Title: COVID-19-Related Research: An Update Author: Dr Siobhán O’Sullivan (inputs from HRB, SFI, HPRA, NREC) Organisation: Department of Health Date: 11th February 2021 Action required: X For noting ☐ For discussion ☐ For decision Approved for future publication: YES (remove as applicable) Introduction Research and innovation have been crucial in informing and shaping Ireland’s public health and policy response to COVID-19. The Government’s ‘Resilience and Recovery 2020-2021 Plan for Living with COVID-19’, published on September 15th 2020, recognises the contribution that research has made across a numbers of domains, and seeks to deliver a nationally coordinated research approach to manage and respond to the health, social and economic consequences of the pandemic as well as build resilience for future emergencies. The plan contains a commitment to: “building further capacity for public health research, research to gauge the social and economic impacts of COVID-19 at a citizen and sectoral level, strengthening epidemiological modelling and behavioural science capabilities, capacity and demand modelling, supporting the clinical trials network, infrastructure to support biorepository studies and data linkages, advances in reliable testing and tracing capabilities”. At the National Public Health Emergency Team (NPHET) meeting on Thursday, September 3rd, the Chair of the Expert Advisory Group (EAG) presented findings of a report prepared by the research subgroup of the EAG. The report noted the significant contribution of research and innovation to date in responding to the current public health emergency. It also noted that as the pandemic evolves, there is a requirement to consolidate those gains and ensure a national, structured, co-ordinated research response to better inform health, education and economic recovery from COVID-19. The group recommended that in order to support research into the current, and future pandemics, new research infrastructure is required, with particular focus on (i) expanding the clinical trials network; (ii) creating a national COVID-19 biorepository; and (iii) public health research infrastructure. The paper was endorsed by the NPHET and was submitted to the Department of An Taoiseach and the Department of Further and Higher Education, Research, Innovation and Science, as a contribution to the cross Government considerations of how Ireland can, through its present infrastructural support systems and funding partners, build on this initial work. Research will be required across a spectrum of domains from basic to translational and clinical research, as well as to address the downstream effects of the disease and its impact on Irish society. The purpose of the current paper is to provide an update to the NPHET with respect to the various COVID-related research activities and infrastructural initiatives ongoing in the healthcare and broader innovation sphere in Ireland. The paper provides a comprehensive (but not complete) snapshot of COVID-related research activities undertaken in the last year and updates in respect of the planned activities and developments. The paper is based on inputs received with thanks from the Health Research Board, Science Foundation Ireland, Health Products Regulatory Authority, and the National Office for Research Ethics Committees. Funding for COVID-19-Related Research In April 2020, the Irish Research Council (IRC), the Health Research Board (HRB), Science Foundation Ireland (SFI), Enterprise Ireland (EI), and IDA Ireland developed a coordinated Rapid Response Research and Innovation programme. All five agencies worked together to support COVID-19-related research to inform the public health response to the national public health crisis. Taking this unique approach allowed funding agencies to focus on their areas of expertise and to avoid duplication or overlap. The research priorities of the call were aligned with the World Health Organisation (WHO) R&D Roadmap and informed by the Global Infectious Disease Collaboration for International Disease Preparedness (GloPID-R). Two funding streams were made available; the first, through the HRB, in cooperation with the IRC, focused on research that addressed: medical countermeasures, health service readiness, and social and policy countermeasures to COVID-19. Details of the awards can be found in Appendix 1. A total of 36 research projects have been supported at a cost of approximately €5.5m over the period 2020-2022. The second funding stream made available through SFI, EI and the IDA focused on supporting the development of innovative solutions based on new or alternative approaches and methodologies to address the pandemic response. SFI (in two phases) provided funding of €18m for a total of 83 