Immunoadsorption in Autoimmune Long COVID

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.

Participants in the placebo group will receive six sessions of sham treament, each lasting 2.5 hours over two weeks. The procedure will be performed without an adsorption column, allowing the blood to circulate through the extracorporeal circuit and be returned to the patient without removal of immunoglobulins or other plasma components.

Device: Sham Comparator

Participants in the intervention group will receive six sessions of immunoadsorption, each lasting 2.5 hours over two weeks. Immunoadsorption will be performed using tryptophan columns, which bind the Fc region of IgG via hydrophobic and aromatic interactions.

Device: Immunoadsorption

Immunoadsorption will be performed using tryptophan columns, which bind the Fc region of IgG via hydrophobic and aromatic interactions.

The immunoadsorption column will be removed from the device, so that the patient's blood passes through the system and is returned to the body without undergoing adsorption or removal of antibodies.

Plazo: At baseline and 28 days after start treatment

Score range 10-50 (10 items, Likert scale 1-5). Higher scores indicate more severe fatigue (worse). The difference in scores from baseline will be measured (MCID of 4 points) as the primary outcome.

Plazo: At baseline and days 28, 60, 90, and 180

Eight domains scored from 0-100. Domain scores are commonly summarized into the Physical Component Summary (PCS) and Mental Component Summary (MCS) (norm-based, mean 50, SD 10). Higher scores indicate better health-related quality of life and functioning.

Plazo: At baseline and days 28, 60, 90, and 180

Raw scores are converted to T-scores (20-80), with a population mean of 50 (SD 10). Higher scores indicate better cognitive functioning. Change in score will be measured (MCID 3-5).

Plazo: At baseline and days 28, 60, 90, and 180

0-100 weighted total score across six domains: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor symptoms. Higher scores indicate greater autonomic symptom burden.

Plazo: From first study intervention through day 180

All AEs and SAEs will be recorded, graded according to CTCAE v5.0, and assessed for relatedness to the study treatment. Specific attention will be given to complications of extracorporeal procedures (e.g., hypotension, bleeding, allergic reactions, infection, and vascular access issues)

Plazo: At baseline and days 28, 60, 90, and 180

Handgrip strength will be assessed using a calibrated handheld dynamometer at four standardized measurement points in accordance with the American Society of Hand Therapists (ASHT) guidelines. Grip strength will be recorded in kilograms (kg). Higher grip strength reflects better muscle function.

Plazo: At baseline and days 28 and 180

The NASA Lean Test is a standardized active standing test used to assess orthostatic intolerance. Participants rest in a supine position followed by an active standing phase while leaning against a wall to minimize skeletal muscle pumping. Heart rate and blood pressure are measured at predefined intervals during standing. Abnormal heart rate and/or blood pressure responses during the test indicate orthostatic intolerance.

Plazo: At baseline (prior to treatment initiation), during treatment, and at days 28 and 180 after treatment initiation.

Immunoglobulin G titers will be measured in blood samples using standardized laboratory assays and reported as concentrations (g/L).

Plazo: At screening and on days 28, 60, 90, and 180

For this assay, IgG will be isolated from patient serum samples obtained during screening and analyzed using a Luminex-based multiplex immunoassay targeting a panel of 15 validated autoantigens. A weighted scoring system is applied to the resulting autoantibody signals.

A Placebo-Controlled, Double-Blind, Randomized Trial Phase I-II With Immunoadsorption in Autoimmune Long COVID