Could persistent extravascular fibrin deposition link microvascular and interstitial pathology in long COVID?

Long COVID is associated with persistent endothelial dysfunction, microvascular impairment, blood coagulation abnormalities, and inadequate oxygen supply to tissues. Researchers propose that chronic intra- and extravascular coagulation (CIEC) may be a continuous pathological mechanism in which COVID-associated immune thrombosis and endothelial injury lead to vascular leakage, local fibrin formation outside blood vessels, and incomplete resolution of the fibrin-containing matrix. The dual-axis microvascular-interstitial model (DMIM) describes how abnormalities on both sides of the vessel wall may functionally interact: impaired tissue supply through microcirculation combined with abnormal mechanics of the interstitial space may contribute to tissue dysfunction and symptoms. This framework links established microvascular pathology with the proposed extravascular component and provides testable predictions for further research.