The most comprehensive molecular study yet of the brains of people who died of Covid-19 has put forth a potential answer to a mystery: Why people with the disease so often develop neurological conditions?
In the process of answering this unknown, the researchers unearthed a slew of new questions.
Serious cases of Covid-19 can wreak havoc on a person’s body. The disease can affect the kidneys, lungs, heart, and crucially, brain function. As many as 80 percent of people hospitalized with Covid-19 report neurological issues like seizure disorders, brain fog, and depression. These conditions can persist long after the virus has cleared the body as symptoms of “long Covid.”
Despite the staggeringly high percentage of hospitalized Covid-19 patients with neurological conditions, what exactly goes on in the brain during this brutal process has been less clear.
How the discovery was made — Researchers at the Stanford School of Medicine and Saarland University in Germany examined the brain tissue of eight people who died of Covid-19 and compared this tissue to the brains of 14 controls.
Despite the fact that none of the patients reported clinical signs of neurological impairment prior to their death, the researchers found “profound molecular markers of inflammation” in the patients’ brain tissue. Their findings were published Monday in the journal Nature.
These markers were so profound, the study team reports they’re akin to what you’d expect to see in the brains of people who died of neurodegenerative diseases like Alzheimer’s Disease and Parkinson’s Disease. Bafflingly, the researchers did not find any evidence of the virus itself in the brain.
What Covid-19 does to the brain
Whether or not SARS-CoV-2, the virus that causes Covid-19, becomes or remains present in the brains of people who become infected is a debated issue in the scientific and medical community. Some studies, like this 2020 pre-print paper examining deceased patients, have found traces of the virus in the brain. Others, like this 2020 paper in which two patients with Covid-19 and neurological symptoms are examined, have not.
Determining whether or not the virus is present in the brain is important because it can help researchers understand whether or not it is the virus itself — or the body’s immune response to the virus — that is causing the damage. This understanding is critical for making the best decision when it comes to treatment.
In an article published in Nature in September 2020, Benedict Michael, a neurologist at the University of Liverpool, explained the importance of finding the mechanism by which these neurological conditions develop.
“If this is direct viral infection of the central nervous system, these are the patients we should be targeting for remdesivir or another antiviral,” he said. “Whereas if the virus is not in the central nervous system, maybe the virus is clear of the body, then we need to treat with anti-inflammatory therapies.”
What’s new — Using “single-cell RNA sequencing,” the researchers behind this new study took 65,309 cells from brain tissue sampled from the deceased Covid-19 patients, as well as controls. They recorded the activation levels of thousands of genes in each cell.
In every case, the activation levels of hundreds of genes in major cell types taken from Covid-19 patients were markedly different from the controls. Many of those genes are associated with inflammatory responses.
Combined with the fact that the researchers couldn’t find any evidence of the virus in the samples, this suggests it is the immune response that is at least partially responsible for the neurological conditions.
The researchers also found irregularities in the cerebral cortex; the area of the brain involved in executive functioning like decision making and memory.
In patients who died of Covid-19, samples taken from the outermost layers of the cerebral cortex showed molecular changes. These changes suggest alterations in brain signaling typically associated with Alzheimer’s Disease and other neurodegenerative conditions.
The researchers found another clue that immune response may be responsible for some of the neurological effects associated with Covid-19: T-cells.
In the brains of deceased Covid-19 patients, T-cells were much more abundant than they were in the control brains. This makes sense: An abundance of T-cells is not something typically found in a healthy brain.
The Inverse analysis — Given that an overactive immune response is known to be one of the causes of poor Covid-19 outcomes, it would make sense if that response extended to the brain, ultimately causing inflammatory changes.
But more work needs to be done to find out precisely how the immune response causes these marked reactions as well as a better understanding of the virus’ direct role, if any, on the brain.
One of the most striking, and still unexplained, aspects of this study is how the Covid-19 patients — whose brains were so vastly and distinctively different from the controls — had no reported clinical neurological symptoms. With more than 179 million cases of Covid-19 worldwide, it is vitally important that we understand exactly what contracting this virus can do to our bodies.
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