# Immune Cell Interactions in Atherosclerosis

> **NIH NIH P01** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2020 · $523,914

## Abstract

Abstract
The coronavirus disease 2019 (COVID-19) pandemic, caused by SARS-Coronavirus-2 (SARS-CoV-2),
represents an unprecedented world health crisis. In addition to causing pneumonia and lung injury,
COVID-19 is linked to increased risk of cardiovascular events including thrombosis, pulmonary
embolism, and stroke, especially in critically-ill patients. Approximately 10% of patients with severe
COVID-19 develop a serious thrombotic event. However, almost all patients show some abnormal
coagulation. Thus, SARS-CoV-2 infection drastically changes the hosts' coagulation cascade, and in
many cases, leads to onset of serious thrombotic events. Monocytes are white blood cells that protect us
from pathogens, including viruses. We have reported that the patrolling action of a subset of monocytes,
nonclassical monocytes, is required to maintain vascular homeostasis. Reduction in activity or number of
nonclassical monocytes causes endothelial activation and dysregulation, thus exacerbating coagulation
events. Early reports by our group indicate decreased numbers of nonclassical monocytes in COVID-19
patients, and this loss associates with disease severity. Some monocytes can also release Tissue
Factor, which causes clotting. Monocytes from severe COVID patients express SARS-CoV-2 RNA. The
monocyte subsets that express SARS-CoV-2 RNA are not known, and whether this is due to scavenging
of viral particles or direct infection of monocytes is unclear. How this infection impacts their release of
Tissue Factor is not known. In the current study, we will assess monocyte changes in mild to severe
COVID-19 patients that clinically present with and without thrombotic events. We will compare these
patients to healthy controls. We will test the hypothesis that monocyte phenotype and function is
changed in COVID-19 patients to drive thrombotic changes in circulation, contributing to
thrombotic events. We will utilize high dimensional profiling via CyTOF mass cytometry and RNA-seq
to study monocyte changes in PBMC from mild and severe COVID-19 patients, including those with
clinically diagnosed thrombotic events. Matching plasma from each patient will tested for coagulation
factors. All monocyte data will be linked with clinical coagulation and immune cell data from each
patient. Understanding mechanisms for how thrombosis occurs by SARS-CoV-2 is critical for effective
treatment of all COVID-19 patients, especially those with life-threatening thrombotic events.

## Key facts

- **NIH application ID:** 10166540
- **Project number:** 3P01HL136275-04S1
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Catherine C Hedrick
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $523,914
- **Award type:** 3
- **Project period:** 2017-08-01 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10166540

## Citation

> US National Institutes of Health, RePORTER application 10166540, Immune Cell Interactions in Atherosclerosis (3P01HL136275-04S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10166540. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*