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REspiratory Syncytial virus Consortium in EUrope - Sofia ref.: 116019

Periodic Reporting for period 5 - RESCEU (REspiratory Syncytial virus Consortium in EUrope - Sofia ref.: 116019)

Reporting period: 2021-01-01 to 2021-12-31

Human Respiratory Syncytial Virus (RSV) is the most commonly identified pathogen in children with acute lower respiratory infections (ALRI) presenting as pneumonia or bronchiolitis. It causes severe disease in the very young, elderly and in high risk groups like those with congenital heart disease, congenital lung disease, immunosuppression etc. RESCEU’s aim is to integrate and exploit existing knowledge and data to provide greater insights into the impact of RSV on health systems and societies throughout Europe, and to engage stakeholders to improve strategic planning and decision-making. It also seeks to access existing clinically annotated biological specimens from prospective studies and to supplement this with bespoke clinical studies to create a powerful new bio-repository for future research. The collaboration within the Consortium has been very productive during these last five years of the project and has progressed according to the plan.
Systematic literature review on RSV and current estimates of burden of disease (WP1) : RESCEU has conducted systematic reviews and assembled unpublished data to inform RSV epidemiology and quantify disease burden (including sequelae) and its resulting economic burden. These systematic reviews have also shed new light on costs of management of RSV-ALRI in young children and older adults; global RSV seasonality association between RSV and RW and asthma in childhood; risk factors for RSV associated ALRI hospitalisation and mortality in young children; RSV comorbidities in adults including the elderly. The project has also revised the global RSV disease burden estimates in children younger than five years with expanded dataset and improved methodology. This systematic review has revealed a substantial RSV morbidity and mortality burden in 0-<6m ; higher community incidence vs lower hospitalisation rate in LMICs highlights poor access to care and limited beds and considerable out-of-hospital RSV mortality burden in LMICs. Consolidation of health care systems data (WP2) : To assess healthcare burden in all age groups (including young children and older adults) RESCEU has accessed relevant national and regional routine health databases, mortality and viral laboratory data. This has resulted in time series models for hospital admissions attributable to RSV has contributed to establish an association between RSV and subsequent wheeze / asthma. RESCEU has fostered interactions between national public health agencies across Europe National and large-scale surveillance systems (ECDC; WHO) to promote data sharing on RSV across Europe and reached consensus on RSV surveillance framework in Europe. The project has engaged with international organisations to foster collaboration and knowledge exchange including WHO and ECDC. A structured systematic review of clinical practice guidelines for diagnosis and management of RSV has highlighted the importance to improve quality of guidelines and promote best practice through promoting the use of best evidence and conducting audits of adherence to current guidelines. Retrospective resource use analyses from existing databases /networks. (WP3): RESCEU has developed a framework to estimate the economic burden of RSV disease, cost-effectiveness of interventions against RSV, and questionnaires to collect data on direct and indirect costs and health outcomes in the observational and case-control studies. Based on the data generated, a generic protocol, detailed collection tools for data analyses on costs and resource use, customised to the country-specific health care characteristics have been produced This has also resulted in several models for impact estimation and the development of database for input parameters. RESCEU has also carried out continuous analyses on cost and disease burden estimates from the literature, with the aim to use them in burden disease models. These estimates have been made for low and lower-middle income countries. Papers on RSV disease, cost effectiveness and cost analyses have been published. Further estimates for the European high-income countries have been submitted. Prospective data collection. (WP4) : Following the beginning of recruitment at all sites, a total 1007 ARTI visits have been recorded until December 2019. For the birth cohort study, active follow up during the RSV season finished in April 2020 and results of RSV PCR of samples of all ARTI episodes were available in the first quarter of 2021. Also in 2021, the first year follow up of all the infants in this cohort and data cleaning process have been largely completed. The serology analysis for the COPD cohort to supplement data from PCR testing begun and an online database of biobanked samples has been established by each site. A framework for access to these samples beyond the lifetime of RESCEU is being developed. WP4 has published 5 manuscripts, a further three under review prior to publication Presumed risk factors and biomarkers for RSV-related severe disease and related sequelae (WP5): Genome wide genetic association study on biobanked samples to identify biomarkers associated with characteristics of protection and severity of RSV disease and sequalae of RSV infection has been undertaken. Three systematic review s of the literature relating to biomarkers of RSV infection have been completed and several studies are ongoing to identify biomarkers associated with characteristics of protection from and severity of RSV diseases. During 2021, WP5 has published two papers and currently has one manuscript under peer review. Project management and outreach to stakeholders. (WP6) : WP6 has commissioned two Journal of Infectious Diseases (JID) supplements to publish outputs from RESCEU project. WP6 has also been very active in pursuing RESCEU´s sustainability and it managed to secure a follow-up funded IMI project following the publication of a restricted call. Furthermore, data management plan has been updated and the legal process for ensuring sustainability of RESCEU data and sample has been taken forward. Several communication and outreach activities have been carried out including the 3rd RSV Awareness Campaign, RSV awareness as part of the Respiratory Health Campaign by The Guardian and disseminating the findings from RESCEU publications through Twitter.
RESCEU will provide sustainable long-term impact on RSV disease burden and thus make a significant contribution to improved health and wellbeing in Europe. RESCEU will form the platform for upcoming future actions on RSV and even other pathogens which are identified as a priority for action in Europe.

It has produced a biobank with respiratory and other specimen, estimates of RSV infection by severity by prospective cohort studies in both infants and older adult, and prospectively collected data on costs and quality of life to inform models CE models.

Furthermore, RESCEU has achieved a vibrant PPP, engage and increase patient involvement in research design and update. Amongst its main outputs it has generated 46 papers in 2 JID supplements to inform policy and reasearch. It has produced regional and national estimates for EU and RSV surveillance recommendations. RESCEU outputs have also informed ECDC decision to request to make RSV notifiable disease.
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