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

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Principal Investigator: Joren C Madsen
Organization: MASSACHUSETTS GENERAL HOSPITAL
Fiscal Year: 2020
Award: $361,494
Funding agency: National Institute of Allergy and Infectious Diseases

PROJECT SUMMARY / ABSTRACT
The rapid progression of the SARS-CoV-2 pandemic and associated COVID-19 disease in the first 3 months of
2020 highlight the urgent need for research to understand the pathogenesis of the disease at the cellular level
and how the immune system responds to this infection. Although persons of any age and gender can be infected
and develop symptomatic disease, patients 60 years or older with or without co-morbidities are particularly prone
to severe consequences of the infection ultimately leading to death. While data from all over the world are
beginning to give a better picture about the epidemiology and clinical progression of COVID-19, limited
information about the pathogenesis of the disease at the cellular level is available. A recent report showed that
the SARS-CoV-2 viral spike protein (S) uses the SARS-CoV receptor ACE2 for binding and that the mammalian
serine 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 are
involved in the immune response to SARS-CoV-2 and whether differences in this immune response could explain
the increased propensity of individuals aged >60 to develop severe consequences of infection. We will begin to
address this knowledge gap via a multi-omics approach using: 1) primary human PBMCs isolated from normal
young and aged individuals and subsequently treated in vitro with the SARS-CoV-2 S protein or infected with
SARS-CoV-2 and 2) samples from patients infected with SARS-CoV-2.

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