# Cerebral vascular pathology of COVID-19

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $148,376

## Abstract

ABSTRACT
COVID-19, which is caused by Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), has resulted
in devastating morbidity and mortality worldwide due to lethal pneumonia and respiratory distress. In addition,
the central nervous system (CNS) is well documented to be a target of SARS-CoV-2, and studies detected
SARS-CoV-2 in the brain and the cerebrospinal fluid of COVID-19 patients. An increased spread of emerging
SARS-CoV-2 variants, such as delta or omicron, appears to be the result of a fitness advantage rather than
founder effects and/or genetic drift; therefore, similar trends are expected to continue in the future. While
respiratory distress dominates acute clinical symptoms of COVID-19, neurological and cerebrovascular
symptoms play a critical role in so called “long-COVID” or chronic COVID. However, the interactions of SARS-
CoV-2 with the brain microvasculature and how they predispose to ischemic stroke are largely unknown. The
current proposal aims to close this gap of knowledge by its focus on the impact of SARS-CoV-2 on brain
microvessels and by focusing on a long-term impact of the infection. The proposal is based on the central
hypothesis that SARS-CoV-2 S1 protein affects the integrity of the brain microvessels and affects stroke
development via inflammatory responses and epigenetic dysregulation of cerebral microvascular
integrity. This hypothesis is novel, and the proposed studies are likely to generate unique data sets. As the
result of substantial financial investments, we completed RNA-Seq analyses of transcriptomics signatures of
human brain microvascular endothelial cells (HBMEC) infected with SARS-CoV-2. The obtained data allowed
us to identify several genes and pathways, which most significantly contribute to SARS-CoV-2-induced cerebral
microvascular pathology. The proposal is built on these results. Specifically, we will explore the role of epigenetic
regulators in SARS-CoV-2-induced cerebrovascular dysfunction, hyperinflammatory reactions, and ischemic
stroke.
The impact of SARS-CoV-2 on the cerebral vasculature is largely unknown, making the proposed studies truly
innovative. Knowledge of the underlying mechanism(s) of SARS-CoV-2-induced microvascular disruption may
provide targets for pharmacological intervention to protect against viral entry into the brain and devastating
cerebrovascular pathologies associated with COVID-19 and, especially with a chronic form of this disease. Thus,
the outcome of this proposal will provide critically important and therapeutically-relevant information on the
involvement of the cerebrovasculature in COVID-19 pathology.

## Key facts

- **NIH application ID:** 10553944
- **Project number:** 3R01HL126559-06S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Michal Toborek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $148,376
- **Award type:** 3
- **Project period:** 2022-08-02 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10553944

## Citation

> US National Institutes of Health, RePORTER application 10553944, Cerebral vascular pathology of COVID-19 (3R01HL126559-06S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10553944. Licensed CC0.

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