Blood Endothelial-Cell Extracellular Vesicles as Potential Biomarkers for the Selection of Plasma in COVID-19 Convalescent Plasma Therapy

Abstract

Despite the advancement of vaccination and therapies currently available, deaths due to the coronavirus disease 2019 (COVID-19) are still heavily documented. Severely infected individuals experience a generalized inflammatory storm, caused by massive secretion of pro-inflammatory cytokines that can lead to endothelial dysfunction, cardiovascular disease, multi-organ failure, and even death. COVID-19 convalescent plasma (CCP) therapy, selected primarily based on anti-SARS-CoV-2 antibody levels, has not been as convincing as expected in the fight against COVID-19. Given the consequences of a dysfunctional endothelium on the progression of the disease, we propose that the selection of plasma for CCP therapy should be based on more specific parameters that take into consideration the effect on vascular inflammation. Thus, in the present study, we have characterized a subset of CCP that have been used for CCP therapy and measured their anti- or pro-inflammatory effect on human coronary artery endothelial cells (HCAECs). Our data revealed that the longer the time lapse between the onset of symptoms and the plasma donation, the more mitochondrial dysfunction can be evidenced. The concentration of blood endothelial cell extracellular vesicles (BEC-EVs) was increased in the plasma of young individuals with mild symptoms. This type of selected convalescent plasma promoted the activation of the blood vascular endothelium, as reflected by the overexpression of ICAM1 and NFκB1 and the downregulation of VE-Cadherin. We propose this mechanism is a warning signal sent by the injured endothelium to trigger self-defense of peripheral blood vessels against excessive inflammation. Therefore, these results are in line with our previous data. They suggest that a more specific selection of COVID-19 convalescent plasma should be based on the time of donation following the onset of the clinical symptoms of the donor, the severity of the symptoms, and the age of the donor. These characteristics are relatively easy to identify in any hospital and would reflect the concentration of plasma BEC-EVs and be optimal in CCP therapy.