Empowering Ourselves Against COVID-19 By Protecting Against Endothelial Dysfunction

Celina Nadelman, M.D., uniquely serves as both a board certified anatomic and clinical pathologist and cytopathologist and a fine needle aspiration (FNA) specialist in Beverly Hills, California. www.drnadelman.com

SARS-CoV-2 is the novel corona virus responsible for COVID-19 and the current world-wide pandemic. It causes a viral pneumonia that leads to acute respiratory failure in up to 20% of symptomatic patients.

Most attention has been paid to this aspect of the disease. Whereas the other aspects, stemming from vascular problems (abnormal conditions of blood vessels), namely, endothelial cell dysfunction, have not been as thoroughly investigated and publicized until recently.

The endothelial cell is the type of cell that makes up our vessels. They are the cells that line arteries, veins and capillaries. They provide a barrier between the outside environment and the inside bloodstream. Endothelial cells not only make up the physical barrier of vessels, they also regulate vasomotor tone (regulate blood pressure), osmotic balance (balance electrolytes) and play a major role in the immune response. Endothelial cells participate in the regulation of local as well as systemic inflammatory and immune reactions.

Figure 1

The endothelium plays a crucial role in the infectious process, spread and prognosis of SARS-CoV-2 infection. What is readily known is that the novel coronavirus infects humans through the ACE 2 receptor in human cells (Figure 1).

ACE 2 receptors are found all over the body. Through this receptor in lung tissue, the virus can invade our bodies, acting as a key that unlocks our bodies’ protection. Because the airways are the first portal of entry for this disease, oftentimes, these sites are the most affected initially, displaying symptoms similar to a cold and sometimes leading to severe pneumonia and ARDS (Acute Respiratory Disease Syndrome) and death.

The main purpose of the lungs is to deliver oxygen to the entire body. This is accomplished through a one-to-one cell interaction between the smallest member of the pulmonary tree, the alveolar cell, with the smallest member of the vasculature, the capillary endothelial cell (Figure 2).

Figure 2
© 2012 by Pearson Education, Inc.

The ACE 2 receptor is not only found in lung cells, but it is also found in endothelial cells. SARS-CoV-2 is inhaled into the lungs, it spreads to the alveolar cell, which then comes into contact with the capillary endothelial cell. Thus, it gains entry to the entire body.

Studies of COVID-19 patient autopsies confirm viral particles in endothelial cells, which corroborates the crucial role the endothelium has in the widespread tissue damage brought on by SARS-CoV-2. Examples of these are thrombi and microthrombi, evidenced by stroke, DVTs and pulmonary emboli. In addition, megakaryocytes, the cells responsible for platelets (clotting cell parts) are found in bizarre places, such as heart muscle.

The endothelium is a delicate but robust organ, and it can become damaged or dysfunctional by physical stress such as high blood pressure, as well as by invading organisms, such as SARS-CoV-2. When targeted by a virus, the endothelium is harmed and responds to this by activating the

Figure 3
Chen, C.-M.; Lu, H.-C.; Tung, Y.-T.; Chen, W. Antiplatelet Therapy for Acute Respiratory Distress Syndrome. Biomedicines 2020, 8, Figure 2.

immune system (Figure 4). In addition, this call to arms increases tissue permeability causing further ease of viral transmission and leakage of cellular elements into the surrounding tissue as well as inflammation, which contributes to the overall severity of the disease.

Pro-inflammatory cytokines (immune system response agents) become elevated, which lead to a pro-coagulant state (blood clots), microvasculature leakage and organ ischemia (a reduction in blood flow that can lead to tissue death). The immune response can go into “overdrive” called “Cytokine Release Syndrome” (CRS) or commonly referred to as a “cytokine storm”. This is characterized by major increases in large numbers of pro-inflammatory cytokines. CRS was found to be a major cause of morbidity and mortality in patients with SARS and MERS (Middle East Respiratory Syndrome).

In particular, the increased pro-inflammatory cytokines associated with the current SARS-CoV-2 cause systemic impairment to the microcirculation with blood clots throughout the entire body, leading to dire consequences in the immediate period of infection such as pulmonary embolism and stroke, as well as in its aftermath. Clinicians have seen small increases in Troponin T (a lab test marker for cardiac muscle damage often found during heart attacks), and autopsies have found myocyte (cardiac muscle) damage brought on by small vessel inflammation (endotheliitis) and clots. Therefore, those who do survive COVID-19 may have long term cardiac consequences.

While the world waits for a vaccine or readily available treatments to combat this deadly illness, why not prepare ourselves by protecting our endothelium? Currently, medications such as dexamethasone, are used when SARS-CoV-2 has already wreaked havoc on the body by trying to curtail the inflammatory response and it’s cytokine storm; however, this is like trying to lasso in a herd of cows once they have long left the barn.

Studies into vascular endothelium with regard to cardiovascular disease have found that, in addition to a healthy diet and exercise, lowering your LDL cholesterol, and controlling hypertension, there are certain supplements that can help protect the endothelium from oxidative stress and increase the availability of nitric oxide (an important molecule for endothelial cell function). Perhaps, with a stronger and more resilient endothelium, the bad outcomes from COVID-19 infection could be avoided or lessened.

The supplements that support endothelial health are Vitamin C (400mg-2g), Vitamin D (600mg-5g), Magnesium (310–400mg), Co Q10 (150–300mg), Flavanoids (as in black tea, purple grapes, & natural cocoa, etc.), Resveratol (<1000mg).

(https://lpi.oregonstate.edu/mic/health-disease/endothelial-dysfunction)

Lipoic Acid, Soy Isoflavones and Vitamin E have varied results. Always consult with your physician before beginning any new regimen or taking new supplements.

As we try to live with the changes brought on by this disease, we are reminded by the phrase by Sir Frances Bacon: “knowledge is power”. By knowing more about the causes and outcomes of COVID-19, we can be better prepared for it, and hopefully, rise out of the pandemic unharmed.

  1. Deanfield John E., Halcox Julian P., Rabelink Ton J. Endothelial Function and Dysfunction. Circulation. 2007;115(10):1285–1295. doi:10.1161/CIRCULATIONAHA.106.652859

Cytopathologist and a Fine Needle Aspiration (FNA) Specialist

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