James Weger-Lucarelli, research assistant professor in the Department of Biomedical Sciences and Pathobiology, has been awarded an NSF-EAGER grant to examine mouse hepatitis virus as a model for SARS-CoV-2, to identify the biomarkers, and to investigate the severity and transmission of the virus by integrating genotype, phenotype, and environment.

TITLE
EAGER: Integrating Genotype, Phenotype, and Environment to Identify Biomarkers of Coronavirus Disease Severity and Transmission

FUNDING AGENCY
National Science Foundation (NSF)

TOTAL AWARD
$300,000
Direct: $196,710
Indirect: $100,672

DURATION OF AWARD
2 years

KEY FACULTY PERSONNEL
PI
: James Weger-Lucarelli
Co-PI/Co-I: Tanya LeRoith, Sheryl Coutermarsh-Ott, and Lin Kang (Edward Via College of Osteopathic Medicine)

SIGNIFICANCE

Currently, no models to study the impacts of co-morbidities or identify biomarkers of disease severity or transmission on COVID-19 exist. The goals of this project are to define the impact of obesity, diabetes, and sex on disease severity and transmission in the context of different viral and host genotypes using a natural model. The two strains of mice display differential susceptibility to severe disease to the two strains of mouse coronavirus—from asymptomatic to 80% mortality. Furthermore, mouse coronavirus is highly transmissible mouse-to-mouse, which is unlikely to occur with SARS-CoV-2 infection in mice. Accordingly, this is an excellent model system with which to gather immunological, viral, and other data from infected mice to identify potential biomarkers of severe disease or transmission. Levels of MHV in the blood and oral passages, gene expression, cytokine levels, blood parameters, clinical disease, tissue pathology, and mortality will be the phenotypes used to compare to disease severity and transmission to identify associations. The hypothesis is that pro-inflammatory cytokines (notably IL-6, TNFa, and CXCL10) and concentration of virus in the blood or oral passages can be used to predict disease severity and transmission, respectively. These studies will increase understanding of the underlying biology of coronaviruses, virus and host interactions, the genotype, phenotype, and environmental factors influencing coronavirus disease and transmission. Finally, if funded, these studies may identify biomarkers to predict disease severity and transmission in people with COVID-19.