NIHRDataInsights/HRCSData huggingface dataset:
Title: Baricitinib, casirivimab/imdevimab, lenzilumab, molnupiravir, nirmatrelvir/ritonavir, remdesivir, sotrovimab, and tocilizumab, for the treatment of COVID-19. [ID4038]
Funder: Department of Health and Social Care

Abstract: Treatment for patients with COVID-19 is beneficial. Results from studies have shown that treatment can prevent hospitalisations, admission to intensive care units and death. However, treating many people, some of whom may have been well without treatment can be expensive. Unlike expensive new treatments in other disease areas, the National Institute for Health and Care Excellence (NICE) has not investigated the cost-effectiveness of many treatments for COVID-19. This work will assess the cost per quality-adjusted life year gained of selected treatments for COVID-19, allowing NICE to decide if they represent value for money and if one treatment is preferred if many treatments are cost-effective compared with no treatment._x000D_ _x000D_ The work will focus on two groups. The first group is those who have needed hospitalisation because of COVID-19, and the second group are those who have not (yet) needed hospitalisation because of COVID-19 but who are believed to be at high-risk of being hospitalised. The cost-effectiveness of treatments will likely depend on the treatment itself, and the setting in which it is being used.

Lay abstract: The objective of the assessment is to determine the clinical and cost-effectiveness chosen antiviral medications, neutralising monoclonal antibodies (mAbs), and immunomodulatory mAbs for the treatment of people with COVID-19 in an endemic situation.

Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Development of sub-20 minute PCR-based diagnostic assays for a current point of care testing device
Funder: Department of Health and Social Care

Abstract: Access to a community-based diagnostic infrastructure providing prompt, inexpensive and accurate testing is an unmet patient need highlighted by the COVID-19 pandemic. This must be addressed now, given the significant risk of more variants of SARS-CoV-2 arising [1]. We plan to exploit our paradigm-changing polymerase chain reaction (PCR) chemistry [2] to develop assays that specifically accelerate test times on an existing Point-of-care testing (PoCT) device, the Optigene Genie 3. PoCT permits earlier diagnosis, results in fewer hospitalisations, lessens risks of infection, and decreases additional costs of referrals and further testing [3]. Its uptake has been hampered by the high cost per test, quality assurance issues and inadequate analytical performance [4]. The Genie 3 has been evaluated for use in the NHS [5] and is used for isothermal PoCT for SARS-CoV-2 detection [6] and more general use [7]. Its use as a real-time PCR cycler is limited by its slow ramp rates and hour-long run times, a universal problem deterring the use of PCR-based PoCT. Our innovative PCR assay designs and protocols exploit the untapped speed potential of the PCR, thus minimising the Genie 3 s major disadvantage (slow cycling speed) whilst maximising its advantages (size, portability, flexibility, low cost). Assays will be run on existing devices, resulting in a PCR-based local diagnostic infrastructure capable of delivering eight test results per device in less than 20 minutes. The combination of a device familiar to NHS staff, novel assays, low reagent usage and speed will address the main concerns hindering clinical PoCT uptake and can be applied to multiple conditions other than infectious diseases.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Using national whole-genome sequence data to inform epidemiological models of COVID-19 variant emergence and outbreak risks in Scotland
Funder: Chief Scientist Office, Scotland

Abstract: New variants of severe acute respiratory syndrome virus 2 (SARS-CoV-2) continue to emerge due to high infection rates in the UK and internationally. Variants of Concern (VOC) in particular are monitored closely as they spread more rapidly, cause more severe disease, and have increased ability to evade immune protection. Consequently, there is uncertainty around whether COVID-19 vaccination campaigns, while providing individual protection, will effectively protect the health and wellbeing of the Scottish population in the long-run. There is also limited understanding of how population immunity, either through vaccination and/or from catching the infection itself, may contribute to emergence of new VOC over the years to come. At the same time, high levels of population immunity should limit the spread of VOC in the community after they have arisen. Our project aims to improve understanding around risk of VOC introductions versus emergence within Scotland, and how population immunity (e.g., high exposure rates to Delta) may shape where they arise and whether they are likely to spread. The project will be co-led by Public Health Scotland in partnership with the Universities of Glasgow and Edinburgh, bringing together cutting-edge molecular phylogenetics and epidemiology using national SARS-CoV-2 whole genome sequencing, serological, and diagnostic testing surveillance, together with demographic and other healthcare data, to inform geographical risk maps of where VOC are likely to arise and outbreak hotspots. It is anticipated that the analytical tools will help to inform the design of national surveillance programmes and provide a basis for evidence-based scenario planning


