Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study)
Lead Research Organisation:
University of Birmingham
Department Name: UNLISTED
Abstract
Background: Some people who have survived COVID-19 infection develop longer-lasting symptoms, known as Long COVID. Many lack support and are given conflicting advice. Aim: To work out which treatments are most likely to benefit people with particular symptoms and test supportive treatments to improve their quality of life. Design and methods Work package 1 will identify people that had COVID-19 from GP records. Study participants will be invited to use a digital platform to report Long COVID symptoms/quality of life. Work package 2 will assess Long COVID symptoms. Participants with severe symptoms will be contacted by a nurse to provide advice/support. Blood test results and wearable data will help us understand which treatments might be best to support specific groups of Long COVID patients. Work package 3 will review evidence for treatments for Long COVID including drugs or supportive interventions (e.g. for mental health or tiredness). Working with patients, doctors and other experts we will recommend treatments that should be tested in Long COVID patients and develop supportive interventions which can be delivered using the Long COVID platform. Work package 4 will establish a digital trial using the Long COVID platform to test whether supportive interventions can benefit Long COVID patients by reducing their symptoms and improving their quality of life and if the intervention is good value for money. Patient and public involvement People with COVID lived experience have co-designed this research proposal and the research platform. A lived experience advisory panel will work with us throughout the project and meet regularly to contribute to all aspects of the study. Dissemination Results will be published, presented at conferences and made available for use by other researchers. We will host a study specific website and Twitter account and will share lay summaries coproduced with our patient partners.
Technical Summary
This COVID-19 Long COVID award is jointly funded (50:50) between UKRI/Medical Research Council and the National Institute for Health Research. The figure displayed is the UKRI/MRC amount only, each partner is contributing equally towards the project so the Total Fund Amount is £2,257,157.
Background Approximately 1 in 20 individuals with COVID-19 experience symptoms and impaired quality of life beyond 12 weeks (‘Long COVID’). Long COVID may comprise several distinct syndromes yet to be fully characterised. Aim: To evaluate symptoms and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals, to coproduce a remotely-delivered intervention, and to establish a virtual trial platform. Objectives and Methods WP1 Establish a representative population-based cohort of individuals with Long COVID. A representative population-based cohort of non-hospitalised individuals with Long COVID will be established using Clinical Practice Research Datalink (CPRD) primary care records. Individuals with a diagnosis of COVID-19 at least 12 weeks prior and matched controls will be identified. We will invite them to report symptoms/quality of life through the Aparito Atom5™ digital platform. WP2 Characterise and immunologically phenotype Long COVID syndromes. Machine learning clustering techniques will be used to identify distinct Long COVID syndromes. Individuals from each cluster(n=50) and controls will be invited to undertake biosampling to measure inflammatory markers, autoantibodies, and T cell function, and wearable devices to provide data on heart rate, oxygen saturation, physical activity and sleep quality to identify potential pharmacological and supportive therapies. WP3 Provide evidence-based recommendations on targeted pharmacological and supportive therapies for Long COVID syndromes. We will review existing evidence on post-viral inflammatory syndromes and existing evidence on Long COVID to prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulated evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers.WP4 Co-produce and evaluate a virtual targeted supportive intervention for Long COVID. A digital trial platform will be established to evaluate the effectiveness, cost-effectiveness, and acceptability of the coproduced virtual supportive intervention in a randomised clinical trial, and for future research.
Background Approximately 1 in 20 individuals with COVID-19 experience symptoms and impaired quality of life beyond 12 weeks (‘Long COVID’). Long COVID may comprise several distinct syndromes yet to be fully characterised. Aim: To evaluate symptoms and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals, to coproduce a remotely-delivered intervention, and to establish a virtual trial platform. Objectives and Methods WP1 Establish a representative population-based cohort of individuals with Long COVID. A representative population-based cohort of non-hospitalised individuals with Long COVID will be established using Clinical Practice Research Datalink (CPRD) primary care records. Individuals with a diagnosis of COVID-19 at least 12 weeks prior and matched controls will be identified. We will invite them to report symptoms/quality of life through the Aparito Atom5™ digital platform. WP2 Characterise and immunologically phenotype Long COVID syndromes. Machine learning clustering techniques will be used to identify distinct Long COVID syndromes. Individuals from each cluster(n=50) and controls will be invited to undertake biosampling to measure inflammatory markers, autoantibodies, and T cell function, and wearable devices to provide data on heart rate, oxygen saturation, physical activity and sleep quality to identify potential pharmacological and supportive therapies. WP3 Provide evidence-based recommendations on targeted pharmacological and supportive therapies for Long COVID syndromes. We will review existing evidence on post-viral inflammatory syndromes and existing evidence on Long COVID to prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulated evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers.WP4 Co-produce and evaluate a virtual targeted supportive intervention for Long COVID. A digital trial platform will be established to evaluate the effectiveness, cost-effectiveness, and acceptability of the coproduced virtual supportive intervention in a randomised clinical trial, and for future research.
