Fig. 3: COVID-associated endothelial dysfunction and endothelialitis.

Multiple factors contribute to endothelial dysfunction and damage in Long COVID, with (1) viral persistence being a key driver of endothelial injury. (2) Endothelial damage leads to (3) the release of intracellular components, such as vWF and FVIII, into circulation, which in turn contributes to the formation of anomalous microclot deposits (7). Elevated levels of ET-1 (4) and SDC-1 (5) serve as markers of vascular and glycocalyx injury, respectively. Platelet hyperactivation is a well-established feature of Long COVID, with endothelial damage further promoting platelet adhesion (6) and coagulation. Additionally, the finding of capillary rarefaction in Long COVID may also indicate vascular damage. (8) Research has shown that the spike protein of SARS-CoV-2 directly induces the formation of anomalous fibrin(ogen) deposits in purified soluble fibrinogen (fibrinaloids)²⁰⁴. Spike protein can also induce anomalous deposits in plasma from healthy individuals. The extent of amyloidogenicity might be related to virulence²⁰⁵. It is therefore evident that the formation of these deposits is on the disease pathway. By A. Kruger created in BioRender (https://biorender.com/shortURL) is licensed under CC BY 4.0.