The SARS-CoV-2 virus may contribute to the damage of small blood vessels in the heart as seen in severely-ill COVID-19 patients, without infecting them, a study shows. The research, published in the journal Clinical Science, indicates blocking antibodies could represent a new treatment to alleviate cardiovascular complications.
A multidisciplinary research team led by the University of Bristol, UK, analysed how SARS-CoV-2 interacts with heart cells causing the myocardial damage seen in COVID-19 patients. Until now, it remained unclear whether heart cells are infected by the virus or damaged because of an excess cytotoxic defence response.
This response, also known as the cytokine storm’, comes from our immune cells, whereby cytotoxic cells attack and kill the infected cells by releasing proteins, called cytokines. The study also investigated whether heart cells contribute to producing excess cytokines.
The team led by Professor Paolo Madeddu exposed human heart pericytes, which are cells that wrap small blood vessels in the heart, to SARS-CoV-2 Alpha and Delta variants, along with the original Wuhan virus. They found the heart pericytes were not infected.
In a second test-tube experiment, the researchers challenged the cardiac pericytes with only the spike protein — which the virus uses to enter and infect the cells — without the virus. The spike protein made pericytes unable to interact with their companion endothelial cells and induced them to secrete inflammatory cytokines, suggesting the spike protein is harmful to human cardiac cells.
The team found that antibodies blocking CD147 — a receptor for the spike protein — protected heart pericytes from damage. The findings suggest that SARS-CoV-2 can damage vascular cells without infecting them, according to the researchers.
Cleaved spike protein particles could also amplify the damage induced by the engagement of the full virion with vascular cells, they added. The researchers identified the presence of the SARS-CoV-2 spike protein in blood samples obtained from COVID-19 patients.
This opens the possibility that spike protein particles traveling through the circulation can reach a site distant from the respiratory system and cause systemic damage, they said. “Pericytes are essential cells of the heart, although their role in maintaining the structural integrity of the coronary vascular tree has emerged only recently,” said Elisa Avolio, the study’s first author from the Bristol Medical School.
“Our ongoing research on human cardiac pericytes indicates these cells co-operate with coronary endothelial cells during healing from a heart attack,” Avolio said. The study shows that the spike protein jeopardises this interaction and transforms pericytes into inflammatory cells.
The researchers noted that CD147 blocking antibodies could represent a new treatment to alleviate cardiovascular complications in COVID-19 patients. “Microvascular complications are frequent and harmful in patients with COVID-19, with up to 11 per cent of those hospitalised in intensive care units having myocardial damage or having suffered a heart attack,” Professor Paolo Madeddu, from the Bristol Medical School, added.
“Furthermore, people with pre-existing cardiovascular diseases are more likely to die of COVID-19,” Madeddu added.