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King’s Together Seed Fund

King’s Together is a seed-funding scheme offering £1,000,000 per annum to support the development of multi and inter disciplinary projects that address our strategic research themes:
  • Sustainable Growth
  • Culture & Identity
  • Healthy Lives
  • Social Justice

This internal competition provides seed-funding for research projects which will lead to external research grant applications that are strategic in nature – thanks either to their size, or their importance to the departmental, School or Faculty research landscape. The goal is the development of large, innovative, externally-funded research projects that showcase King’s’ research expertise.

King's works in close partnership with three leading NHS Trusts, through King's Health Partners. We are therefore ideallly-placed to bring cutting-edge research to bear on the challenges created by COVID-19. In March 2020, King's launched a rapid-response funding call to support the mobilisation of our research community, allowing work to commence immediately. We received over 160 applications and made around 30 awards, totalling over £500,000. In May 2020 we launched a second call for projects, receiving over 190 applications and made an additional 17 awards. Funded research activitiy includes development and validation of diagnostic tests, trials of potential therapies, new ultra-low cost ventilator technologies, and novel approaches to predicting the needs and trajectories of the most vulnerable patients and members of the community.

The drop-downs below provides further detail about the projects we have funded. 

Funding

The scheme offers two types of seed-funding for inter- and multi-disciplinary research projects. Both types of award are designed to support the development of significant, strategic projects which are inter- or multi-disciplinary and will be submitted to an external funder.

These awards are worth up to £100,000; this new, larger award is designed to support longer-term strategic research projects with have a health theme but can come from any part of the university. The awards can last up to 12 months, and should demonstrate a clear path to centre, programme or infrastructure grants or equivalent.

These awards are worth up to £20,000 can be used for research covering any topic.

For seed and strategic awards, the competition is open to all research-active staff: Permanently-employed academics and independently funded research fellows are eligible to be PIs, and Post-Doctoral Research Associates are eligible to be (non-budget holding) joint PIs or Co-Is. Proposals should normally include at least two Departments/Schools/Faculties.

Round 8 of King's Together has now closed. Round 9 of King's Together will be launched in spring 2021, updated guidance will be published in due course.

Updated guidance coming soon

COVID-19 Funding - Mental Health

Team: Professor Dag Aarsland. Co-Investigators: Zunera Khan; Miguel Da Silva. Collaborators: Byron Creese; Anne Corbett & Clive Ballard (Uni of Exeter) Summary: COVID-19 is particularly dangerous to older adults and those with underlying health conditions. Self-isolation may have psychological impacts on older adults expressed in both physical and psychological symptoms. This project will explore the impact of self-isolation on loneliness, quality of life and health care needs in older adults. It will also assess coping strategies used by older adults in quarantine. The study will be conducted using an online research platform developed by the applicants called 'PROTECT' which is a cohort of over 25,000 adults over 50 who are cognitively healthy or have early cognitive impairment. Data on key outcome measures will be collected using online questionnaires (on isolation, social connections, loneliness, mental health and quality of life) at baseline and monthly assessment up to 6 months. PROTECT provides participants with access to brain training games and the team will investigate the impact of these engagement tools on isolation, loneliness, quality of life and mental health.

Team: Dr Claire Steves; Professor Karen Glaser, Dr Rebecca Lynch, Dr Ruth Bowyer Summary: UK government health policy requires all those over 70 to self-isolate (i.e. avoid all social contact and remain indoors) for up to four months in order to avoid contracting COVID-19. However the consequences on the mental and physical health of older people remains unknown. This project utilises the power of the TwinsUK cohort to investigate the mental and physical health consequences of self-isolation due to COVID-19 while taking into account genetic and early life factors which can confound other epidemiological models. Data will be collected by questionnaire at the beginning and towards the end of the isolation period to capture how implications and impacts of self-isolation change over time. This will capture measures of social isolation using social disconnectedness and perceived isolation scales; Loneliness using the revised UCLA scale and loneliness scale and Mental ill-health (including the Hospital Anxiety and Depression Scale, HADS). The team will link data to existing genetic data and health outcomes via linkage to health records. The research will investigate the consequences of COVID-19 related self-isolation and provide insight into the genetic, social and environmental factors that contribute towards resilience and can thus be deployed to safe-guard population health in the event of future global disease outbreak.

Team: Dr Nicola Byrom & Dr Eleanor Dommett, Dept. of Psychology. Co-Investigators: Professor Sally Everett, Vice Dean (Education), King's Business School; Dr Juliet Foster, Interim Dean of Education, IoPPN Summary: COVID-19 has forced universities to rapidly implement online delivery of teaching and assessment. There may be advantages to keeping aspects of education online in the long-term. We have an opportunity to explore how staff and students feel about online education and identify what is required to ensure that they feel supported and retain a sense of university identity while studying or working remotely. This project will develop an understanding of the costs and benefits of taking education online. It will utilise an online survey to collect student and staff responses remotely. The team will collect data to assess how confident students and staff feel within the online environment and how moving online affects their sense of engagement and belonging. The survey will be bolstered by in-depth interviews conducted online, to gain a richer understanding of the student and staff experience.

Team: Dr Mary Docherty; Dr Isabel McMullen; Dr Sean Cross; Dr Martin Parson; Dawn Broderick; Dr Sam Gnanapragasam; Dr James Rubin; Professor Neil Greenberg; Professor Sir Simon Wessely. South London and Maudsley, King's College and Guys & St. Thomas' NHS Foundation Trusts, Dept. of Psychological Medicine, King's Centre for Military Health Research Summary: During the COVID-19 pandemic, many NHS staff will have to make difficult choices they have not before faced, to deliver care which they know is suboptimal and explain this to relatives. These ethical dilemmas will be new, certainly in scale and probably in nature. Moral injury is a relatively new concept with particular relevance to the current COVID-19 outbreak. Originating in the military, moral injury describes the psychological distress resulting from actions, or the lack of them, which violate someone's moral or ethical code. The experience is associated with negative thoughts, intense feelings of shame, guilt or disgust. These symptoms can contribute to the development of mental health difficulties, including depression, PTSD and suicidal ideation. This project will explore 1. What is the best way to support acute hospital staff during the unprecedented COVID-19 pandemic? And 2. How can we help mitigate the negative moral impacts of the COVID-19 in NHS workers? The project will explore how individual factors, professional culture, organisational preparedness and setting, team leadership, quality and honesty of staff briefings or formal interventions such as training on ethical decision in resource constrained/high stress situations may impact on the experience of moral injury.

Team: Gemma Knowles, Charlotte Gayer-Anderson, Stephanie Hatch, Charlotte Woodhead, Craig Morgan Summary: School closures and other social distancing and isolation measures are generating considerable worry and anxiety, especially among young people, who face unprecedented uncertainty about exams, academic progression, peer relationships, family financial and job security, and their own and care givers' health. Those from socioeconomically disadvantaged and marginalised groups and those living in chaotic, overcrowded and unstable households are likely to be the most severely affected, as they face greater job insecurity and have fewer resources to access childcare and basic necessities such as food and medicines. This project will rapidly develop methods to obtain information from young people in inner-London on how they are adapting to - and the mental health consequences of - prolonged social distancing measures, loss of daily structure, and acute household insecurity. This will inform the development and implementation of effective responses, in partnership with young people, schools, and community groups. The project will use our ongoing cohort study of adolescent mental health in inner-city London, Resilience, Ethnicity and AdolesCent mental health (REACH, www.thereachstudy.com), as the platform for this work.

