Infection-Triggered Neurodegeneration in Long COVID: Retinal Biomarkers and Organoid Models for Mechanism and Therapy

Project Summary

This project investigates infection-triggered neurodegenerative protein aggregation as a potential driver of neurological symptoms in Long COVID. It focuses on identifying non-invasive retinal biomarkers and building human organoid models to define how persistent viral signals—such as circulating SARS-CoV-2 proteins—may induce neuronal stress, vascular dysfunction, and chronic neuroimmune activation. 

To achieve this, the team combines advanced retinal imaging and electrophysiology with induced pluripotent stem cell (iPSC)-derived retinal and cortical organoids. These systems are used to detect structural and functional signatures of neuronal injury and to model how viral proteins and inflammatory signals trigger aggregation of neurodegenerative proteins such as amyloid-β and α-synuclein. By linking biomarker discovery with mechanistic modeling and drug screening, the project aims to generate actionable diagnostics and identify therapeutic strategies for neurological Long COVID. 

Project Background

Neurological symptoms—including cognitive dysfunction (“brain fog”), visual disturbances, and neuropsychiatric impairment—are among the most common and debilitating features of Long COVID, yet objective biomarkers and targeted therapies remain lacking. Emerging evidence suggests that persistent viral reservoirs and circulating viral proteins can drive chronic immune activation and neuronal dysfunction, but the mechanisms linking infection to long-term neurological damage are not well understood. 

This project tests the hypothesis that viral persistence can induce pathological protein misfolding and aggregation—processes classically associated with neurodegenerative diseases—and that these changes can be detected through the retina, which shares key structural and functional properties with the brain. Using multimodal retinal imaging and electroretinography alongside human organoid models, the team will map infection-driven neurodegenerative processes, identify candidate biomarkers, and screen for compounds capable of reversing neuronal dysfunction. Together, this work establishes a translational framework to diagnose, model, and treat infection-associated neurological disease in Long COVID and related conditions.