Endothelial Dysfunction in Covid-19 Infection

Abstract

COVID-19 is an evolving systemic inflammatory pandemic disease, predominantly affecting the respiratory system. Associated cardiovascular comorbid conditions result in severe to critical illness with mortality up to 14.8 % in octogenarians. The role of endothelial dysfunction in its pathogenesis has been proposed with laboratory and autopsy data, though initially it was thought of as only acute respiratory distress syndrome (ARDS). The current study on endothelial dysfunction in SARS CoV-2 infection highlights its pathophysiology through the effects of direct viral-induced endothelial injury, uncontrolled immune & inflammatory response, imbalanced coagulation homeostasis, and their interactions resulting in a vicious cycle aggravating the disease process. This review may provide further light on proper laboratory tests and therapeutic implications needed for better management of patients. The main objective of the study is to understand the pathophysiology of COVID-19 with respect to the role of endothelium so that more additional relevant treatment may be incorporated in the management protocol.

COVID-19 Variants in Critically Ill Patients: A Comparison of the Delta and Omicron Variant Profiles

“…These data might suggest a shift in the pathophysiology of COVID-19. In the past two years, different reviews and clinical findings have underlined the role of endothelial dysfunction in the contribution to severe COVID-19 [ 46 , 47 , 48 , 49 , 50 ]. Endothelial dysfunction pathogenesis can be classified as a direct viral effect, cytokine release, oxidative stress, coagulation disruption, and immune cell response.…”

“…Endothelial dysfunction pathogenesis can be classified as a direct viral effect, cytokine release, oxidative stress, coagulation disruption, and immune cell response. The cytokine release is referred to as cytokine storm and is the leading actor in the endothelial damage observed in severely ill COVID-19 patients [ 49 ].…”

“…This knowledge has led researchers and clinicians to explore many therapeutic drugs that might interfere with the endothelial side of the damage [ 47 ]. For this matter, as complement dysregulation is among the “main knights” of the cytokine storm, different complement inhibitors (anti C3 and anti-C5) have been used to soothe the storm and consequently diminish the endothelial damage; anticoagulants such as Low Molecular Weight Heparin and endothelial cell protectors such as Defibrotide have been used for the same purpose [ 49 ]. Anticoagulant therapy has been routinely recommended and shown to reduce mortality in COVID-19 patients, but this increases bleeding risk [ 51 ].…”

Mechanisms of Cardiovascular System Injury Induced by COVID-19 in Elderly Patients With Cardiovascular History

“…The increased levels of von Willebrand factor (VWF) antigen, D-dimers, and tissue plasminogen activator are reported in the COVID-19 group, substantiating endothelial damage and pro coagulation in COVID-19 infection ( 43 , 44 ). Autopsy cases identify lymphocytic endotheliitis, frequent microthrombi as well as venous and arterial thromboembolism ( 16 , 45 , 46 ). A recent study indicates persistent endothelial damage in post-COVID-19 patients; on the other hand, Charfeddine et al demonstrate that the lasting endothelial dysfunction is an independent risk factor of long COVID-19 syndrome ( 47 , 48 ).…”

“…In addition, ECs express different TLRs, mediating PAMPs recognition and antigen presenting to T cells ( 52 ). Regulated EC activation helps in limiting pathogen invasion, whereas the hyperinflammatory profile, often seen in the severe COVID-19 cases, promotes profound endothelial dysfunction and damage, contributing to multiple organ failure ( 46 ).…”