Long Covid and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) study
| ISRCTN | ISRCTN15375673 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN15375673 |
| Sponsor | University of Leeds |
| Funder | National Institute for Health and Care Research |
- Submission date
- 15/04/2026
- Registration date
- 26/05/2026
- Last edited
- 26/05/2026
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Other
Plain English summary of protocol
Background and study aims:
People living with Long Covid and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) often experience long‑term symptoms that affect daily life, work, and wellbeing. Many also struggle to access consistent care and support. The HERITAGE study aims to understand people’s symptoms over time, their experiences of NHS and community services, and what makes care helpful or unhelpful. The study also aims to identify how services can be improved nationally, using feedback from patients, carers, and healthcare professionals.
Who can participate?
Four groups of adults aged 18 years and over can take part:
1. People with Long Covid
2. People with ME/CFS
3. People with both conditions
3. Healthcare professionals, care and individuals involved in supporting people with these conditions
Participants may be currently receiving specialist NHS care (at a participating clinic), have received care in the past, or may not be in specialist services. Some participants will also be invited to take part in an interview.
What does the study involve?
Participants with Long Covid or ME/CFS will be asked to complete questionnaires about their symptoms, daily activities, quality of life, and use of healthcare services. These can be completed online using the ELAROS 'Autonom-e' app/website or on paper.
Some participants, carers (when supporting a participant), and healthcare staff will be invited to take part in a one‑to‑one interview to share their experiences of services, support, and recovery. These interviews can be done by phone, online (Microsoft Teams) or, where possible, in person.
The study also includes a national Quality Improvement Collaborative, where NHS teams, patients, and researchers work together to understand challenges in current services and find ways to improve care.
No treatments, tests, or medicines are given as part of this study.
What are the possible benefits and risks of participating?
There may be no direct personal benefit, but participants may find it helpful to reflect on their experiences and contribute to research that could improve future care for people with Long Covid and ME/CFS.
Risks are minimal. Completing questionnaires or interviews may feel tiring or emotional for some people. Participants can take breaks, skip questions, or stop at any time. All information will be kept confidential.
Where is the study run from?
The study is led by the University of Leeds and run in collaboration with NHS Long Covid and ME/CFS services (in Leeds, Leicester, Hertfordshire and Cornwall) and partner universities (University of Leicester and Oxford) (UK)
When is the study starting and how long is it expected to run for?
May 2026 to December 2028
Who is funding the study?
The National Institute for Health and Care Research (NIHR) (UK)
Who is the main contact?
For any questions about the study, please contact the research team, heritage-studyteam@leeds.ac.uk
Contact information
Principal investigator, Scientific, Public
Leeds Institute of Rheumatic & Musculoskeletal Medicine (LIRMM)
Chapel Allerton Hospital
Leeds
LS7 4SA
United Kingdom
| Phone | +44 (0)1133922564 |
|---|---|
| M.Sivan@leeds.ac.uk |
Study information
| Primary study design | Observational |
|---|---|
| Observational study design | Cohort study |
| Scientific title | Health Effects fRom Infection sequelae: Tailoring services and Advancing GuidancE (HERITAGE) in Long Covid and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) |
| Study acronym | HERITAGE |
| Study objectives | HERITAGE aims to inform high-quality and cost-effective services for LC and ME/CFS. Below, we set out the research questions (RQ), objectives and key milestones for each of the three work packages (WPs). WP1 (RQ1): What is the diagnostic overlap between the two conditions, what are the condition trajectories and long-term clinical outcomes in both conditions? Objective 1a: Estimate the proportion of diagnostic overlap between LC and ME/CFS in people meeting the diagnostic criteria for each condition. Objective 1b: Evaluate long-term clinical outcomes of LC and ME/CFS using a standard set of condition-specific outcome measures and health measures (EQ-5D-5L) in all participants (including a ‘non-clinic’ national cohort). WP2 (RQ2): What is the clinical and cost-effectiveness of alternative service models for LC and ME/CFS? Objective 2a: Assess the health and social care costs and societal costs in LC and ME/CFS. Objective 2b: Evaluate the cost-effectiveness of specialist LC/ME/CFS services in comparison to a non-clinic national cohort. WP3 (RQ3): How to improve the quality of care for LC and ME/CFS and develop a national service framework for both conditions? Objective 3a: Produce longitudinal case studies of service staffing, skill set and multi-condition integration in four specialist service models Objective 3b: Set up and run a Quality Improvement Collaborative (QIC) to address the effectiveness, equity, safety, patient-centredness and timeliness of services and staff skill sets for LC and ME/CFS. Develop training resources and a national service framework for both conditions, that will potentially be applicable to other post-infection conditions. |
