People who died of Covid-19 showed signs that were similar to the brains of individuals who died of neurodegenerative conditions such as Alzheimer's disease and Parkinson's disease, according to a study.

Both groups presented similar inflammation and impairment in brain circuits, said researchers from the Stanford School of Medicine and the Saarland University in Germany.

Alzheimer's disease
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The findings, published in the journal Nature, may help explain why about one-third of individuals hospitalised for Covid report symptoms of neurological problems like fuzzy thinking, forgetfulness, difficulty concentrating, and depression.

The team analysed brain tissues from eight individuals who died of the disease, and brain samples from 14 people who died of other causes were used as controls for the study.

"The brains of patients who died from severe Covid-19 showed profound molecular markers of inflammation, even though those patients didn't have any reported clinical signs of neurological impairment," said Tony Wyss-Coray, Professor of Neurology and Neurological Sciences at Stanford.

"Viral infection appears to trigger inflammatory responses throughout the body that may cause inflammatory signalling across the blood-brain barrier, which in turn could trip off neuroinflammation in the brain," he added.

Different inflammatory processes

Further, the team found that the activation levels of many genes, associated with inflammatory processes, differed in the Covid-19 patients' brains versus the control group's brains.

There also were signs of distress in neurons in the cerebral cortex, the brain region that plays a key role in decision-making, memory and mathematical reasoning.

The outermost layers of the cerebral cortex of patients who died of Covid-19 showed molecular changes suggesting suppressed signalling by excitatory neurons, along with heightened signalling by inhibitory neurons, which act like brakes on excitatory neurons. This kind of signalling imbalance has been associated with cognitive deficits and neurodegenerative conditions such as Alzheimer's disease, the researchers explained.

In addition, the peripheral immune cells called T cells, were significantly more abundant in brain tissue from dead Covid-19 patients. In healthy brains, these immune cells are few and far between.

"It's likely that many Covid-19 patients, especially those reporting or exhibiting neurological problems or those who are hospitalised, have these neuroinflammatory markers we saw in the people we looked at who had died from the disease," Wyss-Coray said. It may be possible to find out by analysing these patients' cerebrospinal fluid, whose contents to some extent mirror those of the living brain.

"Our findings may help explain the brain fog, fatigue, and other neurological and psychiatric symptoms of long Covid," he noted.