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Written by Sabrina Olivares, FL, USA
Since the 2019 coronavirus (SARS-CoV-2), more than 180 million people have been infected and over 3.9 million people have died worldwide (Johns Hopkins University & Medicine, 2021). At first, everyone seemed to be in a state of panic – healthcare workers, the general public, small business owners – but soon enough this panic wore down. As more and more restrictions were being removed, as companies were creating new vaccines, and as people began arriving to the conclusion that most infected cases eventually recovered, COVID-19 appeared to be less lethal.
Although this may sound like good news, the truth is that there is still so much we do not know about the coronavirus pandemic. For the most part, the immediate short-term effects of COVID-19 have been explored, but we cannot be certain about the long term consequences. This review focuses on identifying and compiling the neurological effects of COVID-19, suggested risk factors for developing severe illness from COVID-19, and the most recent findings of neurological disorders triggered by the immune system response to COVID-19.
Immediate short-term neurological effects
Most individuals who have been hospitalized due to COVID-19 have demonstrated symptoms such as an altered taste and smell, headaches, and dizziness, with some even experiencing an extreme state of confusion (delirium). In a few cases, COVID-19 has been known to cause seizures or strokes from blood clots, from vascular damage, and as one study from COVID-19 patients in Finland determined, from lack of oxygen (Kantonen, 2020). The viral infection weakens arteries and veins, causing blood to leak (eLife, 2021). This results in microbleeds in the brain, inflammation that damages blood vessels, and the clumping of blood cells that form blockages, inhibiting the proper flow of blood, oxygen, nutrients, and minerals throughout the body (National Institute of Neurological Disorders and Stroke, 2021). If oxygen levels become too low (hypoxia), permanent damage to the brain is likely to occur, as seen with intensive care unit patients that cannot breathe without the help of artificial ventilation (National Institute of Neurological Disorders and Stroke, 2021).
Possible long-term neurological complications
Several people have experienced lingering short-term neurological effects up to weeks or months after a COVID-19 infection and recovery. These known short term effects suggest increased likelihood of long-term complications. Common symptoms such as fatigue, post-exertional malaise (PEM), muscle, joint, and chest pain, a prolonged loss of smell or taste, headaches, and sleep disturbances have all been reported (Koralnik, 2020). Symptoms of peripheral neuropathy, in which communication networks from the central nervous system have been damaged, have also been observed in some individuals. Impairment to motor nerves has resulted in muscle weakness and cramps, impairment to sensory nerves has left many without a sense of touch or temperature, and impairment to autonomic nerves has led to other symptoms including excess or absence of sweating and difficulty concentrating as well as lightheadedness when standing up, a condition known as postural orthostatic tachycardia syndrome (POTS) (National Institute of Neurological Disorders and Stroke, 2021).
Cognitive decline and motor impairment from brain damage
Damage to the brain in one-third of intensive care unit survivors from COVID-19 infection poses serious dangers similar to those in individuals with moderate traumatic brain injury (Budson, 2021). As previously mentioned, a COVID-19 immune system response could be linked to inflammation surrounding blood vessels (eLife, 2021). That being said, inflammatory processes of the brain, from the activation of astrocytes, microglia, neurons, and endothelial cells, that cause the release of proinflammatory cytokines are also being considered as one of the leading culprits of impaired cognitive effects on memory, attention, and executive function, along with acute respiratory distress and hypoxia (Duraisamy Kempuraj, 2020). These proinflammatory cytokines increase oxidative stress levels that damage cellular membranes and downregulate surface expression of amino acid transporters, resulting in neuronal death, as observed in individuals with neurocognitive, dementia-like syndrome (Erausquin, 2021). Evidence also suggests that the effects of the virus, along with systemic inflammation and strokes could put patients surviving COVID-19 at a high risk for developing Alzheimer’s disease (Heneka, 2020).
Risk factors that increase the development of severe illness
Having one or more of the following conditions may increase someone’s risk of developing severe illness when exposed to COVID-19: cerebrovascular disease, high blood pressure, obesity, diabetes, dementia, and stroke (National Institute of Neurological Disorders and Stroke, 2021). Additionally, social, racial, and ethnic determinants can also affect populations and individuals differently; for example, factors such as healthcare availability or likelihood of developing other conditions (e.g. African Americans have the highest rate of heart disease in the U.S. (American College of Cardiology, 2018)).
