What kind of disease is COVID-19 really?
COVID-19 appears to be a vascular disease, rather than a type of respiratory disease caused by a cold virus. The new findings help to explain the multitude of seemingly unrelated complications of COVID-19 and could possibly enable the development of new therapies.
The characteristic spike proteins of SARS-CoV-2 not only help the virus infect potential hosts, they also play a key role in the disease itself. The experts from the University of California San Diego and the Salk Institute for Biological Studies determined that COVID-19 is actually a vascular disease and demonstrated how the SARS-CoV-2 virus damages and attacks the vascular system at the cellular level. The research group published the associated study in the English-language journal Circulation Research.
Is COVID-19 a respiratory disease?
“Many people think COVID-19 is a respiratory disease, but COVID-19 is actually a vascular disease. This could explain why some people have strokes and why some people have problems in other parts of the body. The commonality between them is that they all have vascular underpinnings,” reports study author Professor Uri Manor of the Salk Institute for Biological Studies.
While the findings themselves are not entirely surprising, the work provides clear confirmation and a detailed explanation of the mechanism by which the spike protein damages vascular cells for the first time, the team further explains.
Does spike protein damage vascular endothelial cells?
There is a growing consensus that SARS-CoV-2 attacks the vascular system, but exactly how it does so has been unknown. Researchers studying other coronaviruses have long suspected that the spike protein contributes to damage of vascular endothelial cells. The current study is the first to document this process.
Spike protein alone can trigger disease
In their study, the experts generated a type of pseudovirus that was surrounded by the classic crown of spike proteins from SARS-CoV-2 but did not contain actual virus. Exposure to this pseudovirus caused damage to the lungs and arteries in an animal model. This proves that the spike protein alone is sufficient to cause the disease. Tissue samples showed inflammation in the endothelial cells that line the walls of the pulmonary arteries, experts said.
Damage to mitochondria alone caused by spike protein
The team then replicated this process in the lab, exposing healthy endothelial cells (which line arteries) to spike protein. This showed that the spike protein damaged the cells by binding ACE2. This binding interfered with ACE2’s molecular signaling to mitochondria (organelles that generate energy for cells), causing mitochondria to become damaged and fragmented, the team explains.
Previous studies have already shown a similar effect when cells were exposed to the SARS-CoV-2 virus, but this is the first study to show that the damage occurs when cells are exposed to the spike protein alone, the experts explain.
“When you remove the replication capabilities of the virus, it still has a major damaging effect on vascular cells simply because of its ability to bind to this ACE2 receptor, the S protein receptor, which is now known thanks to COVID. Further studies with mutant spike proteins will also provide new insights into the infectivity and severity of mutant SARS CoV-2 viruses,” added Professor Uri Manor in a press release from the Salk Institute for Biological Studies.
Next, the team plans to study in more detail the mechanism by which the disrupted ACE2 protein damages mitochondria, causing them to change shape.