Repeat Immunoadsorption Post Covid ME/​CFS (RIA)

Project description

The evidence for an autoimmune etiology in post-infectious ME/CFS is growing (reviewed in Sotzny et al., 2018). Also, COVID-19 is a disease with a high risk for autoimmunity and developing ME/CFS due to the infection of many different cell types and the severity of immune activation. There is evidence from several studies from the investigators and other groups that natural regulatory autoantibodies targeting G protein-coupled receptors (GPCR) are involved in the pathogenesis of various autoimmune diseases. The investigators and others described enhanced levels and dysfunction of ß2R autoantibodies in ME/CFS and their correlation with the severity of key clinical symptoms (Freitag et al., 2021). The investigators' working hypothesis is that GPCR-specific autoantibodies with altered binding affinity or epitope specificity lead to immune dysregulation and autonomous dysfunction, and play a significant role in the pathomechanism of ME/CFS (Wirth et al., 2020). The investigators observed a close correlation of ß2R antibodies with symptom severity in ME/CFS after COVID, similar to ME/CFS after other infections (Freitag et al., 2021). Two small proof-of-concept studies with immunoadsorption (IA) in patients with ME/CFS after other infections have previously shown improvements in symptoms in most patients (Scheibenbogen et al., 2018; Toelle et al., 2020).

In this observational non-controlled clinical trial, as part of the clinical trials within the National Clinical Study Group (NKSG), post-COVID Syndrome (PCS) ME/CFS patients who receive IA will be evaluated for clinical efficacy, a decrease in autoantibodies, and a change of biomarkers. IA with Miltenyi's TheraSorb® column will be performed in the approved use. Patients who have symptom improvement after the first IA will receive two additional IAs at 3 and 6 months, which will also be documented. Symptom severity will be assessed by online questionnaires at repeated time points.

Patients will be recruited for IA from the investigators' ongoing observational study with a follow-up of at least 6 months without disease improvement (Kedor et al., 2022). Patients have received a comprehensive diagnostic assessment to exclude other diseases, central nervous system, or organ comorbidity. ß2R autoantibodies in serum are determined by ELISA (Celltrend). Within 4 weeks prior to IA, patients will be assessed for eligibility for study participation by clinical investigation, laboratory analysis, and symptom questionnaires. In all 20 patients, blood will be collected the week before 4 four weeks after the first IA. 10 patients will also receive vessel diagnostics before (within 4 weeks) and 4 weeks after the first IA. All visits and treatments will take place in outpatient clinics.

The results of this observational study will provide the basis for a randomised controlled trial using IA and, in responders, consecutive B-cell depleting therapy with an anti-CD20 monoclonal antibody versus placebo.

(Description adapted from clinical trial website: see link above)