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: INFECTION
Title: Exploring the role of histone-like proteins in coagulopathy and vascular leak in meningococcal disease in children: a potential biomarker or target for adjunctive treatment?
Funder: Chief Scientist Office, Scotland

Abstract: Sepsis causes 3500 deaths in Scotland every year. One of the deadliest forms is meningococcal disease, which is associated with blood-poisoning spots that do not go away when pressed, and are feared by parents/healthcare professionals. These spots are caused by damage to blood vessels. Even after antibiotics they can continue to spread all over the body and patients can lose limbs or die. This project will investigate sticky proteins called histones, released either from our own cells or from bacteria, that our data suggest may cause this blood vessel damage. We will use a unique archive of stored blood and skin biopsies from children with meningococcal disease to study whether histones are released and stick to blood vessels. If true, detecting histones may be a quick way to diagnose sepsis early. Furthermore, treatments that can block histones could reduce death and disability in children and adults with sepsis.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: A novel class of gram-negative active antibiotic.
Funder: Chief Scientist Office, Scotland

Abstract: We are all at risk from bacterial infections that have become resistant to current antibiotics. We are at the cusp of returning to untreatable bacterial infections, similar to the situation before antibiotics were first discovered. Of particular concern are infections caused by Multi drug-resistant (MDR) Gram-negative bacterial pathogens. Academia is particularly important in addressing this issue because of the low interest of the international pharmaceutical industry. The University of Strathclyde has invented a family of novel chemical and formed a partnership with the SME MGB Biopharma to develop them as antibiotics. This partnership has already been successful in taking one compound, known as MGB-BP-3 to a phase 2a clinical trial for Clostridium difficile associated infections, to which the elderly and immune-compromised are particularly vulnerable. In this project we will extend our success to develop urgently needed development candidates for the treatment of infections caused by MDR Gram-negative bacteria, such as E. coli, K. pneumonia and A. baumannii, by taking advantage of recent understanding of how our S-MGB’ s can accumulate in, and therefore kill, Gram-negative cells.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Rapid new methods for sepsis diagnosis in hospitals using microsystems
Funder: Chief Scientist Office, Scotland

Abstract: Sepsis is a life-threatening consequence of infection that kills 3,500 people every year in Scotland. Due to the high risk of death, multiple broad-spectrum antibiotics are routinely used in patients with sepsis, which contributes to the development and spread of antibiotic resistance. Current methods to identify the underlying infection and target treatment require growth tests, which take several days to establish a positive result. Rapid diagnosis of the infecting bacteria would enable the use of the right antibiotics straight away, reducing the risk of complications for the individual patient, and benefiting society by reducing use of last-resort broad-spectrum drugs. This project aims to tackle the challenge of rapid diagnosis by engineering a miniaturised, portable platform that will isolate bacteria from clinical samples within minutes, without prior knowledge of their identity or growth tests. Importantly, this approach will be coupled to technologies already available in hospitals and new genome-sequencing technologies to perform bacterial identification and antibiotic susceptibility testing in a much-reduced timeframe.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: First in Human Clinical Trial of SARS-CoV-2 Allogeneic Virus Specific T cells
Funder: Chief Scientist Office, Scotland

Abstract: The successful roll out of vaccines against the SARS-CoV-2 virus has mitigated the incidence of severe disease and is helping the UK to live with continuing transmission of the virus in the community. However, the risk of infection and severe disease remain high in those who are unable to mount effective immune responses due to disease or treatment. There is also evidence that persistent infection can increase the risk of generating new virus variants which pose a broader public health concern. SNBTS has long-standing experience in the treatment of viral disease using T cells donated by healthy virus-exposed volunteers (Virus Specific T cells (VST)). These allogeneic VST are stored as cryopreserved cell stocks which can be rapidly deployed and have been used to treat over 100 immunosuppressed people with Epstein-Barr Virus-driven malignancy. We have now adapted our methods to manufacture stocks of anti-SARS-CoV-2 VST for treatment of HLA-matched patients with SARS-CoV-2 infection. We seek funding for the initial First in Human Phase I safety study of this product at a single site, which will be a prelude to a Phase II clinical trial of effectiveness in people who are immunocompromised and develop SARS-CoV-2 infection


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Opportunity-Led - InflaTMP: Design of a novel combination anti-inflammatory and anti-viral biotherapeutic for COVID-19
Funder: Public Health Agency, NI

