Today, the Lancet has published research entitled ‘Efficacy of repeated immunoadsorption in patients with post-COVID myalgic encephalomyelitis/chronic fatigue syndrome and elevated β2-adrenergic receptor autoantibodies: a prospective cohort study' (Stein et all 2025).
“Immunoadsorption may improve symptoms in post-COVID ME/CFS patients. The beneficial effects of IgG depletion suggest a significant role for autoantibodies and disturbed B-cell function in the condition's pathophysiology.”
The Lancet
Extracts:
Background
Since the pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become the leading trigger for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Evidence indicates that autoimmunity plays an important pathophysiological role. We aimed to evaluate the effectiveness of IA treatment in post-COVID ME/CFS patients.
Methods
This pre-post study included 20 post-coronavirus disease 2019 (COVID) ME/CFS patients found to have elevated β2 adrenergic autoantibodies (β2 AR-AB) between October 2022 and October 2023. Patients, with a median disease duration of 22 months (IQR: 15–31), were treated with five immunoadsorption sessions at Charité – Universitätsmedizin Berlin, Germany. Seven were male and 13 female, with a median age of 40 years (IQR: 36–51). The primary end point was the change in the Short Form (36) Health Survey physical functioning domain (SF36 PF) from baseline to four weeks post immunoadsorption. Key symptoms were assessed via questionnaires over six months. Handgrip strength and EndoPAT® measurements were used to evaluate muscle fatigue and vascular dysfunction. Seven patients who worsened after an initial response received a second cycle.
Findings
The treatment was generally well tolerated, reducing total immunoglobulin G by 79% (CI: 73–84%) and β2 AR-AB by 77% (CI: 58–95%). Patients demonstrated a mean increase in the SF36 PF of 17.75 points (CI: 13.41–26.16), with the greatest improvement occurring between months two and three, and significant gains maintained through month six. 14/20 (70%) patients were categorized as responders with an increase in the SF36 PF of ≥ ten points. Further lasting improvements were reported in fatigue, post-exertional malaise, pain, cognitive, autonomic, and immunological symptoms. Female patients had increased repeat handgrip strength at month six.
Discussion
There is increasing evidence that autoantibodies, including those targeting β-adrenergic and muscarinic acetylcholine receptors, may contribute to the pathophysiology of PCS and ME/CFS. We here provide evidence from an observational study that depletion of autoantibodies by IA can lead to improvement in overall physical functioning, as well as the severity of several key symptoms, including PEM, fatigue, pain, immunological, cognitive, and autonomic symptoms in a subset of post-COVID ME/CFS patients.
The clinical improvements observed after autoantibody removal via IA support the hypothesized involvement of these autoantibodies in the pathophysiology of ME/CFS and PCS in the responders. Meanwhile, a smaller group of patients did not show a response to the treatment. This highlights the potential diverse mechanisms underlying this condition, and indicates that autoantibodies may play a role only in a subgroup of patients.
Conclusion
In conclusion, our study suggests that IA treatment may result in rapid clinical improvement in a subset of patients. Further trials with both more patients and clinical outcomes reported are needed to confirm our findings. Our study serves as proof of concept for the initiation of clinical trials using drugs specifically designed to target autoantibodies. Targeting B cells may offer a promising approach to long-term symptom relief by addressing the underlying mechanisms driving autoantibody generation.
These are interesting results from what the researchers acknowledge is a small observational study involving people with a post Covid ME/CFS illness.
Important to note that the trial did not involve a placebo control group – so the results need to be viewed with caution.
By way of background, the immunoadsorption (IA) treatment acts on what are called autoantibodies. These are immune system components that instead of being protective (like most antibodies) they can actually be harmful to various body tissues. And we know that some people with both ME/CFS and Long Covid have autoantibodies present but not to a degree and consistency that would classify them as autoimmune diseases
So, assessing the use of treatments such as this to remove these potentially harmful autoantibodies certainty make sense.
Before drawing any conclusions this treatment needs to be assessed in a much larger placebo controlled trial – which appears to be happening in Germany. If the results are again positive this then needs to be validated by other research groups.
It should also be noted that IA treatment is a highly specialised procedure and that it can cause serious side effects.
To conclude:
These are interesting preliminary results. They indicate that immunoadsorption could become targeted treatment for a sub group of people with ME/CFS who have these particular autoantibodies
Dr Charles Shepherd,
Trustee and Hon. Medical Adviser to the ME Association,
Member of the 2018-2021 NICE guideline on ME/CFS committee,
Member of the 2002 Chief Medical Officer's Working Group on ME/CFS
More Information
- Observational Study of Repeat Immunoadsorption (RIA) in Post-COVID ME/CFS Patients with Elevated ß2-Adrenergic Receptor Autoantibodies-An Interim Report | October 2023
- Chronic post-COVID-19 syndrome and chronic fatigue syndrome: Is there a role for extracorporeal apheresis? | June 17, 2021
- Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Efficacy of Repeat Immunoadsorption | July 30, 2020
- Immunoadsorption to remove ß2 adrenergic receptor antibodies in Chronic Fatigue Syndrome CFS/ME | March 15, 2018
- ME/CFS Research Published 10 – 16 October 2023 | October 20, 2023
- Research Review – What are the current treatments being trialed for Long COVID? | February 21, 2022