How does SARS-COV-2 virus infecting the respiratory system lead to kidney failure, heart attack as well as manifestations in the skin and brain? Studies suggest that sticky blood may be a contributing factor.
Blood clotting closes the vascular circuit to prevent leakage
The vascular system is a closed circuit in which blood is pumped throughout the body by the heart. It comprises a vast network of elastic vessels that in an adult human cover a surface area of 7m2. This network is built and maintained by specialised cells lining the surface of the vessels called endothelial cells. Endothelial cells regulate the flow of blood and control what can pass through the vessel walls. This is critical for the exchange of oxygen and nutrients between the blood and the tissues, but it also allows for immune cells to access the slight of infections.
When we fall and cut our knee, a wound appears on our skin and needs to be sealed quickly to avoid infections. Our body can sense the hole and clot it rapidly. Similarly, vessel leakage occurs when our blood vessels are damaged. This is a life-threatening event which can lead to oxygen deprivation in organs and induces irreversible damage. Therefore, it is essential for the body to rapidly respond to any injuries in the vessels. When damage occurs, it exposes signals at the surface of endothelial cells that are sensed by small particles called platelets and glue-like molecules (fibrin) to form a clot, or thrombus, that seals the leak and restores vascular integrity. This phenomenon is called ‘blood.
Sticky blood is observed in severe COVID-19
Over recent months several studies have tried to understand why some patients with SARS-COV2 infection will develop severe COVID-19 disease and have a high risk of mortality. While it is now clear that patients with pre-existing inflammatory conditions such as diabetes or hypertension are at higher risk of being critically ill, the link between these conditions and the severity of the COVID-19 symptoms remains unknown. By analysing the composition of the blood in patients with mild and severe COVID-19 symptoms, researchers found that signs of blood coagulation were increased in severe COVID-19 patients making the blood on these patients particularly sticky and therefore prone to clotting. (1).
Coagulation and inflammation are thought to cooperate to cause organ failure and death in patients with severe COVID19
In a recent study, post-mortem autopsies of patients who died from COVID-19 were conducted to understand how a virus infecting the respiratory tract can cause severe damaged to other non-respiratory . This study found the presence of blood clots in the small vessels of lungs of COVID-19 patients who died from respiratory failures. These clots are enabling the normal circulation of oxygen from the lung to the rest of the body. Most importantly, it also reveals that blood clots were found in other organs including the heart and the kidneys and likely contributes to multiorgan failure. It suggests that sticky blood is not only restricted to lungs where the infections is localised but can propagate to all organs in the body via the vascular system. To understand how the link between blood clots formation and the SARS-COV-2 infection, researcher analysed the cell composition of the clots under microscopy. They observed the presence of an immune cell called neutrophils which are usually not required to form blood clots. This was interesting because neutrophils are found in larger number in the lung and blood of severe COVID-19 patients compares to non-severe patients and fight virus infections. In the vessel clots, these neutrophils were found to form an unusual net structure with platelets causing the vessel obstruction.
To understand how these blood clots were forming, researchers analysed neutrophils and platelets from the blood of patients with mild or severe COVID-19 disease and found that neutrophils and platelet were spontaneously forming blood clots in severe COVID-19 patients. This suggested that in critically ill COVID-19 patients, neutrophils and platelets in the blood circulation are prone to propagate blood clots to other organs. This process in which the coagulation system and the immune system team up to create blood clots has been described in other severe pathologies and is known to aggravate tissue damage. Therefore, the researcher concluded that the clotting disorder observed in severe COVID-19 is most likely due the excessive inflammation observed in severe COVID-19 which results in the formation of blood clots that can propagate to other tissues through the vascular system. Thus, it likely explains why patients can develop a large array of symptoms ranging from skin and neurologic manifestations to cardiac or kidney deficiencies.
Further research is required to understand why hyperreactive neutrophils and platelet occurs in severe COVID-19 patients but the association between excessive coagulation and severe COVID-19 suggest that treatments suppressing blood clots which are already available could reduce mortality and organ damage in patients with severe COVID-19.