Defining The Immune Response to SARS-CoV-2 in Aging

PROJECT SUMMARY / ABSTRACTThe rapid progression of the SARS-CoV-2 pandemic and associated COVID-19 disease in the first 3 months of2020 highlight the urgent need for research to understand the pathogenesis of the disease at the cellular leveland how the immune system responds to this infection. Although persons of any age and gender can be infectedand develop symptomatic disease, patients 60 years or older with or without co-morbidities are particularly proneto severe consequences of the infection ultimately leading to death. While data from all over the world arebeginning to give a better picture about the epidemiology and clinical progression of COVID-19, limitedinformation about the pathogenesis of the disease at the cellular level is available. A recent report showed thatthe SARS-CoV-2 viral spike protein (S) uses the SARS-CoV receptor ACE2 for binding and that the mammalianserine protease TMPRSS2 primes the S protein to allow viral fusion with the cell membrane and viral entry.However, little is known about how viral binding and entry affects specific immune cells, and what pathways areinvolved in the immune response to SARS-CoV-2 and whether differences in this immune response could explainthe increased propensity of individuals aged >60 to develop severe consequences of infection. We will begin toaddress this knowledge gap via a multi-omics approach using: 1) primary human PBMCs isolated from normalyoung and aged individuals and subsequently treated in vitro with the SARS-CoV-2 S protein or infected withSARS-CoV-2 and 2) samples from patients infected with SARS-CoV-2.