The contribution of lymphocyte-platelet coagulants in the pathogenesis of endothelial dysfunction in patients infected with SARS-COV-2

Abstract

Background. The ability of leukocytes, in particular lymphocytes, to migrate into tissues depends on the state of the endothelium. With COVID-19, damage to the endothelium develops, leading to its dysfunction. Patients with a more severe course have a premorbid background, which also contributes to the development of this pathological process. When implementing an immune response, lymphocytes adhere to the surface of the activated endothelium or attach to proteins of the extracellular matrix, which ensures their passage into the tissue. With the formation of lymphocyte-platelet coaggregates, cell extravasation increases and occurs with the participation of adhesion molecules ICAM-1, VCAM-1, P-selectin-PSGL and CD40-CD40L.

Aim. To evaluate the role of lymphocyte-platelet coaggregates in the development of endothelial dysfunction in patients with confirmed SARS-CoV-2.

Material and methods. The study involved patients with COVID infection of varying degrees of severity. Among the associated diseases are: hypertension, coronary heart disease, widespread atherosclerosis, diabetes mellitus. Blood was drawn at the 6-10 days of the disease, after which the main indicators of inflammation were studied using multiplex panels: soluble form of CD40L (sCD40L), ICAM-1 and VCAM-1. The number of leukocyte-platelet coaggregates and the number of cell populations (platelets, leukocytes and their subtypes) were determined using a CytoFLEXLX flow cytometer (BeckmanCoulter, USA). BioLegend, USA). The level of C-reactive protein in blood plasma was recorded using the immunoturbidimetric method.

Results. In patients with severe disease, compared with patients with mild disease, the levels of ICAM-1 and VCAM-1 were higher. The concentration of sCD40L was increased in all three groups of infected patients compared to controls. Correlations were found between the number of lymphocyte-platelet coaggregates and the level of VCAM-1 (r=-0,276; p=0,002), sCD40L (r=-0,328; p<0,001), C-reactive protein (r=-0,237; p=0,010) , as well as with number of lymphocytes (r=0,839; p<0,001) and leukocyte-platelet rosettes (r= 0,230; p=0,012).

Conclusion. Lymphocyte-platelet aggregates exacerbate endothelial dysfunction in SARS-CoV-2 infection in patients with a premorbid background and contribute to its development in patients without concomitant pathology. During the formation of the aggregate, cytokines isolated from activated platelets and lymphocytes cause not only the expression of adhesion molecules on the endothelium, but also local inflammation.