University of Cambridge: against COVID-19 University
Entity: University of Cambridge
Category: University
Description: The University of Cambridge (legally The Chancellor, Masters, and Scholars of the University of Cambridge) is a collegiate research university in Cambridge, United Kingdom. Founded in 1209 and granted a royal charter by King Henry III in 1231, Cambridge is the second-oldest university in the English-speaking world and the world's fourth-oldest surviving university. The university grew out of an association of scholars who left the University of Oxford after a dispute with the townspeople. The two 'ancient universities' share many common features and are often referred to jointly as 'Oxbridge'. The history and influence of the University of Cambridge have made it one of the most prestigious universities in the world. Cambridge is formed from a variety of institutions which include 31 semi-autonomous constituent Colleges and over 100 academic departments organised into six schools. Cambridge University Press, a department of the university, is the world's oldest publishing house and the second-largest university press in the world. Cambridge Assessment, also a department of the university, is one of the world's leading examining bodies and provides assessment to over eight million learners globally every year. The university also operates eight cultural and scientific museums, including the Fitzwilliam Museum, as well as a botanic garden. Cambridge's libraries, of which there are 116, hold a total of around 16 million books, around nine million of which are in Cambridge University Library, a legal deposit library. The university is home to, but independent of, the Cambridge Union - the world's oldest debating society. The university is closely linked to the development of the high-tech business cluster known as 'Silicon Fen'. It is the central member of Cambridge University Health Partners, an academic health science centre based around the Cambridge Biomedical Campus. In the fiscal year ending 31 July 2019, the central university, excluding colleges, had a total income of £2.192 billion, of which £592.4 million was from research grants and contracts. At the end of the same financial year, the central university and colleges together possessed a combined endowment of over £6.9 billion and overall consolidated net assets (excluding 'immaterial' historical assets) of £12.569 billion. By both endowment size and consolidated assets, Cambridge is the wealthiest university in the United Kingdom. The University of Cambridge has research departments and teaching faculties in most academic disciplines. All research and lectures are conducted by university departments. The colleges are in charge of giving or arranging most supervisions, student accommodation, and funding most extracurricular activities. During the 1990s Cambridge added a substantial number of new specialist research laboratories on several sites around the city, and major expansion continues on a number of sites. Cambridge also has a research partnership with MIT in the United States: the Cambridge–MIT Institute.
1. Project: INTERVAL Study (UK Blood Donors Cohort Study).
Summary: The study is part of the global project "The COVID-19 Host Genetics Initiative". The INTERVAL study has been set up by the Universities of Cambridge and Oxford in collaboration with NHS Blood and Transplant.
Research question: A multipurpose recallable bioresource to understand the genetic determinants of molecular traits and clinical outcomes.
Study design: ~80,000 blood donors aged 18-80 recruited at sites across England from 2012 onwards into a 'multi-omics' bioresource. All participants have genetic data and are linked to health records. Subsets have molecular assays, including transcriptomics, proteomics, blood cell traits, metabolomics, lipidomics etc.
Type: Retrospective (n=800)
Genetic analysis: GWAS
Investigators: Adam Butterworth, Emanuele Di Angelantonio, John Danesh.
2. Project: Facilitating research into the identification of predictors of COVID-19 susceptibility, severity and prognosis.
Research Group: Cardiovascular Epidemiology Unit
Project Description: They are using machine learning to generate polygenic scores of molecular and cellular traits which can be used to identify candidate biomarkers for COVID-19 susceptibility and severity. They plan to make these polygenic scores widely available so that genotyped cohorts can also rapidly integrate their data to improve replicability and statistical power.
Collaborators: Health Data Research UK; Department of Public Health and Primary Care
3. Project: Using linked primary care and viral surveillance data to develop risk stratification models to inform management of severe COVID19.
Research Group: Primary Care Unit
Summary: This project is being led by Dr.Rupert Payne (Bristol). The proposed research aims to 1) establish a new dataset to facilitate COVID19 epidemiological analyses, linking primary care (CPRD), routine hospital data (SUS), and the Public Health England COVID19 surveillance data (CHESS); 2) develop a risk stratification tool to determine which patients in primary care are at highest risk of admission to critical care and which pre-morbid factors predict survival.
Collaborators: Universities of Bristol & Manchester; Department of Public Health and Primary Care
4. Project: ACE-Inhibitors/Angiotensin Receptor Blockers and risk of death for people infected with COVID-19: a prospective cohort study.
