with a longer epidemic period compared with previous seasons. Possible reasons include relaxation of COVID-19 physical distancing measures and a greater proportion of population susceptible to disease. As several factors may change the pattern of RSV activity, countries should implement year-round surveillance RSV surveillance systems. These findings might have an impact on public health planning regarding future RSV surges, namely, on the palivizumab prophylaxis period for high-risk infants.

How has the SARS-CoV-2 pandemic changed the epidemiology and management of acute bronchiolitis?

OBJECTIVE: SARS-COV-2 pandemic profoundly impacted acute bronchiolitis epidemiology worldwide, especially respiratory syncytial virus (RSV) diffusion and the burden of disease, with remarkable implications on the management of health resources. We aimed to study the epidemiology and clinical course of bronchiolitis in the past 5 years in our region and to assess the trends that occurred during and after the SARS-COV-2 pandemic. METHODS: We conducted an observational study including all children aged 0-2 years with bronchiolitis admitted to a tertiary children's hospital during the last 5 years. Demographic, clinical, and microbiological data were collected. Comparisons between patient subgroups were carried out. RESULTS: A total of 647 patients admitted for bronchiolitis were included (median age 78 days). Molecular diagnostic tests were performed in 617 patients (95.4%) with RSV detected in 51.5% of patients in prepandemic years and 74.5% in pandemic years. Through the study period, we observed a progressive increase in the number of children requiring respiratory support, RSV infections, and children with a history of prematurity. Conversely, this was not true for mechanical ventilation, duration of respiratory support, intensive care unit admission, and length of stay. CONCLUSIONS: Clinical course and epidemiology of bronchiolitis showed a significant change through the study years with a heavy impact during the 2021-2022 season. The increase in the number of patients requiring respiratory support, although not associated with an increase in mechanical ventilation, may be explained by the higher prevalence of RSV. The change in epidemiology highlights the importance of surveillance systems to monitor RSV circulation, to plan prophylactic strategies, and prepare healthcare systems.

Respiratory syncytial virus, recurrent wheeze and asthma: A narrative review of pathophysiology, prevention and future directions.

Globally, respiratory syncytial virus (RSV) is the leading cause of bronchiolitis and pneumonia in young children, and the association between severe RSV disease and later recurrent wheeze and asthma is well established. Whilst a causal link between RSV and wheeze/asthma is not yet proven, immunological evidence suggests skewing towards a Th2-type response, and dampening of IFN-γ antiviral immunity during RSV infection underpins airway hyper-reactivity in a subset of susceptible children after RSV infection. Age at primary RSV infection, viral co-infection and genetic influences may act as effect-modifiers. Despite the significant morbidity and mortality burden of RSV disease in children, there is currently no licensed vaccine. Recent advancements in RSV preventatives, including long-acting monoclonal antibodies and maternal vaccinations, show significant promise and we are on the cusp of a new era in RSV prevention. However, the potential impact of RSV preventatives on subsequent wheeze and asthma remains unclear. The ongoing COVID-19 pandemic and associated public health measures have disrupted the usual seasonality of RSV. Whilst this has posed challenges for health-care services it has also enhanced our understanding of RSV transmission. The near absence of RSV cases during the first year of the pandemic in the context of strict public health measures has provided a rare opportunity to study the impact of delayed age of primary RSV infection on asthma prevalence. In this review, we summarise current understanding of the association between RSV, recurrent wheeze and asthma with a focus on pathophysiology, preventative strategies and future research priorities.

Study Pre-protocol for "BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study".

Background: Bronchiolitis (most frequently caused by respiratory syncytial virus; RSV) is a common winter disease predominantly affecting children under one year of age. It is a common reason for presentations to an emergency department (ED) and frequently results in hospital admission, contributing to paediatric units approaching or exceeding capacity each winter. During the SARS-CoV-2 pandemic, the circulation of RSV was dramatically reduced in the United Kingdom and Ireland. Evidence from the Southern Hemisphere and other European countries suggests that as social distancing restrictions for SARS-CoV-2 are relaxed, RSV infection returns, causing delayed or even summer epidemics, with different age distributions. Study question: The ability to track, anticipate and respond to a surge in RSV cases is critical for planning acute care delivery. There is an urgent need to understand the onset of RSV spread at the earliest opportunity. This will influence service planning, to inform clinicians whether the population at risk is a wider age range than normal, and whether there are changes in disease severity. This information is also needed to inform decision on the timing of passive immunisation of children at higher risk of hospitalisation, intensive care admission or death with RSV infection, which is a public health priority. Methods and likely impact: This multi-centre prospective observational cohort study will use a well-established research network (Paediatric Emergency Research in the UK and Ireland, PERUKI) to report in real time cases of RSV infection in children aged under two years, through the collection of  essential, but non-identifying patient information. Forty-five centres will gather initial data on age, index of multiple deprivation quintile, clinical features on presentation, and co-morbidities. Each case will be followed up at seven days to identify treatment, viral diagnosis and outcome.  Information be released on a weekly basis and used to support clinical decision making.

Respiratory syncytial virus bronchiolitis in congenital diaphragmatic hernia: A systematic review of prevalence rates and palivizumab prophylaxis.

BACKGROUND: The seasonality of respiratory syncytial virus (RSV) epidemics have been disrupted during the COVID-19 pandemic, possibly because of lockdowns and social restrictions reducing viral transmission. Given uncertainties around the severity of upcoming RSV bronchiolitis epidemics, debate exists whether palivizumab (RSV prophylaxis) should be administered to infants with Congenital Diaphragmatic Hernia (CDH), who may be vulnerable due to lung hypoplasia and pulmonary hypertension. AIM: To evaluate (1) if CDH infants have higher risk of admission with RSV bronchiolitis than infants in the general population; (2) if palivizumab prophylaxis may reduce this risk. METHODS: We included all eligible studies examining the risk(s) of RSV-positive bronchiolitis requiring hospital admission in (1) CDH infants without palivizumab prophylaxis versus infants in the general population and (2) CDH infants with prophylaxis versus CDH infants without prophylaxis. The primary outcome evaluated was the risk of admission with RSV bronchiolitis. Data are reported descriptively and meta-analysed when appropriate. RESULTS: Three eligible retrospective cohort studies were identified: one study found CDH to be an independent risk factor for RSV hospitalisation (odds ratio, 3.30; 95% confidence interval [CI], 2.01-4.4); two studies compared RSV hospitalisation rates in CDH patients who had palivizumab versus those that did not. The pooled risk ratio was 1.11 (95% CI, 0.29-4.23; p = .88). Overall, the quality of evidence was considered poor and one study was industry funded. CONCLUSION: Whether CDH infants are at particular risk of severe bronchiolitis remains unclear. There is no evidence from this current systematic review that CDH infants should routinely receive palivizumab vaccination prophylaxis.

Delayed respiratory syncytial virus epidemic in children after relaxation of COVID-19 physical distancing measures, Ashdod, Israel, 2021.

Following low incidence of respiratory syncytial virus (RSV) infections in 2020 during the COVID-19 pandemic, we noted a resurgence in hospitalised children in spring/summer 2021 following relaxation of public health measures. We compared this outbreak to previous autumn/winter seasons. We found higher weekly case numbers and incidence rates, more cases from urban neighbourhoods with lower socioeconomic status, and similar clinical presentation and severity. Public health implications include the re-evaluation of palivizumab administration and the need for surge capacity planning.