Long COVID — also known as Post-Acute Sequelae of SARS-CoV-2 (PASC) — affects millions of people worldwide. Patients report persistent fatigue, cognitive dysfunction (“brain fog”), exercise intolerance, breathlessness, and a constellation of other symptoms that can persist for months or years after the initial infection. One of the most promising areas of current research centers on the role of the vascular system: specifically, the formation of fibrinoid microclots and the resulting impairment of microcirculation.
The Microclot Hypothesis
Research conducted by several groups, including important clinical findings by Dr. Beate Jaeger, has identified the presence of abnormal fibrinoid microclots in the blood of Long COVID patients. These microclots are resistant to the body’s normal fibrinolytic (clot-dissolving) processes and can persist in the circulation long after the acute infection has resolved.
Unlike normal blood clots that form in response to injury and are subsequently dissolved by the body’s enzymatic systems, these fibrinoid microclots appear to be structurally different. They are amyloid-like in nature, making them resistant to degradation. Their persistence in the bloodstream is believed to contribute directly to the symptoms that characterize Long COVID.
It is important to note that this area of research is still evolving. The microclot hypothesis represents an important research direction, and while clinical evidence is accumulating, it has not yet been universally adopted as the definitive explanation for all Long COVID symptoms. What is clear, however, is that many Long COVID patients demonstrate measurable abnormalities in their microcirculation and clotting parameters.
Endothelial Dysfunction and Impaired Microcirculation
The endothelium — the thin layer of cells lining every blood vessel in the body — appears to be a primary target of SARS-CoV-2 damage. The virus’s spike protein binds to ACE2 receptors, which are abundantly expressed on endothelial cells. This interaction can trigger endothelial inflammation and dysfunction that persists well beyond the acute infection.
When the endothelium is damaged, it loses its ability to properly regulate blood flow, prevent inappropriate clotting, and maintain the smooth passage of red blood cells through the smallest capillaries. The combination of endothelial dysfunction and circulating microclots creates a state of impaired microcirculation: oxygen and nutrients cannot reach tissues efficiently, and metabolic waste products cannot be cleared.
This impaired microcirculation may explain many of the hallmark symptoms of Long COVID:
- Fatigue — Tissues receiving inadequate oxygen cannot produce energy efficiently
- Cognitive dysfunction — The brain is exceptionally sensitive to reduced microcirculation
- Exercise intolerance — Muscles cannot receive the increased blood flow demanded by physical activity
- Breathlessness — Impaired pulmonary microcirculation reduces gas exchange efficiency
- Chest pain and palpitations — Cardiac microcirculation impairment can produce symptoms that mimic heart disease
Dr. Beate Jaeger’s Clinical Findings
Dr. Beate Jaeger, who collaborates with St. George Hospital on Post-COVID treatment, has contributed important clinical observations in this area. Her work has focused on identifying and characterizing the microcirculatory abnormalities present in Long COVID patients and developing treatment approaches that specifically address these findings.
Dr. Jaeger’s clinical approach includes detailed assessment of clotting parameters, inflammatory markers, and endothelial function, followed by targeted interventions designed to restore normal microcirculation. Her findings suggest that addressing the vascular component of Long COVID can lead to meaningful clinical improvement in many patients.
How Apheresis Addresses the Vascular Component
H.E.L.P. apheresis (Heparin-induced Extracorporeal Lipoprotein/fibrinogen Precipitation) is a blood filtration technology that selectively removes specific harmful components from the bloodstream. In the context of Long COVID, apheresis can target:
- Fibrinogen — The precursor protein from which fibrinoid microclots are formed
- Inflammatory mediators — Cytokines and other molecules that perpetuate endothelial inflammation
- Lipoproteins — Elevated lipoproteins that contribute to blood viscosity and endothelial stress
- Immune complexes — Circulating antibody-antigen complexes that can drive ongoing inflammation
By physically removing these components from the blood, apheresis can produce rapid improvements in microcirculation. Many patients report noticeable symptom improvement within hours to days of their first session. At St. George Hospital, apheresis is typically combined with additional therapies targeting endothelial repair, immune modulation, and metabolic support as part of a comprehensive Post-COVID treatment program.
An Evolving Understanding
The science of Long COVID is advancing rapidly. New studies are published regularly, and our understanding of the underlying mechanisms continues to deepen. The vascular hypothesis — centered on microclots, endothelial dysfunction, and impaired microcirculation — represents one of the most clinically actionable frameworks currently available.
At St. George Hospital, we approach Long COVID treatment with the recognition that this is an evolving field. Our protocols are regularly updated as new evidence emerges, and we are transparent with patients about what is established and what remains under investigation. What we can say with confidence is that many Long COVID patients who present with measurable microcirculatory abnormalities respond to targeted treatment addressing these findings.