Publications
Adab P
(2022)
Comorbidities and covid-19.
in BMJ (Clinical research ed.)
Aiyegbusi OL
(2023)
Considerations for patient and public involvement and engagement in health research.
in Nature medicine
Aiyegbusi OL
(2021)
Symptoms, complications and management of long COVID: a review.
in Journal of the Royal Society of Medicine
Aiyegbusi OL
(2023)
Digitally enabled decentralised research: opportunities to improve the efficiency of clinical trials and observational studies.
in BMJ evidence-based medicine
Brown K
(2022)
Long COVID and self-management.
in Lancet (London, England)
Chandan JS
(2023)
Non-Pharmacological Therapies for Post-Viral Syndromes, Including Long COVID: A Systematic Review.
in International journal of environmental research and public health
Gorst S
(2023)
Core outcome measurement instruments for use in clinical and research settings for adults with post-COVID-19 condition: an international Delphi consensus study
in The Lancet Respiratory Medicine
Description | LOCOMOTION Study Expert Advisory Group member |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
URL | https://clinicaltrials.gov/ct2/show/NCT05057260 |
Description | Participation in national Long COVID working group |
Geographic Reach | National |
Policy Influence Type | Participation in a guidance/advisory committee |
URL | https://www.nature.com/articles/s41591-021-01591-4 |
Description | Post-COVID condition Core Outcome Set (PC-COS) |
Geographic Reach | Multiple continents/international |
Policy Influence Type | Participation in a guidance/advisory committee |
URL | https://www.pc-cos.org/ |
Description | Adaptation and validation of a patient-reported outcome measure capturing Long COVID symptom burden in adolescents: The Symptom Burden Questionnaire for Long COVID in Young People (SBQ-LC-YP) |
Amount | £153,489 (GBP) |
Funding ID | NIHR204942 |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 09/2023 |
End | 09/2024 |
Description | Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient- reported outcomes and immunology to targeted therapies (The TLC Study) |
Amount | £2,257,157 (GBP) |
Funding ID | COV-LT-0013 |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 03/2021 |
End | 03/2023 |
Title | Symptom Burden Questionnaire for Long COVID |
Description | The Symptom Burden Questionnaire for Long COVID (SBQ-LC) is a novel electronic patient-reported outcome (PRO) measure for long COVID. It was developed and validated in the first part of the TLC Study through a systematic scoping of existing PRO measures, a systematic review, interviews with people with lived experience of long COVID, a clinician survey and expert consensus workshop, and a field test. The tool is now available with both non-commercial and commercial licenses. It has been licensed in over 50 countries for use in research studies and clinical practice and is being translated into several languages including Chinese. |
Type Of Material | Physiological assessment or outcome measure |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | The tool has been licensed for use in over 50 countries in research studies and clinical services. It has been cited as a recommended tool for assessing symptoms associated with long COVID in the international Post COVID-19 Condition Core Outcome Set. |
URL | https://www.birmingham.ac.uk/research/applied-health/research/symptom-burden-questionnaire/index.asp... |
Title | SNOMED-CT symptom code lists for Long COVID |
Description | SNOMED-CT code lists for 115 symptoms associated with Long COVID. These code lists enable the extraction of symptom data from GP records. |
Type Of Material | Data handling & control |
Year Produced | 2022 |
Provided To Others? | Yes |
Impact | These code lists can be used by other researchers to investigate symptoms associated with Long COVID as well as other health conditions. |
URL | https://github.com/AnuSub/LongCOVID_Symptoms_CodeList |
Description | Clinical Practice Research Datalink |
Organisation | Medicines and Healthcare Regulatory Agency |
Department | Clinical Practice Research Datalink (CPRD) |
Country | United Kingdom |
Sector | Public |
PI Contribution | Our health informatics research team at the University of Birmingham has partnered with CPRD on the Therapies for Long COVID (TLC) Study. This is a major nationally funded study and was one of the first four funded in England. We are working closely with CPRD to phenotype Long COVID using big data derived from GP records in England. We are also working with CPRD to recruit a cohort of individuals with Long COVID and a matched cohort in order to establish a cohort study in primary care. Our team have led on the research funding application, study protocols, and applications for ethical approval. |
Collaborator Contribution | CPRD has provided big data derived from GP records in England, enabling an analysis of over 400,000 individuals with a diagnosis of SARS CoV-2 infection and 1.6 million matched control patients. Members of CPRD are co-investigators on the grant and have co-authored manuscripts with members of our team. CPRD is supporting the recruitment of individuals with a history of SARS CoV-2 infection and matched controls from GP practices across England to establish a cohort study on Long COVID. |
Impact | We have co-authored several manuscripts from the TLC Study: TLC protocol paper (in press): https://www.medrxiv.org/content/10.1101/2021.12.20.21268098v1 Assessment of 115 symptoms for Long COVID (post-COVID-19 condition) and their risk factors in non-hospitalised individuals: a retrospective matched cohort study in UK primary care (under review): https://www.researchsquare.com/article/rs-1343889/v1 We have also previously published a number of pharmacoepidemiology studies for COVID-19 using data from CPRD, which colleagues from CPRD have co-authored. |