Team: Robert Stewart and Matthew Broadbent (CRIS KCL & SLaM Leads respectively), supported by Fiona Gaughran (SLaM R&D Director), Richard Dobson (Bioinformatics & Cogstack Lead), Mark Ashworth (Lambeth DataNet Lead) & Matthew Hotopf (SLaM NIHR Biomedical Research Centre Director) Summary: The COVID-19 pandemic and the national response to this will inevitably have profound impacts across healthcare. The impact on mental health services and patients using them is likely to be particularly acute. This project builds on SLaM's Clinical Record Interactive Search (CRIS) data platform and aims to develop and informative data platform for both short- and long-term monitoring of service responses to the COVID-19 crisis and relevant clinical outcomes. The platform will enable extraction of information on service metrics and activity profiled by patient subgroups. The team will seek readily extractable data from nearby trusts on A&E attendance and hospital admission metrics for SLaM patients. Monthly mortality rates will be similarly ascertained from current SLaM linkage to the NHS spine. Quarterly data extractions will be made from Lambeth DataNet primary care data. Throughout the project, novel text-mining capability will be developed within CRIS (building on over 70 algorithms in current use) to ascertain entities of particular importance for this proposal from health records, including obvious targets such as COVID-19 status, social isolation, and levels of support and family contact.

Team: Katherine Young (PI), Kirstin Purves, Shannon Bristow, Gerome Breen, Thalia Eley, Christopher Hübel, Jessica Mundy, Matthew Hotopf Summary: Efforts to mitigate the spread of the pandemic include implementing drastic changes in behaviours and daily routines as individuals are encouraged to self-isolate, work from home and implement vigilant self-hygiene. At the same time, rapidly changing advice and constant media updates create a high degree of unpredictability and uncertainty, whilst the real risk of disease may trigger both rational fear and paranoid concerns. Due to the unprecedented nature of this situation, the impact on mental health is unknown but may be severe. The aim of this project is to study the impact of COVID-19 upon: (a) symptoms of common mental health disorders likely to be exacerbated by imposed behavioural change and uncertainty (i.e., anxiety, depression, obsessive-compulsive disorder, paranoia and acute/post-traumatic stress disorder), and (b) life circumstances that may exacerbate or mitigate these (e.g. social support, loneliness, occupation), in a longitudinal design. The team will also examine the public’s perception of risk, their degree of compliance with national preventative measures and psychological predictors of maladaptive mental health responses.

Team: Chief Investigator Professor Sir Simon Wessely. Co-Chief Investigators include Professor Matthew Hotopf, Professor Reza Razavi, Professor Rosalind Raine, Dr Sharon Stevelink. Co-Investigators include Prof Anne Marie Rafferty, Dr Sean Cross, Dr Mary Docherty, Dr Ira Madan, Dr Amy Dewar and Dr Sam Gnanapragasam. Summary: NHS staff who are at the forefront of fighting the COVID-19 pandemic are under pressure as never before. This project addresses a knowledge gap on which interventions are most effective to support the mental health and wellbeing of these staff. NHS CHECK will establish a cohort of NHS-affiliated staff to investigate the short, medium- and longer- term psychosocial impact of the COVID-19 pandemic on staff performance and wellbeing. In addition, it will evaluate staff support programmes. All staff working at, or within, King’s Health Partners will be eligible to take part with possible expansion to NHS Trusts outside London. The project will use a variety of online surveys, qualitative interviews and focus groups. A range of important outcomes will be explored including positive and negative impacts of the COVID-19 pandemic on participants, working environment, teamwork, leadership, social support, mental health, wellbeing and the usage and perceived helpfulness of staff support interventions.

Team: Professor Mitul Mehta, Dr Adam Hampshire, Dr Fiona Patrick, Mr Joseph Barnby, Dr Ndaba Mazibuko, Dr Pete Hellyer & Dr. Teresa D’Oliveira Summary: This project aims to identify the effect of the current SARS-CoV-2 pandemic on the cognitive health, and related social, economic and mental health outcomes, of survivors of infection, including severely affected, hospitalised patients. Typically, a high proportion of individuals surviving critical care treatment for respiratory diseases like ARDS show cognitive deficits at discharge, including deficient executive functioning, memory, learning and psychomotor slowing. This may be due to hypoxaemia, mechanical ventilation and delirium. The project benefits from a collaboration with the Cognitron platform (cognitron.co.uk) which has been validated on 250,000 individuals internationally and has pre-pandemic data from 27,000 individuals with consent for re-contact. Recruitment will be online and study measures will be collected at 3-month intervals over 18 months. Understanding the effect on cognitive function will inform likely areas of need once the pandemic recedes. For example, additional care after recovery including additional psychological services support, social impact and workplace/re-entering the workforce support.

Team: Emily Simonoff, Johnny Downs, Sumithra Velupillai, Lukasz Zalewski (IOPPN). David Edwards, Michael Absoud (GSTT/KCL), Harold Bennison, Bruce Clarke, Garry Moriarty, Matthew Broadbent (SLaM). External Collaborators - European College of Neuropsychopharmacology Child Network (ECNP) Summary: Despite the concern about the impact of the pandemic on Children and Young People’s (CYP) mental health, to date there are very few systematic data for CYP already experiencing mental health disorders. Those attending Child and Adolescent Mental Health Services (CAMHS) may be at greater risk, both due to their pre-existing mental health symptoms and increased social disadvantage and family stress. However, the broad range of symptoms (anxiety, depression, aggression, ADHD, autism) make it likely that there are widely differing responses and need for clinical services. The project will provide evidence on what characteristics confer the greatest risk, enabling CAMHS professionals to tailor support appropriately. The project will take advantage of the >4000 active patients within CAMHS and will be extended subsequently to those attending neurodevelopmental and some physical health services at the Evelina. It will utilise the innovative My-Health-E system to contact caregivers of patients and where suitable for the child to complete a survey based on the gold standard CRISIS questionnaires but adapted for clinical populations to include a wider range of mental health symptoms, educational experience and health care. With parent/child agreement a simple report will be sent to their keyworker.

COVID-19 Funding - Mental Health (cont.)

