# Project 1 - A systems biology approach to identify early networks and signatures associated with mild and severe SARS-CoV-2 infections in vivo

> **NIH NIH U19** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2024 · $403,954

## Abstract

Two years into the COVID-19 pandemic, SARS-CoV-2 infections are still responsible for huge economic
losses, lockdowns and stressed health care systems worldwide. Different from the situation early during the
pandemic, when the virus started circulating in the human population in the absence of pre-existing immunity,
SARS-CoV-2-specific immunity has been increased at the community level due to vaccination or previous
infection. Nevertheless, through the acquisition of mutations, new variants of the virus emerged that were able
to escape pre-existing immunity and to transmit with higher efficiency, thereby causing a continuous threat for
severe disease, especially in people with comorbidities like obesity, advanced age and associated morbidities
like type 2 diabetes and hypertension. In Project 1, we will identify key drivers and biomarkers for severe
disease networks associated with SARS-CoV-2 infection through modeling, based on multi-OMICs data
obtained from clinical and animal studies. Under AIM 1, a first dataset will be generated from clinical
samples of COVID-19 patients in the absence or presence of pre-existing immunity. Multi-OMICs data will also
be generated using established animal models (mouse and hamster) for SARS-CoV-2 infection to recapitulate
clinical characteristics and features from the human cohort studies, thereby taking advantage of our expertise
with animal models for specific comorbidities (obesity, type 2 diabetes, advanced age) while always addressing
sex and immune status as a biological variables. Both human and animal datasets will be used by the
modeling core under AIM 2 to identify networks associated with severe and mild disease outcome, and the
host and virus genes that drive them. Under AIM 3, networks and signature genes identified under AIM 2 will
be validated in vivo using the mouse and hamster infection models for SARS-CoV-1. Hereto, we will rely on the
availability of knock out mice, viral vector-mediated genetic ablation of host genes in cells licensed for SARS-
CoV infection, when available pharmacological interventions, recombinant rSARS-CoV-1 and rSARS-CoV-2
viruses and SARS-CoV-2 variants that have acquired mutations in genes of interest by nature. The
overarching goal of our highly integrated research strategy is to uncover molecular signatures associated with
distinct disease trajectories and outcomes, identifying novel targets for therapeutic interventions.

## Key facts

- **NIH application ID:** 10758545
- **Project number:** 5U19AI135972-07
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Adolfo Garcia-Sastre
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $403,954
- **Award type:** 5
- **Project period:** 2018-01-20 → 2027-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10758545

## Citation

> US National Institutes of Health, RePORTER application 10758545, Project 1 - A systems biology approach to identify early networks and signatures associated with mild and severe SARS-CoV-2 infections in vivo (5U19AI135972-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10758545. Licensed CC0.

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