ME/CFS Research Summaries

Immunoadsorption & Apheresis

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Current Takeaway

Immunoadsorption and extracorporeal apheresis are blood-filtration therapies investigated for their potential to treat severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID. These interventions physically filter pathogenic substances from a patient’s circulation—specifically autoantibodies in the case of immunoadsorption, and microclots, fibrinogen, or inflammatory mediators in the case of Heparin-mediated Extracorporeal Low-density lipoprotein Precipitation (H.E.L.P.) apheresis. The primary objective is to restore microvascular blood flow, reduce systemic inflammation, and clear autoantibodies targeting critical cardiovascular and autonomic receptors.

Clinical interest has been driven by preliminary open-label observational studies showing significant physical and functional improvements in small patient cohorts. Specifically, pilot data suggest that H.E.L.P. apheresis may improve capillary perfusion and resolve symptoms like fatigue and cognitive dysfunction in Long COVID, while open-label immunoadsorption has demonstrated temporary physical and functional improvement in a subset of patients with post-infectious ME/CFS who exhibit elevated autoantibodies targeting G-protein-coupled receptors (GPCRs).

However, the therapeutic value of these procedures is highly uncertain. A 2026 randomized, sham-controlled crossover trial of immunoadsorption in Post-COVID syndrome found no significant benefit over sham treatment despite successfully clearing GPCR autoantibodies. This critical finding indicates that prior positive results in open-label settings may have been driven by placebo or contextual effects, highlighting the necessity of randomized controlled trials (RCTs) to establish the safety, efficacy, and clinical utility of these invasive and resource-intensive therapies.

Why This Matters

These extracorporeal therapies target hypothesized vascular and autoimmune pathomechanisms in ME/CFS and Long COVID. By physically removing circulating microclots, fibrinogen, and autoantibodies from the plasma, these procedures address hypothesized drivers of capillary blockages, hypoxia, and autonomic dysfunction. Specifically, targeting GPCR autoantibodies, such as those against the ß2-adrenergic receptor, addresses the autoimmune model of vascular dysregulation in ME/CFS, while removing fibrinogen-rich microclots targets the microthrombosis and endothelial dysfunction model. Investigating these high-complexity interventions helps clarify whether persistent circulating factors are actively maintaining the disease state and provides therapeutic directions that can be refined through subsequent B-cell depletion or targeted anti-coagulant approaches.

State of Evidence

  • Established: Extracorporeal apheresis and immunoadsorption techniques can successfully deplete targeted substances—such as fibrinogen, inflammatory cytokines, LDL, and IgG autoantibodies—from circulation during the procedure.
  • Plausible but early: Heparin-mediated extracorporeal LDL precipitation (H.E.L.P.) apheresis may resolve severe fatigue, cognitive dysfunction, and perfusion deficits by clearing microclots and improving microcirculation; repeat immunoadsorption (RIA) may temporarily improve physical and functional capacity in a subset of post-COVID ME/CFS patients who have elevated autoantibodies against the ß2-adrenergic receptor.
  • Not established: True clinical efficacy of immunoadsorption (differentiating active treatment from sham/placebo effects) in post-COVID or ME/CFS cohorts, as the first sham-controlled crossover trial found no significant symptom reduction; the durability of symptom improvements beyond 3–6 months.
  • Key limitations: A randomized, sham-controlled crossover trial demonstrated no clinical benefit for immunoadsorption over sham treatment; positive clinical reports are mostly limited to small, uncontrolled observational studies susceptible to placebo and contextual effects; both procedures are highly invasive, resource-intensive, and carry risks such as catheter-associated jugular vein thrombosis; autoantibodies re-accumulate within months, causing symptoms to recur.

