Cerebrum Summer 2020


At first glance, it may seem that these patients have little in common. Yet all three were also suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease, better known as Covid-19. While most individuals infected with this new virus exhibit fever, cough, and respiratory symptoms, doctors across the globe are also documenting patients presenting with a handful of neurological manifestations— leading clinicians and researchers to wonder if Covid-19 also has the ability to invade the human nervous system. “As more people are being tested and diagnosed with this virus, physicians are starting to see more uncommon symptoms and complications, including neurological ones,” says Diane Griffin, M.D., Ph.D., a researcher at Johns Hopkins University’s Bloomberg School of Public Health. “But as Covid-19 is a new virus, we aren’t yet sure why these things are happening. Is the virus getting into the brain directly? Is it affecting the brain through other means? These are important questions to answer.” Viruses and the Nervous System Viruses, simply defined, are submicroscopic infectious agents that can only replicate inside the cells of living hosts. While experts still hotly debate whether these molecules of nucleic acid, protected by a protein shell, should be considered “living,” they are unquestionably insidious in their ability to hijack the inner machinery of cells for their own reproductive purposes, sometimes causing overwhelming damage to their host in the process. Over the last century, the world has seen outbreaks of numerous virus-caused diseases, ranging from polio to influenza to the human immunodeficiency virus (HIV). Some of these have led to devastating pandemics, resulting in millions of deaths. Others, however, only cause mild symptoms, an expected nuisance to deal with each fall and winter. Kenneth Tyler, M.D., chair of the Department of Neurology at the University of Colorado (UC) Anschutz Medical Center, observes there are many viruses that affect the nervous system. Even Diane Griffin / Johns Hopkins

garden variety flu can lead to neurological problems in certain patients—yet, it is important to remember that this remains a rare occurrence. “Millions, perhaps even billions, of individuals are infected with different viruses all the time, and there’s never any issue with the brain,” he says. “Yet, in some cases, we do see encephalitis, or inflammation of the brain due to a particular infection. We are learning there are many reasons why that can occur—

Kenneth Tyler / University of Colorado

and it doesn’t always happen in the same manner or even cause the same type of damage. Some viruses can directly infect different brain cells, both the neurons themselves and glial cells. Others may get to the brain in other ways. It all gets rather complicated rather quickly.”

Taking Different Doors into the Nervous System Dorian McGavern, Ph.D., a senior investigator at the National Institute of Neurological Disorders and Stroke (NINDS), says it is difficult for viruses to gain direct access to the central nervous system (brain and spinal cord). “It’s a relatively closed compartment,” he says. “To get into the brain or spinal cord, a virus has to essentially invade all

Dorian McGavern / NINDS

the brain’s peripheral defenses like the blood-brain barrier as well as the different immune responses. It’s not that easy.” Viruses may enter their hosts through the gastrointestinal tract, the respiratory tract including the nose (and the neurons that reside there), or through the bite of a mosquito or infected animal. The point of entry, and how the virus might spread from that point, likely determine which bodily systems may be most affected. For example, some scientists are hypothesizing that Covid-19 may be targeting blood vessels, which is why we see such widespread damage across different organs. Blood vessel infection would help explain the blood clots seen in some of the young stroke patients, not to


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