Targeting the Host Immune Response in COVID-19 via Adenosine-Mediated Immunomodulation
Abstract
COVID-19 pandemic has devastated our society and economy in the U.S. and worldwide. Over 4 million people have tested positive for COVID-19 globally and the death toll has now reached over 300,000, one-third of which are in the United States. COVID-19 is a complex emerging disease caused by the coronavirus SARS-CoV-2. COVID-19 patients can develop severe symptoms, which often lead to complications and death. Unfortunately, the number of available therapies for COVID-19 patients is currently very limited, making patient care extremely challenging. Vaccines are being studied, but there is no guarantee they will be fully protective even if successful. Our project aims to address the lack of therapies for COVID-19 by exploring new treatments that promote the action of our immune system against viral infections. The immune system is our body’s natural defense against viruses and other germs. This is composed by different cells that have specialized functions to recognize and neutralize germs. Mild viral infections are normally treated by addressing collateral symptoms, like fever and cough, while our immune system eliminates the virus. Antiviral drugs that directly interfere with the virus are occasionally used and these are not available for every viral infection. In COVID-19, SARS-CoV-2 viral infection disables our immune system, thus making it very difficult for our body to fight the infection. Compounds that affect a cell surface receptor called A2AR are being studied to enhance immunity to cancer. We propose to study the effect of selected compounds that act on A2AR and could promote and protect the immune system against the viral infection. We will test the effect of these compounds on specific immune cells and later in a mouse model for COVID-19 infected with human SARS-CoV-2. We will determine if any of these compounds are effective to enhance the response of the immune system against SARS-CoV-2 viral infection, promoting the recovery from COVID-19. Our work could provide the preclinical proof of concept for clinical studies that could transform the way we treat COVID-19 patients. Additionally, stimulating immune responses through A2AR may improve the efficacy of experimental vaccines. The proposed project addresses the FY20 PRMRP Topic Area of “Emerging Viral Diseases” by exploring new therapies that are applicable to COVID-19 and other emerging viral diseases. The findings that could emerge from our research could have a tremendous impact on the health care of COVID-19 patients and people affected by other severe infectious diseases. Therapies that act on the immune system have revolutionized cancer therapy and could do the same for the treatment of infectious diseases. Overall, our project aims to develop new treatments for COVID-19 and other infectious diseases as well as potential additives to experimental vaccines.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110078
Entities
People
- Giulia Monticone
Organizations
- LSU Health Sciences Center New Orleans
- United States Army