Severe COVID-19: Study Investigates A Possible Underlying Mechanism

New research has found a link between increased COVID-19 severity and higher blood levels of neutrophil extracellular traps (NETs). NETs usually help defeat infections, but in some COVID-19 cases, they may have something to do with disease severity.

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In a new study, researchers from the University of Michigan in Ann Arbor, Northwell Health in New York City, and Cold Spring Harbor Laboratory, also in New York, NY, have made a discovery that could help advance scientists’ knowledge about how COVID-19 progresses.

Their study paper, which appears in the journal JCI Insight, reports a link between experiencing a severe form of COVID-19 and having increased levels of NETs in the blood. NETs are networks of fibers made up of white blood cell DNA and proteins.

NETs have generated a lot of interest in the study of the immune system and inflammatory reactions. This is because they can act like a double edged sword — that is, they usually help fight infections, but sometimes, they can end up doing more harm than good.

NETs are extracellular networks of fibers that contain the DNA of neutrophils, a type of white blood cell whose main job is to react to infections.

These networks form as a result of a specific type of cell death called NETosis, which, the scientists explain, is “induced by bacterial breakdown products and inflammatory stimuli.”

‘A possible relationship’

In the new study, the researchers analyzed 84 serum (a blood component) samples from 50 people who had been hospitalized with COVID-19.

Firstly, the team found an association between COVID-19 and increased levels of NET markers.

“We found that patients with COVID-19 infection have higher blood levels of [NETs], which are a product of an inflammatory type of neutrophil cell death called NETosis,” says first study author Dr. Yu Zuo.

Then, the investigators wanted to verify whether or not NET serum levels were also associated with the severity of the disease. To do so, they compared 27 serum samples from people who had required ventilation due to severe COVID-19 with 24 samples from people who had had moderate or mild forms of COVID-19.

This revealed that people with severe COVID-19 appeared to have significantly higher levels of some NET markers, which may “suggest a possible relationship between [the] level of serum NETs and [the] severity of COVID-19,” according to the study paper.

Although NETs typically help fight off infections, when the body does not regulate them properly, they can lead to abnormal inflammatory responses and thrombosis (blood clotting) in the smallest vessels.

That is why the researchers hypothesize that NETs may have something to do with the severity of COVID-19. However, more in depth studies will need to confirm this.

“Our hope […] is that these findings will ignite further research into the role of neutrophil effector functions in the complications of COVID-19,” the researchers write.

In their conclusion, they also outline what they suppose may be the clinical relevance of their recent findings:

“As we await definitive antiviral and immunologic solutions to the current pandemic, we posit that antineutrophil therapies may be part of a personalized strategy for some individuals affected by COVID-19 who are at risk [of] progression to respiratory failure.”

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