PhD Students Institut Pasteur Paris, Ile-de-France, France
Abstract: Since the emergence of COVID-19 in 2019, many patients have reported long-term neurological symptoms, known as Long-COVID syndrome. Evidence suggests that SARS-CoV-2 can infect the human brain, potentially contributing to these symptoms. In addition, COVID-19 patients have been linked to a threefold increased risk of Alzheimer’s disease (AD) and a twofold increased risk of Parkinson’s disease (PD). However, the mechanisms by which the virus reaches the brain remain a critical area of ongoing investigation. In contrast to adult neurons, it has been shown that neuronal progenitor cells (NPCs) are permissive to SARS-CoV-2 infection in vitro, which might have detrimental consequences even years after initial infection. Given that NPCs are the primary regenerative cells after central nervous system (CNS) injury, we hypothesize that SARS-CoV-2 infection might disrupt neurogenesis and lead to neurological anomalies which pave the way to neurodegeneration. Using 2D and 3D human cell cultures (organoids) and cryo-electron microscopy (cryo-EM) strategies, we will study SARS-CoV-2 neuroinvasion and its role in neurodegenerative diseases. Interestingly, preliminary data showed that SARS-CoV-2 transfer from primary human nasal cells to human neuroprogenitors through Tunneling Nanotubes (TNTs), actin-membrane-based structures that connect distant cells. TNT-like structures positive for the SARS-CoV-2 N antigen were also observed, supporting the possibility of a cell-to-cell transmission route to neural cells. This study provides critical insights into the neuropathogenesis of SARS-CoV-2 and its potential contribution to long-term neurological symptoms.
Funding Source: Pasteur Paris University (PPU) International Doctoral Program