Team: PI: Sian Oram, Co-Is: Jane Chevous, Laura Fischer, Helen Fisher, Concetta Perot, Dan Robotham, Angela Sweeney Summary: During ‘lockdown’ schools were open for vulnerable children (defined as children who have a social worker and those <25 years with education, health and care plans). However most at risk children and young people (CYP) will be ‘off-radar’ and unknown to statutory services and therefore unable to attend School. This situation has and will inevitably isolate CYP with abusive caregivers and no or very limited access to normal supports or opportunities for respite and escape such as school, friends and clubs. Simultaneously, perpetrators may experience higher stress, boredom and increased alcohol use, potentially leading to higher rates of abusive behaviour. Therefore, many CYP are at greatly increased risk of experiencing violence and abuse. Maltreatment and domestic violence during childhood and adolescence is associated with increased rates of numerous mental health difficulties across the life-course. This project is a collaboration between the UKRI Violence, Abuse and Mental Health Network and the ESRC Centre for Society and Mental Health at King’s, and ongoing partnerships with Survivors Voices and the McPin Foundation; two charities committed to putting lived experience at the heart of research. It uses a survivor-led approach that will prioritise the safety of research participants. The research will address (1) What support exists for CYP at risk of violence and abuse during the Covid-19 isolation period? (2) How can ‘off radar’ CYP who are at risk of violence and abuse be identified and supported to protect their mental health? This will be done by (1) Extending and analysing an existing survey of survivors, focussing on potential solutions and (2) conducting virtual roundtable discussions with survivors aimed at producing an infographic targeting off radar-CYP visualising the key messages and providing information about existing support.

Team: Katherine Young (PI), Kirstin Purves, Shannon Bristow, Gerome Breen, Thalia Eley, Matthew Hotopf, MQ (external partner) Summary: This project will enhance recruitment of a more diverse and representative sample of participants to the Repeated Assessment of Mental health in Pandemics (RAMP) study (supported with round 1 funding). RAMP is a longitudinal questionnaire based project examining the mental health impact of the Covid-19 pandemic in the general population (https://rampstudy.co.uk). Understanding of the mental health impact of the pandemic on the general public relies on recruitment of a representative sample of the UK population. Despite the effective recruitment to date, the sample is lacking in some key demographics, notably with underrepresentation from males and people from ethnic minority groups. This project will address this through two key elements: 1) increased reach of advertising to underrepresented groups, and 2) renewed creative content and outreach to encourage diverse engagement and follow-up survey completion.

COVID-19 Funding - Therapy

Team: Francesco Dazzi (FD), Professor of Regenerative Medicine/Consultant Haematologist, KHP lead for cell therapies – Jimstan Periselneris (JP), Consultant Respiratory Physician, TPD for IMT – Farzin Farzaneh (FF), Professor of Molecular Medicine, Head of Cell and Gene Therapy – Antonio Galleu (AG), Clinical fellow, MSC manufacturing Lead. Dresden Team. Martin Bornhauser (MB), Professor of Haematology, Director of Haematology, Dresden/KCL Transcampus – Martin Kolditz (MK), Vice-chair of Pneumology Department – Malte von Bonin (MvB), Group Lead, Stem Cell Laboratory. Shanghai/Soochow team. Yufang Shi (YS), Professor and Director, Institute for Translational Medicine in Soochow, China Summary: Acute respiratory tract infection induced by COVID-19 can be complicated by a severe cytokine release syndrome (CRS) which, when progressing to acute respiratory distress syndrome (ARDS), is associated with high mortality. The potent anti-inflammatory activity of mesenchymal stromal cells (MSC) has been successfully exploited for the treatment of acute graft-versus-host disease (GvHD), a complication of bone marrow transplantation, that is also characterised by a severe cytokine storm. The therapeutic activity of MSC depends on the presence in recipient patients, of activated CD8+ cytotoxic T cells that induce MSC apoptosis. Only patients with high cytotoxic activity against MSC respond to MSC infusion, whereas those with low activity do not. Therefore, the level of cytotoxic activity provides a biomarker to stratify patients for MSC treatment with a sensitivity and specificity of 90%. Like patients with GvHD, those with Covid-19 harbour high levels of activated CD8+ T cells, which could therefore make them responsive to MSC therapy. This project will investigate whether MSC therapy can ameliorate the acute inflammatory response induced by Covid-19 and whether clinical responses correlate with the biomarker assay. The project will build on a successful collaboration between KCL and Dresden, with an invaluable contribution from an international leader in MSC immunobiology who has experience in COVID-19 patients in China.

Team: Dr Federico Formenti, Prof. Louise Rose, Prof. Seb Ourselin, Prof. Prashant Jha. University of Oxford: Prof. Andrew Farmery, Prof. Mark Thompson, Prof. Alfonso A. Castrejon-Pita, Major Rob Staruch, Po Chan, Azad Hussain. Summary: Severely ill patients with Covid19 require ventilator support for their breathing. The project aims to produce a mechanical ventilator to offer safe respiratory support to thousands of adult and paediatric NHS patients in the intensive care unit within months. It will employ essential design criteria and operating parameters that match the MHRA requirements for "Rapidly Manufactured Ventilator System". The project will specify components and identify manufacturing challenges for two separate designs: 1) mechanical: an optimised, updated version of the Dickman et al device (https://www.youtube.com/watch?v=1t2t8d8xtD0&feature=youtu.be), 2) gas-driven where the resuscitator is placed within a sealed chamber that is itself cyclically pressurised using compressed air (https://videopress.com/v/3Kylk7mY). In each design, the mechanical ventilator will be capable of delivering a desired air volume (breath size) within the safe and desired limits of air pressure, maintaining a set value of end-expiratory airway pressure, with controllable frequency (breaths per minute), delivering supplemental oxygen, and patient’s expired gas is filtered.

Team: Prof. Mauro Giacca, School of Cardiovascular Medicine & Sciences Summary: This project will perform a high-throughput-screening (HTS) to systematically search for FDA/EMA-approved drugs that might impact on the efficiency of SARS-CoV-2 cell infection by downregulating the ACE2 viral receptor. The project takes advantage of the availability of a collection of 3780 small molecules and of the HTS facility at the KCL James Black Centre. The identified drugs will then be tested on viral replication in collaboration with the ICGEB in Trieste, Italy, where 4 primary SARS-CoV-2 isolates have been recently isolated and cultured. The identified drug(s) can immediately be tested off-label to combat COVID-19.

Team: Edina Rosta, Chemistry, Andre Cobb, Mark Sanderson Summary: The aim of this project is to develop novel inhibitors targeting SARS-CoV-2 with a team of computational chemists, synthetic chemists and structural biologists. The approach is based on one of the most promising protein target candidates: developing novel inhibitors for the essential helicase function of coronavirae. Atomistic simulations are highly valuable tools for structure-based drug design and will be used as a first step to obtain structural information of the essential COVID-19 helicase as potential drug target. The team will focus on Bananin and three of their derivatives that have been shown to exhibit antiviral activity against human SARS-CoV helicase, which is over 98% homologous to the COVID-19 helicase. They will also design COVID-19-specific drugs by modifying known helicase inhibitors targeting either (i) the allosteric site, (ii) the ATP binding site, or, as a contingency plan, (iii) the RNA dependent RNA polymerase function of the COVID-19 Orf1ab polyprotein.

