1. CVD-COVID-UK: Linking UK patient datasets to understand the relationship between Covid-19 and heart and circulatory disease
This enabling project, led by Professor Cathie Sudlow, Director of the BHF Data Science Centre involves over a dozen partners across the UK, including the custodians of all the major national generic and cardiovascular health datasets.
Professor Sudlow will work with these partners to link national hospital, primary care, mortality and Covid-19 test data with cardiovascular datasets and to make them this data available to approved researchers within national trusted research environments to address major questions:
1. What are the effects of cardiovascular diseases, their risk factors and medications on susceptibility to and outcomes from Covid-19 disease?
2. What is the direct impact of Covid-19 infection on acute cardiovascular complications and longer-term cardiovascular risk?
3. What is the indirect impact of the Covid-19 pandemic and the government and NHS response to it on the presentation, diagnosis, management and outcomes of heart and circulatory diseases?
2. COVIDITY-COHORT: Using UK cohort studies to understand which genetic, demographic and lifestyle factors related to cardiovascular health are important in the increased risk of severe consequences of COVID-19 infection
This project complements CVD-COVID-UK and will harness the power of over a dozen large UK cohort studies, where participants have already provided a wealth of information about their cardiovascular health, and general health and wellbeing. For most of these studies, their genetic make-up and a series of other biochemical markers have been analysed.
Professor Aroon Hingorani, Director of the UCL Institute of Cardiovascular Science and holder of a BHF Accelerator Award, with nine additional partner universities, will link the datasets from these studies with Covid-19 cases. This will provide a powerful tool for determining which genetic, demographic (e.g. ethnicity) or lifestyle determinants of cardiovascular health are associated with increased risk of Covid-19 infection, and its severity.
The team will also be able to understand whether some of these associations are causal. This will provide clues to the underlying mechanisms for increased risk and possibly reveal new treatments.
3. CAPACITY-COVID: UK-wide collection of cardiovascular complications due to Covid-19 infection
This project is led by Professor Bryan Williams, Director of the NIHR University College Hospitals Biomedical Research Centre (BRC), with strong regional support.
To accurately measure the acute cardiovascular complications of Covid-19 infection, the team are collecting standardised registry data that describe and quantify these complications in patients in hospitals across the UK. The data will form a significant part of a larger multinational registry already in operation called CAPACITY, adding to the power of the study.
CAPACITY (Cardiac complicAtions in Patients with SARS Corona vIrus 2 regisTrY; chief investigator Professor Folkert Asselbergs UCL/UMC Utrecht) is an international registry of patients with COVID-19 established to answer questions on the role of cardiovascular disease in this pandemic.
It is an extension of the Case Record Form that was released by the ISARIC (International Severe Acute Respiratory and Emerging Infection Consortium) and WHO (World Health Organisation). Since the launch of the registry, 88 centres across 17 countries have registered to join CAPACITY.
4. NIHR HIC CV+: Using the strengths of the NIHR Health Informatics Collaborative (HIC) to analyse the wider implications of the Covid-19 pandemic on cardiovascular health
This project builds on an established dataset from over 250,000 patients gathered from six large NHS Trusts: Oxford University College Hospitals, King’s College Hospital, Guy’s & St Thomas’ Hospitals, University College London Hospitals and Imperial College Healthcare. The data are being used to assess the effects of a series of clinical measures and treatment decisions on the severity of cardiovascular outcomes.
Led by Professor Jamil Mayet, Professor of Cardiology at Imperial College and leader of the HIC Cardiovascular Theme, the team will add Covid-19-related data and substantially increase the number of hospital trusts contributing routine clinical information. With collaborators from HDR UK, NHSX, NHS Digital and NICOR co-ordinated through the BHF Data Science Centre, the project has three initial aims:
1. Estimating the prognostic value of specific cardiac biomarkers to predict severity of acute cardiac complications due to Covid-19 infection.
2. Understanding the pattern of all cardiovascular admissions to hospital during the Covid-19 pandemic, particularly in the light of the observed decline in the number of non-Covid related cardiovascular admissions.
3. Assessing the effects of commonly prescribed medications on predictive biomarkers and outcome
5. Understanding the extent and persistence of damage to the heart and other organs as a consequence of Covid-19 infection
This project will characterise the prevalence and extent of heart muscle and multi-organ damage in patients who have been hospitalised with Covid-19 and assess their recovery status after six months.
