Apheresis for Long COVID: Could It Help Recovery?

Some individuals with Long COVID experience persistent symptoms that significantly impact daily life, leading to a search for potential treatments. One approach under investigation is apheresis, a blood-filtering technique used for various medical conditions.

As researchers assess its possible benefits, understanding the process and its effects on different blood components could offer insights into whether this therapy holds promise for recovery.

Process And Techniques

Apheresis selectively removes or modifies blood components and is being explored for its potential to alleviate Long COVID symptoms. The process involves drawing blood, separating it into individual components using filtration or centrifugation, and returning the modified blood to circulation. While widely used for hyperlipidemia, autoimmune disorders, and thrombotic diseases, its role in post-viral syndromes remains under study.

Therapeutic plasma exchange (TPE), a common method, replaces a portion of the patient’s plasma with a substitute solution like albumin or saline to remove circulating factors that may contribute to symptoms. Another approach, double-filtration plasmapheresis (DFPP), employs a two-step filtration system to selectively eliminate specific molecules while preserving beneficial plasma components. Both methods require careful monitoring to maintain hemodynamic stability and prevent complications such as hypotension or electrolyte imbalances.

Lipid apheresis, traditionally used for severe hypercholesterolemia, has also been considered due to its ability to clear inflammatory mediators and substances that impair microvascular function. This technique uses adsorption columns to remove lipoproteins or other target molecules. Some studies suggest lipid apheresis may improve endothelial function and microcirculatory health, potentially benefiting individuals with vascular-related symptoms, though further research is needed.

Blood Components Addressed

Apheresis modifies specific blood elements to achieve therapeutic effects. Plasma, the liquid portion of blood, carries proteins, hormones, and metabolic byproducts, some of which may contribute to lingering symptoms. By filtering plasma, apheresis can remove molecules implicated in vascular dysfunction or systemic imbalances. Elevated levels of fibrinogen and fibrin degradation products, involved in coagulation, have been observed in some Long COVID patients and may contribute to microclot formation, which could impair oxygen delivery and exacerbate fatigue and cognitive dysfunction.

Beyond clotting factors, apheresis can influence lipoprotein composition, which affects endothelial health and inflammation. Some individuals with persistent post-viral symptoms exhibit dysregulated lipid profiles, including increased oxidized low-density lipoprotein (oxLDL) and other pro-inflammatory lipids. These molecules contribute to vascular stress and endothelial dysfunction, which may underlie symptoms such as brain fog and exercise intolerance. Researchers are investigating whether selectively removing these lipids through lipid apheresis or plasma filtration improves microcirculatory function and alleviates symptoms.

Red blood cells, while not directly removed in most apheresis protocols, are affected by plasma composition changes. Some Long COVID patients show altered blood rheology, including increased erythrocyte aggregation or reduced deformability, which can hinder microvascular perfusion and worsen tissue oxygenation. Apheresis may help by reducing factors that promote red blood cell stacking or rigidity, improving blood flow. Additionally, plasma exchange affects albumin levels, a protein essential for maintaining oncotic pressure and transporting bioactive molecules. Changes in albumin concentration and function have been noted in post-viral syndromes, suggesting its modulation through apheresis could have physiological effects beyond volume replacement.

Immune Complexes In Persistent Post-Viral States

Immune complexes, formed when antibodies bind to antigens, play a role in immune regulation but can contribute to prolonged symptoms if they persist in circulation. In Long COVID, inefficient clearance of these complexes may lead to continued immune activation and tissue damage. Their accumulation has been linked to post-viral syndromes, where they may deposit in blood vessels, joints, or organs, triggering inflammation and perpetuating symptoms.

The size and composition of immune complexes influence their persistence in circulation. Large complexes are typically removed by the liver and spleen, while smaller ones can evade clearance. Persistent viral antigens in Long COVID may drive ongoing immune complex formation, maintaining a cycle of immune activation. Studies on post-viral syndromes suggest prolonged immune complex activity contributes to endothelial dysfunction, which may underlie symptoms such as brain fog and exercise intolerance. Complement proteins within these complexes can further amplify inflammation, as seen in autoimmune conditions where complement-mediated damage exacerbates tissue injury.

Apheresis has been explored as a method to reduce immune complex burden, particularly in conditions involving excessive immune activation. Therapeutic plasma exchange has been used in autoimmune diseases such as lupus and vasculitis, where removing circulating immune complexes has led to symptom improvement. In Long COVID, preliminary findings suggest reducing immune complex load may help modulate inflammation and restore immune balance. While clinical trials are needed to determine efficacy, case reports have documented symptom relief following plasma filtration in individuals with severe post-viral complications.

Circulatory Factors That May Influence Symptoms

Blood flow regulation involves vascular integrity, endothelial function, and microcirculatory dynamics, all of which may contribute to Long COVID symptoms. Many individuals with prolonged post-viral effects report dizziness, temperature dysregulation, and exertional intolerance, potentially linked to circulatory imbalances. One area of interest is altered autonomic control of blood vessels, where disruptions in vasoconstriction and vasodilation can lead to inadequate tissue perfusion. Dysautonomia, including conditions such as postural orthostatic tachycardia syndrome (POTS), has been frequently documented in Long COVID, suggesting abnormal blood distribution may play a role in symptom persistence.

Vascular dysfunction may also result from endothelial damage, compromising the ability of blood vessels to regulate tone and permeability. The endothelium produces nitric oxide, a molecule essential for vasodilation and preventing excessive clot formation. Reduced nitric oxide bioavailability has been implicated in post-viral fatigue syndromes, potentially impairing oxygen delivery to muscles and the brain. Even minor deficits in blood flow can have systemic consequences over time, which may explain widespread fatigue and cognitive difficulties in Long COVID.