projects (Appendix 1). In July, the HRB, jointly with the Health Service Executive (HSE), provided €0.5m funding for four projects (Appendix 1) through the Research Collaborative in Quality and Patient Safety (RCQPS). The European Commission issued two EU COVID-19 funding calls in 2020. The initial call in January allocated €38.5 million to 18 projects involving 140 research teams from across the EU and beyond to develop research on understanding the behaviour of the epidemic through epidemiology and modelling, developing rapid diagnostics, as well as treatments and vaccines. An Irish SME, working with partners from Queens University Belfast, China and Italy, is leading one of these projects, HG nCoV19 test, to develop a rapid molecular diagnostic test. The Health Protection Surveillance Centre (HPSC) is a partner in the I-MOVE-COVID-19 multidisciplinary European network for research, prevention and control of the COVID-19 pandemic led by France and including 20 EU countries. A second call in May 2020 allocated €133m to 24 successful research projects involving over 350 research teams from 40 countries. The funding is supporting researchers to address the pandemic and its consequences by strengthening the industrial capacity to manufacture and deploy readily available solutions, develop medical technologies and digital tools, improve understanding of behavioural and socio-economic impacts of the pandemic, and to learn from large groups of patients (cohorts) across Europe. Ireland performed well and is involved in seven successful projects and leading two projects. Irish success includes a mix of SMEs and universities (TCD, UCD, TUD and UCC). Details of successful COVID applications with Irish involvement can be found in Appendix 1. In September 2020, the EU launched EU-RESPONSE – a five-year multinational project (€15.7M) in order to design and run a new adaptive European platform trial on COVID-19 and emerging infectious diseases. The project seeks to facilitate the European expansion of the DisCoVeRy study, a phase III, open-label, adaptive, randomised, controlled, multi-centre clinical trial designed to evaluate the safety and efficacy of medicinal products in hospitalised adult patients diagnosed with COVID-19. It also seeks to build a new multinational European Adaptive Platform Trial, based on existing initiatives, experiences and competencies – the EU- SolidAct. The project also includes a coordination module with the EU-funded RECOVER ensuring complementarity and cooperation across all large European COVID-19 Adaptive Platform trials, and their capacity to answer the needs of society through dialogue with the EMA, national competent authorities, HTAs and industry partners. Ireland is involved in application discussions, with UCC as a listed partner. The HRB is engaging with partners in Ireland, including CRCI, CRFs and investigators to monitor developments. Clinical Trials The Health Products Regulator Authority (HPRA) authorised eight clinical trials related to COVID-19 in 2020 (Appendix 1). The sponsor for all but one of the trials authorised to date is academic. Most trials were hospital-based, but one trial of a single IV dose of a monoclonal antibody (CT-P59) is authorised for conduct in outpatients. Not all authorised trials have commenced in Ireland and there is ongoing review of a trial of direct-acting oral antiviral in healthy, non-hospitalised patients, and a trial investigating therapeutic anticoagulation in hospitalised patients. The HPRA offers free scientific and/or regulatory advice to sponsors interested in conducting COVID-19 CTIMP research in Ireland. Approximately 20 expressions of interest have been received and teleconferences were conducted with potential sponsors. The HPRA experience is that pre-submission advice is particularly helpful for academic sponsors. REMAP-CAP is an existing EU randomised, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia. REMAP-COVID is a sub-platform of REMAP-CAP that evaluates treatments specific to COVID-19. In Ireland, the trial is being funded by the HRB and led by Professor Alistair Nichol, a Consultant in Intensive Care Medicine at St Vincent’s University Hospital (SVUH) and lead of the HRB’s Clinical Trial Network in Critical Care. The trial is taking place in ICUs in SVUH, University Hospital Galway (UHG), Beaumont Hospital, Cork University Hospital (CUH), St James’s Hospital (SJH), Waterford and University Hospital Limerick (as well as the Royal Victoria Hospital in Belfast). A total of 77 REMAP-CAP patients have been randomised to date in Ireland. As part of the trial, the Irish arm published results showing that the common steroid hydrocortisone, administered to critically unwell patients in ICUs, reduced the mortality rate