Efficacy of synthetic glucocorticoids in COVID-19 endothelites

Abstract

Since March 2020, the world has been fighting a global pandemic caused by a new coronavirus SARS-CoV-2 (COVID-19). SARS-CoV-2 is responsible for severe acute respiratory syndrome, an airway disease that can be severe and fatal in a percentage of cases. Patients with severe COVID-19 can develop extrapulmonary lesions, with renal, hepatic, cardiac, neurological, and tissue involvement that can cause further severe complications. On December 21, 2021, the European Medicines Agency (EMA) authorized the marketing of the first COVID-19 vaccine. However, several randomized trials are ongoing to find effective, safe, and widely available treatments. The most severe stages of COVID-19 infection are characterized by a multi-system inflammatory state induced by a cytokine storm causing multi-organ injury. Epidemiologic evidence has shown that glucocorticoids (GCs), particularly dexamethasone, are used in severe, hospitalized patients with COVID-19 with good therapeutic benefit. COVID-19 can also damage the endothelial system, causing microcirculatory disturbances and consequently leading to functional organ disorders. The combination of endothelial dysfunction with a generalized inflammatory state may contribute to the general pro-coagulative state described in patients with COVID-19 with increased risk of venous and arterial occlusions. The aim of this article is to describe the therapeutic utility of GCs in stabilizing the vascular endothelial barrier in COVID-19 infection. Indeed, we believe that the stabilization of the endothelial barrier and the anti-inflammatory effect of GCs could be the main effect underlying the therapeutic efficacy in COVID-19 patients.

Keywords: COVID-19; Desametasone; Inflammatory; Pandemic; SARS-CoV-2.

Fig. 1

The substances produced by the endothelium are vasoactive compounds, growth factors, mediators of inflammation, adhesion molecules, proteins of the hemostatic system. Through this wide range of compounds the endothelium intervenes in the control of vascular homeostasis, inflammation, immunity, hemostasis and performs a number of important metabolic functions The invasion of endothelial cells (EC) by the virus and the release of inflammatory cytokines cause inflammation of the endothelium. The resulting endotheliitis is characterized by endothelial cell dysfunction. Endothelial dysfunction causes a systemic condition in which the endothelium loses its physiological and functional properties, such as vasodilation, fibrinolysis, and antiplatelet. This induced endotheliitis may be responsible for tissue edema and the risk of thrombosis leading to organ damage in the COVID-19 patient