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. Multiple 2026 investigations—including the randomized sham-controlled IAMPOCO trial of immunoadsorption, a sham-controlled pilot of gravity-driven plasmapheresis, and prospective studies tracking objective functional endpoints—found no benefit over sham on their measured outcomes or no measurable functional improvement from baseline. These results show that biomarker clearance does not necessarily translate into recovery; improvements in earlier uncontrolled studies cannot be attributed to the procedure and are consistent with placebo, contextual effects, or natural fluctuation. Small trials have therefore not demonstrated clinical benefit in unselected post-COVID cohorts, but they do not prove that no biomarker-defined subgroup could respond. Whether patient stratification or selective “precision apheresis” column technologies can identify such a subgroup remains an open question requiring controlled validation.
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, though autoantibody titers typically rebound to baseline within 3–6 months.
- 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 or therapeutic plasma exchange (differentiating active treatment from sham/placebo effects) in post-COVID or ME/CFS cohorts, as multiple 2026 studies—including randomized sham-controlled trials and prospective studies tracking objective functional endpoints (such as 6-minute walk distance, grip strength, spirometry, and wearable step counts)—demonstrate no therapeutic superiority over sham treatment or measurable functional improvement.
- Key limitations: Randomized sham-controlled trials in Long COVID demonstrate substantial within-group symptom improvements in placebo arms, so improvements in open-label apheresis case series cannot by themselves establish treatment efficacy; procedures are highly invasive and resource-intensive, frequently requiring central venous catheterization (in up to 94% of participants) with attendant risks of jugular vein thrombosis and transient profound hypogammaglobulinemia (IgG <3 g/L); severe and bedbound patients have been systematically excluded from recent trials; clinical trials have historically evaluated unselected patient populations without biomarker-guided stratification, which may mask efficacy within specific immunological subgroups; protocols and patient selection criteria for newer ‘precision apheresis’ column technologies remain under active investigation.
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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- Stein 2026, ME/CFS Symposium 2026
- Note: An English presentation of these findings is scheduled to premiere at the International ME/CFS Conference on 2026-07-08 (Stein 2026, YouTube).
2026-07-10 - Narrative review advocates for biomarker-guided patient stratification in trials
A narrative review by Dr. Gary Kaplan synthesized research on shared immunological dysregulation—including chronic inflammation, GPCR autoantibodies, and cellular dysfunction—across post-infectious syndromes such as ME/CFS, Long COVID, PTLDS, and PANS/PANDAS. The author evaluated immunomodulatory therapies including intravenous immunoglobulin (IVIG), rituximab, and therapeutic plasma exchange (TPE). A key focus of the review is that trials using unselected patient populations, such as the RituxME phase III study and certain post-COVID TPE trials, are prone to failure because broad cohort definitions mask subpopulation efficacy. Kaplan argued that future trials must utilize biomarker-guided patient stratification, such as immunologic phenotyping and autoantibody screening, to restrict these invasive therapies to patients with documented immunological abnormalities. However, as a narrative review, this work does not present new primary clinical data. The review also notes that high-risk interventions like TPE, IVIG, and rituximab carry serious safety risks, and there remains a lack of randomized, double-blind, placebo-controlled trials validating this biomarker-guided approach.
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2026-07-10 - Editorial review outlines transition to selective precision apheresis
A guest editorial review in Transfusion and Apheresis Science described the ongoing clinical transition of therapeutic apheresis from broad, non-selective plasma exchange toward targeted ‘precision apheresis’ methodologies. This evolution involves using selective column technologies (such as the MTx.100) designed to isolate and remove specific pathological drivers—including autoantibodies, lipids, and cytokines—while preserving essential plasma proteins. The review coincided with the publication of the American Society for Apheresis (ASFA) Ninth Edition guidelines in the Journal of Clinical Apheresis Special Issue, which updates evidence-based fact sheets for 166 indications. Transitioning to selective adsorbers could reduce treatment side effects and improve therapeutic safety compared to non-selective methods. However, this editorial is a general review and does not present new primary clinical trial data or patient outcomes. Additionally, specific protocols and selection criteria for precision apheresis in complex conditions like ME/CFS and Long COVID are not yet established.
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2026-08-05 - Randomized sham-controlled plasmapheresis pilot in Suriname finds no benefit over placebo
A double-blind, randomized, sham-controlled pilot trial evaluated therapeutic plasma exchange using a gravity-driven crossflow microfiltration system (HemoClear) in 18 adult outpatients with Long COVID in Suriname: 11 received active plasma filtration and 7 received a sham blood-draw-and-reinfusion procedure. Participants underwent five sessions, with primary outcomes assessed at 90 days. Both groups exhibited substantial, near-identical reductions in fatigue (Chalder Fatigue Scale scores improving from 20 to 10 in active treatment versus 22 to 12 in placebo; p = 0.8770); 9 of 11 active-treatment participants and 5 of 7 sham participants met the clinical responder criterion (>30% fatigue reduction). Secondary functional instruments (SF-36 and Fatigue Assessment Scale) showed concordant null between-group findings, so the marked symptomatic improvements cannot be attributed to plasma clearance and are consistent with non-specific or placebo effects. The study was constrained by early termination due to slow recruitment, an unstratified cohort lacking biological marker enrichment, and the explicit exclusion of bedridden or severe ME/CFS patients. Furthermore, the report was published on F1000Research, where articles appear before formal peer review completes, leaving peer-review status unrecorded.
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2026-08-11 - Rostock study finds autoantibody clearance without objective functional improvement in post-COVID patients
A prospective exploratory study evaluated five consecutive immunoadsorption sessions using Miltenyi Biotec columns in 18 adult post-COVID syndrome patients selected for elevated autoantibodies against adrenergic and muscarinic receptors. The procedure achieved profound immediate depletion of total IgG (<3 g/L) and targeted G-protein-coupled receptor (GPCR) autoantibodies, but antibody titers returned to baseline within 3 to 6 months. Crucially, objective functional performance endpoints—including 6-minute walk test distance, handgrip dynamometry, spirometry, and continuous smartwatch daily step counts—showed no statistically significant improvement at any follow-up point, even at the autoantibody nadir. While patients reported slight descriptive reductions in subjective fatigue and pain diaries, correlation analyses confirmed that autoantibody reduction was decoupled from symptomatic change. These findings directly converge with the sham-controlled IAMPOCO trial results, demonstrating that clearing circulating autoantibodies does not translate into measurable functional recovery in unstratified post-COVID cohorts. The study carried substantial procedural burden and safety signals, requiring central venous catheterization in 17 of 18 participants and causing transient profound hypogammaglobulinemia. Limitations include the small open-label sample size without a parallel sham arm, recruitment based on WHO post-COVID criteria rather than formal ME/CFS consensus definitions, and the exclusion of severely ill, bedbound patients.
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