| Ethics approval(s) |
Submitted 20/03/2026, North West – Greater Manchester (GM) East Research Ethics Committee (Barlow House, 4 Minshull Street, Greater Manchester, M1 3DZ, United Kingdom; N/A; gmeast.rec@hra.nhs.uk), ref: 26/NW/0105 |
| Health condition(s) or problem(s) studied | Long Covid and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) |
| Methodology | The HERITAGE study will use a mixed‑methods design, combining quantitative and qualitative data from individuals with Long Covid (LC) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) recruited from four locality‑based service models (Leeds, Leicester, Hertfordshire, and Cornwall) and a non‑clinic national cohort of individuals who do not have access to specialist services. The study will enrol approximately 3,000 individuals with LC and/or ME/CFS. Allowing for an estimated 50% attrition rate, we anticipate that over 1,500 participants will complete the 12‑month longitudinal follow‑up, providing robust trajectories of symptoms, functioning, and service use over time. Quantitative data will include patient‑reported outcome measures, vocational outcomes, and health economic data, including patient‑borne and NHS costs, to support cost‑effectiveness analyses. The qualitative work package will employ a combination of purposive and stratified sampling to ensure a representative and analytically robust sample across conditions, service models, and levels of service engagement. Up to 106 qualitative participants will be recruited in addition to the quantitative cohort. This will include: Up to 52 people with LC or ME/CFS, comprising 32 participants recruited from the four specialist services (Leeds, Leicester, Hertfordshire, and Cornwall) and 20 participants not engaged with specialist services, recruited nationally. These participants may also form a sub-sample of the 3,000 quantitative participants. Up to 24 healthcare professionals or staff providing, commissioning, or supporting LC or ME/CFS services across the four localities. Participation in the Quality Improvement Collaborative (QIC) by up to 30 additional individuals, including people with LC or ME/CFS (from within the quantitative cohort or Patient Advisory Group) and staff or professionals linked to the study sites. A small number of additional expert contributors (up to 10) may be included where required. Qualitative data collection will include interviews and observations, with up to 150 hours of observation undertaken across the four delivery sites (up to 37.5 hours per site). Observations will focus on patient-clinician interactions, service delivery models, referral pathways, and system‑level processes relevant to care for LC and ME/CFS. |
| Intervention type | Other |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) |
1. Diagnostic overlap between Long Covid and ME/CFS is assessed using participant-reported diagnostic information collected via the HERITAGE general health questionnaire at baseline and at 3, 6, 9 and 12 months |
| Completion date | 31/12/2028 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 100 Years |
| Sex | All |
| Target sample size at registration | 3060 |
| Key inclusion criteria | Inclusion criteria for WP1 and WP2: 1. Aged 18 years and over 2. All genders 3. Ability to provide informed consent 4. Have had symptoms of persistent LC or ME/CFS for >2 years Clinic cohort: 1. Individuals who at study baseline, have received, are currently receiving or are about to receive (i.e., known appointment date within <3 months) specialist LC/ME/CFS services at one of the four participating NHS sites (‘HERITAGE clinics’ refers to existing NHS services and not research‑specific clinics). 2. Individuals who are initially part of the non-clinic cohort (defined below) and who receive specialist services from HERITAGE clinics during study follow-up and have at least 3 months of follow-up data after service receipt. Non-clinic cohort: 1. No history of receiving specialist services for LC or ME/CFS from HERITAGE or non-HERITAGE clinics in the last 3 years. 2. GP diagnosis of LC or ME/CFS or subjective report of LC or ME/CFS, or self‑reported LC or ME/CFS symptoms without requiring a confirmed diagnosis at enrolment. Any diagnostic assessment undertaken during follow‑up forms part of routine NHS care and is not conducted as part of this study. During study follow-up: 1. Those who receive specialist service (including diagnosis) from HERITAGE clinics will join the clinic cohort, provided that they have at least 3 months of follow-up data after service receipt. 