Published: 18 February 2021
The NIHR and UK Research and Innovation (UKRI) have funded four new research studies to better understand and address the longer term effects of COVID-19 on physical and mental health.
The new research projects, which have been awarded a total of £18.5 million, will help to better understand the causes, symptoms and treatment of what is known as ‘long COVID’.
The projects were chosen following a UK-wide call to fund ambitious and comprehensive research into causes, mechanisms and management of the longer term symptoms of COVID-19 in people who were not unwell enough to be admitted to hospital.
Approximately one in 10 people with COVID-19 continue to experience symptoms and impaired quality of life beyond 12 weeks. Long COVID can present with clusters of symptoms that are often overlapping and fluctuating. A systematic review has highlighted 55 different long-term effects, but common symptoms of long COVID include breathlessness, headaches, cough, fatigue, and cognitive impairment or ‘brain fog’.
One of the studies, led by the University of Birmingham, will identify and recruit thousands of non-hospitalised people into a major clinical digital study. These findings will be used to recommend what existing drugs and treatments should be tested in long COVID patients and to develop and test a digital supportive treatment.
Co-Principal Investigator Melanie Calvert, Professor of Outcomes Methodology and NIHR Senior Investigator, added: “Our study aims to reduce their symptom burden and improve quality of life. Ultimately, people want to be able to enjoy life again and spend time with their friends and family.
“Our digital trial platform in primary care will not only facilitate research exploring the underlying cause of long COVID, but also the evaluation and co-production of suitable interventions.”
Another study, led by Professor Nishi Chaturvedi at University College London (UCL), will use data from more than 60,000 people to help define what long COVID is and improve diagnosis. It will also elucidate why some people get the condition, the typical effects on a person’s health and ability to work, and the factors that affect recovery.
Chief Medical Officer for England and Head of the NIHR, Professor Chris Whitty said: “Good research is absolutely pivotal in understanding, diagnosing and then treating any illness, to ease symptoms and ultimately improve lives.
“This research, jointly funded through the NIHR and UKRI, will increase our knowledge of how and why the virus causes some people to suffer long term effects following a COVID-19 infection - and will be an important tool in developing more effective treatments for patients.”
NIHR and UKRI are also jointly funding major studies to characterise longer term disease in hospitalised patients. The Post-HOSPitalisation COVID-19 study (PHOSP-COVID), backed by £8.4 million in funding, is investigating the long-term effects of COVID-19 to support the development of new measures to treat patients. Both funders will continue to consider research proposals on long COVID.
Living with long COVID
Amy, 27, has been experiencing ongoing breathing problems after first contracting COVID-19 three months ago. She said: “I expected to be fully recovered within two weeks, but I actually isolated for three weeks because I just didn’t feel comfortable going out, I was still really poorly.
“At my age, I didn’t expect to suffer symptoms for more than just a few days. Feeling that poorly for that long, hearing all the horror stories and things, I wondered if I would actually go back to normal. I exercise a lot and it was really scary thinking that I might not actually get back to that again. It’s quite shocking to me actually that three months on I’m still not really myself.”
Patients with long COVID and members of the public were involved throughout the process of deciding which research proposals to fund. Monique, 32, has long COVID and was part of the funding decision-making. She said
“As a relatively young, fit and healthy person I have been surprised to suffer from the debilitating effects of long COVID. I was very keen to participate in the funding process of long COVID research and hope the work from these studies will lead to furthering understanding and treatment for this new disease.
“The impact of long COVID is being felt on a global scale and will influence times to come. It is crucial that more funding for research continues in this area.”
REACT long COVID (REACT-LC)
Professor Paul Elliott, Imperial College London - £5.4 million
This project aims to characterise and better understand the genetic, biological, social and environmental signatures and pathways of long COVID. It will also identify factors affecting why some people experience long term health effects of COVID-19, while others do not.
