Therapies for Long COVID in non-hospitalised individuals: From symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study)

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.

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.