The Endothelium: A Common Denominator Underlying “Atypical” Manifestations of COVID-19?

Is There a Common Thread Connecting the “Atypical” Presentations of COVID-19?

As we hear more about atypical presentations of what was initially viewed as a respiratory infection, it raises the question: is there a common thread related to the pathophysiology of COVID-19 that underlies its presentation in stroke, cardiovascular manifestations, renal failure, coagulopathies, and a multisystem inflammatory syndrome? A group of Italian researchers recently hypothesized that it is actually the endothelium that is being targeted by this mysterious and “invisible” enemy.

Comorbidities Associated with Endothelial Dysfunction increase Risk of Severe COVID Infection

Throughout the course of the pandemic, the over-representation of those with hypertension and/or diabetes, particularly in those with severe infections has been demonstrated. Pre-existing cardiovascular disease is associated with worse COVID-19 outcomes. Age, of course, has emerged as the strongest predictor of Covid-19 related death; those >60, and especially those > 70 have been urged to be particularly diligent about social distancing. Endothelial dysfunction (ED) is a common factor among diabetes, hypertension, cardiovascular disease, and age-related endothelial dysfunction.

What We Are Learning About the Disease Process

In exploring the pathophysiology of the coronavirus, it has been demonstrated that the virus invades the cells through the angiotensin-converting enzyme 2 (ACE-2) receptor, which are expressed in the lungs, the heart, the vascular endothelium, and the kidneys.  It follows that respiratory symptoms are common as ACE-2 is very abundant in the lungs. COVID-19 may attack the respiratory system in a pathway not fully understood. A recent comparison of post-mortem findings in COVID-infected patients with acute respiratory distress syndrome (ARDS) secondary to influenza A infection and 10 age-matched, uninfected control lungs revealed distinctive vascular features, including endothelial damage associated with intracellular virus and disruption of cell membranes. In addition, widespread thrombosis and microangiopathy were seen. An accompanying editorial notes several limitations to this study including small sample size, its observational nature, as well as whether differences in pathologic findings may have been associated with variation in time points with the COVID-infected patients vs the influenza A-associated ARDS victims. However, the observation of what appears to be a novel disease process opens up the potential of further study into new targeted or supportive treatments for vascular manifestations in COVID-infected patients.

What We Still Hope to Learn About Endothelial Dysfunction and COVID-19

Studies continue into precisely how ED may contribute to adverse clinical outcomes in COVID-infected patients. In patients with ED, the endothelium loses its normal functional properties, including the promotion of vasodilation, fibrinolysis, and anti-aggregation of platelets. The loss of these 3 physiologic properties would help to explain CV events like acute coronary syndrome, stroke, and renal failure that occur as initial manifestations or complications of COVID.

While research continues into the development of antiviral treatment and a safe and effective vaccine for COVID-19, what we are learning about the effect of this yet-to-be fully understood novel virus on the cardiovascular system and on the endothelium, in particular, may help us more effectively manage the vascular manifestations of COVID-infected patients and improve clinical outcomes.