Autoantibodies against G-protein-coupled receptors can be detected in post/long-COVID-19 patients with fatigue syndrome (ME/CFS) as well as in healthy blood donors

Background

Several providers of therapeutic apheresis hypothesize that autoantibodies (AABs) against G protein-coupled receptor (GPCRs) play a crucial role in the development of post-COVID Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Their detection is used as an indication for multiple sessions of immune adsorptions as experimental treatment. We investigated whether such AABs also occur in healthy subjects, such as blood donors, in addition to patients with post-COVID ME/CFS.

Methods

Serum samples from 41 healthy platelet donors and 8 employees of the department for Transfusion Medicine were tested for 5 different AABs against GPCRs: ß1-, ß2-adrenergic receptor-AABs, M3-, M4-muscarinic acetylcholine receptor-AABs and anti-AT1R. The frozen samples (-80°C) were sent to a special laboratory (IMD Labor Berlin). The IgG type AABs were determined using commercial ELISA kits (CellTrends GmbH, Germany) according to the manufacturer's instructions. The experimental procedure has been approved by the university"s ethics committe.

Results

In 29 of 49 healthy subjects (59.2%) at least one and in 16 persons (35%) all five of the AABs examined were detected above the cut-off. Anti-M3-AABs (61%) and anti-ß2-AABs (59%) were detected most frequently. The mean age of the AAB-positive subjects was 30.9 years (20-55y), with 68.75% being younger than 35 years of age. The COVID-19 history indicated that 62.5% had both recovered and been vaccinated, while 31.25% were vaccinated without ever having experienced confirmed SARS-CoV-2 infection. 6.25% of those testing AAB positive reported being neither vaccinated nor infected with SARS-CoV-2. The gender distribution was: 27 (55%) men, 22 (45%) women. None of the people examined stated to have ever had symptoms of ME/CFS.

Conclusion

The fact that GPCR-AABs can be detected in a high proportion of healthy individuals suggests that there is no direct causal relationship between AABs and ME/CFS and also raises the question of whether these laboratory findings are indeed clinically relevant. The understanding and significance of the mere detection of AABs as the main indication for immunoadsorption should be seriously reconsidered until causality between them and post-COVID ME/CFS is based on sufficient evidence.

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