Study Delves into Neuro-COVID Causes

Researchers in Switzerland report new insights into how SARS-CoV-2 causes neurological symptoms—including loss of taste and smell, concentration problems, and even strokes—despite the fact that the virus does not infect nerve cells. The findings also offer some indications of how to prevent this “neuro-COVID.”

Led by Professor Gregor Hutter from the Department of Biomedicine at the University of Basel, the study investigated how different severities of neuro-COVID can be detected and predicted by analyzing the cerebrospinal fluid and blood plasma of affected individuals. They compared samples from 40 COVID-19 patients with differing degrees of neurological symptoms with samples from a control group. They also measured the brain structures of test subjects and surveyed participants 13 months after their illness in order to identify any lasting symptoms.

The researchers identified a link with an excessive immune response, especially in the group with the most serious neurological symptoms. Affected individuals showed indications of impairment of the blood-brain barrier, which the study’s authors speculate was probably triggered by a cytokine storm—the term describing a massive release of pro-inflammatory factors in response to the virus. The researchers also found antibodies that targeted parts of the body’s own cells, indicating an autoimmune reaction as a result of the excessive immune response.

“We suspect that these antibodies cross the porous blood-brain barrier into the brain, where they cause damage,” says Hutter. The authors also identified excessive activation of microglia, the immune cells specifically responsible for the brain.

Hutter and his team further investigated whether the severity of neurological symptoms is also perceptible in brain structures. They found that people with serious neuro-COVID symptoms had a lower brain volume than healthy participants at specific locations in the brain and particularly at the olfactory cortex.

“We were able to link the signature of certain molecules in the blood and cerebrospinal fluid to an overwhelming immune response in the brain and reduced brain volume in certain areas, as well as neurological symptoms,” says Hutter.

It is important to examine these biomarkers in a greater number of participants, Hutter adds. Potentially, the biomarkers could be used to develop a blood test that can predict serious cases, including neuro-COVID and long COVID, at the start of an infection.

These same biomarkers also point to potential targets for drugs aimed at preventing consequential damage due to a COVID-19 infection. One of the biomarkers identified in blood—factor MCP-3—plays a key role in the excessive immune response, and Hutter believes there is the potential to inhibit this factor medicinally.

“In our study, we show how coronavirus can affect the brain,” he says. “The virus triggers such a strong inflammatory response in the body that it spills over to the central nervous system. This can disrupt the cellular integrity of the brain.” Accordingly, Hutter says that the primary objective must be to identify and halt the excessive immune response at an early stage.

The findings were published recently in the journal Nature Communications.