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Principal Investigator: David J Erle
Organization: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
Fiscal Year: 2021
Award: $81,105
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY/ABSTRACT
COVID-19, the pandemic illness caused by the novel virus SARS-CoV-2, is a serious respiratory illness that
has high infectivity and a mortality rate that varies from <1% to up to 20% depending on underlying risk factors.
Indeed, disease severity varies markedly based on recognized clinical risk factors (age and co-morbidities).
The biological underpinnings of this clinical variability are unknown but likely relate to variation in both the virus
and the host response. A detailed understanding of the risk factors for severe disease, including genetic and
environmental factors and the nature of the host immunological response, is essential for the development of
prognostic biomarkers and effective therapies. To meet this urgent need we propose to help develop and to
participate in the IMPACC multi-center longitudinal clinical study of hospitalized patients with COVID-19 and to
immunophenotype participants using shared immunological methods that will be designed an carried out by
core laboratories at UCSF and at other participating institutions. Our specific aims are 1) to develop a
prospective observational convenience cohort of adult subjects hospitalized with known or presumptive
COVID-19, 2) to use this cohort to describe the relationship between specific immunologic assessments and
clinical course of COVID-19 in hospitalized patients, and 3) to implement three core laboratories at UCSF to
support immunophenotyping in this multicenter cohort. These core laboratories will perform bulk RNA
sequencing of blood peripheral blood mononuclear cells (PBMC), bulk metagenomic next-generation
sequencing (mNGS) on endotracheal aspirate samples, and serologic phage display assays (PhIP-Seq).
Successful completion of these aims will yield critical information regarding the relationship between viral load,
host immunological responses, and poor clinical outcomes that are urgently needed for biomarker
development and rational therapeutic targeting. In addition, the cellular samples banked in this study may
directly contribute to the development of neutralizing antibodies and vaccine strategies that will be our ultimate
defense against recurrence of this extraordinary pandemic. A rapid and robust scientific and medical response
of the type proposed by the NIAID and the academic community in this consortium is an essential element of a
broad response required to protect the health and well-being of all individuals, our health care system, and the
broader social structures that maintain global health and welfare.
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