Expression of extracellular vesicles in plasma and cerebrospinal fluid is associated with the procoagulant state in patients with neurological complications of COVID-19

ABSTRACT

Background: Extracellular vesicles (EVs) have been described to be associated with hemostatic disturbances in different clinical settings. (Table Presented) Aims: In this study we have investigated EVs in plasma from patients with COVID-19 in relation to the activation of coagulation. Moreover, we assessed the presence of EVs in the cerebrospinal fluid (CSF) of patients suffering neurological symptoms during COVID-19. Method(s) Eighteen patients with COVID-19 and neurological symptom admitted to the Uppsala University Hospital, Sweden were included. Median age of the patients was 64 (39-85) years, 39% were women. Twenty-one aged matched healthy individuals were included as controls. Informed consent was obtained. EVs derived from platelets (CD61+), neutrophils (MPO+) and endothelial cells (CD51/61+);together with EVs-expressing phosphatidylserine (PS+), tissue factor (CD142+), complement components C5b-9 (TCC+), C3a and C4d were determined by flow cytometry. Overall hemostasis potential (OHP), including overall coagulation potential (OCP) and overall fibrinolytic potential (OFP) were measured and scanning electron microscopy of fibrin clots was performed. Result(s) Significantly higher OCP (p < 0.01) and OHP (p < 0.001) and lower OFP (p < 0.05) were observed in Covid-19 patients (p < 0.05), compared to controls. Denser fibrin structure was found in COVID-19 patients (Figure 1). Increased concentrations of PS+, MPO+, CD61+ and TCC+ EVs were found in plasma from Covid-19 patients compared to healthy controls, and the concentrations of PS+, CD61+ and TCC+ EVs were positively correlated with OCP and OHP in Covid-19 patients. The presence of CD61+, CD51/61+, MPO+ EVs and EVs exposing PS and TCC was identified in the CSF obtained from 17 patients (Figure 2). Conclusion(s) Procoagulant state together with elevated levels of circulating EVs of different cell origin was found in patients with Covid-19. The unique finding of this study is the presence of EVs in CSF of Covid-19 patients with neurologic manifestations. EVs may represent potentially novel biomarkers of blood-brain barrier damage during SARS-COV- 2 infection.