# Nanocrystal Quantum Dot Biomimetics of SARS-CoV-2 to Interrogate Neutrophil-Mediated Neuroinflammation at the Blood-Brain Barrier

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2022 · $423,500

## Abstract

PROJECT SUMMARY/ABSTRACT
Public/health/relevance: Chronic, or recurring, neurological deficits in 60% of recovered COVID-19 patients 
are now an unmet medical need to treat the aftermath of SARS-CoV-2 infection of the central nervous system 
(CNS). A recent study from Germany suggests that these symptoms persist beyond a year, similarly to patients 
suffering from chronic symptoms due to SARS-CoV-1 infection. Thus, there is clear need for interventions 
against chronic neurologic symptoms after COVID. Elucidating the mechanism for SARS-CoV-2 impact on the 
CNS is essential to inform the design of such interventions.
Objective: This proposal aims to identify a pathway for SARS-CoV-2’s effects on the CNS through a 
dysregulated blood-brain barrier (BBB) mediated by a neutrophil-dependent “storm” of bradykinin (BK). We
hypothesize that this storm induces neuroinflammation that ultimately disrupts normal neuronal signaling, 
providing the substrate for enduring neurological symptoms.
Research Plan: Recent studies have reported altered integrity of the BBB in response to the spike (S) protein 
of SARS-CoV-2, thereby suggesting a neuroinvasive pathway for SARS-CoV-2 or inflammatory immune cells 
through the BBB. In line with these observations, this proposal will investigate how pro-inflammatory mediators 
associated with COVID infection activate neutrophil-mediated upregulation of BK; this leads to an increased 
permeability through paracellular gaps across the BBB due to dysregulated tight junctions (TJs). Such a model 
aligns with the upregulated levels of BK observed in bronchoalveolar fluid taken from COVID-19 patients coupled 
with the ability of neutrophils to engage the kinin system to remodel endothelial barriers in acute inflammation. 
As a proxy for native SARS-CoV-2, we will construct S protein coated quantum dots as high fidelity biomimetics 
of SARS-CoV-2 to investigate the size and structural constraints regulating SARS-CoV-2 permeability across 
the BBB. These constructs will be used to bias neutrophils to a pro-inflammatory state in the presence of relevant 
kallikrein-kinin factors to increase the permeability of cultured bEnd.3 monolayers, a high-fidelity in vitro model 
system for murine BBB. A leakier BBB will be indicated by increased permeability of our fluorescent SARS-CoV-2 biomimetic and corroborated with complementary measurements of global barrier health, as measured by 
transendothelial electrical resistance (TEER). Lastly, we will construct a correlated scanning ion conductance 
and confocal microscope system to examine the heterogeneity of dysregulated barrier function and the specific 
nanoscale changes in TJ expression and localization that regulate it.

## Key facts

- **NIH application ID:** 10510611
- **Project number:** 1R21NS128502-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** HARRIS A GELBARD
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $423,500
- **Award type:** 1
- **Project period:** 2022-08-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10510611

## Citation

> US National Institutes of Health, RePORTER application 10510611, Nanocrystal Quantum Dot Biomimetics of SARS-CoV-2 to Interrogate Neutrophil-Mediated Neuroinflammation at the Blood-Brain Barrier (1R21NS128502-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10510611. Licensed CC0.

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