Endothelial Dysfunction in COVID-19: Potential Mechanisms and Possible Therapeutic Options

Abstract

SARS-CoV-2, a novel coronavirus found in Wuhan (China) at the end of 2019, is the etiological agent of the current pandemic that is a heterogeneous disease, named coronavirus disease 2019 (COVID-19). SARS-CoV-2 affects primarily the lungs, but it can induce multi-organ involvement such as acute myocardial injury, myocarditis, thromboembolic eventsandrenal failure. Hypertension, chronic kidney disease, diabetes mellitus and obesity increase the risk of severe complications of COVID-19. There is no certain explanation for this systemic COVID-19 involvement, but it could be related to endothelial dysfunction, due to direct (endothelial cells are infected by the virus) and indirect damage (systemic inflammation) factors. Angiotensin-converting enzyme 2 (ACE2), expressed in human endothelium, has a fundamental role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In fact, ACE2 is used as a receptor by SARS-CoV-2, leading to the downregulation of these receptors on endothelial cells; once inside, this virus reduces the integrity of endothelial tissue, with exposure of prothrombotic molecules, platelet adhesion, activation of coagulation cascades and, consequently, vascular damage. Systemic microangiopathy and thromboembolism can lead to multi-organ failure with an elevated risk of death. Considering the crucial role of the immunological response and endothelial damage in developing the severe form of COVID-19, in this review, we will attempt to clarify the underlying pathophysiological mechanisms.

A systematic review and meta‐analysis of new‐onset atrial fibrillation in the context of COVID‐19 infection

“…Myocardial injury may also affect the atrial refractory period and promote reentry circuits, facilitating atrial fibrillation 42 . Viral entry into myocardial cells can disrupt the heart's typical electrical properties, predisposing to atrial fibrillation 2,43 . A comprehensive understanding of these mechanisms is essential for developing targeted preventive and therapeutic strategies for NOAF in COVID‐19 patients, ultimately improving their clinical outcomes.…”

Cardiovascular and Renal Comorbidities Included into Neural Networks Predict the Outcome in COVID-19 Patients Admitted to an Intensive Care Unit: Three-Center, Cross-Validation, Age- and Sex-Matched Study

“…Having pinpointed the age- and sex-independent importance of cardiovascular and renal comorbidities in the prediction of COVID-19 fatal outcomes in the ICU setting, we suggest that incorporation of other clinical factors such as age or body mass index into the neural networks may further improve their sensitivity and specificity, as the pathophysiological background of the such predictive model has been clarified in this study. In addition, the finding the specific endothelial dysfunction marker, which is currently lacking [ 47 , 48 , 49 ], may finalize the model, as pro-thrombotic and pro-inflammatory activation of endothelial cells represents a characteristic feature of COVID-19 [ 50 , 51 , 52 , 53 ].…”

Posterior reversible encephalopathy syndrome and reversible cerebral vasoconstriction syndrome in patients with COVID-19 infection: is there a link? A systematic review and case report analysis

“…New COVID-19 variants have been shown to be more diffusive but less aggressive leading to a substantial reduction in complications. Furthermore, they seem to show lower endothelial toxicity [ 151 , 152 ]. However, the importance of these findings is not diminished, because they may clarify some of the molecular mechanisms implicated in these brain vascular diseases.…”