COVID Variants Can Infect Developing Neural Stem Cells According to New Study

New Evidence Links SARS-CoV-2 Variants to Potential Risks for Developing Neural Cells

Emerging research indicates that the neural stem cells responsible for building the human brain and spinal cord are highly vulnerable to SARS-CoV-2. The study, which analyzed both the original viral strain and the Omicron BA.1 and BA.2 variants, highlights a potential pathway for how maternal COVID-19 infections could impact the long-term neurological development of a fetus.

The findings, published in the journal PLOS One, suggest that while transmission of the virus from mother to fetus is already recognized, the susceptibility of specific early-stage progenitor cells remains a critical area of concern. By using modified, non-replicating spike pseudoparticles, researchers at the University of California, Riverside, were able to observe how these viral components infiltrate developing neural tissues.

Vulnerability in Early Development

Neural stem cells originate from the ectoderm, an early embryonic tissue that serves as the foundation for the central nervous system. Because these cells are fundamental to the architecture of the brain, any interference during their development could lead to significant health outcomes, ranging from pregnancy loss to developmental disorders that might not manifest until years after birth.

“Such subtle damage might only appear years later as learning, behavioral, or cognitive difficulties,” explains Ann Song, a postdoctoral researcher in the lab of Prue Talbot and the study’s lead author.

The research team successfully demonstrated that neural stem cells are significantly more susceptible to the virus than undifferentiated embryonic stem cells. These results align with broader clinical health-record data, which have previously identified an increased statistical risk of neurodevelopmental diagnoses in children by age 3 when exposed to SARS-CoV-2 in utero.

Mechanisms of Viral Entry

To understand the biological “gateways” the virus uses to infiltrate these cells, the investigators differentiated human embryonic stem cells into neural stem cells. Their experiments revealed that the Omicron variants primarily enter these cells through endocytosis—a process where the cell membrane folds inward to engulf external particles. When the team used the compound filipin to inhibit this pathway, viral entry plummeted by as much as 85%.

The study also identified that the surface of neural stem cells is covered by a relatively sparse layer of sugar molecules. When these sugar groups were removed, the researchers observed a two- to fourfold increase in viral entry, suggesting that this surface layer acts as a natural barrier to infection.

Clinical Implications and Future Directions

While the study provides a clear look at how viral particles interact with developing nervous system cells, the authors caution that further investigation is required to confirm whether this infection pathway definitively leads to neurological impairment in human pregnancies. Nevertheless, the researchers stress that the high susceptibility of these cells warrants closer observation of children who were exposed to the virus before birth.

“Our data emphasize the need for monitoring children exposed in utero to SARS-CoV-2 for evidence of deficiencies in the central nervous system,” Song noted. Prue Talbot, who led the research team, added that the next phase of study will focus on deciphering whether and how these early-stage infections ultimately alter the trajectory of human brain development.