Host Mediator Modulation in COVID-19

Summary: I review the clinical features of acute COVID-19 briefly before illustrating the clinical stages of COVID-19. The stages of COVID-19 matter A LOT because therapies are optimized according to patient stage. The early pre-clinical stage is the arena for primary prevention by behaviours and use of vaccination. The early viral stage is managed with anti-virals and antibodies. Some have recently suggested a role for anti-inflammatory agents early, but this is uncertain. The later hospitalization stage is when anti-inflammatory and immune modulators appear to play a role. I then review important host mediators in COVID-19, the classes of host mediators and the strategies for mitigating some of the aberrant host-mediated responses to COVID-19. I choose several classes of mediators and review prominent trials of host mediators, prominent for efficacy and prominent for design features. I present an update on our BC-grown international CIHR-funded ARBs CORONA program and present results of plasma renin angiotensin (RAS) components and proteomics studies, preliminary results of our pan-Canadian COVID-19 cohort evaluation of angiotensin receptor blockers (ARBs) in COVID-19, related meta-analyses (acute cardiac injury and acute kidney injury in COVID-19) , and an update of our recently launched international pivotal randomized controlled trial of an ARB (losartan) vs. usual care in adults hospitalized with COVID-19. Generic losartan is $0.25-0.50 per day, so if it proven effective, it could be used globally. I close with a future vision of COVID-19 prevention, care, and follow-up. Presenter: Dr. Russell is Professor of Medicine at University of British Columbia (UBC) and a Principal Investigator in the Centre for Heart Lung Innovation (HLI) at the University of British Columbia and St. Paul’s Hospital where he focuses on septic shock and COVID-19 research. He is on the editorial board of 5 journals, has 290 peer-reviewed publications, 277 international presentations, 45 chapters (including the chapter on septic shock in Cecil Medicine), 200 abstracts and 12 patents. Dr. Russell has four major current themes of research (1) randomized controlled trials in patients with septic shock and (2) the genomics and pharmacogenomics of septic shock. He is now developing two new themes (3) the renin angiotensin system (RAS) in COVID-19 and (4) operating characteristics and predictive value of short-term versus long-term outcome measures in sepsis. Dr. Russell’s research highlights (1) direct high impact on care of critically ill septic patients around the world, (2) publication in high impact journals, and (3) most important, illustrate the fundamental strategy of his research career, the successful coupling of expertise in clinical trials with biobanking and discovery of novel biomarkers that explain mechanisms of therapies in sepsis.

BC CDC Presenters

12/1/2020 8:00:00 PM