Team: Professor Richard Beale (Professor of Intensive Care Medicine) Co-Investigator(s): Dr Manu Shankar-Hari (Consultant in Critical Care); Dr Luigi Camporota Consultant in Critical Care) Guy’s and St Thomas’ Hospital; Professor Mitul Mehta, Mr Eric Lynch, Dr Ndaba Mazibuko, Dr Chloe Farrell - Centre for Innovative Therapeutics (C-FIT) / KCL SEEK (Repurposing) Joint Venture; Professor Steve Williams Summary: The aim of this proposal is to support the set-up of an open label, randomised critical care trial to evaluate a unique lipid formulation of ibuprofen to improve lung injury outcome in acute respiratory distress syndrome (ARDS). ARDS is the major complication in patients with COVID-19 which commonly requires admission to intensive care and mechanical ventilation. Studies exploring initial phase viral triggered cytokine modulation have not shown any significant advantage over placebo. However, modulation of the cytokine response in the middle stage of the immune response (i.e. early stage of the adaptive response) to the viral pathogen, results in a significant reduction in the mortality and morbidity of treated animals compared to placebo. The project will undertake a human late clinical phase anti-inflammatory intervention using Flarin - a licensed lipid formulation of ibuprofen OTC product typically used in chronic inflammatory conditions that has also demonstrated ability to arrest macrophage mediated inflammatory cytokine storm in an ARDS mouse model.

Team: Sasieni (statistics & clinical trials), Fox (Prevention Clinical trials) Madan (occupational health, GSTT), Murphy (operations), Kelly (operations), Dobson (informatics), Folarin (software development), Waller (health behavioural) Lim (clinical trials), Carter (Statistician, IoPPN), Cape (pharmacy), Goodman (infections disease, GSTT) Lee (Junior GSTT Doctor representative). Summary: Onward transmission of COVID-19 within hospitals is of enormous concern to staff welfare, staff shortages and morbidity of patients and healthcare workers alike. Whilst standard practices are effective, further measures are needed. In a hospital setting, even a modest reduction in transmission, duration or severity of infection would have a dramatic impact on patient health outcomes and staff capacity. HIV Pre-exposure prophylaxis has dramatically reduced HIV incidence in key populations This project aims to investigate a similar strategy for COVID-19 through a three arm RCT including hydroxychloroquine vs remdesivir vs standard of care. These drugs are safe and cheap and are promising candidates for COVID treatment. As well as preventing individual virus acquisition, effective Covid-PrEP will prevent onward transmission for those acutely infected yet asymptomatic and attending work.

Team: Steven Williams, Kawal Rhode, Steven Niederer, School of Biomedical Engineering and Imaging Sciences. Summary: There is worldwide concern at the availability of specialist equipment to care for the most unwell Covid-19 patients. A particular concern is the occurrence of severe viral pneumonia and acute respiratory distress syndrome requiring advanced respiratory support including ventilation. There is currently a limited number of ventilators available to support these patients. Whilst there are rapid ongoing efforts to develop and manufacture more ventilators, the aim of this project is to develop a 3D-printable splitter which allows two patients to be ventilated using one ventilator whilst customising the ventilatory pressures delivered to each patient. The team will establish design requirements, undertake CFD modelling and develop candidate parts specifications for subsequent 3D printing, develop prototypes and test using established hardware for testing ventilators to verify the flow and pressures delivered to each simulated patient. The team will build and launch a website describing the invention in full and hosting the designs for the 3D printed parts.

Team: Simon Redwood, Christopher Allen, Tiffany Patterson Summary: Studies of the novel coronavirus SARS-CoV-2 have consistently highlighted baseline cardiovascular disease, hypertension and diabetes mellitus as adverse prognostic markers; associated with acute respiratory distress syndrome, myocardial injury, multi-organ failure and death. The angiotensin‐converting enzyme 2 (ACE2) receptor, highly expressed in the heart and lungs, is heavily implicated in the disease pathophysiology as it mediates SARS‐CoV‐2 tissue uptake. This project will investigate role of regulators of the renin-angiotensin system (RAS) pathway including ACE inhibitors (ACEi) or angiotensin receptor blockers (ARB)) on SARS‐CoV‐2 severity. The project will include linked observational and randomised clinical studies. Objective data on the safety of these widely applied therapies in patients with SARS-CoV-2 is an urgent unmet need. The study findings can therefore be expected to of high clinical interest to the cardiovascular community regardless of the direction of the result.

Team: Michael Malim, Katie Doores, Stuart Neil & Jonathan Edgeworth. Dept of Infectious Diseases, School of Immunology & Microbial Sciences, King’s College London; Centre for Clinical Infection and Diagnostics Research, Guy’s & St Thomas’ NHS Foundation Trust. Summary: This project aims to develop anti-infectives for SARS-CoV-2, and to understand and exploit antibody-mediated (humoral) immunity against this virus. The team will undertake the molecular cloning of antibody genes and development of potential immunotherapeutics capable of potent SARS-CoV-2 neutralisation. This will be achieved in four phases: 1. Establishment of a viral pseudotype assay as a rapid and quantitative surrogate for wild-type SARS-CoV-2 infection. Pseudotypes comprise cores of one virus carrying the Envelope (Env) glycoproteins of another and are capable of one round of infection in cells carrying the virus entry receptor. 2. Screening of sera from hospitalised COVID-19 patients for viral neutralisation using pseudotype-based assays. 3. Cloning of spike-specific paired immunoglobulin (Ig) heavy and light chain cDNAs from COVID-19 blood (PBMCs). 4. Monoclonal antibody expression and neutralisation. These antibodies will reveal fundamental information about the humoral immune response to SARS-CoV-2, and will inform passive immunisation efforts aiming for therapeutic or preventative vaccination of vulnerable individuals.

COVID-19 Funding - Diagnostics

Team: The KHP COVID-19 nanopore team (CIDR St. Thomas’ Hospital: Jonathan Edgeworth; Department of Virology: Malur Sudhanva, Mark Zuckerman Guy’s Genomics Innovation Unit: Ali Awan, Chloe Fisher; Viapath diagnostics: Penny Cliff, Fearghal Tucker Emma Cunningham; Infectious Diseases clinical team: Geraldine O’ Hara, Anna Goodman, Nick Price, Bill Newsholme, Blair Merricks; CIDR core team: Rahul Batra, Amita Patel; University of East Anglia Justin O’Grady) Summary: This project utilises the nanopore rapid whole genome sequencing facility on the St Thomas’ Hospital site to sequence covid-19 isolates from respiratory swabs identified in Viapath Infection Sciences laboratories at St Thomas’ and Denmark Hill. The sample collection will comprehensively cover the vast majority of the population across Lambeth and Southwark. It has potential to provide rapid insights into the frequency of introduction of different strains, the pathways and location of transmission, and potential emergence of subspecies. It will allow the team to make recommendations to KHP infection prevention & control, PHE and other national bodies about whether there are any new potential intervention points. It will also add to the development of ongoing routine real-time nanopore sequencing capability that can include early warning of emerging strains and links with different patient outcomes and severe diseases on ICU.

