Grant: Operating Grant: COVID-19 Rapid Research Funding Opportunity - Therapeutics

The clinical and scientific community are at a complete loss trying to understand what happens inside patients that are infected with SARS-CoV-2. They may have some clotting in blood, some platelet clumping and some inappropriate inflammation but what is causing this is unclear and so right now clinical trials are designed on best guesses on what is going on. If researchers could look inside the patients and had all the different cell types color coded, they would know exactly what is going on. Our team proposes to do this in special humanized mice so they behave much more like humans in response to SARS-CoV-2, in hamsters a natural animal model of SARS-CoV-2 and finally in human blood vessels and human lung organoids which are small versions of real human lungs that can be perfused with human blood from COVID-19 patients or infected directly with SARS-CoV-2. We have stained endothelium, neutrophils, platelets, monocytes, macrophages and NK cells different colors so we can watch using a special intravital microscope what each of these cells do during infections. These are the key responders during an infection and because there is clotting and platelet clumps forming and inflammation, we know that the lining of blood vessels the endothelium is likely involved in this inappropriate response. We will look at whether the immune cells and platelets are interacting to determine whether this leads to hyper-activation of the immune cells leading to the release of many toxic molecules into the blood stream. We have a number of lead compounds that we believe can prevent this from happening. Dr Paul Kubes leads this team of immunologists, virologists, pathologists, ICU doctors and lung specialists. Dr Kubes is one of maybe 2-3 labs in the world publishing on visualizing immune responses in lung infections in living animals and together with the various experts they will unveil the intricate problems SARS-CoV-2 causes and find therapies to cure this problem.