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WesternU researchers developing better understanding of COVID-19

by Rodney Tanaka

June 19, 2020

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WesternU Senior Vice President for Research and Biotechnology Devendra K. Agrawal, PhD, MBA (Jeff Malet, WesternU)

Researching COVID-19 to develop treatments is a global effort, and Western University of Health Sciences is contributing to this scientific knowledge. WesternU faculty recently published two separate articles investigating COVID-19.

WesternU Senior Vice President for Research and Biotechnology Devendra Agrawal, PhD, MBA, and Assistant Professor in Tissue Engineering and Regenerative Medicine Finosh Thankam published Thankam FG, Agrawal DK, Molecular chronicles of cytokine burst in COVID-19 patients with cardiovascular diseases in The Journal of Thoracic and Cardiovascular Surgery (2020), doi: https://doi.org/10.1016/j.jtcvs.2020.05.083.

Apart from the respiratory system, COVID-19 displayed severe pathological impact on other organs, especially in the cardiovascular system as evident from the increased risk of infection and mortality among cardiovascular disease (CVD) patients, according to the article. The paper provides insight into the possible molecular targets to intervene the effects of COVID-19-induced exacerbations and complications in CVD patients. The paper concludes that further understanding of these molecular mysteries in ideal in-vitro and in-vivo models would open novel translational avenues for effective management of COVID-19-CVD comorbidity.

“Although several viruses and bacteria often encode proteins that interfere with the immune system to promote pathogenesis, it appears that the inflammasome activation due to SARS-CoV-2 envelope proteins results in a robust pro-inflammatory response leading to high mortality rates,” Agrawal said. “Currently, there is no effective treatment. However, identification of key targets to intervene should accelerate the development of novel therapeutic approaches.”

Two Australian doctors published a commentary on Agrawal and Thankam’s article, emphasizing the importance of attaining a mechanistic understanding of the molecular and cellular pathophysiology of COVID-19 disease. Commentary: Evolving understanding of COVID-19: molecular biology, immunology and surgery. Edward Buratto, Igor E. Konstantinov DOI: https://doi.org/10.1016/j.jtcvs.2020.05.087 Published online: June 6, 2020.

WesternU Senior Vice President and Provost David Baron, DO, MSEd

WesternU Provost and Senior Vice President David Baron, DO, MSEd, co-authored a review of remdesivir as a COVID-19 treatment. Musa, A., Pendi, K., Hashemi, A., Warbasse, E., Kouyoumjian, S., Yousif, J., et al. (2020). Remdesivir for the Treatment of COVID-19: A Systematic Review of the Literature. Western Journal of Emergency Medicine: Integrating Emergency Care with Population Health. Retrieved from https://escholarship.org/uc/item/9z6961f2

Remdesivir, an anti-viral prodrug originally developed to treat Ebola virus disease, has shown broad spectrum activity against the Coronavirus family. A recent case report reported improvement of clinical symptoms with remdesivir in a patient with COVID-19, according to the paper. After conducting a systematic search of 18 clinical trial registries and three large scientific databases, the authors conclude that despite supportive data from in vitro and in vivo studies, the clinical effectiveness of IV remdesivir for treatment of COVID-19 and potential side effects remain incompletely defined in the human population.

The paper was submitted April 11, 2020 and accepted May 1. Studies on COVID-19 are moving rapidly, and therefore the knowledge base is constantly evolving. Baron and his collaborators followed up with an Addendum to Systematic Review of Remdesivir for the Treatment of COVID-19, electronically published May 22, 2020, which analyzes the results and conclusions of new publications. On May 1, based on two recent trials, the ACTT and Gilead open-label trial, the U.S. Food and Drug Administration issued an Emergency Use Authorization (EUA) for use of remdesivir for COVID-19.

“Physicians may find it difficult to make informed decisions regarding treatment of patients with COVID-19,” according to the addendum. “Given the recent EUA, we recommend making the decision to administer remdesivir based on the highest quality of evidence in the literature, which suggests decreased time to recovery and the possibility of increased survival.”

“The disruption COVID-19 has created has resulted in an unprecedented time urgency to develop a vaccine and safe and effective therapeutics,” Baron said. “Now, more than ever, it is important to remain focused on quality clinical research to determine optimal treatments to achieve health and safety for patients worldwide.”

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