Is It All About Endothelial Dysfunction and Thrombosis Formation? The Secret of COVID-19

Abstract

The world is in a hard battle against COVID-19. Endothelial cells are among the most critical targets of SARS-CoV-2. Dysfunction of endothelium leads to vascular injury following by coagulopathies and thrombotic conditions in the vital organs increasing the risk of life-threatening events. Growing evidences revealed that endothelial dysfunction and consequent thrombotic conditions are associated with the severity of outcomes. It is not yet fully clear that these devastating sequels originate directly from the virus or a side effect of virus-induced cytokine storm. Due to endothelial dysfunction, plasma levels of some biomarkers are changed and relevant clinical manifestations appear as well. Stabilization of endothelial integrity and supporting its function are among the promising therapeutic strategies. Other than respiratory, COVID-19 could be called a systemic vascular disease and this aspect should be scrutinized in more detail in order to reduce related mortality. In the present investigation, the effects of COVID-19 on endothelial function and thrombosis formation are discussed. In this regard, critical players, laboratory findings, clinical manifestation, and suggestive therapies are presented.

New laboratory evidence for the association between endothelial dysfunction and COVID‐19 disease progression

“… 7 A growing body of research has proposed that endothelial dysfunction may be an essential factor in the rapid progression of COVID‐19, but laboratory evidence is still lacking. 8 , 9 , 10 …”

Mucormycosis and COVID-19-Associated Mucormycosis: Insights of a Deadly but Neglected Mycosis

“…Pre-existing diabetes is the main risk factor in most CAM cases [ 12 ] and is also related to an increase in the severity of SARS-CoV-2 infection [ 146 ]; Low pH, caused by diabetic ketoacidosis or metabolic acidosis caused by corticosteroid use [ 147 ], which reduces the leukocytes’ phagocytic activity and impairs bronchoalveolar macrophages migration and functions [ 12 , 148 ]; Immunosuppression, caused by SARS-CoV-2 infection and hypoxia, corticosteroids, and tocilizumab use [ 148 , 149 ] or patients’ previous comorbidities. Endothelial damage, thrombosis, and lymphopenia are usually observed during COVID-19, which contribute to the host immunosuppression [ 150 , 151 ]; Free iron availability, caused by hyperglycemia, the COVID-19 cytokine storm, or by acidosis. Hyperglycemia and diabetic ketoacidosis cause dissociation of iron from ferritin and lactoferrin, thus elevating free iron concentrations [ 152 ], and some cytokines, mainly IL-6, stimulate ferritin synthesis and decrease iron export, increasing intracellular iron storage [ 153 , 154 , 155 ] and causing tissue damage and thus the release of iron into circulation [ 156 ].…”

“…Immunosuppression, caused by SARS-CoV-2 infection and hypoxia, corticosteroids, and tocilizumab use [ 148 , 149 ] or patients’ previous comorbidities. Endothelial damage, thrombosis, and lymphopenia are usually observed during COVID-19, which contribute to the host immunosuppression [ 150 , 151 ];…”

Vascular dysfunction in COVID-19 patients: update on SARS-CoV-2 infection of endothelial cells and the role of long non-coding RNAs

“…Currently, the clinical complications in patients with COVID-19 and CVD are supposed to be the direct consequences of SARS-CoV-2 infection and dysregulation of ECs [13,14,31,32,38,116,[124][125][126][127][128]. Under normal physiological conditions, the vascular endothelium regulates the systemic blood flow, immune response, coagulation, and tissue perfusion in line with the underlying SMCs or pericytes of the microvasculature [19,23,28,31,72,75,[129][130][131].…”

“…COVID-19 disease has been described as being accompanied by arterial and venous thrombotic events, particularly in patients suffering from CVD [ 95 , 116 , 237 ]. Up to 30% of COVID-19 patients admitted to the intensive care unit acquired various thrombotic complications [ 74 , 131 , 237 ]. The pathophysiology of coagulopathy associated with COVID-19 disease involves several pathways.…”