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Severe COVID-19 infections may be caused by overactive immune cells

Experts are urgently investigating whether overactive immune cells are to blame for the most severe cases of COVID-19 infection. 

Eleven international medical research organizations have teamed up to form a consortium known as the NETwork.

In a paper published today, the researchers describe the late stage of severe COVID-19 infection, which is characterized by pulmonary inflammation, Acute Respiratory Distress Syndrome (ARDS), thick mucus secretions in the airways, extensive lung damage, and blood clots. Patients with these complications require invasive mechanical ventilation and many are still unable to survive. 

The NETwork has found evidence that the worst cases of COVID-19 may result from overactive white blood cells known as the neutrophils. 

Triggered by the body’s immune system, neutrophils can expel their DNA to attack bacteria with a gauzy web of DNA that contains toxic enzymes, called a NET. 

Although NETs can bind and kill pathogens, they can also cause damage to the lungs and other organs. 

“Given the clear similarities between the clinical presentation of severe COVID-19 and other known diseases driven by NETs, such as ARDS, we propose that excess NETs may play a major role in the disease,” said study co-author Dr. Betsy Barnes. “As samples from patients become available, it will be important to determine whether the presence of NETs associates with disease severity and/or particular clinical characteristics of COVID-19.”

Study co-author Dr. Mikala Egeblad is a cancer biologist at the Cold Spring Harbor Laboratory who organized NETwork research group.

“NETs were identified in 2004, but many scientists have never heard of them. Most of the researchers in the NETwork have worked on NETs in other diseases, and when we started hearing about the symptoms of the COVID-19 patients, it sounded familiar,” explained Dr. Egeblad.

Dr. Jonathan Spicer is a thoracic surgeon who has witnessed the devastating effects of COVID-19 infection firsthand. 

“We see in these patients severe lung damage known as ARDS, another serious problem caused by excess NETs and seen in cases of severe influenza,” said Dr. Spicer. 

“In addition, their airways are often clogged with thick mucus and unlike most severe lung infections, these patients tend to form small clots throughout their body at much higher rates than normal. NETs have also been found in the blood of patients with sepsis or cancer, where they can facilitate the formation of such blood clots.”

If the researchers conclude that excess NETs are causing the severe symptoms of COVID-19, new treatments may be deployed to help COVID-19 patients recove. Treatments that are currently used in other NET-driven diseases may inhibit the activity of NETs in COVID-19 patients, which may reduce the need for invasive mechanical ventilation.

The study is published in the Journal of Experimental Medicine.

By Chrissy Sexton, Staff Writer


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