It is co-led by Professor John Greenwood, NIHR Leeds CRF Cardiovascular Director, and Professor Stefan Neubauer, NIHR Oxford BRC Imaging Theme lead and Steering Committee member of the Oxford BHF Centre of Research Excellence. The project forms part of the larger national consortium study (the Post-Hospitalisation COVID-19 study, PHOSP-COVID), led by Professor Chris Brightling at the University of Leicester, co-funded by the MRC and NIHR, to set up a cohort of up to 10,000 patients who have been hospitalised with Covid-19 and who will be tracked to understand all of the possible longer-term health outcomes from the infection.
More than 300 patients recovering from relatively severe acute symptoms of Covid-19 infection will be recruited, from over a dozen academic health centre hospitals across the UK. The team will take measurements of important biomarkers and cardiac magnetic resonance images (MRI) of their hearts, with follow-up scans at six months.
In six of the centres, over 600 patients will undergo additional tests, including whole-body MRI, chest computed tomography (CT) scans and cardiopulmonary exercise testing. Quality of life and mental health questionnaires will also be completed. This will help the team define the damaging effects of the virus on the brain, lungs, heart, liver, kidney, exercise capacity, and overall well-being.
The CT scans will be analysed for evidence of inflammation using the techniques in the Flagship Project led by Professor Antoniades (UK C19-CRC). The results will document the impact of Covid-19 infection on people’s quality of life in the longer term and shed light on the mechanisms of organ damage. Understanding organ damage could also help the team understand how people’s pre-infection health and demographic status influences their risk and could lead to improved treatments in the future.
6. UK C19-CRC: Using AI to measure increased acute and longer-term cardiovascular risk in Covid-19 patients
The project takes advantage of novel artificial intelligence (AI) techniques applied to CT chest scans to accurately measure the level of inflammation in the heart which is suspected to be a cause of severe responses to the virus. CT scans are now frequently used to estimate the involvement of the lungs and hearts of Covid-19 patients.
These AI methods were developed by Professor Charalambos Antoniades, BHF Senior Clinical Research Fellow and Professor of Cardiovascular Medicine at the University of Oxford, who will lead the project with collaborators across the UK.
Linking their results to the data generated in the other Flagship Projects will guide the use of anti-inflammatory drugs in Covid-19 patients. This study will be strengthened by the availability of previous CT scans in many patients with existing heart disease and repeat CT scans after infection has subsided. This will allow a direct comparison of inflammation before, during and after infection to understand whether Covid-19 has lasting effects on heart health and therefore whether these patients should be treated more actively with medicines to reduce their cardiovascular risk.
7. Prevalence and impact of pulmonary vascular complications of Covid-19
This project forms part of the larger national consortium study (the Post-Hospitalisation COVID-19 study, PHOSP-COVID), led by Professor Chris Brightling at the University of Leicester, co-funded by the MRC and NIHR, to set up a cohort of up to 10,000 patients who have been hospitalised with Covid-19 and who will be tracked to understand all of the possible longer-term health outcomes from the infection.
It is led by investigators from Imperial College and the Universities of Cambridge and Sheffield. Hospitalised patients often have evidence of acute blood vessel damage in the lungs and this study will define the risk of longer-term pulmonary vascular complications, leading to guidelines for referral of patients to the UK network of seven Specialist Pulmonary Hypertension centres.
The frequency of vascular complications in the lung at least 3 months after admission to hospital will be assessed using imaging and measuring blood oxygen levels in 1000 patients in the PHOSP-COVID cohort. Those with evidence of complications will be followed up in the specialist centres with a series of more intensive tests and measurement of biomarkers (‘omics) to understand the features of the lung damage in more detail. Machine learning will be used to identify whether these cluster in groups suggesting different mechanisms of damage, and how different they may be from the features of pulmonary artery hypertension previously investigated in similar detail in patients before the pandemic.
The results will lead directly to targeted clinical trials of medicines that are expected to help specific groups of patients with evidence of lung blood vessel damage as a consequence of Covid-19 infection.
Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, said:
"This virus may be a respiratory infection, however, the most common underlying health conditions in those who die are cardiovascular. People with heart disease are among the most likely to die from the virus and the risk for people with diabetes is two to three times higher than the general population. And we are rapidly learning that the virus can have devastating effects on the heart and circulation and increase the risk of blood clotting, heart attacks and strokes.
By awarding flagship status to a handful of projects, we hope to mobilise resources and research effort behind studies that have the best chance of swiftly improving care and saving lives. The speed at which we’ve done this is testament to the strength of UK cardiovascular science."
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