Brain fog is not a medical term. It is a term that describes a condition where the brain becomes unable to concentrate. This can be caused by multiple sclerosis, chronic fatigue or cancer. Recent reports have highlighted the fact that COVID-19 patients are often affected by this condition.
COVID brain symptoms are more than just mental fuzziness. These symptoms include headaches, anxiety and depression, vivid dreams, hallucinations, and other well-known smell or taste abnormalities. Seizures and strokes are also included. A study found that over 80 percent of COVID patients experienced neurological complications.
Investigators are still trying to figure out how the virus enters and lives in the brain's no-fly zone. The 50th Annual Meeting of the Society for Neuroscience (or SFN) featured a series of research reports that chronicle the entire journey of the COVID-causing SARS COV-2 virus in the brain. These reports cover cell penetration, dispersion among brain regions and disruption of neural function.
Investigators have struggled to locate the virus's entry point into nerve cells. This is because these cells lack the molecular anchorpoints (found in lung cells for example) that are required for an invasion into the cells interior. A Science study last year identified another possible route of entry. The study showed that NRP1, which is found on both nerve cells in the brain as well as in the olfactory system, combines with furin, an enzyme that allows viral passage.
The question was still open: Is this the preferred route to a cell? Researchers from the All India Institute of Medical Sciences - Patna presented at an SFN 2021 Press Briefing on their computer analysis of gene-protein data. This revealed the presence of NRP1 (and furin) in certain brain areas, particularly the hippocampus. The hippocampus is the main memory and learning locus.
The peripheral nervous system may also be a portal. It transmits motor and sensory impulses from the muscles, organs, and skin to the brain, and the spinal cord. Jonathan Joyce, a doctoral candidate in the laboratory of Andrea Bertke Virginia Polytechnic Institute, and State University, described how his research team infected mice infected with the SARS/COV-2 virus. They then found viral RNA (instructions to make proteins), as well as the virus itself, in clusters of peripheral nervouss that were previously thought to be possible entry points. These nerve groups provided connections to different areas of the brain. Joyce says that these routes could be used by SARS COV-2 to invade your brain. Joyce also suggests that they might help explain nerve pain and tingling some COVID patients may experience.
There is no consensus on what happens during a viral infiltration of the brain. Walter J. Koroshetz (director of the National Institute of Neurological Disorders and Stroke) stated that there is no definitive evidence of SARS COV-2 infecting neurons during a separate SFN-2021 press conference.
Koroshetz stated that he would likely say, "As a director of the NIH, I would probably not bet and say we'll just have to wait and see what the evidence is." Others have suggested that COVID neurological symptoms could be caused by inflammation, leakage of blood brain barrier or mucosal cells dying and becoming infected in the nose, leading to the death nearby neurons.
Another question labs are interested in is how the virus travels once it has entered the brain. John H. Morrison is a professor of neurology at University of California Davis School of Medicine. He also directs the primate research centre. Their study found that SARS-CoV-2 infected rhesus monkeys, including a subgroup of diabetics. Researchers found evidence of the virus in several brain regions, particularly in diabetic animals, after a week. Researchers also found that neurons died from inflammation in the olfactory cortex. Morrison states that the most likely causes of neurological complications in COVID-19 are the direct entry of the virus to the olfactory systems, the production of infections of neurons and the transport to multiple brain areas. The entorhinal cortex was one area in which the virus was found in diabetic monkeys. Morrison describes it as the "single most susceptible brain region to Alzheimer’s disease." Once the virus is present, mild cognitive impairment or dementia can result.
Another avenue of inquiry is the effect COVID has on brain function. Electroencephalography measurements conducted by several Canadian institutions--the Rotman Research Institute, McMaster University, the University of Toronto and the Sunnybrook Institute--revealed that even mild COVID cases can lead to altered brain activity. Researchers compared 42 people who had been positive for COVID and were then sent home to be quarantined.
When assessed on average four months later, a composite measure of brainwave strength in the COVID participants was lower than that in the control group. Some of the abnormal signaling in COVID patients had resolved by eight months. The overall readings of some measures were lower in this group than the rest. This could be due to the combination COVID/social distancing. Allison B. Sekuler (Rotman Research Institute senior scientist) says that COVID appears to have an effect on EEG power similar to the effects we see in people with mild cognitive impairment. This can lead to Alzheimer's disease or related dementias. However, this does not necessarily mean that all people with COVID will develop Alzheimer's. It is worth further research to see if COVID's direct effects on the brain increase dementia risk.
These findings reveal how the virus travels to the brain and leave many unresolved questions. Rita Balice–Gordon moderated and organized the SFN press conference, but she was not involved in research. She said that the findings "show the incredible advances that have been made over 20 months in understanding how this virus affects central nervous system." However, it also raises many questions such as how long an infection can persist, how severe the neuropsychiatric and neurological symptoms of COVID are, and whether there is a greater risk of dementia. Muna Therapeutics, which creates therapies, is headed by Balice-Gordon.
The potential for increased collaborations between neuroscientists and virologists is raised by the pandemic. This pandemic is a reminder of the fact that the brain is not impenetrable, despite the blood-brain barrier. Coxsackie, varicella and Epstein-Barr viruses, as well as other viruses, can enter brain cells. Adenoviruses can even be used to deliver gene therapies inside the organ. There is increasing interest in the unique ways viruses can enter and cause havoc. Morrison states that this is a major issue. "And I think this is going be a major, main area of study for Society for Neuroscience Members." The integration of these two disciplines is only the beginning. At a future SFN meeting, neurovirology might be included alongside sessions on long term memory, synapses, and glia.