Start Year | 2020 |
Description | Collaboration with the CLOCK Study |
Organisation | University College London |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Members of the TLC Study team have collaborated with members of the Long COVID in Children and Young People (CLOCK) Study on an RfPB grant to adapt the Symptom Burden Questionnaire for Long COVID for adolescents. |
Collaborator Contribution | The principal investigators of the CLOCK Study are co-investigators on the RfPB grant-funded adaption of the Symptom Burden Questionnaire for young people. |
Impact | The project is still underway and does not yet have any outputs or outcomes. |
Start Year | 2023 |
Title | Symptom Burden Questionnaire for Long COVID TM |
Description | A novel electronic patient-reported outcome measure for long COVID was developed called the Symptom Burden Questionnaire for Long COVID (SBQ-LC). Non-commercial and commercial licenses are now available and have been issued to teams across more than 50 countries. The licensing portal can be accessed here: https://www.birmingham.ac.uk/research/applied-health/research/symptom-burden-questionnaire/index.aspx#:~:text=The%20Symptom%20Burden%20Questionnaire%E2%84%A2,best%2Dpractice%20and%20regulatory%20guidance. |
IP Reference | |
Protection | Trade Mark |
Year Protection Granted | 2022 |
Licensed | Yes |
Impact | There has been significant national and international interest in the use of the SBQ-LC in research studies and clinical service provision. As of January 2023, 162 licenses had been issued to teams across 55 countries. It has also been sited in the WHO Post-COVID-19 Core Outcome Set as a recommended tool for capturing patient-reported outcome data on long COVID symptoms for research studies. |
Description | Interview on Long COVID for BBC Health Check |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Media (as a channel to the public) |
Results and Impact | I gave an interview on Long COVID for BBC Health Check. This was aired on BBC World Service in February 2021. |
Year(s) Of Engagement Activity | 2021 |
URL | https://www.bbc.co.uk/programmes/p0980lpb |
Description | Long COVID research dissemination project |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Gave a presentation on the Therapies for Long COVID study to a school that we have partnered with. The school students are undertaking a project to produce lay friendly summaries of our research, targeted at a younger audience. |
Year(s) Of Engagement Activity | 2022 |
Description | Patient and public involvement event |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | We held a PPIE workshop with long COVID sufferers and members of the Caribbean community in Manchester to talk about widening research participation in underrepresented groups. The meeting formed part of the wider PPIE work undertaken by the team. |
Year(s) Of Engagement Activity | 2023 |
Description | Poster presentation on long COVID at the European Respiratory Society Annual Congress 2023 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Professional Practitioners |
Results and Impact | Members of our research team presented research findings on long COVID at the annual European Respiratory SOciety Congress in Milan. There was a high level of interest and engagement among attendees who were a mixture of healthcare professionals and researchers. |
Year(s) Of Engagement Activity | 2023 |
URL | https://erj.ersjournals.com/content/62/suppl_67/PA5343 |
Description | Presentation at the NHSE Post COVID Clinical Network Meeting |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | I gave a presentation on the findings of the TLC Study at the NHSE Post COVID Clinical Network Meeting on Monday 6th March 2023. This was a national meeting attended by clinicians across the country involved in long COVID services. I received positive feedback about our study findings and explored opportunities to embed the Symptom Burden Questionnaire for Long COVID (SBQ-LC) in NHS Services. |
Year(s) Of Engagement Activity | 2023 |
Description | Presentation on Long COVID at the annual Primary Care Respiratory Society Conference |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Professional Practitioners |
Results and Impact | Professor Brendan Delaney and I gave a talk on long COVID to a group of approximately 100 attendees at the annual Primary Care Respiratory Society Conference in Telford in 2023. The event was highly interactive and the audience posed several questions about long COVID research and clinical management. Attendees were provided an update on the latest research findings about this common postviral syndrome. |
Year(s) Of Engagement Activity | 2023 |
Description | Public webinars |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | National |
Primary Audience | Public/other audiences |
Results and Impact | A series of six webinars were held to summarise different research activities and outputs arising from the TLC Study. These were attended by members of the public and people experiencing long Covid. The webinars were followed by Q&A from members of the research team. Each webinar was attended by 10-20 people. |
Year(s) Of Engagement Activity | 2022 |
URL | https://www.birmingham.ac.uk/research/applied-health/research/tlc-study/videos/latest-videos.aspx |