Team: Rocio Martinez Nunez, Mike Malim, Stuart Neil, Manu Shankar-Hari (ICU); CIDR St Thomas’: Jonathan Edgeworth; Viapath diagnostics: Penny Cliff, Fearghal Tucker, Eithne ManMahon; GSTT virology: Sam Douthwaite, Gaia Nebbia; Infectious Diseases clinical team: Geraldine O’Hara, Helen Winslow, Anna Goodman, Nick Price, Bill Newsholme, Abishek Das, Blair Merricks; CIDR core team: Amita Patel, Rahul Batra, Karen Bisnausthing. Summary: As the COVID-19 pandemic unfolds, hospitals will come under increasing pressure to deliver the increases in sample testing required. A key bottle neck in the COVID19 crisis is qRT-PCR (quantitative reverse transcription-PCR) testing. This bottle neck is comprised of sample preparation time, staff needed and reagents that will run low. This project will leverage the local resources in the School of Immunology and Microbial Sciences to create reserve contingency diagnostics to facilitate rapid COVID19 testing of NHS samples at Guy’s. It is anticipated that such a facility will have the potential to increase GSTT testing capacity by 4-5 fold. The team will deploy its BSL3 laboratory for COVID19 sample storage/preparation to facilitate diagnostics at Guy’s. This will support translational research in COVID19 Immunophenotyping, SARS-CoV2 Serology/Neutralizing Antibody identification, SARS-CoV2 molecular pathophysiology. It will validate new one-step qRTPCR tests to enable usage of a range of manufacturers in order to increase the testing capacity for GSTT. It will also validate Point of Care Tests (POCTs) for serology.

Team: Sebastien Ourselin, Tim Spector, Claire Steves, J Wolf (CEO ZOE global) Summary: King’s College London and ZOE Ltd, in March 2020 jointly launched a Covid-19 symptom tracker mobile application to assist health planners manage the present pandemic. The app currently has over 3.1 million users in the UK, US and Sweden. Outcomes from the app so far have offered information on geographical "Covid-19 hotspots", prediction on hospitalisation requirements for people exhibiting symptoms 5 days before event and has identified a wider range of symptoms than previously reported including anosmia. This project aims to further advance the big data analytics programme and provide robust prediction models at individual and population levels. The team will continue to address the following questions using data collected through the app: - Weekly R prediction model across sub-regions of the UK; - Risk factor investigation; - Disease presentation subtypes: symptoms appear to vary greatly in the strength of presentation and duration from one individual to another; - Longitudinal prediction, severity prognosis This data and analyses will have a profound impact on informing government and the NHS on future planning of resource management and care of patients during the ongoing pandemic. It has also the potential to shape an entirely new research programme and any virus management across a country through the develop of mobile app technology combined with big data science.

COVID-19 Funding - Social Science & Humanities (ROUND 1)

Team: Dr Matthew Moran (DWS); Prof Richard Sullivan (FLoSM), Ivanka Barzashka (DSD) Summary: Covid-19 has spread rapidly beyond China, with major outbreaks all over the globe. However it is not clear why some densely populated areas - particularly those with strong links to China, such as Taiwan and Hong Kong - have seen more success in containing the virus than others. One suggestion is that the SARS epidemic of 2003 forced these countries to prepare for similar future events and to rapidly enact containment plans. With this in mind, this project seeks to draw on novel gaming techniques to develop a customizable, scenario-based exercise that will, on the one hand, allow policy-makers and relevant authorities to work through the second and third-order effects of rapidly spreading infectious diseases such as Covid-19, and on the other, contribute to preparations for similar events in the future. This will be developed with the support of official partners such as the NHS, DFID, and the UK Cabinet Office. The project builds on a recent revival of interest in wargaming as government officials, military leaders, and other figures of authority seek more structured ways of understanding and responding to complex political and social events, both at home and abroad.

Team: Catherine Boyle, Arts and Humanities Summary: We construct the world around us by telling its stories, shaping the language we use to describe what is happening to us; language that is used and adapted in the media in response to moments of crisis. This language in turn shapes how we see the world. This is what we call ‘worldmaking’. This project seeks to analyse the ways in which Covid-19 has been narrated across the world. Linguists examining sources from European languages, Mandarin and Arabic will explore the most salient terms and will use digital tools to compare and analyse the ways in which the pandemic has been narrated. We know from literary, cultural, linguist and historic research that words like war, conflict, contagion, invasion, fear, sanity and cleansing inhabit the ways in which we articulate our responses – collective and subjective – to moments of crisis. It is important that we have a clear understanding of these articulations at the present moment in an already volatile geo-political situation.

Team: Shaun Hargreaves Heap, Christel Koop, Konstantinos Matakos, Asli Unan and Nina Weber Department of Political Economy, Faculty of Social Sciences & Public Policy Summary: Governments face many difficult (and crucial) policy trade-offs in their efforts to stop the COVID-19 pandemic. How much should economic and social life be restricted to prevent transmission? Should these restrictions be targeted at particular groups or applied universally? Should restrictions be enforced or enacted voluntarily? The success of any policy intervention in this (or any) area depends on citizen compliance. In turn, the rate of compliance is crucial for any effective policy implementation. However, little is known about citizen preferences over these possible dimensions and trade-offs of Covid-19 policy. This project addresses this gap for the UK by conducting a unique online conjoint survey experiment in two waves to identify citizen preferences.

Team: Professor Catharine MacMillan (Dickson Poon School of Law) Summary: Current UK governmental responses to COVID-19 are having unprecedented and unforeseen impacts upon the contractual obligations of millions of individuals and corporations; these impacts will continue after the pandemic in later litigation. This project seeks to both: (a) analyse the existing decisions concerned with frustrated contracts within England and related common law jurisdictions such as Canada, Australia and Singapore; and, (b) ascertain the existence and functioning of existing force majeure clauses in contracts, particularly whether these will cover the COVID-19 outbreak given governmental responses to this outbreak are unprecedented. This will provide recommendations which will allow greater clarity in the existing law and is important not only to private parties and courts but also to governments.

Team: Dr Michael Sanders, Reader in Public Policy, the Policy Institute; Susannah Hume, Director of Evaluation, the Policy Institute; Professor Peter John, Department of Political Economy. Summary: The British government has reportedly made extensive use of behavioural insights, or ‘Nudge’ theory in its response to the crisis, emphasising handwashing and other measures. Nudges can be an effective way to change the behaviour of all non‑symptomatic people, whose compliance is difficult to observe and enforce. For example, emphasising reciprocity and social connections has the potential to lead to sustained behaviour change. This project will explore when, and how, nudging may be effective in encouraging compliance with public health guidelines – specifically handwashing, social distancing and not stockpiling groceries. The team will conduct a set of survey experiments on the crowdsourcing platform, Prolific. Prolific is supported by the University of Oxford and is highly-regarded as a survey platform. The project will draw on the evidence around effective social influence to develop an intervention, and to test it in a variety of settings.

Team: Bobby Duffy (Director of the Policy Institute), James Rubin, Simon Wessely, and Christoph Meyer (SSPP). Summary: Governments’ responses to COVID-19 rely on influencing public behaviour in profound ways. In turn, this requires the public to have a clear understanding of both the relevant ‘realities’ and the advice. Motivation and action will also be informed by how the public see likely future outcomes, including economic and financial impacts, where different expectations may lead to excessive confidence or fear. Varying levels trust and confidence in government actions and communications will also inform behaviour. This project seeks to understand these interactions, and how they vary between sub-groups of the population. This is crucial both for short term action by government and long-term policy development and pandemic planning into the future. Existing general public survey work on COVID-19 has mostly not focused on connecting these aspects. A key element of this project will be to bring together the best available information on measurable realities and future predictions, drawing on expertise in King’s and the teams’ extensive connections externally.

