Endothelial Damage & Microclots

The endothelium is a single-cell layer lining every blood vessel in the body. It regulates blood flow, controls clotting, manages inflammation, and governs the exchange of nutrients and oxygen between blood and tissues. SARS-CoV-2 has a well-documented affinity for endothelial cells through the ACE2 receptor, and damage to this lining is now recognized as a central feature of Long COVID pathology.

When the endothelium is injured, several downstream problems emerge. Damaged vessels become more permeable, allowing inflammatory molecules to leak into surrounding tissues. The clotting cascade may activate inappropriately, forming fibrin-rich microclots that resist the body’s normal breakdown processes. These microclots are too small to cause a stroke or pulmonary embolism, but they can obstruct capillaries, reducing oxygen delivery to tissues at the microscopic level. This may help explain why Long COVID patients experience fatigue, cognitive impairment, and exercise intolerance even when standard blood tests and imaging appear normal.

Supporting vascular recovery in Long COVID involves addressing both the endothelial damage and the abnormal clotting. Nattokinase, a fibrinolytic enzyme derived from fermented soybeans, has attracted research interest for its potential to help support the breakdown of fibrin deposits. Omega-3 fatty acids may help support endothelial function and reduce vascular inflammation. Antioxidants like vitamin C and quercetin may help protect endothelial cells from ongoing oxidative stress. Dr. Groysman evaluates vascular markers in his Long COVID patients and considers endothelial support an important component of treatment, particularly for patients whose primary symptoms involve exercise intolerance, brain fog, or unexplained shortness of breath.