How Exactly Do the Brain and COVID-19 relate?

New studies offer insight into how COVID-19 affects the brain but also raise questions about potential permanent brain damage.

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Virtually nothing was known about the new coronavirus that shook the world and changed life as we knew it 20 months ago. Through extensive studies and experiments, however, scientists have created several successful vaccines and collected essential information about the virus’s effects on the human brain and body. The most worrisome of these discoveries are the permanent effects of COVID-19 on the body’s functions, especially its neurological processes.

New studies on COVID-19 and the brain reveal that neurological symptoms such as memory loss and strokes are frequently associated with the virus. One study revealed that nearly 80 percent of hospitalized COVID-19 patients experienced neurological symptoms including headaches, loss of smell or taste, comas, and strokes. A few preprints of scientific journals have associated COVID-19 with severe neurological effects such as a decrease in gray matter, the tissue in the brain that processes information from passing signals and is responsible for emotions, movement, and memory, in some regions of the cerebral cortex.

It is unclear exactly how the virus accesses the brain and damages it. A previous theory stated that SARS-CoV-2 infects the brain and causes problems in information transmission and processing. However, it was quickly disproven when studies showed that the virus was unable to cross the blood-brain barrier (BBB) and enter the brain, leaving neurons with little impairment. One plausible explanation is that SARS-CoV-2 infiltrates the brain through the olfactory mucosa, the upper lining of the nasal cavity. Other recent studies suggest that SARS-CoV-2 attacks astrocytes—cells that perform necessary tasks in the brain ranging from keeping neurons healthy by supplying nutrients to regulating their electrical activity.

Experiments exposing brain organoids, miniature imitations of the brain created with stem cells, to the virus found that astrocytes were the main target. One study that analyzed the brains of those who died from COVID-19 revealed that astrocytes consisted of 66 percent of the total infected cells. While it is not definitive, the infection of astrocytes and subsequent disruption of their function could account for some COVID-19 related neurological symptoms like mental fatigue, depression, confusion, and forgetfulness.

Another theory is that SARS-CoV-2 reduces blood flow to the brain, effectively weakening neurons and disabling them. A report in February revealed that SARS-CoV-2 targets pericytes, cells located in capillaries all around the body and brain. Pericytes are essential for maintaining the BBB, regulating blood flow, and managing the overall homeostasis of the body. David Attwell, a neuroscientist at University College London, conducted an experiment that observed the effect of SARS-CoV-2 on hamster brains. Attwell’s team studied slices of hamster brains that were treated with a substance that blocked the same receptors as SARS-CoV-2. The results were that the virus could influence pericytes by disrupting the functions of pericyte receptors, leading to capillary constriction in tissues. These consequences are quite severe and may provide an explanation for the permanent damage COVID-19 has on the brain. Moreover, since restricted blood flow is both a symptom of COVID-19 and high blood pressure, some researchers have considered using drugs that treat high blood pressure such as losartan, which widens blood vessels, to treat COVID-19.

Other researchers credit the COVID-19 neurological symptoms to malfunctions of the immune system, which include overreactions and misfiring. This can occur when the body’s immune system mistakenly makes “autoantibodies” as a response to infections, targeting essential tissues rather than infectious particles. A team in the German Center for Neurodegenerative Diseases in Berlin discovered that patients who were critically ill with COVID-19 produced autoantibodies that could bind to neurons and brain tissues. Patients injected intravenously with immunoglobulin, a kind of antibody that suppresses autoantibodies, had some improvement in their condition.

A study from August 2021 looked for neurological changes by comparing those who were infected by COVID-19 to those who weren’t. The researchers used the UK Databank, a database that includes brain images of thousands of UK people since 2014, to formulate the baseline data and brain images of healthy people. Accounting for demographic factors and disease risk differences in their grouping and examination of the differences between COVID-19 participants and the database’s patients, the researchers found clear differences of gray matter present. The differences included reduced thickness of gray matter in the frontal and temporal lobes of the brain in the COVID-19 group, a pattern that was not observed in those who were not infected with COVID-19. While it is normal for gray matter in the brain to shrink as people age, the changes seen in the COVID-19 participants were abnormal. Surprisingly, even patients who suffered a mild infection showed the same degree of loss of brain volume as those afflicted with greater severity.

One of the most infamous symptoms of COVID-19 is the loss of smell and taste, which are senses controlled by the olfactory bulb. Coincidently, the regions of the brain that the UK researchers analyzed were related to the olfactory bulb, which is connected to the frontal lobes and the hippocampus. The hippocampus holds an important role in memory and cognition in humans and may also be involved with the aging process. Surprisingly, despite being two different diseases, COVID-19 and Alzheimer’s disease may share some similarities, especially since they both affect the hippocampus and memory-related changes in the brain. While nothing is conclusive yet, studying the possible relationships between memory and COVID-19 could reveal long-term effects and possible implications for Alzheimer's disease and other memory disorders.

While one may feel that the era of a normal, familiar, and maskless society was long ago, scientists are only beginning to observe and understand the long-term effects of COVID-19. There has been much evidence from new and old studies that have provided insight into the neurological effects of COVID-19, but scientists are still attempting to uncover the method of action in which COVID-19 takes to manifest those symptoms. Assembling these puzzle pieces will provide us with treatment options for these far-reaching effects. The role of the brain as the body’s master may allow the future understanding of COVID-19’s neurological effects to be applied to other areas of neuroscience.