Research Group: Prevention Group, Primary Care Unit
Summary: Analysis of RCGP Research Surveillance data of routinely collected GP records from May to August 2020 covering 530 practices. In the UK, as of 24th March 2020, there were 8077 cases and 422 deaths from COVID-19. This figure is predicted to rise. Globally, mortality rates and severe complications have been high amongst those with hypertension (23.7%), cardiovascular disease (8%) or type 2 diabetes (16.2%). (Guan et al., 2020; Wu et al., 2020; Yang et al., 2020) Reports from the COVID-19 epicentre in China and a recent letter in the Lancet noted that amongst those with severe complications including death, ACE-I and ARBs were frequently prescribed. (Fang, Karakiulakis and Roth, 2020) COVID-19 binds to target cells through angiotensin-converting enzyme 2 (ACE2) which is expressed by epithelial cells in the lungs, kidneys and blood vessels. ACE-I and ARBs are thought to increase the expression of ACE2. It is hypothesised that these medications, therefore, make people more susceptible to COVID-19 and could also increase the severity of the infection leading to ARDS and death.(Patel and Verma, 2020) (Jia et al., 2005) This has caused some concern amongst prescribers and is leading to non-compliance amongst patients such that the British and Irish Hypertension Society, European Hypertension Society, Renal Association have released position statements calling for urgent evidence. While a mechanistic link is plausible, to date, there are no studies in human subjects while animal models show mixed results. Given that 65 million prescriptions of ARB/ACE-I have been issued by GPs in the UK in the last year alone and the COVID-19 epidemic is close to reaching its peak, it is essential and timely that this hypothesis is tested.
Collaborators: Dr Hajira Dambha-Miller, Prof Paul Little, Dr Beth Stuart, Dr Simon Fraser (University of Southampton), Prof Julia Hippisley-Cox, Prof Simon de Lusignan, Dr Ali Alrasbi, Mr William Hinton (University of Oxford). Department of Public Health and Primary Care
5. Project: HDRUK Cambridge COVID-19 Risk Factors Consortium
Summary: The HDRUK Cambridge COVID-19 Risk Factors Consortium aims to understand risk factors for COVID-19, clinical trajectory and associated health outcomes through linkage of population and patient cohort bioresources led from Cambridge (with over 230,000 participants) with SARS-CoV-2 test results provided by Public Health England and other electronic health records. Once this data has been linked, researchers will be able to use this data to identify risk factors that influence susceptibility to SARS-CoV-2 infection and the likelihood of adverse consequences of infection.
Collaborators: This consortium is a collaboration between HDRUK Cambridge (Department of Public Health and Primary Care, University of Cambridge and the Wellcome Sanger Institute) and Public Health England.
6. Project: COVID-19 Genomics UK (COG-UK) Consortium
Project Description: The COVID-19 Genomics UK (COG-UK) Consortium aims to increase the current capacity for SARS-CoV-2 genetic sequencing in the UK. This sequencing data will be used to understand the epidemiology and spread of the virus, and to monitor and evaluate interventions for COVID-19. SARS-CoV-2 genomic data will be integrated with NHS electronic health records and other existing genomic data to generate insights into susceptibility to COVID-19. From within the DPHPC, Professor John Danesh is a member of the COG-UK Steering Group, Dr Ewan Harrison will serve as the Scientific Project Manager and Dr Michael Chapman will lead the health informatics component.
Collaborators: This consortium is a collaboration between the NHS, Public Health England and other UK public health agencies, the Wellcome Sanger Institute, University of Cambridge and other academic institutions.
7. Project: COGENT (COvid-19 Genomic Evaluation of Novel Therapies)
Research Group: Cardiovascular Epidemiology Unit
Summary: The COGENT (COvid-19 Genomic Evaluation of Novel Therapies) portfolio of studies is an international collaboration of investigators lead by the Centre for Naturally Randomized Trials at Cambridge that aims to conduct an integrated suite of studies that a) nests a series of naturally randomized genetic experiments within an ensemble of artificial intelligence algorithms to identify each person’s unique genomic vulnerability to developing severe symptoms if infected with SARS-CoV-2; b) discover what causes some people to be more vulnerable to developing severe symptoms when they become infected with SARS-C0V-2; c) identify targets for therapies that can decrease the risk of developing severe symptoms if infected with SARS-CoV-2; d) conduct a portfolio of pragmatic naturally randomized trials to identify therapies that can potentially most effectively prevent the development of severe symptoms of SARS-C0V-2 infection; and e) use this information to rapidly design and conduct a series of adaptive pragmatic clinical trials to evaluate the clinical safety and efficacy of the identified novel therapies to prevent progression to severe complications among persons infected with SARS-CoV-2.
