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£19.6 million awarded to new research studies to help diagnose and treat long COVID

People experiencing long COVID will benefit from a comprehensive package of new NIHR-funded research to help improve understanding of the condition, from diagnosis and treatment through to rehabilitation and recovery.

An extensive range of 15 projects from across the UK have been awarded a total of £19.6 million to examine causes of long COVID, trial drugs to tackle it, and investigate symptoms such as breathlessness and ‘brain fog’ that have become synonymous with the condition. Studies will also evaluate health services, such as long COVID clinics, and explore ways patients can monitor the condition to optimise their recovery and return to work.

Recent research shows that as many as a third of people who report being infected with the coronavirus also report long COVID. The condition can present with a number of ongoing symptoms including fatigue, breathlessness and cognitive impairment known as ‘brain fog’.

NIHR’s long COVID themed review, which considered over 300 papers and academic opinion pieces from across the world, indicated that long COVID could be up to four syndromes: post-ICU syndrome; long-term organ damage; post-viral syndrome, and, potentially, an entirely novel syndrome that could more specifically be identified as ‘long COVID’.

Health and Social Care Secretary, Sajid Javid, said: “Long COVID can have serious and debilitating long-term effects for thousands of people across the UK, which can make daily life extremely challenging. This new research is absolutely essential to improve diagnosis and treatments and will be life-changing for those who are battling long-term symptoms of the virus.

“It will build on our existing support with over 80 long COVID assessment services open across England as part of a £100 million expansion of care for those suffering from the condition, and over £50 million invested in research to better understand the lasting effects of this condition.”

Diagnosing and treating long COVID

One of the new studies, STIMULATE-ICP, led by University College London Hospitals NHS Trust and University College London, will be the largest long COVID trial to date, recruiting more than 4,500 people with the condition. With £6.8 million of funding, the project will test the effectiveness of existing drugs to treat long COVID by measuring the effect of 3 months’ treatment on symptoms, mental health and other outcomes such as returning to work. It will also assess the use of MRI scans to help diagnose potential organ damage, as well as enhanced rehabilitation through an app to track their symptoms.

Chief investigator, Professor Amitava Banerjee said: “Individuals with long COVID have long been asking for recognition, research and rehabilitation. In our two-year study across six clinical sites around England, we will be working with patients, health professionals, scientists across different disciplines, as well as industry partners, to test and evaluate a new ‘integrated care’ pathway from diagnosis to rehabilitation, and potential drug treatments.

“We will also be trying to improve inequalities in access to care and investigating how long COVID compares with other long-term conditions in terms of use of healthcare and burden of disease, which will help to plan services.”

The EXPLAIN project, led by Professor Fergus Gleeson at Oxford University and funded with £1.8 million, will seek to diagnose ongoing breathlessness in coronavirus patients who were not admitted to hospital, using MRI scans to trace inhaled gas moving into and out of the lungs to assess disease severity and whether breathlessness improves over time.

Prof Gleeson said: “Following on from our earlier work using hyperpolarised xenon MRI in patients following hospitalisation with COVID-19 pneumonia, where we showed that their lungs may be damaged even when all other tests were normal, it is critical to determine how many patients with long COVID and breathlessness have damaged lungs, and if and how long it takes for their lungs to recover.

"Hyperpolarised xenon MRI takes a few minutes and does not require radiation exposure, so it may be repeated over time to see lung changes. Using this technique, we can see if there has been damage to the airways in the lungs, or to the areas where oxygen crosses into the bloodstream, which appears to be the area damaged by COVID-19.”

NIHR’s commitment to long COVID research

The new funding has been awarded following a UK-wide call for ambitious and comprehensive research into understanding and addressing the longer term physical and mental health effects of COVID-19 in non-hospitalised people. It is a second slice of funding to research long COVID following a first round in February, which saw £18.5 million awarded to four projects.

Professor Nick Lemoine, Chair of NIHR’s long COVID funding committee and Medical Director of the NIHR Clinical Research Network (CRN), said: “This package of research will provide much needed hope to people with long-term health problems after COVID-19, accelerating development of new ways to diagnose and treat long COVID, as well as how to configure healthcare services to provide the absolute best care.

“Together with our earlier round of funding, NIHR has invested millions into research covering the full gamut of causes, mechanisms, diagnosis, treatment and rehabilitation of long COVID.”

“Long COVID has taken away time with my grandchildren”

Education consultant Penny Tassoni, 59, contracted COVID-19 in March 2020 and is still experiencing a variety of symptoms 16 months later.

Penny, who was awarded an MBE for services to early education in 2018, said: “When I caught COVID I was not hospitalised, but was close to it three times in the two-week acute phase. I was extremely weak following the infection, but over six weeks managed to get back onto my feet, quite literally, and to manage short walks and light physical activity.”

Yet last July she found herself suffering from persistent fatigue and pain in her legs, long-term symptoms that continue to affect her and have reduced her quality of life.

Penny added: “Before this I had a huge zest for life and people used to tell me to slow down. Now I live half a life rather than the full one I had before, and I have to pace myself and take regular naps. I can’t commit to go for a walk with anybody because I don’t know if it’s a day that I’m going to be too tired.

“Lack of energy means my husband and I can't offer the amount of time to have our grandchildren overnight, and they are a huge part of our lives.”

Earlier this year Penny volunteered to be a public contributor to help review research proposals submitted to NIHR’s second long COVID funding call. As she continues her recovery, she is hopeful that the new studies will help to provide answers for others with the condition.

