SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml−1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies

Reporting on a partnership to co-design a digital health intervention with young people who have experienced technology assisted sexual abuse

IntroductionWhile Patient and Public Involvement and Engagement (PPIE) is a key element of research best practice across healthcare, the co-design process for digital health interventions (DHIs) remains underreported. This study explores the co-design process of the i-Minds DHI, developed for young people exposed to technology-assisted sexual abuse (TASA), with a focus on advancing PPIE in DHI development. The research team collaborated with a Lived Experience Advisory Group (LEAG) to co-design the intervention, detailing activities, experiences, benefits, challenges, and priorities identified throughout the process.MethodsThe study involved four participatory co-design workshops and focus groups with LEAG members. Key activities included identifying key features of the app design and content, gathering feedback on prototypes, discussing priorities for the app’s function and trial design, and refining language and content of user-facing materials. Features were prioritised using the MoSCoW method.ResultsRecruitment of LEAG members, facilitated by The Marie Collins Foundation, emphasised the importance of involving trusted organisations when addressing sensitive topics like TASA, as many young people do not initially recognise themselves as victims. Key findings highlighted the importance of clear communication, structured processes (e.g., Terms of Reference), and financial remuneration for members to promote equity of opportunity. Agile development methods enabled iterative refinement of the app, integrating user feedback in real time. However, time and budget limitations constrained the integration of all desired features, with the MoSCoW method providing transparency in decision-making.ConclusionWe offer recommendations for effective PPIE, including prioritising lived experience input early in research, allocating sufficient resources, and fostering transparent communication. Despite challenges, such as limited diversity within the LEAG and remote meeting formats, PPIE was considered meaningful by members. This study provides a valuable framework for co-designing DHIs and improving inclusivity in PPIE efforts, particularly in sensitive research areas like TASA.Patient and Public Contribution This study was supported by a LEAG who undertook the role of partners and were involved in study design, ethical considerations, recruitment, content revision, and project oversight. Authors included lived experience members and people with intersecting lived experience and research identities.<br/

Spinal presentations in children with type 1 spinal muscular atrophy on nusinersen treatment across the SMA-REACH UK network: a retrospective national observational study

Background Prior to the introduction of disease-modifying treatments (DMTs), children with type 1 spinal muscular atrophy (SMA) typically did not survive beyond the age of 2 years; management was mainly palliative. Novel therapies have made this a treatable condition, resulting in increased life expectancy and more time spent upright. Survival and improved function mean spinal asymmetry is a new complication with limited data on its prevalence and severity and no current guidelines on management and treatment. This study aimed to evaluate the spinal presentation and management of type 1 SMA children on nusinersen across the SMA-REACH UK network.Methods Spinal presentation and management of 80 children (age range 4 months–14 years, median 4 years 2 months) with type 1 SMA on nusinersen across the SMA-REACH UK network were reviewed through retrospective data analysis.Results There were 60 type 1 children who developed a spinal asymmetry, of which 40 had kyphosis and 50 used a supportive thoraco-lumbar-sacral orthosis (TLSO). TLSOs were predominantly a one-piece jacket with abdominal hole, advised to be worn when upright during the day. Reduced neck range of movement was found in 33, 1 of these had plagiocephaly and 5 had torticollis. Of those with reduced neck range of movement, 26 (79%) had spinal asymmetry. Spinal surgery was performed in 7.Conclusions Our study confirms high prevalence of spinal asymmetry in this cohort, requiring long-term management planning. It provides information on presentation and treatment options, facilitating development of guidelines for these new complications observed in children surviving longer with DMTs