Scientists are still learning about SARS-CoV-2, and the illness it causes, COVID-19. While we know a lot about how the virus infects cells and what the viral genome is, there are still many questions about how it causes illness, both in the short- and long-term, and how to treat the disease. SARS-CoV-2 is known to damage blood vessels, and sometimes organs. Research has now suggested that the cells that line the tiniest blood vessels are damaged during COVID-19, and the consequences of that damage may be very serious. The findings have been reported in Nature Communications.
The study authors have been comparing blood samples from healthy individuals to those who have have COVID-19 since the start of the pandemic. They were intrigued by some clinical observations of people who had severe COVID-19 cases; their blood became unusually thick. There were clotting abnormalities in both adult and pediatric patients, and in adults, one pathway related to blood flow and vessel health stood out in the adults, said senior study author Cheryl Maier, MD, PhD, an assistant professor at Emory University.
The study authors created models of the tiny blood vessels using microfluidic devices, and used them to compare the likely characteristics of blood flow in COVID-19 patients and healthy individuals. Videos from the devices show the real-time impacts of the virus in blood vessels, said Maier. "These lab-made blood vessels are lined with real human vascular cells called endothelial cells. You can put in plasma and red cells, any of the key components of blood. and in different combinations to watch how it behaves and see how the damage happens."
Previous work has shown and confirmed that in severe COVID-19 patients, levels of a protein called fibrinogen are abnormally high in blood, even compared to other disease states in which fibrinogen is elevated. Fibrinogen forms fibrin as the body generates blood clots, but fibrinogen was not thought to create clots directly, and anti-clotting agents don't affect fibrinogen levels.
This study showed, however, that the excess of fibrinogen in COVID-19 patients can indeed trigger red blood cell clumping that alters blood flow and damages a protective lining in microvessels called the endothelial glycocalyx.
"Fibrinogen is one of the top three most abundant proteins in plasma," Maier said. "It's been hiding in plain sight."
When plasma from COVID-19 patients was combined with red blood cells in the blood vessel model, clumping could actually be seen, and damage to the glycocalyx could be measured.
Maier suggested that the clumping caused by high fibrinogen levels and subsequent damage in microvessels may be the primary driver of organ damage and death from COVID-19.
No existing medications target high fibrinogen levels in the blood for reduction, but this study also showed that if plasma that is high in fibrinogen is removed from COVID-19 patients and replaced it with donor plasma, it may be possible to reduce fibrinogen levels and treat disease. Hundreds of people still die from COVID-19 every week, and this work could help save lives.
Sources: Emory University, Nature Communications
