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According to the scientific team, an increase of fibrinolysis could be achieved by increasing ACE, or by administering T4. Fibrinolysis is the breakdown of fibrin in blood clots and T4 has been shown to prevent actin from binding to fibrin, which is a major component of blood clots. Blood clots in the blood stream and organs of patients with COVID-19 have been shown to lead to extensive morbidity and patient death.
The researchers also found that COVID-19 elevates bradykinin levels in multiple tissues and systems that cause significant increases in vascular dilation, vascular permeability, and hypotension in infected patients. Previous studies have shown that elevated bradykinin levels induce pain and cause blood vessels to expand and become leaky, that can lead to swelling and inflammation of the surrounding tissue. This bradykinin-storm in COVID-19 patients induces leakage of fluid into the lungs and excessive release of hyaluronic acid preventing oxygen uptake and carbon dioxide release in the lungs of severely affected COVID-19 patients. These bradykinin-driven outcomes suggest that a bradykinin storm may be responsible for many of the more severe symptoms of COVID.
In their study, the researchers also looked at differences in male/female morbidity and mortality and noted a number of interesting points linked with other studies. It is known that older age and a high number of co-morbidities are associated with increased severity and mortality in patients with COVID-19 and other similar infectious viruses such as SARS. They reported that age was comparable between men and women in all data sets. In the case data series, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.
'That men with COVID-19 are 2.4 times more likely than women to die from the virus is extremely interesting because the gene for Thymosin beta 4 resides on the X chromosome. Women have two X chromosomes while men only have one. As the researchers suggested, this could explain the lower incidence of COVID-19 induced mortality in women because it is found on the X chromosome and escapes X-inactivation. Women, therefore, would have increased levels of T4 compared to men; thus, the possible explanation why women have an improved chance of survival. If true, then administering pharmacological levels of T4 to COVID-19 patients may significantly reduce morbidity and improve survival,' stated Dr.
'Additionally, the potential impact of T4 in the treatment of COVID-19 merits further consideration as this, and other published studies, have shown T4's ability to not only down-regulate inflammatory chemokines and cytokines and proinflammatory processes such as the bradykinin storm, but also increase fibrinolysis and accelerate wound repair in the heart, lungs, kidneys and other organs that are often affected by COVID-19 infection. Moreover, previously published data have demonstrated a significant decrease of T4 in blood, tears, and saliva with age in humans. Thus, finding a way to control and dampen this 'storm' may be the key to successfully treating COVID-19 patients, especially in older and more vulnerable patients,' said
The research, entitled A mechanistic model and therapeutic interventions for COVID-19 involving a RAS-mediated bradykinin storm, was published in eLife 2020;9:e59177 DOI: 10.7554/eLife.59177. The research was conducted by Michael R Garvin et al., at
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RegeneRx is focused on the development of novel therapeutic peptides, including Thymosin beta 4 (T4) and its constituent fragments, for tissue and organ protection, repair, and regeneration. RegeneRx currently has three drug candidates in clinical development for ophthalmic, cardiac/TBI and dermal indications, four active strategic licensing agreements in the
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