Grant: Project Grant

COVID-19, caused by SARS-CoV-2 has caused a worldwide pandemic. Male patients have a worse outcome compared to the females. COVID-19 infection leads to SARS but the cardiovascular (CV) system is also highly involved. This is because the molecule that mediates entry of SARS-CoV-2 virus, ACE2, is a protein that is widely expressed in multiple cells types, and is critical for optimal CV function. When the virus binds to ACE2, they both enter the cell (internalize), which leads to loss of ACE2 from the cell membrane and its protective effects. In addition, after entering the cell, SARS-CoV-2 triggers an inflammatory response and induces expression of another enzyme (disintegrin and metalloproteinase-17, ADAM17) that also cleaves ACE2, further depriving the CV cells from the beneficial effects of ACE2. Our research team has a strong background in understanding the function ACE2 and ADAM17 in CV diseases, and viral myocardial disease and immunity. We have also initiated collaborations with world-reknowned Vaccine and Infectious Disease Organization-International Vaccine Centre at U of Saskatchewan (Dr. Darryl Falzarano) who has established the novel and unique in vivo model of COVID-19 infection in hamster. In collaboration with Dr. Del Nonno, National Institute for Infectious Diseases (Rome, Italy), we have obtained heart specimens from deceased COVID-19 patients. In collaboration with our locals teams (NACTRC and CBSR), we have started to collect plasma from COVID-19 patients from the full spectrum of disease severity. Our proposed study takes a comprehensive approach that extends from in vitro cell culture, to preclinical animal model, to heart specimens and plasma from patients, to determine if ACE2 or ADAM17 can serve as biomarkers for CV complications in response to COVID-19, and to determine if inhibiting the heightened renin-angiotensin system, or inhibiting ADAM17, could protect against exacerbation of CV complications in these patients.