Beatrix Kele

Background: Effective community surveillance of respiratory diseases relies on the timely collection and analysis of high quality clinical and virology data. The aim was to develop interactive dashboards for general practice, public health, and researcher groups. This would improve the visualisation, utilisation, and quality of virology data from an English sentinel network, support disease trend monitoring, early outbreak response, and thereby reduce poor health outcomes and their societal impact. Methods: The study was conducted in the Oxford-Royal College of General Practitioners (RCGP), Research and Surveillance Centre (RSC) sentinel network sponsored by the UK Health Security Agency (UKHSA). A collaborative user-centred design (UCD) approach was used to identify three use cases for general practices, national public health collaborators, and researchers in the internal team. Reference laboratory virology data, and electronic primary care health records were processed, cleaned, linked, and aggregated in a secure Trusted Research Environment (TRE). Dashboards were developed using Microsoft Power BI (Business Intelligence). The effectiveness, usability, and user satisfaction of the dashboards were not formally evaluated. Results: Interactive dashboards were co-designed to present spatiotemporal trends of circulating respiratory viruses in the community, in near real-time, with weekly updates on a Wednesday until the previous week ending on Sunday. The dashboard allowed primary care users to filter data to their own results, and it presented key metrics such as virus positivity rates, with benchmarked targets for team incentives. The dashboard also supported public health planning, and research and surveillance activities of the internal RSC team. Conclusion: The user-centred dashboards created a data feedback loop. Future work requires formal evaluation of usage metrics, user impact and satisfaction, data quality, and the quality of virology samples.

Background Respiratory syncytial virus (RSV) is a virus with two antigenic types, A and B, that cause significant morbidity and mortality in infants globally. A recently developed maternal vaccination based on the prefusion F protein (“RSVpreF”) could have a significant impact on disease burden, if introduced globally. Whether or not the effectiveness of this vaccine is affected by circulating viral genomic variability is currently unknown. Objectives To examine whether the vaccine effectiveness of maternal RSVpreF administration in preventing hospitalisation in infants is affected by RSV type or lineage. Methods We will conduct whole genome sequencing of RSV positive samples from infants hospitalised with acute lower respiratory tract infection (ALRI) in the 2024-2025 winter season, at multiple hospitals in England and Scotland, to calculate the relative vaccine effectiveness (rVE) of maternal RSVpreF vaccination by virus type (RSV-A and RSV-B). rVE will be calculated using a case control logistic regression with adjustment by infant age and admission date; sex, socioeconomic status and hospital location will be included as potential confounders if they are associated with a >3% change in rVE. We will also perform a test negative design to examine the VE for RSV-A and RSV-B separately, using RSV-negative controls from hospitals where cases were admitted. Finally, we will compare viral lineages in vaccinated versus unvaccinated infants. Results and conclusions Our study will identify whether currently circulating RSV genomic variability impacts on rVE. Confirmation of the null hypothesis - that there is no impact of viral genomic variability on rVE – will provide reassurance to policymakers and public health bodies as RSVpreF is rolled out globally. Conversely, an association between RSV type or lineage and decreased vaccine effectiveness will highlight the need for the enhanced comprehensive national and global molecular surveillance of RSV.

Background The World Health Organisation recommends integrating viral genome sequences and sentinel surveillance data. We report progress in linking clinical, virology, and sequence data to enable genomic surveillance of influenza, respiratory syncytial virus (RSV), and severe-acute-respiratory-syndrome coronavirus-2 (SARS-CoV-2). Methods We linked individual-level clinical data from the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) sentinel network to virology results from the UK Health Security Agency (UKHSA) reference virology laboratory. We identify where publicly accessible repositories, the Global Initiative on Sharing All Influenza Data (GISAID), or others hold viral genome sequence data from test-positive cases. Our metadata also identifies test-negative controls contemporaneous to test-positive cases. We summarise the scope of data availability in the Wellcome Quinquagenarian (QQG) biomedical resource. Results We report respiratory virus sampling for influenza, RSV, and SARS-CoV-2 between 1992 and 2023. Samples were collected from a nationally representative subset of RSC general practices participating in the virological surveillance programme. QQG contains 13,665 positive influenza samples, 3,791 positive RSV samples, and 5,068 positive SARS-CoV2 samples. There were 2,819 sequenced influenza genomes, of which 97.1% were linked to clinical records, 1,251 sequenced RSV genomes of which 96.8 were linked to clinical records, and 2,486 sequenced SARS-CoV-2 genomes of which 98.9% were linked to clinical records. Conclusion We have described the scale of QQG, created to enable genomic surveillance linked to clinical metadata to facilitate research on the impact of different viral variants on clinical outcomes, vaccine effectiveness, and therapeutic strategies.

Background: We report 2023/2024 season interim influenza vaccine effectiveness for three studies, namely, primary care in Great Britain, hospital settings in Scotland and hospital settings in England.Methods: A test negative design was used to estimate vaccine effectiveness.Results: Estimated vaccine effectiveness against all influenzas ranged from 63% (95% confidence interval 46 to 75%) to 65% (41 to 79%) among children aged 2–17, from 36% (20 to 49%) to 55% (43 to 65%) among adults 18–64 and from 40% (29 to 50%) to 55% (32 to 70%) among adults aged 65 and over.Conclusions: During a period of co‐circulation of influenza A(H1N1)pdm09 and A(H3N2) in the United Kingdom, evidence for effectiveness of the influenza vaccine in both children and adults was found.

Background: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2–13 (and 14–15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom.Methods: End‐of‐season adjusted vaccine effectiveness (VE) estimates against sentinel primary‐care attendance for influenza‐like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders.Methods: Results In the mainland United Kingdom, end‐of‐season VE against all laboratory‐confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: −6% to 54%). VE for those aged 18–64, who largely received cell‐based vaccines, was 47% (95% CI: 37%–56%). Overall VE for 2–17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%–76%).Conclusion: The paper provides evidence of moderate influenza VE in 2022/23.

Background: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO’s mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. Objective: We aim to describe the RSC’s plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. Methods: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA’s sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA’s reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. Results: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC’s pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. Conclusions: The RSC extended its surveillance activities to meet more but not all of the mosaic framework’s objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

Immune imprinting: For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), immune responses to heterologous variants are influenced by a person’s infection history. Healthcare workers (HCWs) may be exposed to several doses and types of antigens, either by natural infection or by vaccination. Reynolds et al . studied a cohort of UK HCWs followed since March 2020. The immunological profiles of these people depended on how often the subject had encountered antigen and which variant was involved. Vaccine responses after infection were found to be less effective if the infection involved heterologous spike from a variant virus. Unfortunately, the N501Y spike mutation, found in many variants, seems to induce the regulatory T cell transcription factor FOXP3, indicating that the virus could subvert effective T cell function. Changes to antibody binding between variants also means that serology data using the Wuhan Hu-1 S1 receptor-binding domain sequence may not be a reliable measure of protection. —CA