An explanation for multi-organ failure
Peter Carmeliet, a leading Belgian researcher in the field of vascular biology, has used these studies and his own laboratory experiments to hypothesize how the SARS-CoV-2 coronavirus attacks the endothelium and triggers the multiorgan failure seen in some patients.
As explained last May in the prestigious journal Nature Reviews Immunology, COVID-19 would progress in several phases:
In the first, as soon as the viral infection occurs, SARS-CoV-2 binds to the ACE2 receptor and infects endothelial cells in the lung capillaries. This affects the integrity of the endothelium and increases vascular permeability. Endothelial damage causes blood vessels to become more patent, promoting the appearance of pulmonary edema and respiratory failure.
The white blood cells are then directed to the “activated” pulmonary endothelium. The signaling molecules, generated by both the endothelium and the cells of the immune system that flock, would increase the damage done to the cells of the lung tissue. Some of those cells may even “commit suicide,” initiating a process called apoptosis.
To make matters worse, direct damage to the endothelium can be accompanied by other serious indirect consequences. Without going any further, disruption of the junctions between endothelial cells can trigger uncontrolled blood clotting. On the other hand, obstruction of the small capillaries by inflammatory cells, together with possible thrombosis in larger vessels, can cause ischemia (decreased blood flow) in the lung tissue, and even give rise to what is known as “Cytokine storm”.
Although inflammation and coagulation are essential defense mechanisms in the body, in COVID-19 its uncontrolled hyperactivation can cause irreversible and lethal harm to the patient.
What has been described so far could also explain why diabetes, high blood pressure and obesity are an important risk factor. In all three diseases the endothelium is damaged.
Treatments targeting the endothelium
Once the decisive role of endothelial cells in the most severe forms of COVID-19 has been confirmed, it is urgent to develop therapeutic strategies that protect it. In this regard, there are already pathophysiological foundations for using statins as an adjunctive treatment. Statins, present in the medicine cabinet of many houses, are known for their stabilizing effect on the endothelium and their ability to lower cholesterol, prevent clotting and prevent plaque formation in the arteries.
In addition, clinical trials are underway with various treatments to correct endothelial dysfunction. This is the case of drugs directed against angiopoietin-2, a protein involved in the generation of new blood vessels. Or bevacizumab, an antibody that can block uncontrolled activation of endothelial cells.
Although it is still early to have a definitive answer, everything points to the fact that treatments that avoid endothelial damage could be beneficial for COVID-19 sufferers.