Immunoadsorption in Patients With Chronic Fatigue Syndrome Including Patients With Post-COVID-19 CFS

The Chalder Fatigue Scale measures the extent and severity of tiredness and has been used in multiple randomized trials of behavioral interventions in patients with ME/CFS. Each of the 11 items is answered on a 4-point scale with an overall score ranging from 0 (asymptomatic) to 33 (maximum symptomology). Intra-patient change in physical and mental fatigue from baseline to month three will be documented as indexed by the Chalder Fatigue Scale.

Intra-patient change in physical and mental fatigue from baseline to follow-up points will be documented.

Number of treatment emergent adverse events (TEAEs), serious adverse events (SAEs), and discontinuation due to TEAEs

The Fluge score uses a visual analogue scale ranging from 1 to 10 (1 = no symptom, 10 = very severe symptom) to assess 32 self-reported CFS symptoms including fatigue, pain, cognitive, and other CFS-related symptoms. Intra-patient change in Fluge score from baseline to follow-up points will be documented.

The Short Form 36 Health Survey (SF-36) is an established and widely used health-related quality of life measure. The Physical Function (PF) domain asks patients to report limitations on ten mobility activities, such as walking specified distances, carrying groceries, and bathing or dressing. Scores are weighted and transformed into a scale ranging from 0 (greatest possible health restrictions, i.e., severe disability) to 100 (no health restrictions). An intra-patient change in SF-36-PF from baseline to follow-up points will be documented.

The Bell disability scale is a standard assessment in ME/CFS that evaluates functional ability in adult ME/CFS patients. Eleven statements describe patient status such as level of symptoms at rest, level of symptoms with exercise, activity level, and ability to perform work, travel and self care. Its score ranges from 0 (bedridden) to 100 (no symptoms). Intra-patient change in Bell score from baseline to follow-up points will be documented.

The PEM questionnaire determines frequency (from 0 to 20 points, higher scores equate to greater frequency), severity (from 0 to 20 points, higher scores equate to greater severity), and length (from 0 to 6 points, higher scores equate to longer duration) of PEM. Intra-patient change in PEM score from baseline to follow-up points will be documented.

Intra-patient change in hand grip strength (HGS) from baseline to follow-up points.

The Composite Autonomic Symptom Score (COMPASS-31) is a refined, internally consistent, and markedly abbreviated quantitative measure of autonomic symptoms. It is based on the original Autonomic Symptom Profile (ASP) and COMPASS, applies a much-simplified scoring algorithm, and is suitable for widespread use in autonomic research and practice. It evaluates six domains of autonomic function: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor domains. The score ranges from 0 (no symptoms) to 100 (strong autonomic dysfunction). Intra-patient change in autonomic dysfunction from baseline to follow-up points will be documented as indexed by the COMPASS-31.

The Schellong Test is a test for circulatory function. The patient is required to stand for 10 to 20 min, during which time the blood pressure is measured continuously. A fall of systolic pressure of 20 mm Hg or more indicates poor circulatory function. Intra-patient change in Schellong Test from baseline to follow-up points will be documented.

MoCA is a sensitive and validated cognitive screening tool to test subjects quickly and accurately for mild cognitive impairment, irrespective of etiology. A person can gain a maximum of 30 points, and professionals consider a score of 26 or above to be normal. A score of 25 points or less may indicate some degree of cognitive impairment (18-25 = mild cognitive impairment, 10-17 = moderate cognitive impairment, fewer than 10 points = severe cognitive impairment). Intra-patient change in neurocognitive functions at month 3 and at month 6 (if required by the investigator) after IA completion compared to baseline.

The SDMT (oral version) detects cognitive impairment in less than five minutes and will be used to assess change in cognitive function over time. SDMT is a validated and established measure of cognition in multiple sclerosis capturing impairments such as processing speed and working memory, visual search and scanning and oculomotor functioning. Patients are provided a sheet with nine symbols, each paired with a number on top of the page. The remainder of the page consists of a randomized, sequential assortment of these symbols. Participants are asked to verbally respond with the number that corresponds with each symbol. The final score is the correct number of substitutions in 90 s (range 0 to 110, higher score = higher neurocognitive function). Intra-patient change in neurocognitive functions at month 3 and at month 6 (if required by the investigator) after IA completion compared to baseline.

PROMIS is a set of person-centered measures that evaluates and monitors physical, mental, and social health in adults and children. PROMIS measures can be used with the general population and with individuals living with chronic conditions. Intra-patient change in PROMIS score from baseline to follow-up points will be documented.

Intra-patient changes in biomarkers of autoimmune activity (autoantibody titers against neurotransmitter receptors; among others ß2-adeno-receptor- and muscarine- receptor-antibodies) in blood and optional in cerebrospinal fluid at month 3 after IA completion compared to baseline.

Intra-patient change in biomarkers of inflammation (CRP, ferritin, MBL, white blood cell count, complement factors, cytokines, immunoglobulin level and subtype) in blood at month 3 and 6 after IA completion compared to baseline.