To date, most research on long COVID has been in hospitalised patients. The researchers will survey 120,000 people in the community who have taken part in the REACT study. Over 30,000 participants from REACT who tested positive for COVID-19, plus 90,000 who tested negative, will be invited to take part. Participants will be sent a survey about their health, symptoms and experiences. Participants with long COVID will be asked to join a panel to provide regular updates; while 60 will be invited for in-depth interviews. The researchers will develop a set of patient-reported outcomes that reflect the symptoms most important to people living with long COVID in the community.
Researchers will also invite up to 8,000 people with positive tests, including at least 4,000 with long COVID, for health tests and samples to test for genetic and other biological markers. This will help researchers understand mechanisms causing persistent symptoms and may point to possible treatments.
Therapies for long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study)
Dr Shamil Haroon and Professor Melanie Calvert, University of Birmingham - £2.3 million
This project aims to identify which treatments are most likely to benefit people with particular symptoms of long COVID and test supportive treatments to improve their quality of life.
The researchers will identify around 2000 patients with long COVID from GP records. Study participants will be invited to use a digital platform to report long COVID symptoms/quality of life.
A subgroup of around 300 patients will receive blood and other biological tests to understand the immunology of long COVID and will wear a device that will measure their heart rate, oxygen saturation, step count and sleep quality.
The researchers will review evidence for long COVID treatments, including drugs or supportive interventions (e.g. for mental health or tiredness). Working with patients, doctors and other experts, the researchers will recommend treatments that should be tested in long COVID patients and co-produce a targeted intervention for long COVID, tailored to individual patient need.
This will be delivered remotely in the community, via the Atom5TM app, providing critical support and information to empower patients in self-managing long COVID. In addition, they will provide tailored resources to support symptom management and nurse-led support for those with the severest symptoms.
The researchers will also use the digital platform to assess whether the treatments and supportive interventions reduce symptoms, improve quality of life, and are good value for money.
Characterisation, determinants, mechanisms and consequences of the long-term effects of COVID-19: providing the evidence base for health care services
Professor Nishi Chaturvedi, University College London - £9.6 million
This project aims to provide an evidence base for healthcare services to define what long COVID is and improve diagnosis. It will address why some people get the condition, the typical effects on a person’s health and ability to work, and the factors which affect recovery. It will also look at how best to ensure patients are able to access the right treatment and support through health services.
The researchers will use data from more than 60,000 people drawn from a combination of national anonymised primary care electronic health records and longitudinal studies of people of all ages across the country. From these studies, people reporting long COVID and comparator groups, will be asked to wear a wrist band measuring exercise ability, breathing, and heart rate. Participants will also complete online questionnaires on mental health and cognitive function. They will also be invited to a clinic for non-invasive imaging to look at potential damage to vital organs, such as the brain, lungs and heart.
Findings will be shared with bodies involved in clinical guidelines (NICE, as collaborators in this project), with government (via the Chief Scientific Advisor), with the public via social media and other outputs, and the scientific community via research publications
Non-hospitalised children and young people with long COVID (The CLoCk Study)
Professor Sir Terence Stephenson, UCL Great Ormond Street Institute of Child Health - £1.4 million
This research project aims to characterise symptoms typical of long COVID in non-hospitalised children and young people. It will also assess risk factors, prevalence and how long it lasts. This research will establish a medical diagnosis and operational definition of the condition, and look at how it might be treated.
The researchers aim to enrol 6,000 children and young people in the study, in two equal size cohorts - consisting of 3,000 who have had a positive COVID-19 test, and 3,000 who have not. Participants will be asked whether they still have physical or mental problems at 3, 6,12 and 24 months afterwards infection. Comparisons will then be made between the two cohorts. Carers and children and young people taking part will be involved in co-production of this study, and encouraged to complete surveys.
Results will be published, used to inform NHS services and health policy - and made available to participants. The study will provide data to help doctors to diagnose long COVID, establish how common it is, risk factors, and how long it goes on for