Therapeutic Apheresis · Review 03
Therapeutic apheresis for Long COVID: early signals, then a null controlled trial
Small uncontrolled studies reported improvement and biomarker reduction, but a sham-controlled randomized trial did not demonstrate efficacy.
- PROCEDURE STATUS
- Established procedure; off-label proposed use
- INDICATION EVIDENCE
- Controlled trial did not demonstrate efficacy
- REVIEW STATUS
- Clinical review required
- NEXT REVIEW
- January 2027
In short
Early case reports and uncontrolled cohorts described symptom improvement after therapeutic apheresis and documented reductions in selected biomarkers. A 2025 double-blind randomized trial comparing plasma exchange with sham treatment found no difference in symptoms, function, quality of life, cognition or laboratory efficacy measures. Therapeutic apheresis is therefore not an established Long COVID treatment.
The clinical question
Does therapeutic plasma exchange or filtration-based apheresis improve symptoms or function in people with Long COVID?
Why the treatment attracted attention
Long COVID can involve heterogeneous immune, vascular and inflammatory abnormalities. Because plasma exchange and filtration-based apheresis can remove circulating proteins, autoantibodies, lipids or inflammatory mediators, investigators proposed that selected patients might improve after treatment.[2][1]
A 17-patient H.E.L.P. apheresis case series reported substantial patient-reported improvement. A separate INUSpheresis cohort measured reductions in autoantibodies, inflammatory markers, lipids and fibrinogen in 27 treated patients who reported clinical improvement.[1][2]
Why those findings could not establish efficacy
Neither study had a randomized sham control. Participants knew they were receiving an invasive intervention, outcome selection was vulnerable to bias and biomarker removal was expected from the procedure itself. The INUSpheresis paper explicitly states that its findings describe association rather than causality.[2][1]
A removed marker is not proof of recovery
If a filter removes fibrinogen, lipids or antibodies, lower post-treatment levels show that the filter acted. They do not by themselves show that Long COVID improved because those markers fell.
What happened when plasma exchange was compared with sham treatment
In 2025, 50 participants with post-COVID condition were randomized to plasma exchange or sham plasma exchange in a double-blind phase II trial. Both groups had a similarly favorable safety profile, but there were no differences between groups in any evaluated efficacy parameter, including symptoms, functional status, quality of life or neurocognitive measures.[3]
This trial does not prove that every apheresis technology is ineffective for every biological subgroup. It does substantially weaken broad claims that plasma exchange is an effective Long COVID treatment and raises the evidence threshold for device-specific or biomarker-selected claims.[3][4]
What this means for you
AION does not present therapeutic apheresis as a proven Long COVID therapy, and you will not hear success percentages quoted from uncontrolled studies. If you and your physician discuss it for this reason, that conversation includes the negative randomized trial alongside the earlier positive signals, is specific about which apheresis technology is actually being considered, and stays a case by case clinical judgment rather than a general recommendation.[3]
Source register
Every material source used in this review, with the study design and the limitation that matters when interpreting it.
- [1]Jaeger BR, et al. Long Covid Patients Successfully Treated by Means of H.E.L.P. Apheresis.
Infectious Diseases Diagnosis & Treatment · 2023 · Uncontrolled 17-patient case series
DOI 10.29011/2577-1515.100216
- WHAT IT ADDS
- Reports substantial patient-reported improvement after H.E.L.P. apheresis.
- LIMITATION
- Small, uncontrolled case series with no sham comparison and high risk of selection and expectation bias.
- [2]Achleitner M, et al. Clinical improvement of Long-COVID is associated with reduction in autoantibodies, lipids, and inflammation following therapeutic apheresis.
Molecular Psychiatry · 2023 · Uncontrolled biomarker cohort
PMID 37131073 · DOI 10.1038/s41380-023-02084-1
- WHAT IT ADDS
- Documents expected biomarker reductions in 27 INUSpheresis-treated patients reporting improvement.
- LIMITATION
- No randomized or sham control; association does not establish that biomarker removal caused improvement.
- [3]Vidal-Alaball J, et al. Plasma exchange therapy for the post COVID-19 condition: a phase II, double-blind, placebo-controlled, randomized trial.
Nature Communications · 2025 · Randomized double-blind sham-controlled phase II trial
PMID 39994269 · DOI 10.1038/s41467-025-57198-7
- WHAT IT ADDS
- Found no between-group difference in any evaluated efficacy parameter among 50 participants.
- LIMITATION
- Phase II sample size and one plasma-exchange protocol; cannot answer every device-specific subgroup hypothesis.
- [4]Current status and future perspectives on the mechanistic and pathophysiological understanding of long COVID.
Communications Medicine · 2026 · Current expert review
DOI 10.1038/s43856-025-01300-z
- WHAT IT ADDS
- Places apheresis biomarker signals beside the recent randomized null efficacy result.
- LIMITATION
- Narrative synthesis rather than a treatment-effect meta-analysis.
Research changes the question.
A physician owns the answer.
This review is educational and remains marked for clinical review. It does not determine whether any therapy is appropriate for an individual patient.