2. Those who receive specialist service (including diagnosis) from non-HERITAGE clinics will be excluded from further follow-up. 3. Those with subjective report of LC or ME/CFS who subsequently receive an alternative diagnosis to LC or ME/CFS will be excluded from further follow-up. 4. Those with subjective report of LC or ME/CFS who do not receive GP or specialist diagnosis during study follow-up (due to delays in the diagnostic pathway) will be followed up until study completion. Their data will be excluded from base case analysis but included in sensitivity analyses. Inclusion criteria for WP3: 1. Aged 18 years and over 2. All genders 3. Ability to provide informed consent 4. Ability to communicate in English Clinic cohort: 1. Currently using, referred to, or recently discharged from existing NHS specialist LC/ME/CFS services at HERITAGE study sites (Leeds, Leicester, Hertfordshire, Cornwall) Non-clinic cohort: 1. No specialist LC/ME/CFS service use in the last 3 years 2. GP diagnosis or self‑reported LC/ME/CFS symptoms (no requirement to undergo diagnostic work‑up as part of the study) 3. Participants may join WP3 by contacting the WP3 research team directly via the study email (as advertised on the HERITAGE website and public materials) 4. Clinical diagnosis of LC and/or ME/CFS or subjective symptoms of LC and/or ME/CFS and set to receive specialist diagnostic work-up during study follow-up. Any diagnostic work‑up they may undergo is part of routine NHS care and is not performed for, or required by, the study. 5. For those living with LC, have had LC symptoms for >2 years (persistent LC) Staff cohort: 1. Working within, referring to, or involved in providing, planning, or supporting LC/ME/CFS specialist services in Leeds, Leicester, Hertfordshire or Cornwall (HERITAGE Clinics) 2. Identified and approached by site Principal Investigators or Clinical Research Fellows The Quality Improvement Collaborative (QIC) cohort: 1. People involved in providing, referring to, or receiving LC/ME/CFS specialist services at the participating NHS sites 2. May include staff, patients and carers (where relevant) Carers: Carers may take part in WP3 only when supporting a patient participant at the request of that patient during an interview, clinic observation or QIC activity. Carers must be aged ≥18 and able to provide informed consent. Carers are not independently recruited into WP1, WP2 or WP3. |
| Key exclusion criteria | Exclusion criteria for WP1 and WP2: Clinic cohort: 1. Individuals who, during follow‑up, receive an alternative diagnosis or enter non‑HERITAGE specialist services will be withdrawn from follow‑up for WP1/WP2 2. Individuals will be excluded if they are receiving or due to receive LC/ME/CFS specialist care at an NHS service not participating in HERITAGE 3. Individuals unable to consent or aged under 18 years will be excluded Exclusion criteria for WP3: Participants will be excluded from WP3 if: 1. They cannot provide informed consent for qualitative activities 2. They are too unwell to take part safely or meaningfully, even with breaks and adjustments WP3 non-clinic cohort – exclusion criteria: Participants will be excluded from WP3 if: 1. They cannot provide informed consent for qualitative participation 2. They are unable to participate safely or meaningfully in an interview, even with reasonable adjustments 3. English‑language communication is insufficient for qualitative data collection Carers (WP3 only) – exclusion criteria: 1. Carers may be involved only when supporting a WP3 participant (patient) during: 1.1. Interviews 1.2. Clinic observations, or 1.3. QIC meetings 2. Carers will be excluded if: 2.1. They are aged under 18 years 2.2. They cannot provide informed consent 2.3. Their participation would introduce safeguarding concerns, or 2.4. They are unable to participate safely or meaningfully in the activity 2.5. Carers are not independently recruited into WP1, WP2 or WP3 and do not have clinical inclusion/exclusion criteria beyond the above Staff (WP3) exclusion criteria: Staff participants will be excluded if: 1. They do not work in, refer to, or support specialist LC/ME/CFS services at participating HERITAGE NHS sites 2. Their employing NHS organisation does not grant permission for participation 3. Individuals will be excluded from QIC participation if they do not work within, receive care from, or provide support to LC/ME/CFS specialist services at participating HERITAGE NHS sites 4. Individuals will be excluded from QIC participation, if they are unable to participate safely or meaningfully in QIC meetings 5. Individuals will be excluded from QIC participation, if they are unable to attend the scheduled QIC sessions Exclusion criteria for all work packages: 1. Individuals under 18 years of age 2. Individuals unable to provide informed consent 3. Individuals who do not have experience of Long Covid (LC) or ME/CFS healthcare needs and therefore do not meet study aims 4. Individuals for whom participation is deemed inappropriate due to safeguarding or clinical concerns, based on advice from their GP or usual clinical team |
| Date of first enrolment | 01/05/2026 |
| Date of final enrolment | 31/12/2028 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
Infirmary Square
Leicester
LE1 5WW
England
14 Tewin Road
Welwyn Garden City
AL7 1BW
England
Treliske Hospital
Treliske
Truro
TR1 3LJ
England
Millshaw Park Lane
Leeds
LS11 0DL
England
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
17/04/2026: Study's existence confirmed by North West – Greater Manchester (GM) East Research Ethics Committee.
