Frontiers in neurologyJul 28, 2026

How the SARS-CoV-2 spike protein may affect the brain in neuro COVID

Long Covid Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Aug 3, 2026

Abstract

Up to 50 percent of patients may experience cognitive and neuropsychiatric issues after SARS-CoV-2 infection.

Long-COVID syndrome is characterized by lingering physical and mental fatigue, brain fog, and neuropsychiatric symptoms.
Inflammation around blood vessels in the brain may be linked to the presence of the Spike protein in 'reservoirs,' particularly in the meninges.
Spike protein is associated with stimulating immune cells, such as mast cells and microglia, to release substances that are pro-inflammatory and neurotoxic.
These neuroinflammatory responses could contribute to Long-COVID and other neurodegenerative disorders.
Understanding the role of the Spike protein and neuroinflammatory molecules is urgent for regulating these effects.

Simplified

Many patients develop cognitive and neuropsychiatric issues after viral infections, but the mechanisms are not well understood. A case in point is Long-COVID syndrome, which may affect as many as 50 percent of patients after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is characterized by lingering physical and mental fatigue, brain fog and neuropsychiatric symptoms. Meanwhile, emerging evidence suggests the presence of inflammation around blood vessels in the brain due to the Spike protein remaining in "reservoirs" especially in the meninges that contain great numbers of the unique tissue immune cells, mast cells (MCs). In fact, Spike protein has been reported to stimulate MCs and microglia to release pro-inflammatory, neurotoxic and vasoactive mediators leading to Long-COVID and other neurodegenerative disorders. Thus, it is of great urgency to gain insight into how the Spike protein and neuroinflammatory molecules contribute to Long-COVID and how to regulate this response.

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Competing interests

TCT is the Scientific Director of Algonot LLC, Sarasota, FL, USA. The remaining author(s) declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author PP declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

PubMed

How the SARS-CoV-2 spike protein may affect the brain in neuro COVID

Abstract

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Funding

Competing interests

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