Blood: Neutrophil extracellular traps or the culprits for COVID-19 complications!

, July 2, 2020 /
PRNewswire/ -- An overactive defense response can lead to increased blood clots, disease severity and COVID-19 deathA phenomenon known as NETosis, in which infected cells release a mesh substance to trap invading viruses, is part of an increasingly active immune response in people who use ventilators and those who die from the diseasea team led by the University of Utah Health Research Center and PEEL Therapeutics, in collaboration with Cold Spring Harbor Laboratory and Weill Cornell Medical School, published a new study in the journal Blood"This study reveals to us the potential mechanism of COVID-19 lung damage, which was not previously considered a possible therapeutic target," said Elizabeth Middleton, M.D., a specialist in intensive care at the University of Utah Health Research Center who ledthe studyphoto source: Lauren Moulton
the study also reported that in laboratory experiments, a natural protein first found in the umbilical cord blood inhibited the mesh immune response, which could open up new avenues for treatmentit is estimated that up to 10% of PATIENTs with COVID-19 are in serious condition with respiratory distressThe cause of lung injury is a subject worthy of further study, and there is growing evidence that increased blood clots can lead to complications caused by illnessMiddleton, a health scientist at the University of Utah and senior author Christian Con Yost, M.D., and Joshua Schiffman, M.D., and colleagues studied whether a special immune response called NETosis was related to thisas part of the immune response, white blood cells release mesh neutrophil extracellular traps (NETs) to capture and kill pathogensWhile these NETs are usually beneficial, previous studies by Yost have shown that overactive NETs can exacerbate certain diseasesIn cases such as severe infections, NETs can clog blood vessels and cause damage to inflammatory tissuesto determine whether NETs caused complications in COVID-19, the team examined plasma from 33 patients and trachea in the lungsThey found that NETs activity was associated with the severity of the disease patients receiving life support and those who died from COVID-19 had significantly more signs of NETs activation than those with milder illness or continued recovery The NETs immune response is lower in healthy people THE LEVEL OF NETS CAN ALSO BE USED TO TRACK THE AMOUNT OF BLOOD OXYGEN LEVEL INDICATORS (INDEPENDENT INDICATORS OF DISEASE SEVERITY) , blood plasma from patients is also used to initiate NETs reactions In laboratory experiments, the plasma of PATIENTs with COVID-19 triggered the production of white blood cells in healthy patients, 50 times more than cells exposed to the plasma of healthy adults "This study may tell us that NETs levels in the blood may help predict the severity and mortality of COVID-19 disease," said Yost, an internal medicine specialist at the American University School of Health "In this pandemic, we urgently need more information about which patients will improve and which will worsen Larger studies are needed to determine whether NETs can become biomarkers of COVID-19 severity Importantly, we believe that overuse of NETs may be a cause of COVID-19 morbidity and mortality "
support this view, co-authors at cold spring harbor laboratories found that the blood vessels in the lungs of patients who died in COVID-19 were covered with mesh cell blocks, as well as a key blood cell used for clotting, the platelets Another recent study showed that platelets become abnormally active during the disease Investigations are under way to determine whether NETs and platelets increase COVID-19's blood clotting risk and other clinical manifestations photo source: Xue-Yan He and David Ng, Egeblad Lab Cold Spring Harbor Lab lab "In COVID-19, thrombosis is the leading cause of death So our findings tell us that we should learn more about the role of NETs in coagulation in COVID-19," said Dr Mikala Egeblad, a cancer researcher at Cold Spring Harbor Laboratory "Thrombosis is also the leading cause of death in patients with advanced cancer, as there are also elevated levels of NETs in the blood of patients with advanced cancer So I think what we learned from COVID-19 will help us treat other diseases, including cancer "
, laboratory experiments have shown that a small protein called "neonatal NETs inhibitor" (nNIF) found in neonatal cord blood inhibits the hyperactive NETs reaction of white blood cells treated with plasma in PATIENTs with COVID-19 The peptide is thought to protect babies from harmful inflammation early in life, explains Schiffman, CEO of PEEL Therapeutics His company is evaluating whether the protein can be used as a basis for clinical treatment "There is a natural treatment in the blood of newborn babies that prevents inflammatory events that we believe may lead to the death of PATIENTs with COVID-19," Schiffman said This targeted method of blocking NETs may be more effective and have fewer side effects than other drugs currently being tested in patients with COVID-19 that block the entire immune system references: Clues to COVID-19 Complications come from NET-likey Elizabeth A Middleton et al, Neutrophil Extra Trapcellulars (NETs) Contribute to to Ebele Sembo S Brembos in COVID-19 Saud Sien.
co.uk DOI: 10.1182/blood.2020007008