Mild COVID-19 and Impaired Blood Cell-Endothelial Crosstalk: Considering Long-Term Use of Antithrombotics?

Background Current COVID-19 pandemic reveals thrombotic, vascular and endothelial disfunctions at peak disease, or even after vaccination. However, the duration, degree of damage, and appropriate long-term therapeutic strategies are unclear. Most post-COVID data are yielded from random clinical observations or autopsy of postmortem samples, while precise cellular data in survivors are insufficient. Methods We analyzed blood erythrocytes (RBC), endotheliocytes, and echinocytes by electron microscopy and flow cytometry in patients with confirmed COVID-19 (n=31) and matched controls (n=32) on admission and at hospital discharge. Results All patients experienced mild disease, none required pulmonary support, and all survived. Admission number of circulating endotheliocytes was significantly (40-100 times) higher in COVID-19 patients. Cells were massively damaged by multiple fenestrae in membranes with diameter comparable to the size of supercapsid in SARS CoV-2 virus. COVID-19 also provoked formation of stacked aggregated RBC capable to clog microvascular bed and to diminish oxygen supply. In some patients, such abnormalities persisted at hospital discharge revealing remaining penetration of COVID-19 intracellular where it may be replicated and returned to circulation. Conclusion Cell-endothelial injury cause blood vessels denuded; their increased permeability resulted in tissue edema, inflammation, platelet activation, and augmented thrombosis. Such sequelae can provoke long-term delayed vascular complications following COVID-19. Controlled outcome-driven trials are urgently needed for exploring optimal antithrombotic and vascular protection strategies following even mild COVID-19.