Studies link NETs to severe COVID-19: All you need to know about neutrophil extracellular traps
Studies have shown that in people with severe COVID-19, the neutrophils get strongly activated and adopt a low-density phenotype.
As per an interview of the CEO of Serum Institute of India, Adar Poonawalla, on 14 September 2020, there likely wouldn’t be enough vaccines against COVID-19 for everyone until the end of 2024. Until immunisation is available for everyone, all that can be done is to try and treat the patients suffering from severe symptoms and complications of the infection.
While some people get minor flu-like symptoms of the disease, others suffer from severe life-threatening complications. The severity of COVID-19 has previously been associated with older age, comorbidities, weaker immune systems and more.
Additionally, some scientists have found that excessive release of Neutrophil extracellular traps (NETs) in the lungs and blood vessels is one of the factors that increase the severity of COVID-19 disease.
What are Neutrophil extracellular traps?
Neutrophils are one of the components of white blood cells (the natural immune cells of the body), which jump into action when there is any threat to the body. But if these immune cells become overactive, they can wreak havoc in the body, mostly seen in the form of autoimmune or chronic inflammatory diseases.
These activated neutrophils also have the ability to form NETs, which are web-like structures, rich in host DNA, that contain modified histone proteins (proteins that condense the DNA structure) and granule proteins such as neutrophil elastase and myeloperoxidase.
Neutrophil elastase stimulates the release of mucus and other inflammatory cells whereas myeloperoxidase is released during the state of inflammation. Neutrophil granule proteins have been involved in a number of chronic inflammatory conditions and diseases.
Why is the excess release of NETs dangerous for COVID-19 patients?
It has been seen that excessive release of NETs chokes the blood vessels, which disturbs the microcirculation of blood and may result in organ damage.
Studies have shown that in people with severe COVID-19 , the neutrophils get strongly activated and adopt a low-density phenotype. Low-density phenotype allows the spontaneous formation of NETs.
This presence of NETs in blood vessels can lead to the formation of fibrin-rich clots which can result in thrombosis and even lung damage. An excessive amount of NETs also causes hyperactivation of the immune system resulting in a cytokine storm, which is marked with the presence of numerous inflammatory cells in the body that can end up damaging the vital organs.
Presence of NETs in COVID-19 patients
It has already been noted that hospitalized patients of COVID-19 show infiltration of neutrophils in their lungs. While initially it was thought to be a sign of immune activity, it turned out that the neutrophils were releasing NETs, which are contributing to a wide range of infectious or noninfectious diseases.
A recent study published in the Journal of Experimental Medicine on 14 September 2020, showed the presence of NETs in patients who died due to severe complications of COVID-19 . Dr Coraline Radermecker, the first author of the study, stated that the presence of NETs was seen in three different regions of these patients. The major proportion of NETs was seen in the airway compartment of the patients, then in the interstitial compartment (the space between blood capillaries and cells). The researchers further found the NET-rich zones in the blood vessels of the lungs, particularly seen in the arterioles along with the presence of small clots of platelets, fibrin and red blood cells.
Another study published in The Lancet on 1 August 2020 also showed congestion in the micro-blood vessels due to aggregation of NETs in the deceased patients of COVID-19 .
With all these research studies, scientists conclude that NETs can be formed in the lungs if the person is suffering from an infection caused by respiratory viruses. Moreover, these NETs also have the ability to result in severe forms of COVID-19 , presenting with lung damage, thrombosis (formation of a blood clot in the blood vessel) and fibrosis.
For more information, read our article on Cytokine storm.
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