Scientific Rationale

Why Therapeutic Plasma Exchange (TPE) has Been Explored for Long COVID

Long COVID — formally designated as Post-Acute Sequaelae of SARS-CoV-2 (PASC) — is a complex, multisystem syndrome that can persist for months or years following SARS-CoV-2 infection. Researchers have identified several pathophysiological mechanisms that provided the scientific basis for exploring TPE as a therapeutic intervention.

• Autoantibody Formation
  Studies have identified functionally active autoantibodies in Long COVID patients, including those targeting G-protein-coupled receptors (GPCRs) such as adrenergic and angiotensin receptors. These autoantibodies may disrupt normal cellular signaling and contribute to symptoms like fatigue, tachycardia, and cognitive impairment.
  
• Fibrin Amyloid Microclots
  Researchers have documented the presence of anomalous, fibrinolysis-resistant amyloid fibrin microclots in the plasma of Long COVID patients. These microclots may obstruct capillaries, impairing oxygen exchange and contributing to fatigue, brain fog, and exercise intolerance.
  
• Persistent Inflammatory Milieu
  Elevated levels of inflammatory cytokines, immune complexes, and endothelial activation markers — including von Willebrand factor, E-selectin, and serum amyloid A — have been observed in Long COVID patients, suggesting an ongoing pro-inflammatory state that TPE could theoretically help clear.
  
• Viral Persistence Hypothesis
  Some research suggests that SARS-CoV-2 spike protein fragments or viral reservoirs may persist in tissues, driving continued immune activation. TPE was hypothesized to remove circulating viral antigens and downstream inflammatory mediators.