Team: Stephanie Janes (CMCI), Chihiro Sato (Keio), Graeme Earl (Digital Humanities), Sarah Atkinson (CMCI), Keiko Okawa (Keio), Kate Devlin (Digital Humanities), Alison Duthie (Culture), Flora Smyth Zahra (FoDOCS), and Ellen Adams (Classics). Summary: Globally, as part of social distancing measures, the recent COVID-19 outbreak has seen an unprecedented number of cultural institutions abruptly close their doors to the public. It has never been more crucial to maintain access to arts and culture for all, and to find ways remotely to foster their associated empathy, intimacy, emotion, creativity and closeness. This project will research and deliver alternative cultural experiences to vulnerable audiences, through in-the-wild and prototyping design experiments. Our work will in turn provide pragmatic solutions which respond not only to the current crisis but to wider questions of access in the sector. This will build on an existing strategic relationship between King’s and Keio Graduate School of Media and Design centred on Digital Creativity, Ageing & Wellbeing.

COVID-19 Funding - Social Science & Humanities (ROUND 2)

Team: Professor Jill Manthorpe, Dr Baginsky of Quest Research and Evaluation Ltd. Summary: This project will provide a better understanding of how resilient multi-agency responses have been to concerns about the safety and welfare of children and young people raised by schools during the ‘lockdown’ and in the period immediately afterwards. Previous research by the team has shown that engagement of schools in multi-agency responses is pivotal. During the ‘lockdown’ only child protection or high-level child in need referrals were accepted by social care. Schools were open for vulnerable children but take up was below expectations. The team will work with six local authorities to conduct telephone or video linked interviews with local authority staff based in multi-agency safeguarding hubs, children’s social care, early help, and school-based mental health support to understand how the COVID-19 arrangements have impacted on the services they provide. Individuals in CAMHS and school nursing service will also input on the findings. The team will also survey via online questionnaire, a sample of ten schools in each area that have been open during the ‘lockdown’. The project will report their findings on whether the multi-agency arrangements of which schools are a part have been sufficiently robust to protect children, including when transitioning back into ‘pre-COVID 19’ arrangements.

Team: Dr Rachel Loopstra, KCL; External collaborators: Anna Taylor, Director, The Food Foundation; Dr Hannah Lambie-Mumford, Department of Politics and International Relations, University of Sheffield Summary: In the first three weeks of the UK’s COVID-19 lockdown, the Food Foundation’s YouGov survey revealed an estimated 8.1 million adults skipped meals, ate less, or experienced hunger but went without food because of a lack of food access. This was 4 times higher than pre-covid levels. At the same time, there has been a significant rise in food bank use across the UK since the lockdown. Adults who experienced acute income losses arising from the COVID-19 lockdown or who were self-isolating or shielding were found to have increased risk of food insecurity, over and above background risk factors. New governmental measures have been put in place to increase physical and economic food access for vulnerable groups. Food parcels are being provided to people who are shielded; DEFRA is coordinating additional food parcel provision for people who are self-isolating; the DWP has increased the basic Universal Credit allowance; the Treasury is providing income support for people who are self-employed or furloughed; and the DoE is providing supermarket vouchers for families in receipt of Free School Meals. However, there are concerns that some of these measures do not go far enough and that they are not reaching everyone within target groups. This project, in partnership with the Food Foundation, will monitor how vulnerability to food insecurity changes for at-risk groups. Comparison will be made against the UK’s Food and You survey provided by NatCen from 2016 and 2018 to compare baseline risk to risk under COVID-19. This comparison will enable finer-grained analyses of specific groups (e.g. people claiming Universal Credit, low income children). Multivariate regression analyses and matching procedures will be used to examine changes in risk of food insecurity for vulnerable and targeted intervention groups. The project will allow evaluation of the current scale of food insecurity, whether new intervention measures are having an impact and what gaps exist in current interventions.

Team: KCL: Dr Andy Guise (FoLSM), Dr PJ Macleod (FoLSM), Dr Michelle Cornes (Health and Social Care Workforce Research Unit), with Groundswell: Martin Burrows and Dr Jo Brown, and London School of Hygiene and Tropical Medicine: Prof Lucy Platt and Dr Sujit Rathod. Summary: COVID-19 and its response are severely impacting people who are homeless as they live in environments conducive to vulnerability, e.g. crowded hostels where social distancing is impossible. Radical measures for COVID-19 have been taken, such as housing people in hotels, with reportedly significant short-term impact, including improved health and opportunities to engage people in housing and health services. However, other reports highlight continuing and deepening problems for those outside these formal systems and unable to access them. Further, we are seeing new social norms and networks developing among homeless populations, which could improve or exacerbate health and social outcomes associated with COVID-19. This project will explore urgent questions as the COVID-19 epidemic and response evolves: 1) What happens to people when emergency measures – e.g. hotel provision – end? 2) how do people adhere to social distancing guidelines in the context of drug dependency and mental ill-health? 3) what is the experience of being ‘outside the system’ of the formal COVID-19 response and unable to access hotels and other additional forms of support? 4) How could new social norms and networks, including those enabled by phones, have a longer-term role in health and social care? 5) how can contact tracing and potential vaccine uptake be best implemented given a context of limited trust in government and technologies? This will inform evolving service responses and their evaluation. The project will implement rapid ethnographic assessment in London. The team will conduct interviews with people who are homeless (via phone, email, text/whatsapp), and develop ongoing contacts with particular ‘key informants’ who can especially explore experiences ‘outside the system’. We will also develop case studies of selected hostels, day centres and outreach teams, by collecting data, including available documentary data, with service clients and site staff. These will be supplemented by stakeholder interviews with relevant staff, e.g. outreach workers and Groundswell’s peer advocates.

Team: PIs: Dr PJ Macleod (FoLSM), Prof Diana Rose and Dr Aoife Sadlier (IoPPN). Co-Is: Dr Andrew Guise (FoLSM), Dr Alex Miller Tate (DPSoL), Dr Angela Sweeney (IoPPN). Collaborator: Mary Mason (Solace Women’s Aid). Summary: Lockdown measures serve to shut down routes to safety and support for people experiencing domestic violence, and function as a tool for coercion and control by perpetrators. This is corroborated by reports of rising domestic abuse in the UK and globally in recent months. Those who escape risk homelessness, with refuge providers overwhelmed by increased demand and reduced resources. Social isolation also poses challenges for the mental health of survivors recovering from trauma. This project addresses a challenge at the intersection of health, sociology, law and policy to ensure that the UK’s coronavirus response moving forward is implemented in ways that enable services to safely and effectively support survivors and those who remain at risk. The team will collect qualitative data via short telephone interviews with 10 domestic violence organisations in England and Wales in order to answer the following questions: 1) How have the needs of domestic abuse organisations in England and Wales changed during the coronavirus response period? 2) What steps has the government taken to meet these needs? 3) What needs are likely to arise or persist as lockdown measures begin to be lifted, and how should they be addressed?