Neurological disorders triggered by the COVID-19 immune response
Reports of other neurological conditions that were most likely triggered by the COVID-19 immune response days to weeks after infection include: multi-system inflammatory syndrome, transverse myelitis, dysautonomia, Guillain-Barreé syndrome, facial nerve palsies, Parkinson’s disease-like symptoms, acute disseminating encephalomyelitis, and acute necrotizing hemorrhagic encephalopathy (National Institute of Neurological Disorders and Stroke, 2021). These disorders and diseases can result in severe forms of inflammation, paralysis, lack of nerve function and nerve fibers, or tissue death that could be difficult or even impossible to treat.
Limitations to current findings
Limitations to current findings of the studies mentioned in this review include the fact that it is not known how COVID-19 infection causes persistent symptoms, if injury to the nervous system will cause chronic disorders or if long-term effects will resolve on their own, if the COVID-19 immune response may lead to autoimmune diseases, and how many individuals will develop neurological disorders over time. It is still too early to tell but continuous research efforts are being made to resolve these concerns. Nevertheless, we based this paper on available systematic reviews and studies from reliable sources to provide readers with a general summary of the neurological long haulers of the COVID-19 pandemic.
Author Information
Sabrina Olivares is a high school student at Somerset Academy, located in South Florida. She is an avid reader and has great aspirations to become a researcher, programmer, and writer, with an interest in public health, infectious disease, and bioinformatics. When she’s not pursuing academic opportunities, Sabrina regularly enjoys binging crime documentaries, playing tennis, and spending quality time with those that she loves most.
References
American College of Cardiology. (2018, October 19). Cover Story: One Size Does Not Fit All: The Role of Sex, Gender, Race and Ethnicity in Cardiovascular Medicine. American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2018/10/14/12/42/cover-story-one-size-does-not-fit-all-sex-gender-race-and-ethnicity-in-cardiovascular-medicine
Budson, A. E., M. D. (2021, March 4). The hidden long-term cognitive effects of COVID-19. Harvard Health. https://www.health.harvard.edu/blog/the-hidden-long-term-cognitive-effects-of-covid-2020100821133
Duraisamy Kempuraj, G. P. S. (2020, July 18). COVID-19, Mast Cells, Cytokine Storm, Psychological Stress, and Neuroinflammation - Duraisamy Kempuraj, Govindhasamy Pushpavathi Selvakumar, Mohammad Ejaz Ahmed, Sudhanshu P. Raikwar, Ramasamy Thangavel, Asher Khan, Smita A. Zaheer, Shankar S. Iyer, Casey Burton, Donald James, Asgar Zaheer, 2020. SAGE Journals. https://journals.sagepub.com/doi/full/10.1177/1073858420941476
eLife. (2021, March 23). Prolonged immune response may contribute to post-COVID-19 blood clots. ScienceDaily. Retrieved July 11, 2021 from www.sciencedaily.com/releases/2021/03/210323103843.htm
Erausquin, G. A. de, Snyder, H., Carrillo, M., Hosseini, A. A., Brugha, T. S., & Seshadri, S. (2021, January 5). The chronic neuropsychiatric sequelae of COVID‐19: The need for a prospective study of viral impact on brain functioning. Alzheimer's Association. https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12255
Heneka, M. T., Golenbock, D., Latz, E., Morgan, D., & Brown, R. (2020, June 4). Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimer's Research & Therapy. https://alzres.biomedcentral.com/articles/10.1186/s13195-020-00640-3
Johns Hopkins University & Medicine. (2021). COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). Johns Hopkins Coronavirus Resource Center. https://coronavirus.jhu.edu/map.html
Kantonen, J., Mahzabin, S., Mäyränpää, M. I., Tynninen, O., Paetau, A., Andersson, N., Sajantila, A., Vapalahti, O., Carpén, O., Kekäläinen, E., Kantele, A., & Myllykangas, L. (2020, August 28). Neuropathologic features of four autopsied COVID‐19 patients. Wiley Online Library. https://onlinelibrary.wiley.com/doi/full/10.1111/bpa.12889
Koralnik, I. J., & Tyler, K. L. (2020, June 23). COVID‐19: A Global Threat to the Nervous System. Wiley Online Library. https://onlinelibrary.wiley.com/doi/full/10.1002/ana.25807
National Institute of Neurological Disorders and Stroke. (2021, June 22). Coronavirus and the Nervous System. National Institute of Neurological Disorders and Stroke. https://www.ninds.nih.gov/Current-Research/Coronavirus-and-NINDS/nervous-system
