# COVID-19: HDL's Role in Innate Immunity and Cardiovascular Protection with COVID-19

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

COVID19: HDL’s Role in Innate Immunity and Cardiovascular Protection with COVID-19
 The novel coronavirus (SARS-CoV-2) causes a disease called COVID-19. For many people, COVID-19 has
almost no symptoms, yet for others, COVID-19 is particularly dangerous and has high morbidity and mortality
rates. People with pre-existing type-2 diabetes and atherosclerotic cardiovascular disease (ASCVD) have twice
the risk of SARS-CoV-2 infection and are more likely to have poor outcomes. 70% of patients with ASCVD and
elevated troponin die of COVID. We don’t know what intrinsic factors contribute to these disparate outcomes.
 High Density Lipoprotein (HDL) particles play a critical role in the innate immune system and are protective
against viral and bacterial infections. HDL particles best are known for their roles protecting from atherosclerotic
cardiovascular disease (ASCVD). The cardiovascular protection conferred by HDL is largely mediated by HDL’s
associated proteins, which comprise about half of HDL’s mass. Mechanisms for HDL’s protection from ASCVD
are shared with mechanisms for HDL’s protection from viral infections. These protective properties center around
the HDL-associated proteins that mediate its anti-inflammatory and antioxidative functions. The goal of this
project is to define how HDL may protect from Sars-CoV-2 infection and limit the inflammatory response to
COVID-19 illness. Obesity and type-2 diabetes (DM2) lead to hypertriglyceridemia and metabolic changes that
impair HDL’s anti-inflammatory and antioxidative functions. We will define if DM2 leads to HDL dysfunction and
contributes to severe COVID-19 outcomes.
 Our overarching hypothesis is that HDL’s antiviral properties can limit SARS-CoV-2 infection and that HDL’s
anti-inflammatory and antioxidative capacity limit the systemic inflammatory response to COVID-19. We have
initiated a collaboration with Dr. Malall, an immunology expert running a large trial with COVID-19 patients whose
de-identified samples are paired with de-identified EMR outcomes data. In AIM1 we will test the hypothesis that
SARS-CoV-2 infection impairs HDL’s antioxidative and anti-inflammatory capacities, and that these changes can
be predicted by proteomic signatures of HDL. We also have collaboration with Dr. Denison, an expert in
coronavirus biology. In AIM2 we will test the hypothesis that HDL can reduce SARS-CoV-2 infectivity of lung
epithelial cells, but that COVID-19 impairs HDL’s antiviral capacity, which can be improved with Remdesavir
treatment. In AIM3 we will test the hypothesis that type-2 diabetes alters the HDL-associated protein networks
that limit systemic inflammation with COVID-19 and protect against SARS-CoV-2 infection.
 Diabetes and cardiovascular disease are among the most prevalent problems among United States
Veterans, making Veterans more likely to have poor COVID-19 outcomes. An asset to this project is that we can
relate our HDL function and antiviral assays with clinical outcomes. Our studi...

## Key facts

- **NIH application ID:** 10153344
- **Project number:** 1I01BX005459-01
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** John Michael Stafford
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10153344

## Citation

> US National Institutes of Health, RePORTER application 10153344, COVID-19: HDL's Role in Innate Immunity and Cardiovascular Protection with COVID-19 (1I01BX005459-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10153344. Licensed CC0.

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