Team: Prof. Bobby Duffy (PI), Dr Kirstie Hewlett and Rachel Hesketh. Summary: Among its many damaging effects, Covid-19 is likely to widen inequalities in Britain. Lower earners are significantly more likely to work in sectors that have been required to shut down and an economic downturn will have negative health effects, particularly for those already vulnerable to poor health. While some suggest that the pandemic will increase public support for government intervention to address societal inequalities, judgements about inequality can run counter to such expectations: studies have shown that the more unequal a society, the more prevalent the belief that income gaps are deserved. This project will examine how public perceptions of and attitudes to inequality are being affected by Covid-19, focusing on income and health inequalities. This will inform our understanding of the salience of inequality in Britain, and the potential support for policy measures to address it post-pandemic. To gather data on public perceptions of and attitudes to the impact of Covid-19 on health and income inequalities via an online survey. The survey will run on the YouGov omnibus, with a representative sample of 2,000 adults in Great Britain.

Team: PI: Caitjan Gainty (KCL); Co-Is: Jesse Olszynko-Gryn (Strathclyde); Agnes Arnold-Forster (Roehampton); Geoffrey Rees (Chicago); Collaborators: Helmie Stil, filmmaker; A.R. Hopwood, artist and curator; Lucas Canino, photographer and videographer Summary: The COVID-19 pandemic has given new voice to some of the most profound and fundamental epistemological problems of health care. Some of these are directly related to how healthcare systems work and others are to the nature and reliability of expertise and evidence. Fundamental questions and tensions have arisen around nonpharmaceutical interventions (NPIs) such as quarantine and isolation and the wearing of face masks and how we parse scientific knowledge, judging what is ‘right’ and what is ‘wrong,’ when considering scientific evidence in a pandemic? Each of these overlapping areas will be interrogated by an interdisciplinary group of scholars and will utilise a ‘mixed methodology’ of artistic and scholarly research.

Team: Dr Louise Smith, Dr G James Rubin, Professor Nick Sevdalis Prof Richard Amlôt, (Public Health England), Dr Susan Sherman (Keele University), Professor Julius Sim (Keele University). Summary: This project will assess the UK public’s attitudes towards a COVID-19 vaccine and their evolution over a 12-month period. Vaccination is widely seen as the greatest hope for emerging from the Covid-19 crisis. Vaccine acceptability is a major driver of vaccination uptake in Western countries; low acceptability has historically impacted the seasonal flu adult vaccine and also the MMR children’s vaccine, amongst many other vaccines – with corresponding low vaccination coverage and outbreaks of these diseases. Unfortunately, there are early signs of vaccination denial emerging in relation to a COVID-19 vaccine, endorsed by celebrities. The project will employ a longitudinal design which enables tracking of fluctuations in vaccine acceptability as the pandemic continues and to respond to any unforeseen events, such as adverse vaccine trials as the vaccine launch approaches. The findings will be fed into the UK’s national COVID-19 immunisation campaign design.

COVID-19 Funding - Immunology

Team: Professor Tim Spector, Department of Twin Research & Genetic Epidemiology; Professor Charles Wolfe, School of Population Health & Environmental Sciences; Professor Michael Malim, Professor Adrian Hayday, School of Immunology & Microbial Sciences; Professor Matt Brown, Director, GSTT-KCL NIHR BRC. Summary: Susceptibility to infection varies between individuals and whilst much of this is likely to be related to chance of exposure to virus and behavioural factors, it is also likely that other factors known to have major effects on immune function, such as genetics, microbiome and immunological parameters. This project will utilise the unique and densely characterised TwinsUK cohort to: 1. Investigate host factors which determine risk and severity of COVID-19 infection. This will include a classical twin heritability study of infection risk, GWAS of risk of developing infection, and studies investigating background immunological characteristics and microbiome profiles on infection risk. 2. Study aspects of coping with the pandemic and the social distancing/isolation management initiatives. This will include both established validated questionnaires and new screening tools implemented through apps to get deep as well as near real time data. 3. Study longitudinally the immunological response to COVID-19 infection.

Team: David Fear, Peter Gorer Department of Immunobiology; Co-I: Manu Shankar-Hari, Intensive Care Medicine GSTT Summary: One of the key characteristics of the adaptive immune system is the ability to maintain long-lived memory cell populations that allow an immediate, appropriate, response to be mounted against previously encountered pathogens. Following clearance of a respiratory virus such as Respiratory syncytial virus (RSV), long-lived memory is maintained by a population of low affinity IgM+ and high affinity IgG+ memory B cells. The development of an effective memory response to SARS-CoV-2 is critical to ensure protection against re-exposure, both at an individual and population level. However, the degree to which recovered individuals develop a true, long-lived memory response, and how this is affected by severity of the initial infection is not known. This project will use flow cytometry, mass cytometry and transcriptomics to investigate humoral memory responses in COVID-19 patients following convalescence. This will extend our very limited knowledge on the pathology of this disease. Further, we will gain important insight into the potential success of future vaccination strategies and allow methodologies to be developed that could investigate the unknown proportion of asymptomatic patients.

Team: Professor Adrian Hayday, Peter Gorer Dept of Immunobiology (Guy’s); Professor Jonathan Edgeworth, Centre for Infectious Disease Research [CIDR] (St.Thomas’), Dr Manu Shankar-Hari, NIHR Clinician Scientist; Consultant in Intensive Care Medicine (St.Thomas’). Summary: There is a large amount of variation between patients admitted to hospital with Covid-19. Currently, approx. ~20% are admitted to ICU. Why are their symptoms more severe than the remaining 80% who are ward-treated? Second, why do ~50% of the latter respond poorly, progressing to intensive-care and/or to irreversible decline? Third, why are some disease durations long, occupying ICU beds for several weeks? The distinction between these different trajectories is not obviously explained by "underlying condition". This project will explore the adaptive immune response and determine if parameters segregate with clinical metrics and outcome. It will test four lines of argument: 1. Adaptive responses may over-produce IL6 and other proinflammatory cytokines, reflecting an exaggerated activation of memory T cells that are more prevalent but less adaptable in older persons. 2. Poor patient recovery likely reflects failure to develop robust, appropriately skewed B and T cell immunity, combining immunodeficiency de facto with a vulnerability to repeated infections that in turn promote chronic immune activation and dysregulated cytokine release. 3. T cells are enriched in airways and can regulate the pro-inflammatory response to the virus. Hence, inter-individual variation in T cell activation may underpin inter-individual variation in memory cell development, and the ordered regulation of immune effector responses. 4. Plasmablast activation will be required to generate anti-viral neutralising antibodies; however precocious transitional B cell activation is a marker of adverse clinical responses to vaccination.

