# Multiplexed imaging of Renin-Angiotensin System (RAS) pathways, endothelial and immune dysfunction in COVID-19 Lung

> **NIH NIH UH3** · GENERAL ELECTRIC GLOBAL RESEARCH CTR · 2020 · $99,973

## Abstract

PROJECT SUMMARY
SARS-CoV2 pandemic has already taken a high toll with ~700,000 (~155,00 US) deaths and 18
million (~5 million US) infections globally with unabated spread in many countries and new hotspots
reemerging on a regular basis. While frantic efforts are underway to develop vaccines and therapies
and there is high hope that these will be available over the next 6-12 months, there are no answers to
how much and how long these will be effective. A continued effort on understanding the disease
etiology, particularly in the organ first infected, and identifying new avenues of intervention therefore
is important. The major route of virus infection is via the respiratory tract and virus is reported to
spread via lung to other organs by vascular leakage by directly (through infection) or indirectly (by
impairing ACE2 activity) affecting the endothelial and immune cells. Cells expressing ACE2 enzyme
and other viral coreceptors (TMPRSS2 or Cathepsin L) are the major targets of viral infection. ACE2
is a key player in regulation of the Renin-Angiotensin system (RAS) pathway. By converting the
product of ACE activity, angiotensin II (ang II), to angiotensin 1-7 (ang 1-7), ACE2 diminishes Ang II
mediated deleterious effects that can include promoting vascular wall inflammation, endothelial
dysfunction, endothelial cell and vascular smooth muscle cell migration, growth, proliferation, and
thrombosis. Disruption of ACE2 by viral binding may reduce this protective effect. The inhibition of
nitric oxide production, activation of megakaryocytes, complement and platelets can also cause
thrombosis and thrombolytic dysfunction leading to clot formation in lung arteries and other organs.
Since the early unprecedented global effort to identify the cellular targets of SARS-CoV2 using single
cell RNA sequencing (scRNAseq) data from multiple human and non-human single cell datasets,
several in depth reports on individual organs infected and cells and cellular pathways affected by this
virus have appeared. Most of these reports are based on transcriptomic analysis of homogenized or
disaggregated samples although some singleplex immunofluorescence analysis have been reported.
COVID-19 tissue histology shows a very heterogenous disease which may be a function of multiple
factors including cellular composition, spatial organization and neighboring cell activation. To
understand these factors, here we propose an in situ multiplex immunofluorescence study of SARS-
CoV2 positive and negative patient samples to spatially profile the cell types affected in the upper and
lower respiratory tract and the role of RAS pathway activation in endothelial and immune cell
dysfunction related to COVID-19 morbidity and mortality.

## Key facts

- **NIH application ID:** 10230749
- **Project number:** 3UH3CA246594-02S1
- **Recipient organization:** GENERAL ELECTRIC GLOBAL RESEARCH CTR
- **Principal Investigator:** Yousef Al-Kofahi
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $99,973
- **Award type:** 3
- **Project period:** 2019-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10230749

## Citation

> US National Institutes of Health, RePORTER application 10230749, Multiplexed imaging of Renin-Angiotensin System (RAS) pathways, endothelial and immune dysfunction in COVID-19 Lung (3UH3CA246594-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10230749. Licensed CC0.

---

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