Although the Sars-CoV-2 coronavirus does not affect nerve cells, Covid-19 disease can cause damage to the nervous system. Researchers from the University of Basel and the University Hospital Basel have elucidated the mechanisms behind “Neuro-Covid” and identified starting points for preventing it.

Quite a few have lost their sense of smell and taste with the coronavirus infection. For others, the disease has taken its toll on the nervous system, ranging from persistent inability to concentrate to strokes. Researchers around Prof. Dr. Gregor Hutter from the Department of Biomedicine at the University of Basel and the University Hospital Basel are now reporting on new findings on the development of “Neuro-Covid” in the journal “Nature Communications”.

The team examined more precisely how different degrees of severity of neuro-Covid can be recognized and predicted in the cerebrospinal fluid and blood plasma of those affected. Their findings also provide indications of how neuronal damage caused by Covid-19 can be prevented.

The study included 40 Covid-19 sufferers with varying degrees of neurological symptoms. The research team examined their cerebrospinal fluid and blood plasma in comparison to samples from a control group in order to identify changes typical of neuro-Covid. In addition, the researchers measured the brain structures of the test subjects and interviewed them 13 months after their illness in order to determine any lasting symptoms.

Holes in the blood-brain barrier

The researchers found a connection with an excessive immune response, particularly in the group with the most severe neurological symptoms. On the one hand, there were indications that the blood-brain barrier of those affected was impaired. The study authors suspect that the so-called cytokine storm is probably the trigger, i.e. the massive release of inflammatory factors in response to the virus.

On the other hand, as a result of the excessive immune response, the researchers found antibodies that were directed against the body’s own targets – i.e. signs of an autoimmune reaction. “We suspect that these autoantibodies get through the perforated blood-brain barrier into the brain and cause damage there,” explains Hutter. The immune cells specifically responsible for the brain, the microglia, were also activated excessively.

Blood test as a long-term goal

In a further step, Hutter and his team investigated whether the severity of neuronal symptoms is also noticeable in brain structures. In fact, they found that those affected with severe neuro-Covid symptoms had lower volume at specific locations in the brain compared to healthy subjects. The olfactory center, i.e. the olfactory brain area, was particularly affected.

“We were able to link the signature of certain molecules in blood and cerebrospinal fluid with an excessive immune response in the brain, reduced brain volume in various areas and neurological symptoms,” says Hutter. These biomarkers now need to be tested with a larger number of participants. The aim would be a blood test that can predict severe courses, including neuro-Covid and long-Covid, right from the start of an infection.

Points of attack against consequential damage

The same biomarkers provide indications of which points of attack drugs could target in order to prevent consequential damage from Covid-19 disease. One of the biomarkers identified in the blood, the factor MCP-3, plays a central role in the excessive immune response. Hutter sees potential here to inhibit this factor with medication.

“With our study, we are showing how the coronavirus can affect the brain,” summarizes Hutter. “The virus triggers such a strong inflammatory reaction in the body that it spills over into the central nervous system. This can disrupt the cellular integrity of the brain.” The primary goal must therefore be to recognize and slow down the excessive immune response at an early stage.

original publication

Manina M. Etter et al.
Severe Neuro-COVID is associated with peripheral immune signatures, autoimmunity and neurodegeneration: a prospective cross-sectional study
Nature Communications (2022), doi: 10.1038/s41467-022-34068-0