Endothelial dysfunction in COVID-19: Current findings and therapeutic implications

Abstract

Coronavirus disease 2019 (COVID-19) increases the risk of several non-pulmonary complications such as acute myocardial injury, renal failure or thromboembolic events. A possible unifying explanation for these phenomena may be the presence of profound endothelial dysfunction and injury. This review provides an overview on the association of endothelial dysfunction with COVID-19 and its therapeutic implications. Endothelial dysfunction is a common feature of the key comorbidities that increase risk for severe COVID-19 such as hypertension, obesity, diabetes mellitus, coronary artery disease or heart failure. Preliminary studies indicate that vascular endothelial cells can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and evidence of widespread endothelial injury and inflammation is found in advanced cases of COVID-19. Prior evidence has established the crucial role of endothelial cells in maintaining and regulating vascular homeostasis and blood coagulation. Aggravation of endothelial dysfunction in COVID-19 may therefore impair organ perfusion and cause a procoagulatory state resulting in both macro- and microvascular thrombotic events. Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins are known to improve endothelial dysfunction. Data from smaller observational studies and other viral infections suggests a possible beneficial effect in COVID-19. Other treatments that are currently under investigation for COVID-19 may also act by improving endothelial dysfunction in patients. Focusing therapies on preventing and improving endothelial dysfunction could improve outcomes in COVID-19. Several clinical trials are currently underway to explore this concept.

Hypertension and COVID-19: Ongoing Controversies

“…However, high BP variability was related with high risks of mortality and ICU admissions, underlying the importance of maintenance of stable in-hospital BP in these patients. Increased BP variability could reflect increased arterial stiffness and endothelial dysfunction that are associated with cardiovascular events ( 24 , 25 ). Additional explanation could be a sudden BP decline because of progressive deterioration of underlying conditions.…”

Statins and clinical outcomes with COVID-19: Meta-analyses of observational studies

“…On the other hand, great care should be taken to avoid any adverse interactions between lipid-lowering medications and drugs that might be used to treat COVID-19 (for instance, some antiviral agents) [59] , especially in patients with abnormal liver function tests or myopathies [77] . One caveat is that, while there is no reason to stop statin therapy in patients hospitalized for COVID-19, the level of evidence remains too low—in the absence of RCTs, some of which are ongoing as reported elsewhere [38] , [78] , [79] , although the impact of their results may be attenuated by successful vaccine strategies in the future—to justify initiating statin therapy in statin-free patients in hopes of reducing the burden of disease and improving clinical outcomes [38] , [80] .…”

Impact of COVID-19 infection on the cardiovascular system: An evidence-based analysis of risk factors and outcomes

“…As the endothelial system primarily functions to prevent the passage of harmful substances into our circulatory system, this renders multiple organ systems vulnerable to COVID-19 infiltration and infection ( 61 ). Despite ACE2 serving as the entry point for this virus, ACE2 also has protected against pulmonary infections, indicating that increasing ACE2 is a possible treatment option for COVID-19 infections ( 75 ).…”

“…Further studies have shown significant promise in utilizing rein-angiotensin inhibitors and statins to improve endothelial function and offer protective effects. These drug classes have known benefits on the endothelium, such as quelling inflammation, reversing endothelial tissue damage, and preventing thrombus formation ( 75 ). It is not surprising that statins are currently being evaluated for their efficacy in reducing COVID-19 symptoms associated with endothelial dysfunction, as prior studies have suggested these drugs may be promising treatment options for other viral infections, including viral pneumonia and the influenza virus ( 73 ).…”

“…It is not surprising that statins are currently being evaluated for their efficacy in reducing COVID-19 symptoms associated with endothelial dysfunction, as prior studies have suggested these drugs may be promising treatment options for other viral infections, including viral pneumonia and the influenza virus ( 73 ). These medications should not be stopped at the minimum as there was no noted benefit to discontinuing these medications in hospitalized patients unless there are acute and specific contraindications ( 75 ).…”