# Neuroimaging and Behavioral Studies to Assess For Neuroinflammation in COVID-19 During Convalescence

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $424,875

## Abstract

Project Summary
This R21 Exploratory/Developmental Research Grant is written in response to PAR-20-177:
Emergency Awards: Rapid Investigation of Severe Acute Respiratory Syndrome Coronavirus 2
(SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19). SARS-CoV2 is the virus that
causes COVID-19, and is known to have high affinity binding to the angiotensin-coverting
enzyme 2 (ACE-2) receptors. This receptor is expressed on endothelial lining, innate immune
cells, including monocytes and macrophages, as well as astroglial and microglial cells in the
brain. SARS-CoV2 virus was shown to be neuroinvasive, but whether it causes persistent or
residual neuroinflammation or neuronal injury is unknown. We will use a multi-parametric MRI
approach to evaluate markers of neuroinflammation and neural integrity in COVID-19 patients,
and a comprehensive NIH Toolbox® and PROMIS® battery to assess cognitive performance,
emotional distress, fatigue, pain, motor function and global health outcomes in convalescent
COVID-19 patients. We will also determine whether serum and cerebrospinal fluid (CSF) levels
of neuroinflammatory markers, i.e. cytokines and chemokines, would predict the neuroimaging
and behavioral measures. We propose three specific Aims: Aim 1: Structural MRI, proton
spectroscopy (1H-MRS) and diffusion tensor imaging (DTI), will be used to evaluate regional
neuroinflammation or neuronal injury in convalescent COVID-19 patients and in healthy controls
with negative COVID-19 tests. Aim 2: Cognitive and motor function will be evaluated using the
NIH Toolbox®, while emotional distress, fatigue, pain and overall health will be assessed using
PROMIS®. Neural correlates of these behaviors will also be assessed with blood oxygenation
level dependent-functional MRI (BOLD-fMRI). Aim 3: CSF and blood will be collected during
early convalescence to quantify soluble markers of inflammation using a multiplex ELISA
cytokine panel. Levels of D-dimer and C-reactive protein will also be repeated to compare with
those obtained during the patients’ acute hospitalization. This project will generate novel data
regarding possible residual or ongoing neuroinflammation or brain injury in convalescent
COVID-19 patients. We will also investigate whether such brain abnormalities might be related
to cognitive or behavioral outcomes that might affect their overall health. Furthermore, we will
determine whether the soluble inflammatory markers night predict brain or neurobehavioral
outcomes. Findings from these studies can lead to a larger study that may guide future
treatments to ameliorate neuronal injury or neuroinflammation in COVID-19 patients.

## Key facts

- **NIH application ID:** 10193009
- **Project number:** 1R21NS121615-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** LINDA CHANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $424,875
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10193009

## Citation

> US National Institutes of Health, RePORTER application 10193009, Neuroimaging and Behavioral Studies to Assess For Neuroinflammation in COVID-19 During Convalescence (1R21NS121615-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10193009. Licensed CC0.

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