Coronavirus Breakthrough: Scientist Discover That Thrombosis In COVID-19 Caused By Localized Lung inflammation And Deficiency Of Protein S
Source: Coronavirus Breakthrough Sep 19, 2020 3 years, 7 months, 4 days, 18 hours, 16 minutes ago
Coronavirus Breakthrough: Researchers from University of Kentucky College of Medicine in a new study have discovered that as a result localized inflammation in the lungs, a deficiency of the anticoagulant protein S results that leads to thrombosis in COVID-19 patients. The localized inflammation also leads to elevated levels of tissue factor, a protein found in blood that initiates the clotting process.
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Protein S also known as S-Protein is a vitamin K-dependent plasma glycoprotein synthesized in the liver. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b-binding protein (C4BP). In humans, protein S is encoded by the PROS1 gene.
Protein S is partly homologous to other vitamin K-dependent plasma coagulation proteins, such as protein C and factors VII, IX, and X.
The best characterized function of Protein S is its role in the anti-coagulation pathway.
This new study may provide answers for why so many COVID-19 patients experience thrombosis, or the formation of blood clots that obstruct blood flow through the circulatory system.
The study was that led by Dr Jeremy Wood, Dr Zach Porterfield and Dr Jamie Sturgill from the Department of Internal Medicine; Dr Beth Garvy in Microbiology, Immunology & Molecular Genetics; and Dr Wally Whiteheart in Molecular & Cellular Biochemistry, suggests that localized inflammation in the lungs caused by COVID-19 may be responsible for the increased presence of blood clots in patients.
Importantly, the study also provides evidence suggesting the risk of thrombosis could persist after the infection clears.
The research examined the blood of 30 COVID-19 patients including 15 who were inpatients in the intensive care unit, and 15 who received care as outpatients at UK's Infectious Diseases Clinic, along with eight disease-free volunteers who acted as a control group.
It was found that when compared to baseline, the COVID-19 patients had elevated levels of tissue factor, a protein found in blood that initiates the clotting process.
Importantly patients also had reduced levels of protein S, an anticoagulant that helps prevent blood clotting.
The study team concluded that lung inflammation caused by COVID-19 is what leads to a decrease in protein S. This inflammation also causes immune and possible endothelial cell activation, which leads to increased tissue factor protein.
Dr Jeremy Wood from the department of internal medicine at the University ofKentucky College of Medicine told Thailand Medical News, “
What we have learned is that the clotting is not caused by anything systemic. Localized inflammation in the lungs is what's driving this whole process. With an increase in tissue factor and a deficiency in protein S, COVID-19 patients get more blood clotting without the ability to shut it down or control it."
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The research additionally showed that protein S levels remained low in some patients even after they tested negative for COVID-19, which suggests that blood clotting issues may persist after infection and long-term monitoring of thrombotic risk may be necessary.
Dr Wood warns this preliminary data could be a cause for concern. Certain viruses like HIV are linked to a long-term deficiency in protein S, which causes an ongoing risk of thrombosis in patients. It is not yet known if COVID-19 could cause a similar persisting protein S deficiency.
Dr Wood added, "Tissue factor and protein S are good markers to monitor for long-term thrombosis risk and the data suggest that we need to be monitoring these patients because we're not seeing these parameters corrected immediately."
The study team recently received a grant from UK's Center for Clinical and Translational Science (CCTS) to begin a longitudinal study to look at these levels in patients over the next year.
The team said, "This will help answer the question: will this risk remain like it is in the HIV patients or will it go away?"
Besides those earlier mentioned, additional collaborators include Dr Martha Sim, Dr Meenakshi Banerjee and Dr Hammodah Alfar from the Department of Molecular and Cellular Biochemistry; Dr Melissa Hollifield and Dr Jerry Woodward with Microbiology, Immunology and Molecular Genetics; Dr Xian Li with the Saha Cardiovascular Research Center; Dr Alice Thornton with the Division of Infectious Disease; and Dr Gail Sievert, Dr Marietta Barton-Baxter and Dr Kenneth Campbell with CCTS.
The study findings have yet to be submitted for publications in any preprint servers or journals yet.