Collaborators: Cambridge Centre for Naturally Randomized Trials (lead); Cambridge Centre for AI in Medicine; TIMI Study Group Harvard Medical School; Imperial College London Clinical Trial Unit; Monash Heart; Oxford CTSU; University of Milan Department of Pharmacological and Biomolecular Sciences, University of Bristol; 23and Me; Benevolent AI
8. Project: Addressing the challenges of End-of-Life Care prescribing in the community during the COVID-19 pandemic
Research Group: Palliative & End of Life Care Group, Primary Care Unit
Summary: Led by Dr Stephen Barclay (University Senior Lecturer) the group are addressing the considerable challenges for prescribing for people at the end of their lives with both COVID-19 and other conditions. A UK-wide survey of clinicians concerning changes in medications prescribed and the involvement of family caregivers in medication administration is to be published shortly.
9. Project: Frequency and duration of dynamic suppression interventions to control COVID-19 pandemic: a multi-country comparison
Research Group: Cardiovascular Epidemiology Unit
Summary: Aims: To mathematically model the COVID-19 epidemic trajectory in 16 countries andimpact of dynamic interventions
Collaborators: 9 universities worldwide (led by IPSM, Bern).
10. Project: Strategies to reduce individual risks of adverse COVID-19 outcomes
Research Group: Cardiovascular Epidemiology Unit
Aims: To describe simple, lifestyle based strategies to promote optimal cardiometabolic/respiratory health and immune function in individuals, based on available evidence.
Collaborators: IPSM, Bern
11. Project: Estimating delayed cancer diagnosis and impact on the NHS in England per week following lock-down due to COVID-19
Research Group: Cancer Group, Primary Care Unit
Aims: To model accumulating demand for primary and secondary care diagnostic tests and 2WW pathways and consequences for stage at diagnosis, emergency admissions and deaths, in order to estimate NHS capacity and diagnostics requirements as the immediate impact of COVID-19 settles into routine care.
Collaborators: This is a collaboration between the Cancer Research UK-funded CanTest Collaborative and the NIHR Cancer Policy Research Unit, led by Fiona Walter (Cambridge) and Richard Neal (Leeds). Other collaborators include Greg Rubin (Newcastle), Yoryos Lyratzopoulos (UCL), Stephen Duffy (UCL), Willie Hamilton (Exeter) and the National Cancer Registration and Analysis Service (NCRAS).
12. Project: Building consensus on good practice for managing post-partum haemorrhage in women with diagnosed or suspected COVID-19
Research Group: THIS Institute
Summary: The aim is to build consensus around best practice for the clinical management of women who are known or suspected to have COVID-19 during the medical emergency that is post-partum haemorrhage. Consultation will take place with experts in the fields of maternity care, infection, prevention and control and human factors. This consultation and engagement exercise will result in the production of resources demonstrating how women’s care needs to be adjusted to account for the confirmed or possible presence of COVID-19. The project will be conducted in collaboration with the Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives. THIS Institute’s citizen science platform, Thiscovery, will be used to facilitate the work. The Health Foundation’s grant to THIS Institute will be used to support this project.
Collaborators: The project will be conducted in collaboration with the Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives. THIS Institute’s citizen science platform, Thiscovery, will be used to facilitate the work.
13. Project: Building consensus on good practice for remote antenatal care in response to the COVID-19 outbreak
Research Group: THIS Institute
Summary: The aim is to develop guidance on what good looks like for antenatal care at a time when face-to-face appointments are not possible. Existing practice in this area will be reviewed. Interviews and other consultations will be conducted with key stakeholders including women, partners, midwives and other clinicians. Co-design will be utilised to enable the drafting of guidelines, including but not limited to monitoring of blood pressure and urine analysis. Simulated video consultations will be co-produced to illustrate new ways of working and feedback will be sought. A consensus-building process facilitated by Thiscovery, THIS Institute’s citizen science platform, will be used. Collaborators include the Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives. Major charities in this field have already been engaged and indicated their support. The Health Foundation’s grant to THIS Institute will be used to support this project.
Collaborators: Collaborators include the Royal College of Obstetricians and Gynaecologists and the Royal College of Midwives.
14. Project: A rapid evidence review of interventions to reduce social isolation and/or loneliness during COVID-19 self-isolation measures.
Research Group: Prevention Group, Primary Care Unit
Project Description: A rapid evidence review of interventions to reduce social isolation and/or loneliness during COVID-19 self-isolation measures
Collaborators: The project is being led by a medical student (Chris Williams, cykw2@cam.ac.uk).