Timeline

2023-05-26 - H.E.L.P. apheresis case series reports symptom resolution in Long COVID

A retrospective pilot study evaluated Heparin-mediated Extracorporeal LDL Precipitation (H.E.L.P.) apheresis in 17 patients with severe Long COVID (symptoms lasting 2–12 months), showing that 16 patients experienced immediate, substantial improvement in fatigue, breathlessness, and cognitive dysfunction. Following 1 to 7 sessions, 12 patients reported complete or near-complete symptom resolution, with benefits maintained or improved in 15 patients at a 6–10 month follow-up. This work supports the hypothesis that persistent microclots, fibrinogen, and inflammatory mediators restrict capillary blood flow and oxygen transport in Long COVID. By physically filtering these components, the procedure aims to improve blood rheology and microvascular perfusion, offering a potential therapeutic avenue directed at vascular pathology. However, the study does not prove clinical efficacy due to its small size, retrospective case-series design, and lack of a control group. It remains unclear whether the observed improvements were due to the procedure itself, a placebo response, or natural recovery over time. Additionally, the optimal number of treatments and the long-term safety profile of repeated sessions in this patient population are undetermined.

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2023-10-09 - Observational study of repeat immunoadsorption shows physical improvement in post-COVID ME/CFS

An interim report of a prospective observational study in 10 post-COVID ME/CFS patients with elevated ß2-adrenergic receptor autoantibodies showed that 7 patients achieved clinically significant improvements in physical function (as measured by SF-36 scores) four weeks after receiving five immunoadsorption sessions over 10 days. The treatment successfully depleted the targeted autoantibodies in all patients, though these levels began to rise again within four weeks. This study provides early clinical evidence supporting the role of autoantibodies—specifically those targeting GPCRs like the ß2-adrenergic receptor—in the pathogenesis of post-infectious ME/CFS. The physical and functional improvement in responders suggests that clearing these antibodies from circulation may help restore normal vascular and autonomic function. However, the study does not establish definitive therapeutic efficacy or confirm that autoantibody removal is the primary driver of recovery. There was no correlation between the extent of autoantibody reduction and the degree of clinical improvement, suggesting other mechanism-of-action pathways (such as B-cell modulation) may be responsible. Furthermore, the study lacked a control or sham-apheresis group, was limited to a very small cohort, and showed no significant change in patients’ subjective fatigue scores.

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2026-06-11 - Randomised sham-controlled trial finds immunoadsorption ineffective in Post-COVID syndrome

The IAMPOCO randomised, patient-blinded, sham-controlled crossover trial evaluated immunoadsorption with tryptophan adsorbers versus sham treatment in 40 patients with post-COVID syndrome. Although immunoadsorption successfully depleted G-protein-coupled receptor (GPCR) autoantibodies, there was no statistically significant difference in symptom improvements between the active and sham arms across scales measuring fatigue, cognitive function, and grip strength. These findings directly challenge earlier uncontrolled observational studies that suggested clinical benefit, indicating that prior positive results may have been driven by placebo or contextual effects. The trial also highlighted safety concerns, with a higher rate of adverse events during immunoadsorption, including jugular vein thrombosis associated with central venous catheters. While the study indicates that temporary autoantibody clearance is unlikely to provide therapeutic benefits, it does not rule out potential benefits of immunoadsorption in early-stage disease or using alternative adsorber columns.

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2026-06-15 - Charité cohort updates and upcoming trial designs presented at German symposium

At the ME/CFS Symposium 2026, Elisa Stein presented clinical updates from Charité’s open-label, uncontrolled immunoadsorption studies. In an initial cohort of 20 Post-COVID patients with elevated beta-2 adrenergic receptor autoantibodies, immunoadsorption using a Miltenyi column achieved a two-thirds responder rate at four weeks, showing improvements in physical function, fatigue, pain, PEM, and autonomic symptoms. A subsequent cohort of 15 patients evaluated at week 8 (to allow recovery from treatment-induced crashes) showed seven responders, with improvements lasting 3–6 months before returning to baseline as autoantibodies re-accumulated. Stein announced the launch of the Impact study (n=50) to validate responder immunophenotypes, which will help select candidates for a future B-cell depletion trial. She also summarized three ongoing or completed German randomized sham-controlled trials, including the Berlin study and the Mainz tryptophan adsorber trial, which will provide essential controlled validation.

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