“It has been a journey of discovery," she said, "and I welcome the prospect of joined-up robust research to allow a better understanding of the condition and funding that allows different approaches to be tested to see which one suits.”

The funded projects

STIMULATE-ICP (Symptoms, Trajectory, Inequalities and Management: Understanding Long-COVID to Address and Transform Existing Integrated Care Pathways)

Professor Amitava Bannerjee, University College London Hospitals NHS Trust - £6.8m

Developed with the help of patient organisations, this project will test the efficacy of existing drugs to treat long COVID, and measure the different effects of three months’ treatment on patients with regards to their symptoms, mental health and other outcomes such as returning to work.

It will also assess the use of MRI scans to help diagnose potential organ damage in those recovering from the coronavirus, as well as enhanced rehabilitation - the provision of joined-up specialist care centred around an app for patients allowing them to track their symptoms.

LOCOMOTION (long COVID multidisciplinary consortium: optimising treatments and services across the NHS) study

Dr Manoj Sivan, University of Leeds - £3.4m

This study focuses on identifying and promoting the most effective care for long COVID patients, ranging from accurate assessments in specialist clinics to the best advice and treatment in surgeries, as well as home monitoring methods that can show flare-ups of symptoms.

Drawing from the experiences of current long COVID patients and NHS professionals, the research aims to establish a gold standard of care that can be shared across England and the rest of the UK.

Analysis will be conducted in 10 long COVID clinics, at home and in doctors’ surgeries, and the study will track referrals and evaluate different services through patient interviews to make sure they are efficient, accessible and cost-effective. Specialists in healthcare inequality will also ensure that views are sought and recorded from people who are not visiting clinics.

EXPLAIN (Hyperpolarised xenon magnetic resonance pulmonary imaging in patients with Long-COVID)

Professor Fergus Gleeson, University of Oxford - £1.8m

The EXPLAIN project will seek to diagnose ongoing breathlessness in coronavirus patients who were not admitted to hospital, using MRI scans to trace inhaled xenon gas moving into and out of the lungs.

A 15-minute scan using low levels of the gas will display lung function and - if abnormalities are found - comparisons of data across different groups of participants recruited from Oxford and Sheffield can help assess their severity and whether they improve over time.

Some EXPLAIN patients will also have a separate scan to see if heart damage can be identified. If the MRI scans separate patients with and without lung disease, further CT scans can be analysed, using artificial intelligence and blood samples to identify associated conditions and inform the development of treatments.

CICERO (Cognitive Impairment in long COVID: PhEnotyping and RehabilitatiOn)

Dr Dennis Chan, University College London - £1.2m

Up to three quarters of people who experience long-term symptoms after COVID-19 report problems with memory, attention or other cognitive functions - symptoms known collectively as ‘brain fog’.

This project will first determine which elements of brain function are most affected in people with long COVID. The relationship between brain function and other symptoms of long COVID, such as fatigue and anxiety, will be explored, and MRI scanning will be used to identify the affected brain networks.

The researchers will then develop and test a new rehabilitation strategy to help people recover from the cognitive aspects of long COVID and return to normal life and working ability. This will support production of a freely available COVID-19 Cognitive Recovery Guide on how best to offer the new rehabilitation approach depending on the patient’s symptoms.

LISTEN (Long COVID Personalised Self-managemenT support - co-design and EvaluatioN)

Professor Fiona Jones, Kingston University - £1.1m

In recognition that each person with long COVID can experience markedly different symptoms, the LISTEN project will work in partnership with patients to design and evaluate a package of self-management support that can be tailored to individual needs.

The researchers will first work with people living with or recovered from long COVID, plus a social enterprise with expertise in reaching seldom heard populations, to design the package and associated patient and training resources.

The team will then test the self-management package alongside up to six one-to-one virtual coaching sessions from trained rehabilitation practitioners, to test whether the treatment improves how people with long COVID feel and how they cope with everyday activities. The researchers will also evaluate how the package could be implemented more widely, with the aim that self-management for people with long COVID can be delivered at scale.

ReDIRECT: Remote Diet Intervention to Reduce long Covid symptoms Trial

Dr David Blane, University of Glasgow - £999,679

The immunologic and virologic determinants of long COVID

Professor David Price, Cardiff University - £774,457

Quality-of-life in patients with long COVID: harnessing the scale of big data to quantify the health and economic costs

Dr Rosalind Eggo, London School of Hygiene and Tropical Medicine - £674,679

Percutaneous Auricular Nerve Stimulation for Treating Post-COVID Fatigue (PAuSing-Post-COVID Fatigue)

Dr Mark Baker, Newcastle University - £640,180

Immune analysis of long COVID to inform rational choices in diagnostic testing and therapeutics

Professor Daniel Altmann, Imperial College - £573,769

Understanding and using family experiences of managing long COVID to support self care and timely access to services

Professor Sue Ziebland, University of Oxford - £557,674

Development of a robust T cell assay to retrospectively diagnose SARS-CoV-2 infection and IFN-γ release assay as diagnostic and monitoring assay in Long COVID patients

Dr Mark Wills, University of Cambridge - £372,864

Using Activity Tracking and Just-In-Time Messaging to Improve Adaptive Pacing: A Pragmatic Randomised Control Trial

Professor Nicholas Sculthorpe, University of the West of Scotland - £317,416

Impact of COVID-19 vaccination on preventing long COVID: a population-based cohort study using linked NHS data

Professor Daniel Prieto-Alhambra, University of Oxford - £224,344

Long COVID Core Outcome Set (LC-COS) project

Dr Tim Nicholson, King’s College London - £139,619