A group of researchers at the University of Alabama at Birmingham have claimed that high levels of plasmin (a protease) in the body may be the reason why those with comorbidities get severe COVID-19.
Plasmin is an enzyme that breaks down fibrin (a protein that forms mesh in a blood clot) and dissolves blood clots in the body. Those with severe COVID-19 show high levels of fibrin degradation products and platelets (blood cells that are involved in clotting) points to increased fibrinolysis (breakdown of fibrin).
The study, available before peer-review in March 2020, has now been published in the journal Physiological Reviews.
The research team is already enrolling volunteers to do clinical trials to affirm their findings.
Blood clotting, plasmin and COVID-19
Lung biopsies from COVID-19 patients have previously shown the presence of pneumonia, swelling, inflammation and fluid buildup. Damage to lung sacs (alveoli) and hemorrhage are seen in the interstitial space (area between the walls of alveoli and blood vessels) in the lungs in the later stages along with fibrotic clots (clots with scarring).
Presence of microthrombi (microscopic pieces of fibrin) and hemorrhage point to the imbalance between coagulation and dissolution of blood clots.
SARS-CoV-2, the causative agent of COVID-19, uses its spike protein to bind with the ACE2 protein present on the surface of host cells. The spike protein has two parts, S1 and S2. While S1 helps the virus bind with host ACE2, S2 helps it enter inside the cell.
The latest study suggests that plasmin may cleave furin-like sites present in the spike protein of the SARS-CoV-2 virus and increase the infectivity of the virus. Furin is an enzyme in the human body that converts certain inactive proteins into their active versions.
However, lab studies have shown that even in the absence of furin, other proteases like plasmin and trypsin can cleave the furin sites.
The study mentions that furin is only present in some types of alveoli cells while plasmin is present in both the alveoli cells as well as the airways and the endothelial cells (the cells that make the inner lining of blood vessels).
Possible drug and clinical trials
The researchers proposed that plasmin proteases may be used as drug targets for the treatment of COVID-19.
In a news release, the researchers pointed out that tranexamic acid (TXA), an inexpensive and FDA-approved drug that targets plasmin protease, is already being used to manage heavy menstrual bleeding. The drug has been used for long and is also given off-label for preoperative preparation of patients before various surgeries.
The clinical trial for the use of TXA for treating COVID-19 outpatients had started enrolling volunteers early in April. It is a double-blind placebo-controlled trial where the patients will either get a 1,300 mg pill of TXA thrice a day for five days or a placebo.
Another arm of the study will include patients who will be given anticoagulant drugs or a placebo. Any adult 19 years or above who have tested positive for COVID-19 can be enrolled in the study. The patients will also get the standard care for the disease along with TXA.
All the patients will be monitored for about a week to check if they have a lesser need for hospitalisation.
For more information, read our article on COVID-19 prevention tips for older people and those with comorbidities
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