A Longitudinal Study on Longstanding Complicated Fatigue

The purpose of the study is to investigate if there are common biopsychosocial vulnerability factors for developing and maintaining fatigue, regardless of the diagnosis. The investigators also believe that subgroups differ in terms of these factors. Participating patients with ME/CFS, burnout syndrome and post-covid fatigue complete a web form at inclusion and after 1, 2, 4, 6, 12, 18 and 24 months. There is no upper limit for the number of participants in the web survey. 150 participants are asked to submit blood samples at a local laboratory in connection with the questionnaires for analysis of inflammatory markers and one urine sample for analysis of nutritional markers. Two control groups are included, 150 patients with rheumatoid arthritis and 50 healthy individuals. The longitudinal design makes it possible to investigate how inflammatory markers, nutritional status, symptom burden, health related quality of life co-vary over time and how work ability and sick leave is affected.

Fatigue is associated with impaired health and severely impaired quality of life and function and there is a need to explore similarities and differences regarding biopsychosocial vulnerability and maintenance factors and consequences in terms of work ability and sick leave in chronic fatigue syndrome (ME / CFS), burnout syndrome (BS) and post-covid fatigue to be able to improve individualized interventions for patient with persistent fatigue. The study examines inflammatory markers, nutritional status, symptom burden, neuropsychiatric conditions, work ability, and sick leave in a longitudinal cohort study over 2 years in patients with different diagnoses who all suffer from persistent fatigue. The hypothesis is that there are common biopsychosocial vulnerability factors for developing and maintaining fatigue, regardless of the diagnosis. The investigators also believe that subgroups can be identified that differ in terms of these factors. The longitudinal design makes it possible to investigate how inflammatory markers, nutritional status, symptom burden, health related quality of life co-vary over time and how work ability and sick leave is affected.

In this study participating patients with ME/CFS, BS and post-covid fatigue complete a web form at inclusion and after 1, 2, 4, 6, 12, 18 and 24 months.

Adult patients registered with a diagnosis of chronic complicated fatigue (ME/CFS or post-covid syndrome) in Take Care (medical record system in Stockholm County, Sweden) or with burnout syndrome from Stressmottagningen Stockholm, will be asked to participate in the study.

* Patients with ME/CFS will be recruited at the Department of Behavior Medicine, Karolinska University Hospital Solna or reached by advertising on social media
* Patients with Post-covid-syndrome will be recruited at Karolinska University Hospital or reached by advertising on social media
* Patients with burnout syndrome will be recruited at Stressmottagningen Stockholm

At baseline, a clinical assessment is performed at the clinic and the patient is asked to leave a venous blood sample and complete a questionnaire. The patients are asked for further blood samples and questionnaires at 1, 2, 4, 6, 12, 18, and 24 months after baseline. 150 participants, 50 in each diagnostic group, are asked to submit blood samples for biobanking at a local laboratory in connection to the questionnaire time points for analysis of inflammatory markers. C-reactive protein (CRP) is analysed at the time of blood samples. They are also asked to give one urine sample for analysis of nutritional markers and to submit a 3-day diet diary for evaluation of dietary intake by a registered dietitian. Participants that only fill out the web-based questionnaire will be included. There is no upper limit for the number of participants in the web survey.

A pilot study with 20 participants with ME/CFS started in 2018 to test and revise the design of the present study. These subjects will be counted in the group of 50 participants with ME/CFS diagnosis when available data allow.

In addition to the participants with persistent fatigue, two control groups are included in the study. 150 patients with rheumatoid arthritis (RA) recruited from the Karolinska University Hospital Rheumatology department and 50 healthy controls. The RA controls fill out the illness generic questionnaires on paper and disease information is taken from the national registry for rheumatic disease and CRP and erythrocyte sedimentation rate (ESR) data is taken from the medical record. The healthy controls follow the same procedure as the patients with persistent fatigue but only fill out the form and give blood samples at one time point.

Research questions:

* Are there differences in patient reported fatigue dimensions, symptom burden including post exertional malaise, sleep disorders, health related quality of life, or inflammatory markers, nutritional markers and dietary intake, between patients with ME/CFS, BS and post-covid fatigue, patients with RA and healthy controls?
* Are inflammatory markers and nutritional status associated with the development/recovery of fatigue and symptom burden in ME/CFS, BS and post-covid fatigue?
* Can different subtypes of patients be identified based on latent factor analysis including fatigue dimensions, symptom profile, neuropsychiatric symptoms, inflammatory markers and nutritional status?
* How does inflammatory markers, nutritional status, symptom burden and health related quality of life influence work ability and sick leave in patients with persistent fatigue over time?

The project group consists of a multidisciplinary team from Stockholm and Linköping universities as well as clinically active at clinics in the two regions who often meet patients with persistent fatigue.

Eligibility Criteria:
Inclusion Criteria:

* Diagnosis set within Stockholm County of ME/CFS, burnout syndrome or post-COVID-19-syndrome according to the Swedish version of the international classification of disease (ICD)-10
* Control group (rheumatic disease): Diagnosis of rheumatoid arthritis
* Control group (healthy): no diagnosis related to inflammatory disease or fatigue

Exclusion Criteria:

* Organic or neuropsychiatric disease that explain the fatigue among cases diagnosed with ME/CFS, burnout syndrome or post-COVID-19-syndrome according to the Swedish ICD-10