VIDEO: Why does COVID-19 damage vascular beds?

"At the outset of COVID-19, everyone thought it was just pneumonia, but even if you look at the early data from the outbreak in Wuhan, China, a substantial minority of patients had cardiovascular involvement," Libby said. "It is not just pneumonia, it is a cardiovascular disease."

The SARS-CoV-2 virus causes thrombosis throughout the body and has caused issues with the heart in the form of myocarditis, pericarditis and arrhythmias. The clotting issues can manifest as heart attacks, stroke, pulmonary embolism, organ ischemia or infarcts and deep vein thrombosis (DVT). 

Libby said the big question has been what is the cause of the clotting and cardiac issues and how to address these issues in both acute and long-COVID phases. 

"The best evidence we have today by my read is that this is not caused by a direct infection with a cytopathic connection to the virus in the myocardial cell, but an effect largely on the blood vessels," Libby explained. 

He said the ACE2 receptors of the virus can be found on the pericytes that surround the small blood vessels in the heart in infected patients.

"There is now a lot of emerging evidence that there is a lot of microvascular thrombosis that can contribute to myocardial damage and dysfunction in the acute phase, and even in the chronic phase," he explained. "Even five months later, we can still see disturbances in the microvascular function when we do sophisticated nuclear medicine tests. So part of the long-COVID mystery may be due to microvascular damage."

Libby has studied the impact of infections on endothelial function since the 1980s and how it can cause inflammation in arteries that facilitates atherosclerosis. Bacterial infections can release endotoxins in cells that lead to and inflammatory response. Viruses can cause pathogen-associated molecular patterns (PAMPs), which causes some of the same effects as endotoxins. 

"What we learned early on is that when we activate these pathogen-associated molecular patterns, we trigger a coordinated series of changes in the endothelial surface. There are only a few surfaces, synthetic or natural, that can maintain blood in a liquid state in prolonged contact. When we expose the endothelial lawyer of blood vessels to these PAMPS, we flip from the hemostatic, anticoagulant, pro fibrinlytic, anti-inflammatory, vasodilatory set of functions of a normal endothelium to just the opposite," Libby explained. 

However, knowing the source of the clotting issues and vascular damage in COVID patients has not been enough, and there have been big disappointments in research efforts to solve how to best treat or what drugs to use as prophylaxis for the thrombosis issue.

While most centers use standard anticoagulation or antiplatelet protocols in COVID patients, Libby said this has not been effective in all patients.

"That has been sobering when we try to translate this endothelial biology to practice," he said. 

For most inpatient COVID admissions, the standard of care is to given them heparin, but in more severely sick patients anticoagulation is not always effective.

For patients with long-lasting COVID symptoms weeks or months after infection, he said there is still ongoing research own how to best treat these patients. Paxlovid has been shown to help diminish symptoms, and Libby said it is possible other antivirals and monoclonal antibody treatment may help diminish damage and symptoms.

Long-term, he has concerns that some patients are found to have small areas of fibrosis in their hearts on MRI that may lead to arrhythmias or other issues years after their infections.

While research to help patients continues, Libby said prevention of COVID needs to be priority for all cardiologists.  

"The bottom line is all of us need to do our utmost to get our patients vaccinated, get them boosted and to prevent the disease because we have no idea what the Pandoras box will be for the long-term consequences of COVID, and I can think of several scenarios where they can be considerable for the cardiovascular system," Libby stressed.