Some people continue to have serious symptoms long after COVID-19, such as extreme fatigue and feeling worse after activity. In some patients, this may happen because the immune system is attacking the body by mistake.

This study will test a treatment called immunoadsorption, which filters the blood to remove harmful antibodies. People with long COVID who have these antibodies will be randomly assigned to receive either the real treatment or a placebo. The main goal is to see whether fatigue improves after one month, and whether other symptoms and daily functioning improve over six months.

This research will help us find out if this treatment can benefit the group of long COVID patients with immune-related disease.

Growing evidence indicates that autoantibodies may drive symptoms in a subset of people with long COVID, as demonstrated by symptom transfer to mice following administration of IgG from affected patients. This provides a strong rationale for targeted immunotherapy aimed at removing pathogenic antibodies. Immunoadsorption is a well-established method to reduce circulating IgG, but studies suggest that only a specific subgroup of patients benefits.

Using HuProt autoantibody microarray technology, we identified several autoantibodies uniquely present in long COVID patients compared with healthy controls. We subsequently developed and validated a disease-specific Luminex multiplex immunoassay to detect this autoimmune phenotype. This study will use these findings as a novel selection method of identifying long COVID patients with pathogenic IgG, thereby enriching the population most likely to benefit from immunoadsorption therapy.

This biomarker-guided personalized medicine approach could enhance treatment efficacy and advances long COVID therapeutic strategies. Additionally, the placebo-controlled and double blinded design will be needed to evaluate the true potential of autoantibodies adsorption therapy in long COVID. This study can add to our understanding on the role of autoantibodies in the pathogenesis of long COVID and could help in the development of precision-based immunotherapy for patients such as immunoadsorption.

Inclusion Criteria:

• Long COVID based on the WHO-criteria
• PEM according to the DSQ-PEM
• BELL's functionality score 20-70%
• Good health prior to the long COVID diagnosis (WHO performance score 0)

Exclusion Criteria:

• Medical history of clinically significant respiratory- or cardiovascular disease
• Prior interventional cardiac procedure within 3 months prior to randomization
• Active immunosuppresive treatment for systemic autoimmune disorders
• Diabetes type 1
• Solid organ malignancy in the last 5 years
• Active psychiatric disorder currently under treatment by a psychiatrist
• BMI > 35
• Pre-existing fatigue
• Poor performance score prior to the long COVID diagnosis (WHO performance >0)
• Pregnancy or breastfeeding

all request will be discussed within the study team