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


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.


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Aiyegbusi OL (2021) Symptoms, complications and management of long COVID: a review. in Journal of the Royal Society of Medicine

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Brown K (2022) Long COVID and self-management in The Lancet

Description LOCOMOTION Study Expert Advisory Group member
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Description Participation in national Long COVID working group
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Description Post-COVID condition Core Outcome Set (PC-COS)
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
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 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. 
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): 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): 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 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
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