Team: LA Magee (Dept Women and Children’s Health, KCL), E Castillo (Depts Med & Obstet, U Calgary, Canada), SA Silverio (Dept Women and Children’s Health, KCL), LE Carson (Dept Psychological Med, IoPPN, KCL), A Easter (Section for Women’s Mental Health, IoPPN, KCL), M Chandiramani (Dept Obst Gynaecol, GSTT), N Kametas (Dept Obstet Gynaecol, KCH), L Poston (Dept Women and Children’s Health, KCL), P von Dadelszen (Dept Women and Children’s Health, KCL). Summary: The risk for pregnant women infected with COVID-19 remains unknown, however other coronaviruses (SARS & MERS) and pandemic influenza are risk factors for maternal morbidity & mortality. The UK government has classed pregnant women as a high-risk group. There are reports of preterm birth [PTB] and stillbirth associated with severe maternal illness, however the causes are unclear and may be secondary to an evolving cytokine storm associated with severe illness, or iatrogenic in light of maternal clinical deterioration. Co-morbidities remain unexplored although outside of pregnancy, hypertension is reported to be a risk factor for COVID-19-related morbidity and mortality. The aim of this project is to understand how COVID-19 interacts with hypertension and other mental and physical co-morbidities during pregnancy, to evaluate the influence of the virus on the risk of adverse maternal and fetal/newborn outcomes, and to describe the lived experience of this unique population and their care-providers during this pandemic. The team will obtain pregnancy outcome information on cases and controls from KCL’s eLIXIR (early-LIfe data cross-LInkage in Research) research platform that uniquely links clinical records from pregnant women, infants, and children with health record data from across services: maternity, neonatal, mental health, and primary care.

Team: Dr Michael Carter, Dr Manu Shankar-Hari, Mr Matthew Fish, Ms Aislinn Jennings Summary: Children are as likely as adults to acquire SARS-Cov-2 infection, and yet their incidence and severity of Covid-19 syndrome is considerably lower. Accurate characterisation of the childhood immune response to SARS-Cov-2 infection is therefore vital. Differences in innate immunity or acquired cellular immunity and humoral immunity (including a relatively antigen-naïve immune repertoire in children) may contribute towards different immunopathology across age groups. Alternatively, Covid-19 may represent deleterious effects of trained immunity, with older children and adults predisposed to a maladaptive immune response to SARS-Cov-2. However there have been cases of potentially fatal inflammatory complications linked to the novel coronavirus afflicting a small number of children. Cases of pediatric multi-symptom inflammatory syndrome or PMIS describe cardiovascular shock and coronary artery dilatation in the absence of pulmonary disease in children with no evidence of acute SARS-Cov-2 infection, but serological evidence of previous exposure. Blood results from these children show evidence of highly dysregulated immunity with persistently high C-reactive protein, ferritin, and d-dimers. These children have been treated with high doses of methylprednisolone, aspirin and monoclonal antibodies to TNF-alpha, IL-1 and IL-6, but the biological rationale and clinical evidence for this strategy is scarce. This project analyses samples of 18 children with Covid-19 and/or PIMS-TS and their controls. Analysis of these samples will enable us to characterise the childhood immune response to SARS-Cov-2 infection and impact of immunosuppressive therapy.

Team: Stuart Neil, Rui Pedro Galao, Rocio Martinez-Nunez, Mauro Giacca, Michael Malim, Gordon Proctor, Katie Doores Summary: SARS-CoV-2 is a new virus to the human population, and hence little is known about the cell and molecular basis for viral pathogenesis. In this project we will use both clinical isolates of SARS-CoV-2 or a newly documented reverse genetic system for the virus to establish live SARS-CoV-2 investigations in the Category 3 laboratories at KCL. WP1 will Establish live virus SARS-CoV-2 research at KCL: Plaque assays and virus replication assays will be established using reference strain isolates of SARS-CoV-2. Virus infection will be measured over time by in-house RT-qPCR assays for viral genomes. Once established we will prioritise the following questions: (1) In clinical swabs where the individual is viral RNA positive but either has no symptoms or has recovered from COVID-19, is there still evidence of recoverable SARS-CoV-2? This is essential information to manage the reopening of non-COVID clinical research. (2) Confirming the antiviral activity candidate small molecule inhibitors, neutralizing sera and monoclonal neutralizing antibodies cloned from human B cells. WP2 will establish a reverse genetic system for SARS-CoV2. This will allow molecular manipulation and high-throughput screens of the virus to address questions like: (a) Understanding the determinants of cell tropism of the virus in lung and oral epithelial cells; (b) Determining the role of cellular factors that regulate the replication of the virus; (c) Identifying mechanisms by which the cell intrinsic innate immune response blocks SARS-CoV-2 replication and the countermeasures to these processes encoded by the virus; (d) Understanding the mechanisms of antibody mediated neutralization of the virus by human sera.

COVID-19 Funding - Global Health & Other

Team: Professor Jackie Sturt (PI); Professor Frances Griffiths (Warwick); Prof Senga Pemba (SFUCHAS Ifakara); Richard Harding, Kennedy Nkhoma. Summary: In May the United Nation’s predicted that the coronavirus peak in low and middle income countries is 3-6 months away. Many high income countries have managed primary and secondary care health needs during the Covid 19 pandemic by switching rapidly from face to face to remote consultations. This helped minimise peak size and ensure healthcare delivery. The delivery of remote telephone and digital healthcare in the developing world is compromised by low levels of statutory and commercial digital and telecomms health infrastructure. Providing remote health information, triage and care over large distances and into marginalised communities will reap significant population health benefits and preserve Africa’s fragile healthcare provision. The team have recently adapted and digitised an existing remote consulting training package for Tanzanian health providers and have piloted Remote Consulting Training in rural Tanzania. They will upscale the training to 1000 health workers and evaluate the impact on care delivery. Process evaluation will determine barriers, facilitators and impacts and include telephone interviews with up to 30 registered health professionals and 30 community health workers pre and post-delivery of remotely delivered health care and analysis of digitised training engagement data. The team aim subsequently to upscale and evaluate in Nigeria, Uganda, Kenya and Rwanda with the aim to result in 40,000 remote consultations per day replacing face to face healthcare across these 5 countries.

Team: Prof Louise Rose (PI), NMPC, KCL; Joel Meyer, ICU consultant, GSTT; Amelia Cook, Research Fellow, GSTT; Joseph Casey, Deputy Programme Director, KHP; Victoria Metaxa, ICU consultant, KCH; Pam Ramsay, Senior lecturer, Dundee Uni; Prof Natalie Pattison, Herts Uni. Prof Anne Marie Rafferty, NMPC, KCL. Summary: Restrictions to family visiting during the COVID19 pandemic has been a significant challenge for UK intensive care unit (ICU) clinical teams. Inability to visit in person has created substantial stress/anxiety for ICU families already experiencing a huge psychological burden due to having a critically ill loved one. Life Lines, a rapid COVID-19 response, provides ICUs with 4g enabled electronic tablets with aTouchAway, a bespoke secure e-platform supporting virtual visiting and communication for families of critically ill patients. Life Lines has now supplied over 1000 tablets to over 150 NHS hospitals https://www.kingshealthpartners.org/our-work/lifelines . This project will provide empirical data describing how virtual visiting enabled through aTouchAway influences family and ICU staff experience of communication. It will contribute to the understanding of the emotional impact of virtual visiting/communication on both family and ICU staff as well as understanding of barriers and facilitators. The data will be used to inform further improvements and increased adoption of virtual visiting including extension of this visiting modality after the COVID19 pandemic.

Contact us

If you have questions about the scheme, please get in touch Dr Chris Bird and Dr Camilla Darling.