Abstract: The lack of effective vaccine or pharmaceutical interventions for SARS-CoV-2 raises the possibility of further waves of CoVID-19. Early enforcement of lockdowns and effective implementation of social distancing measures and personal protection are effective interventions at limiting the spread of the virus. In the near future, rapid virus testing by reverse transcription loop-mediated isothermal amplification (RT-LAMP), a one-step nucleic acid amplification method, use of saliva rather than swabs for viral detection and sensitivity and specificity antibody testing by enzyme-linked immunosorbent assay (ELISA) my complement or replace existing approaches. Nonetheless, although widespread test– trace–isolate strategies may be equally or locally more effective and may minimize the economic and social costs of lockdowns, these are outside the reach of most countries. Presently it appears that further infection and spread of SARS-CoV-2 is inevitable and therefore requires the development of novel therapeutic approaches to control viral replication and reduce the exuberant inflammatory response observed in many COVID-19 patients. COVID-19-related local lung and systemic inflammation can result in cytokine storms that can lead to organ damage and death, especially in older or obese individuals and those with underlying medical conditions. There is an urgent need to better characterise the pathogenesis of COVID-19 and the host response to the virus particularly in vulnerable populations who suffer from chronic diseases. Inflammation and dysregulated immune responses are major contributing factors in multiple chronic diseases. Patients with a chronic inflammatory disease are at greater risk for developing other inflammatory related conditions. Age is also a risk factor for inflammation/immune dysregulation. ‘Inflammaging’ in an ageing population that is living longer is not only has a negative impact on the aging individuals but is also imposing extensive socio-economic burdens on society. Management of these diseases represent a major clinical challenge especially in the current pandemic. Immunology is at the heart of some of the most pressing issues in this pandemic. There is a greater need now to better understand the underlying immuno-aetiologies contributing to co- and multi-morbidities. There remains a lack of understanding of how multiple pathologies or conditions co-evolve or interact and importantly how treatments should be combined to effectively improve outcomes. The objective of this project is to develop novel immune-based biotherapeutics to prevent or treat COVID-19-related disease in a multimorbid population in the midst of a viral pandemic.


Research activity codes: 3.3 NUTRITION AND CHEMOPREVENTION;5.1 PHARMACEUTICALS
Health categories: INFECTION
Title: Opportunity- Led 2020 - COVRES2: Identifying temporal immune responses associated with COVID-19 severity
Funder: Public Health Agency, NI

Abstract: Surveillance of immunity to SARS-CoV-2 was initially dominated by development of tests to detect antibody to key antigens expressed by the virus, especially spike and nucleocapsid. With research focus expanded to consider wider facets of cellular immunity to the virus has come a strong interest in accessible tests that can also evaluate these parameters, especially T cell immunity, in exposed populations. While many research findings have been reported, assays invariably depend on research-lab based, high-tech methodologies such as ELISpot (cell culture to count responding T cells with a coloured label) or flow cytometry (using lasers to detect activation of fluorescent-tagged cells). These are relatively hard to translate beyond a research setting and at high throughput as would be needed for wider roll-out. The work planned in this proposal will seek to develop novel strategies to bridge this gap. The proposal brings together seven immunology research groups across the UK to optimise rapid development of new approaches for measuring cellular immunity in COVID-19. The teams will develop complementary workstreams looking at new, small-scale tests that can be accessibly done with blood samples in a non-specialist setting.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: Optimising Covid-19 Testing System (OCTS)
Funder: Economic and Social Research Council

Abstract: 1. To provide briefings notes to stakeholders in order to inform the Covid-19 response in the UK and internationally, on topics including mass testing strategies, PCR-based test and trace systems, and informal testing systems. 2. To provide evidence to official reviews in order to support the learning of lessons from the Covid-19 pandemic so as to enhance preparedness for future pandemics. 3. To engage with a wide range of stakeholders in order to enhance knowledge exchange and to aid the uptake of relevant concepts and findings from social science research relevant to understanding the role of diagnostic innovation in managing Covid-19. 4. To publish academic outputs, based on the above, that contribute to the understanding of diagnostic innovation in the field of infectious disease.

Lay abstract: This study asks how leading countries are organising and using national and regional diagnostic testing systems for Covid19 ('testing systems') in order to reduce Covid-19 mortality per capita in their populations, to avoid or shorten 'lock-downs', and reduce economic impacts from the pandemic. We will explain how testing systems have been shaped during the pandemic, and how challenges related to testing are overcome. The research will span North America, Europe, Africa, Asia and Australia as well as the UK. The project builds on an established Covid-19 UK research and knowledge exchange hub at the University of Sussex that has been facilitating rapid dialogue and dissemination of research on Covid-19 diagnostic testing between the international research team and policy makers in the UK and beyond. The hub has a track-record of reporting results that have been widely welcomed and valued by the UK civil service and reported widely to public audiences in the media. As the pandemic continues, understanding the use of testing systems remains vital to optimise the Covid-19 response and save lives. With innovation and learning continuing (e.g. around the UK government's ambitious mass-testing programme), we propose to undertake further comparative research to share lessons across contexts. In order to support Covid-19 responses internationally, we will engage with governments and share deliverables from the early months of this 15-month project. Additionally, to inform preparations for future outbreaks and pandemics, we will contribute to national and international fora seeking to learn lessons from the current crisis.

