ASBTRACT Overview
Every day, Californians continue to experience high levels of exposure to the novel severe acute respiratory
coronavirus 2 (SARS-CoV-2) virus. There is an ever-growing urgent need to better understand the nature of
exposures, course of illness and recovery, and potential for immunity among persons at particularly heightened
risk for the worst COVID-19 outcomes. As part of a rapid scientific response to the present public health crisis,
we convened on March 18, 2020 a collaborative of frontline clinicians and scientists to form the Coronavirus Risk
Associations and Longitudinal Evaluation (CORALE) studies (corale-study.org). We established two base study
cohorts with enrollment centered on (i) patients with suspected or confirmed COVID-19 treated in our health
system (currently N>8,300) and on (ii) healthcare workers directly or indirectly involved in delivering their care
(currently N=6,679). In response to NIH RFA-CA-20-038, we are now highly motivated and prepared to leverage
our existing infrastructure to directly address the critical need for comprehensive longitudinal data collection and
analyses to advanced our understanding of SARS-CoV-2 risks, the course of disease, the nature of recovery,
and the potential for immunity across populations at risk. By establishing the CORALE-SeroNet U54 program,
our goal will be to form a robust and sustainable structure of academic activities centered on investigating the
responses elicited by SARS-CoV-2 exposure and the extent to which carefully phenotyped clinical and molecular
profiles can signal robust immune reconstitution and complete functional recovery. Our study will be centered
on the ethnically/racially diverse population served by our health system in Los Angeles, given then critical need
for more knowledge regarding the determinants of COVID-19 related risks in these minority subgroups. Our
scientific objectives will be achieved by an outstanding collaborative team of clinician-scientists, epidemiologists,
immunologists, basic and translational scientists, analytical chemists, and biostatisticians. Leveraging our
collective experience, resources, and infrastructure at major academic institutions from across Southern
California (Cedars Sinai, UCSD, UCLA, and USC), we will advance the scientific enterprise through the three
distinct yet closely integrated research Projects: Project 1 will elucidate the natural history and longitudinal
trajectories that represent the diversity of SARS-CoV-2 exposure, infection, recovery, and clinical immunity
patterns across the spectrum of persons at risk. Project 2 will investigate the determinants of SARS-CoV-2
response in persons with altered innate immune function, with a focus on individuals with pre-infection
susceptibility traits (e.g. metabolic disease states); and, Project 3 will investigate the determinants of SARS-
CoV-2 response in persons with altered adaptive immune function, with a focus on individuals with immune-
altered status arising from select malignancies, autoimmune disease, and/or their directed therapies. As a whole
this research program will integrate population, clinical, translational, and basic science resources with a world-
class investigator team to meet the urgent need for new mechanistic insights and therapeutic approaches to
address key knowledge gaps regarding SARS-CoV-2 susceptibility and potential for immunity.