Grant: Op. Gr.: Addr. the Wider Impacts of COVID- Exacerb. of disp. among marg. pops.

Inflammation is a key aspect of the disease process in COVID-19. Older persons are at greater risk for severe COVID-19 due to the negative or adverse convergence of aging and inflammation. The consequences of COVID-19 on the brain are uncertain but we know that over 25% of people who recover from COVID-19, subsequently experience brain problems including memory, language, concentration, sleep and mood disabilities (www.cbc.ca/player/play/1970781763780). It is also unclear to what extent brain damage occurs during acute COVID-19 and its contribution to long term consequences of COVID-19, termed 'long covid' or post-acute sequelae of COVID-19 (PASC). Nonetheless, these brain disabilities can prevent people with PASC from returning to work and regular day-to-day activities together with causing depressed mood, social isolation and increased use of the healthcare system. Our proposed research will examine the fundamental disease mechanisms in the brain during COVID-19 using autopsied brain tissues and a mouse model of COVID-19. In people with PASC, we will study the frequency, severity, types of brain function abnormalities using psychological testing. In addition, we will discover risk factors and signs of brain abnormalities measured in the blood in relation to aging and brain resilience or adaptability that can guide diagnosis and treatments. We are a multidisciplinary team and are comprised of early, mid, and senior clinical and experimental researchers with unique expertise in Canada. In fact, our preliminary data show marked inflammation in the brains of humans dying with COVID-19. These proposed studies will discover the disease pathways that cause the brain function abnormalities in people with PASC and will lead to a better understanding of PASC-associated brain problems and new treatment approaches.