Research activity codes: 4.3 INFLUENCES AND IMPACT;4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: INFECTION
Title: Randomised controlled trial of cipro vs standard of care in plague
Funder: Wellcome Trust

Abstract: Background: In 2017 Madagascar experienced a large outbreak of pneumonic plague, with cases being treated with the national recommended schedule of streptomycin. Two seperate post-outbreak technical workshops in 2018 (Pasteur Institute, 9-10 July; and joint Madagascar Ministry of Public Health and WHO meeting, July 17-20), which together convened around 100 plague experts, recommended a clinical trial of alternative treatments for plague. Aim: To test the hypothesis that ciprofloxacin monotherapy (orally, intravenously, or combination) for 10 days is non-inferior to streptomycin (given on days 1-3) followed by ciprofloxacin (given on days 4-10) in the treatment of bubonic plague. Methods: An open-label, individually randomised, non-inferiority trial of the efficacy and safety of ciprofloxacin versus active control for the treatment of bubonic plague in Madagascar. Primary outcome: Therapeutic response assessed at day 10 after randomisation Duration: Three years Sample size: 190 confirmed/probable bubonic plague patients (95 per group) will provide 90% power to demonstrate non-inferiority of treatment success of ciprofloxacin compared to streptomycin plus ciprofloxacin, within a non-inferiority margin of 15% and based on a 2.5% one-sided confidence interval. Calculations assume 10% loss to follow up of patients before the endpoint assessment on day 10.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: INFECTION
Title: African COVID-19 Preparedness (AFRICO19)
Funder: Wellcome Trust

Abstract: Our project, AFRICO19, will enhance capacity to understand SARS-CoV-2/hCoV-19 infection in three regions of Africa and globally. Building on existing infrastructures and collaborations we will create a network to share knowledge on next generation sequencing (NGS), including Oxford Nanopore Technology (MinION), coronavirus biology and COVID-19 disease control. Our consortium links three African sites combined with genomics and informatics support from the University of Glasgow to achieve the following key goals: 1. Support East and West African capacities for rapid diagnosis and sequencing of SARS-CoV-2 to help with contact tracing and quarantine measures. novel diagnostic tools optimized for this virus will be deployed. An African COVID-19 case definition will be refined using machine learning for identification of SARS-CoV-2 infections. 2. Surveillance of SARS-CoV-2 will be performed in one cohort at each African site. This will use established cohorts to ensure that sampling begins quickly. A sampling plan optimized to detect initial moderate and severe cases followed by household contact tracing will be employed to obtain both mild to severe COVID-19 cases. 3. Provide improved understanding of SARS-CoV-2 biology/evolution using machine learning and novel bioinformatics analyses. Our results will be shared via a real-time analysis platform using the newly developed CoV-GLUE resource.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION
Title: COVID-19 Intervention Modelling for East Africa (CIMEA)
Funder: Wellcome Trust

Abstract: COVID-19 is a global threat to health, with many countries reporting extended outbreaks. To date 9 countries in Africa have recorded infection and it seems imminent that East Africa will have introductions and onward transmission. The SARS-CoV-2 virus (the aetiological agent of COVID-19) spreads rapidly (R0~2, serial interval about 1 week), and hence control will be difficult. National plans for dealing with this public health emergency will benefit from predictions of the expected rate, distribution and extent of spread in countries throughout the region, and on the likely impact and feasibility of isolation and contact tracing interventions. We will support the emergency preparations through bespoke modelling, incorporating known demographic population structure, age-related contact patterns and existing mobile phone population movement data. In Uganda and Kenya we will collect epidemiological, genomic and behavioural data through health facility surveillance, household follow-up and contact studies to quantify uncertainties of SARS-CoV-2 virus epidemiology and contact patterns in well and unwell individuals. Results from the study will be rapidly communicated to the relevant authorities, and modelling code and analysis, and data including sequences, placed in the public domain in near real-time. This project could have lasting impact on the role of research in policy decisions.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: INFECTION