Dr. Andreas Michael Brosig (Regensburg/ DE), Dr. Morad Mohrez (Regensburg/ DE), Dr. Irene Pamler (Regensburg/ DE), Ikram Tlili (Regensburg/ DE), Adelina Florina Bica (Regensburg/ DE), Prof. Dr. Ralph Burkhardt (Regensburg/ DE), PD Dr. Robert Offner (Regensburg/ DE)
Background
Autoantibodies (AABs) against G-protein-coupled-receptors (GPCRs) may underlie the symptom complex of cognitive and physical deficits in patients with post-COVID-19 syndrome (PCS). Based on this assumption, the hypothesis arose that an AAB removal therapy, e.g. immunoadsorption (IA), could causally lead to symptom relief. To investigate this, we performed IA in two patients using the LIFE21 system and adsorbers Omni 1 and 5, respectively.
Methods
Two patients (f28; m36) with PCS and pre-known AABs against GPCRs each received one cycle IA (5 treatment days) using the LIFE21 system (Miltenyi Biotec, Germany) with the Omni 1 adsorber (f28) and the Omni 5 adsorber (m36). Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) was evaluated by the Bell fatigue scale before and after completion of the IA cycle, and immunoglobulins (IgG, IgM, IgA, IgE) were analyzed (Cobas ProRoche) before and after each IA session. At time points before and after each completed IA cycle, relevant pre-existing AABs against β1-/ β2- adrenergic and M3-/ M4- muscarinic acetylcholine receptors and angiotensin II type I receptors (ELISA, IMD laboratory, Berlin) were determined.
Results
IA sessions with the adsorbers Omni 5 (m36, 5x IA over 13 days) and Omni 1 (f28, 5x IA spread over 44 days - interrupted for 35 days after day 1 due to SARS-CoV-2 re-infection) were clinically well tolerated, and mean plasma volumes treated were 1.3-fold for m36 and 1.8-fold for f28. For each IA, average IgG reduction was 57.1% (m36) and 70.2% (f28). When comparing baseline to final, IgG was reduced by 88.4% (m36) and 90.4% (f28). Elevated AABs (pre-treatment: m36: ß1, ß2, M3, M4, ATII-T1; f28: ß1, ß2, M3, ATII-T1) fell below their reference values in both patients after the IA cycle. Bell fatigue scale did not change when comparing results before/ after the IA cycle and about 4 weeks after (f28: 20/20/10; m36: 50/50/50).
Conclusion
The Omni 1 and Omni 5 adsorbers are highly capable of removing immunoglobulins non-selectively in a safe and tolerable setting. In both patients, IA was technically successful without the need to treat extraordinary high plasma volumes. However, Bell fatigue scale indicated no improvement in ME/CFS in both patients. Hence, the present investigation does not support a causal relationship between elevated AABs against GPCRs and ME/CFS symptoms.
Offenlegung Interessenkonflikt:
Techniqual equipment and consumable material was provided by Miltenyi Biotec, Germany.