# COVID-19: Multi-Omics Approach to Identify Molecular Mechanisms Responsible for Risk and Resilience to Adverse Outcomes

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2022 · —

## Abstract

Objective: Emerging data from the COVID-19 pandemic indicate that men and African Americans have higher
mortality, and cardiometabolic risk factors, including obesity, diabetes, and hypertension, cluster in patients who
develop adverse outcomes to SARS-CoV-2 infection. The Veteran population is particularly vulnerable to
COVID-19 because of the very high prevalence of cardiometabolic risk factors. However, not all Veterans with
COVID-19 experience severe disease, and there is an urgent need to identify novel molecular pathways
underlying risk and resilience to COVID-19. Previous work and preliminary studies from our team have
demonstrated that targeted proteomics, metabolomics, and miRNA-omics can identify novel biomarkers and
molecular pathways associated with cardiovascular health and disease. In this project, we will use a multi-omics
to elucidate novel biomarkers and pathways associated with risk and resilience to severe COVID-19.
Research Plan: In Aim 1, we will compare expression of pathway-specific biomarkers in hospitalized patients
with severe COVID-19 with expression of these biomarkers in patients who do not develop severe COVID-19.
Pathway-specific biomarkers reflecting activation of the renin-angiotensin-aldosterone system, systemic
inflammation, oxidative stress, immune activation, thrombogenesis, and myocardial injury and stretch will be
assessed. The primary endpoints for severe disease will be pathologic elevation of IL-6 levels or troponin I levels.
Secondary endpoints will be requirement for mechanical ventilation, congestive heart failure, change in SOFA
score, and death. In Aim 2, we will assess the extracellular miRNA and metabolomic profiles of the same two
groups of hospitalized COVID-19 patients and determine miRNAs and metabolites differentially expressed
between the two groups. Subsequently, we will examine connectivity between miRNA-metabolome networks
and clinical endpoints in COVID-19 patients by performing an integrative analysis of differentially expressed
miRNAs and metabolites, which will identify metabolic pathways associated with severe infection.
Methods: The proposed studies will analyze de-identified blood samples and clinical data from COVID-19
patients hospitalized at the Atlanta VAMC and Emory University Hospital. The samples will be obtained from a
bio repository that is currently banking residual plasma and serum from routine laboratory testing of COVID-19
patients. In Aim 1, we will measure levels of aminothiol (oxidative stress), suPAR (thrombogenesis/immune
dysregulation), hsCRP (inflammation), hsTnI (myocardial injury), BNP (myocardial stretch), D-dimers
(thrombogenesis), angiotensin II, angiotensin-(1-7) and plasma renin activity. Logistic regression modeling will
be performed to identify biomarkers predictive of clinical endpoints. In Aim 2, we will use next generation
sequencing, RT-qPCR, and high-throughput metabolomics profiling to assess expression of extracellular
miRNAs and metabolites. A me...

## Key facts

- **NIH application ID:** 10382290
- **Project number:** 5I01BX005442-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** CHARLES D SEARLES
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-04-01 → 2024-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10382290

## Citation

> US National Institutes of Health, RePORTER application 10382290, COVID-19: Multi-Omics Approach to Identify Molecular Mechanisms Responsible for Risk and Resilience to Adverse Outcomes (5I01BX005442-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10382290. Licensed CC0.

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