15. Project: BELIEVE COVID-19 Data Collection in Bangladesh
Research Group: Cardiovascular Epidemiology Unit
Summary: The BELIEVE cohort study in Bangladesh, which has over 73,000 participants, will collect data on COVID-19 symptoms in its participants through questionnaires administered over the phone. This data will be linked with the baseline data collected in the BELIEVE study including lifestyle factors, socioeconomic factors and medical history. This will be used to understand the risk factors for COVID-19 infection, severe illness and death.
Collaborators: DPHPC and partner institutions in Bangladesh (National Heart Foundation, icddr,b, BSMMU and IEDCR).
16. Project: NIHR Bioresource
Research Group: NIHR Bioresource
Summary: Recruitment of COVID (confirmed or suspected) patients being admitted into hospital to our national database. Started at Addenbrookes w/c 30.03.2020 & aim to extend to other local BioResource centres.
Collaborators: Ken Smith & Ravi Gupta (CovidX)
17. Project: Understanding the role of ACE2 in COVID-19
Research Group: Cardiovascular Epidemiology Unit
Summary: Researches will combine measurements of plasma ACE2 levels, ACE2 gene expression levels, germline DNA variation, other molecular factors, clinical information and COVID-19 outcomes to understand more about the role of ACE2 (the key SARS-CoV2 receptor protein) in susceptibility to COVID-19 and COVID-19 prognosis/outcomes.
18. Project: Human genetics to inform potential therapeutic targets for COVID-19
Research Group: Cardiovascular Epidemiology Unit
Aims: to evaluate a large panel of proteins that have been suggested as potential therapeutic targets for COVID-19 using causal inference methods.
Methods: Working with an international collaborative team, we will develop genetic instruments for druggable proteins predicted to be relevant to COVID-19 using data from INTERVAL and several other cohorts. We will then test these instruments in datasets with imputed genetic data linked to COVID-19 outcomes (e.g. Million Veteran Program, UK Biobank) to prioritise these potential therapeutic targets.
Collaborators: We co-lead the project with JP Casas from the Veterans Affairs. The project also involves investigators from several other sites, including UCL, Stanford, potentially the MRC Epidemiology Unit etc.
19. Project: Coronavirus Psychosocial Impacts Asia study (provisional working title)
Research Group: Cardiovascular Epidemiology Unit
Summary: The world is currently in the grip of the new Coronavirus Disease (COVID-19). Whilst ‘flattening the curve’ and a race for a vaccine are the main foci, the population mental health impacts of the pandemic are going to last much longer than the physical health impacts. Dr Tine Van Bortel at the Cambridge Institute of Public Health and collaborating Principle Investigators in India, Sri Lanka and Malaysia are investigating the psycho-social impacts of the Coronavirus pandemic in these particular contexts against the backdrop of the respective governments’ interventions and health systems preparedness. The study will allow for comparison as well as contextual understanding and tailored interventions to the needs of the respective populations and gain insights into how best to “Build Back Better”.
20. Project: UK-wide Mental Health Impacts of Coronavirus (provisional working title).
Research Group: Cardiovascular Epidemiology Unit
Summary: The world is currently in the grip of the new Coronavirus Disease (COVID-19). Whilst ‘flattening the curve’ and a race for a vaccine are the main foci, the population mental health impacts of the pandemic are going to last much longer than the physical health impacts.
The Mental Health Foundation UK (P.I.) has teamed up with Dr Tine Van Bortel at the Cambridge Institute of Public Health (Co-P.I.) and three collaborating universities across the UK (Swansea, Belfast and Glasgow) to monitor the psychological wellbeing of the nation as the Coronavirus pandemic sweeps around the world. This longitudinal study conducts fortnightly surveys as well as qualitative research with people in the UK to ensure that emerging mental health problems are spotted early on and appropriate interventions are developed and implemented.
Collaborators: This research is a collaboration between the Mental Health Foundation UK (P.I.), the University of Cambridge (Academic Co-P.I.) and three additional collaborating universities (Co-Is) in Swansea, Belfast and Glasgow, ensuring presence of each devolved nation in the UK.
21. Project: Risk calculator developed to show how underlying health conditions can affect mortality rates in COVID-19 pandemic Case Study
Summary: Researchers at University College London, University College London NHS Trust, the University of Cambridge and Health Data Research UK have collaborated to find out how underlying health conditions could affect mortality rates during the COVID-19 pandemic. Their health data study has revealed that having an underlying health condition, such as heart disease or diabetes, increases a person’s risk of death fivefold over the next year. The team have developed a prototype online ‘risk calculator’ to show how age, sex and underlying health conditions can affect mortality rates.
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