Quantum Dot Biomimetic for SARS-CoV-2 to Interrogate Blood–Brain Barrier Damage Relevant to NeuroCOVID Brain Inflammation

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Abstract
Despite limited evidence for infection of SARS-CoV-2 in the central nervous system, cognitive impairment is a common complication reported in "recovered" COVID-19 patients. Identification of the origins of these neurological impairments is essential to inform therapeutic designs against them. However, such studies are limited, in part, by the current status of high-fidelity probes to visually investigate the effects of SARS-CoV-2 on the system of blood vessels and nerve cells in the brain, called the neurovascular unit. Here, we report that nanocrystal quantum dot micelles decorated with spike protein (COVID-QDs) are able to interrogate neurological damage due to SARS-CoV-2. In a transwell co-culture model of the neurovascular unit, exposure of brain endothelial cells to COVID-QDs elicited an inflammatory response in neurons and astrocytes without direct interaction with the COVID-QDs. These results provide compelling evidence of an inflammatory response without direct exposure to SARS-CoV-2-like nanoparticles. Additionally, we found that pretreatment with a neuro-protective molecule prevented endothelial cell damage resulting in substantial neurological protection. These results will accelerate studies into the mechanisms by which SARS-CoV-2 mediates neurologic dysfunction.
Funding Information
  • Division of Chemistry (CHE 1904528, CHE 1904847)
  • NIH Office of the Director (S10OD030302)
  • American Heart Association (18CSA34020064)
  • National Institutes of Health (R01 AG057525, R21 AG074232, T32 GM118283, T32 GM135134)

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