Apheresis for Post-COVID Syndrome

Post-COVID syndrome (PCS), often also referred to as Long COVID, comprises persistent or newly developed symptoms following a SARS-CoV-2 infection. Common symptoms include severe fatigue, exercise intolerance or post-exertional malaise (PEM), impaired concentration and memory (“brain fog”), circulatory problems, shortness of breath, sleep disturbances, and muscular or neurological symptoms.

The underlying causes of Post-COVID syndrome are not yet fully understood. Several potentially overlapping mechanisms are currently being investigated, including immune dysregulation and autoimmunity, persistent inflammatory responses, endothelial and vascular dysfunction, alterations in coagulation, and possibly the persistence of viral components.

Why has apheresis been investigated in Post-COVID syndrome?

Alterations in various immunological and vascular biomarkers have been described in some patients with Post-COVID syndrome. These include autoantibodies against G-protein-coupled receptors (GPCR autoantibodies), inflammatory mediators, and changes in coagulation and endothelial parameters.

This has led to the hypothesis that extracorporeal blood purification procedures might reduce certain circulating factors and thereby potentially influence symptoms.

However, these pathophysiological concepts are still under investigation. The presence of such factors does not prove that they are responsible for Post-COVID syndrome, nor does their removal necessarily result in clinical improvement.

What do current studies show?

Early case reports, case series, and small uncontrolled studies reported improvements in symptoms in some patients following therapeutic apheresis or immunoadsorption.

In a pilot study conducted at our center involving 20 patients with severe Post-COVID syndrome, some patients reported subjective improvements, particularly in fatigue, cognitive symptoms, and circulatory complaints. Changes in several laboratory parameters were also observed, including GPCR autoantibodies, inflammatory markers, and lipid levels.

Korth J. et al. A Single-Center Pilot Study of Therapeutic Apheresis in Patients with Severe Post-COVID Syndrome. Horm Metab Res. 2024;56:869–874. DOI: 10.1055/a-2445-8593

However, this was a small, non-randomized and non-placebo-controlled study. Therefore, it could not establish whether the observed clinical changes were caused by the apheresis treatment itself.

Randomized controlled trials are now available

The scientific evidence has developed considerably since these early studies.

In a randomized, double-blind, placebo-controlled trial published in 2025, 50 patients with Post-COVID syndrome received either six therapeutic plasma exchange procedures or sham treatment. No significant differences were observed between the groups in functional impairment, fatigue, quality of life, neurocognitive symptoms, or other investigated clinical outcomes.

España-Cueto S. et al. Plasma exchange therapy for the post COVID-19 condition: a phase II, double-blind, placebo-controlled, randomized trial. Nature Communications. 2025;16:1929. DOI: 10.1038/s41467-025-57198-7

In 2026, results from the randomized, sham-controlled IAMPOCO trial investigating immunoadsorption were also published. Forty patients underwent five immunoadsorption sessions and five sham procedures in a crossover design.

Immunoadsorption resulted in a substantial reduction in GPCR autoantibodies. Despite this biological effect, however, no significant improvement in clinical symptoms was observed compared with sham treatment, including functional impairment, fatigue, Bell score, cognitive performance, and handgrip strength.

Thus, two controlled studies have now demonstrated that removing potentially relevant plasma components or autoantibodies does not necessarily translate into clinical improvement in Post-COVID syndrome.

Current scientific assessment

Based on the current state of scientific evidence, the clinical efficacy of apheresis or immunoadsorption for the treatment of Post-COVID syndrome in general has not been established.

Current German Long/Post-COVID guidelines emphasize that procedures such as immunoadsorption remain under scientific investigation.

However, the available results do not rule out the possibility that specific, as yet insufficiently characterized subgroups of patients may respond differently to immunomodulatory or extracorporeal treatments. Further controlled studies with improved characterization of different Post-COVID phenotypes are required.

Which apheresis procedures have been investigated in Post-COVID syndrome?

Immunoadsorption

During immunoadsorption, plasma is first separated from the cellular components of the blood. The plasma is subsequently passed through an adsorber that binds immunoglobulins and therefore also removes numerous autoantibodies.

The treated plasma is then returned to the patient.

The IAMPOCO trial demonstrated that this procedure can effectively reduce GPCR autoantibodies. However, no clinical benefit compared with sham treatment was demonstrated.

Therapeutic plasma exchange

During therapeutic plasma exchange, part of the patient’s plasma is removed and replaced with a substitution solution, such as albumin. This results in the non-specific removal of numerous circulating substances, including immunoglobulins, inflammatory mediators, and coagulation proteins.

In a randomized controlled trial involving 50 patients with Post-COVID syndrome, six plasma exchange procedures did not provide a significant clinical benefit compared with sham treatment.

H.E.L.P. apheresis

H.E.L.P. apheresis was originally developed for the treatment of severe lipid disorders. The procedure reduces several circulating components, including LDL cholesterol, lipoprotein(a), and fibrinogen.

For the treatment of Post-COVID syndrome, there is currently insufficient controlled evidence demonstrating clinical efficacy.

Double-filtration plasmapheresis (DFPP) / Therapeutic Apheresis

During double-filtration plasmapheresis, plasma is first separated from the cellular components of the blood and then passed through a second filter. Depending on the characteristics of the filter, larger plasma proteins such as immunoglobulins, lipoproteins, and other macromolecules can be reduced.

Clinical efficacy of DFPP for Post-COVID syndrome has not yet been demonstrated in sufficiently large randomized controlled trials.

Our current approach to apheresis in Post-COVID syndrome

In view of the controlled studies now available, we do not consider apheresis an established standard treatment for Post-COVID syndrome.

The positive observations from early case series and from our own pilot study remain scientifically interesting. However, these findings have not yet been confirmed by randomized, sham-controlled trials.

We therefore consider further scientific investigation of potential Post-COVID subgroups and biomarkers to be important. Treatment should, however, not be associated with the promise that removing autoantibodies, inflammatory mediators, “microclots,” or other plasma components will result in clinical improvement.

Last updated: August 2026