Therapies for Long COVID in non-hospitalised individuals: from symptoms, patient-reported outcomes and immunology to targeted therapies (The TLC Study)
Tom Marshall,
Elizabeth Sapey,
Krishnarajah Nirantharakumar,
Anuradhaa Subramanian,
Christel McMullan,
Melanie Calvert,
Alastair K Denniston,
Joht Singh Chandan,
Louise J Jackson,
Gary Price,
George Gkoutos,
Tim Williams,
Sarah E Hughes,
Janet Lord,
Krishna Gokhale,
Puja Myles,
Dawit T Zemedikun,
Kirsty McGee,
David C Wraith,
Shamil Haroon,
Kirsty Brown,
Karen Jones,
Grace Turner,
Olalekan Lee Aiyegbusi,
Elin Haf Davies,
Amy Bamford,
Anita Walker,
Christopher Frost,
Thomas Taverner,
Nikita Simms-Williams,
Steven Marwaha,
Gary McNamara,
Karen Matthews,
Jennifer Camaradou,
Edward Leggett,
Clare Iles,
Michael Saint-Cricq,
Sumita Kumar,
Yvonne Alder,
David E Stanton,
Lisa Agyen,
Megan Baber,
Hannah Blaize
Affiliations
Tom Marshall
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Elizabeth Sapey
PIONEER Hub, University of Birmingham, Birmingham, UK
Krishnarajah Nirantharakumar
University of Birmingham Institute of Applied Health Research, Birmingham, UK
Anuradhaa Subramanian
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Christel McMullan
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Melanie Calvert
director and centre director and academic lead
Alastair K Denniston
Department of Ophthalmology, University Hospitals Birmingham NHSFT, Birmingham, UK
Joht Singh Chandan
University of Birmingham College of Medical and Dental Sciences, Birmingham, UK
Louise J Jackson
Health Economics Unit, University of Birmingham, Birmingham, UK
Gary Price
Patient Partners, Not applicable, UK
George Gkoutos
1 Centre for Computational Biology, Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
Tim Williams
Clinical Practice Research Datalink, Medicines and Healthcare Products Regulatory Agency, London, UK
Sarah E Hughes
Centre for Patient Reported Outcome Research, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Janet Lord
3 NIHR Surgical Reconstruction Microbiology Research Centre, Edgbaston, UK
Krishna Gokhale
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Puja Myles
2University of Nottingham, Epidemiology and Public Health, Nottingham, United Kingdom
Dawit T Zemedikun
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Kirsty McGee
Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK
David C Wraith
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, UK
Shamil Haroon
University of Birmingham Institute of Applied Health Research, Birmingham, UK
Kirsty Brown
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Karen Jones
9 Department of Paediatrics, Glangwili General Hospital, Carmarthen, Carmarthenshire, UK
Grace Turner
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Olalekan Lee Aiyegbusi
Centre for Patient-Reported Outcomes Research (CPROR), University of Birmingham Institute of Applied Health Research, Birmingham, UK
Elin Haf Davies
Aparito Ltd, Wrexham, UK
Amy Bamford
University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
Anita Walker
Centre for Patient Reported Outcome Research, Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Christopher Frost
Aparito Ltd, Wrexham, UK
Thomas Taverner
Institute of Applied Health Research, University of Birmingham, Birmingham, UK
Nikita Simms-Williams
University of Birmingham Institute of Applied Health Research, Birmingham, UK
Steven Marwaha
Institute for Mental Health, University of Birmingham, Birmingham, UK
Gary McNamara
Cognitant, Oxford, UK
Karen Matthews
Patient Partners, Not applicable, UK
Jennifer Camaradou
Patient Partners, Not applicable, UK
Edward Leggett
Clinical Practice Research Datalink, Medicines and Healthcare Products Regulatory Agency, London, UK
Clare Iles
Clinical Practice Research Datalink, Medicines and Healthcare Products Regulatory Agency, London, UK
Introduction Individuals with COVID-19 frequently experience symptoms and impaired quality of life beyond 4–12 weeks, commonly referred to as Long COVID. Whether Long COVID is one or several distinct syndromes is unknown. Establishing the evidence base for appropriate therapies is needed. We aim to evaluate the symptom burden and underlying pathophysiology of Long COVID syndromes in non-hospitalised individuals and evaluate potential therapies.Methods and analysis A cohort of 4000 non-hospitalised individuals with a past COVID-19 diagnosis and 1000 matched controls will be selected from anonymised primary care records from the Clinical Practice Research Datalink, and invited by their general practitioners to participate on a digital platform (Atom5). Individuals will report symptoms, quality of life, work capability and patient-reported outcome measures. Data will be collected monthly for 1 year.Statistical clustering methods will be used to identify distinct Long COVID-19 symptom clusters. Individuals from the four most prevalent clusters and two control groups will be invited to participate in the BioWear substudy which will further phenotype Long COVID symptom clusters by measurement of immunological parameters and actigraphy.We will review existing evidence on interventions for postviral syndromes and Long COVID to map and prioritise interventions for each newly characterised Long COVID syndrome. Recommendations will be made using the cumulative evidence in an expert consensus workshop. A virtual supportive intervention will be coproduced with patients and health service providers for future evaluation.Individuals with lived experience of Long COVID will be involved throughout this programme through a patient and public involvement group.Ethics and dissemination Ethical approval was obtained from the Solihull Research Ethics Committee, West Midlands (21/WM/0203). Research findings will be presented at international conferences, in peer-reviewed journals, to Long COVID patient support groups and to policymakers.Trial registration number 1567490.
