# Genetic Analysis of COVID-19 Susceptibility and Resistance Determinants in the Collaborative Cross

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $748,384

## Abstract

Abstract:
The 2019 nCoV (SARS-CoV2 or nCoV2) is currently causing a global pandemic, and is on track to cause millions
of infections, hundreds of thousands of deaths, and significantly disrupt healthcare systems and economies
globally. nCoV2 is a group 2B coronavirus that is 75% identical to Severe Acute Respiratory Syndrome
Coronavirus (SARS-CoV), which emerged in 2003. Approximately 10% of nCoV2 infections result in COVID-19
pneumonia that progresses to acute respiratory distress syndrome (ARDS), while a significant fraction of other
individuals are asymptomatic or develop mild disease. While age, gender, and underlying health conditions
predispose individuals to severe disease/death, we have a poor understanding of the factors that drive disease
outcome. This knowledge is essential for understanding the pathogenesis of COVID-19, and for
developing and testing safe and effective nCoV vaccines and therapies. However, while patient studies
can provide insights into the disease risk factors, mechanistic analysis of these factors will require robust animal
models of COVID-19 disease. Unfortunately, nCoV does not replicate in standard laboratory mice, and a
significant need exists for new animal models that reproduce human-like COVID-19 disease, including ARDS.
Collaborative Cross (CC) mice vary significantly in their response to SARS-CoV, and we were able to take
advantage of this variation both to develop new models SARS-CoV-induced disease, while also identifying host
genetic factors that regulate disease outcome. Based on this experience, we propose take advantage of a new
mouse adapted SARS-CoV2 virus (maCoV2), which was recently developed in the Baric laboratory, to screen a
panel of CC mouse strains for susceptibility to maCoV2-induced disease. This work will accomplish two critical
research objectives by: 1) developing critically needed mouse models of nCoV2-induced disease, and 2)
identifying polymorphic host genes/pathways that regulate resistance or susceptibility to nCoV2-disease.

## Key facts

- **NIH application ID:** 10144708
- **Project number:** 1R01AI157253-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Ralph S Baric
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $748,384
- **Award type:** 1
- **Project period:** 2020-09-25 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144708

## Citation

> US National Institutes of Health, RePORTER application 10144708, Genetic Analysis of COVID-19 Susceptibility and Resistance Determinants in the Collaborative Cross (1R01AI157253-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10144708. Licensed CC0.

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