Targeting thrombotic and inflammatory processes associated with COVID-19
Summary
The US Centers for Disease Control and Prevention’s most recent forecast projects a total of 332,000 to 362,000 COVID-19 deaths by January 2, 2021. With over 15 million infected individuals in the U.S. alone, the health and economic impact of this disease on our society is unprecedented. The number of infected individuals and increased length of stays has placed an unparalleled demand on the healthcare system and front-line workers. The hospitalization rates from COVID-19 are especially higher for certain populations (such as patients over the age 65, Hispanic or Latino persons, non-Hispanic African American and American Indians) as well as for patients with co-morbidities (such as diabetes, hypertension). Although multiple COVID 19 vaccines are available and a few are already being tested in Phase 3 clinical trials, the ability to vaccinate a substantial part of the population to have any significant impact from the vaccines will not occur until late 2021. Therefore, there is an urgent need to develop therapeutic strategies that can be implemented quickly in the clinic to mitigate pathologies associated with COVID19.
The two major complications of COVID-19 are increased inflammation and increased blood coagulation (coagulopathy) particularly in the lung and both major causes of deaths among hospitalized patients. We intend to test 3 clinically relevant agents in a unique Syrian hamster model utilizing live SARS-Cov-2 infection, which demonstrates similar disease progression as that seen in COVID-19 patients. N-acetylcysteine, gamma-tocotrienol, and delta-tocotrienol have been previously demonstrated to reduce inflammation and decrease coagulopathies in numerous studies against different exogenous stressors. Since they have been either approved by FDA or have been in clinical trials for other indications, where preclinical safety studies have already been completed, these agents can be promptly re-purposed for alleviating the COVID-19 pathologies. Thus, successful results obtained from this project could have an immediate impact on COVID-19 patients and the overburdened healthcare system.