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COVID-19 Sleep

Chronic Fatigue Syndrome in the Time of COVID-19: Understanding the Connection

Bhavana Soma—McMaster Life Sciences 2024

Imagine constantly feeling tired to the point where it is difficult to perform daily activities, having no amount of rest make you feel energized, having difficulty sleeping, taking a long time to recover after physical activity, and having issues with thinking, concentrating and remembering. This miserable slew of symptoms that deeply affect the quality of one’s life is characteristic of a debilitating condition known as chronic fatigue syndrome (CFS). Presentation of these symptoms, in addition to physiological symptoms including heart palpitations, general malaise, flu-like symptoms and body pains, over an extended period of time can lead to a diagnosis of CFS if not thoroughly explained by underlying medical conditions [1]. This complicated disorder affects anywhere between 836 000 to 2.5 million Americans, and millions more worldwide [2].

SOURCE: Medical News Today

Scientists have identified a similar condition in those that have contracted COVID-19. COVID-19 starts with a respiratory infection that produces common flu-like symptoms. However, it can have extensive systemic effects on the body as the virus attacks cells and disrupts bodily functions. This means that it may eventually affect the heart, blood vessels, brain, liver, eyes, and kidneys in the long term, in addition to the respiratory system and immune system [3]. The long-term effects become apparent when the test that initially detected the virus is no longer able to, which implies that affected individuals should return to normal since the virus is no longer present in their bodies [4]. However, COVID-19 research has demonstrated that this is not always the case.

Ongoing research suggests that up to a year after having COVID-19, 20% of adults have at least one medical condition that may be a result of the viral infection. This increases to 25% for seniors above the age of 64 [5]. The development of new conditions may be attributed to damage to different organ systems throughout the body and the experience of severe COVID-19, resulting in hospitalization, could trigger mental health conditions [5]. Not only have individuals been diagnosed with new conditions after supposedly having recovered from COVID-19 within a few weeks, many have been experiencing long-term symptoms including, but not limited to, fatigue, difficulty thinking, remembering or concentrating, cognitive difficulties, sleep disturbances, shortness of breath, increased instance of mental health issues, and body pains [6]. These ongoing symptoms are collectively being referred to as a condition called “Long COVID [4].”

SOURCE: RCNi

With the significant overlap between the symptoms of Long COVID and CFS, and the fact that the onset of both Long COVID and up to 75% of CFS cases are confirmed to be linked to a viral infection, many researchers have begun to wonder if the two conditions are actually the same the condition [7].

As of present, there is no cure for either condition. The treatment of CFS is mainly concerned with searching for underlying causes and treating any that are found, as well as alleviating symptoms. Doctors attempt to address the most debilitating symptom prior to treating others that are present [8].

As for Long COVID, researchers all over the world are currently conducting studies and trials to learn more about the condition. In one recent study, people who had been infected with the virus prior to vaccination had a 9 percent lower risk of developing Long COVID after receiving two doses of an mRNA or adenoviral vector vaccine. According to many researchers, we can learn more about the disease and how to better treat it by looking at in-depth analyses of markers such as autoantibodies that are associated with the disease. Current trials that are being conducted include anti-inflammatory drugs, and future potential research could be conducted on immune-suppressing drugs [9].

Since the overlap between Long COVID and CFS has been identified and the question of Long COVID being a form of CFS has been raised, influential CFS researchers believe that the similarities between the two could help millions manage their condition. Their research has shown how CFS may develop due to an overactive immune response in the early stages of the disease that results in immune exhaustion which is also found in chronic viral infections. Future research suggestions include examining biological markers of those who successfully made a full recovery from COVID-19 to better understand the mechanisms that result in a full recovery [7].

References

  1. Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) [Internet]. NHS. NHS; 2021 [cited 2022 Nov 28]. Available from: https://www.nhs.uk/conditions/chronic-fatigue-syndrome-cfs/
  2. Institute of Medicine, Board on the Health of Select Populations, Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Beyond myalgic encephalomyelitis/chronic fatigue syndrome: Redefining an illness. Washington, District of Columbia: The National Academies Press; 2015. 
  3. How COVID-19 affects your body in pictures [Internet]. WebMD. WebMD; 2020 [cited 2022 Nov 28]. Available from: https://www.webmd.com/lung/ss/slideshow-covid-19-body-effects
  4. Komaroff AL, Bateman L. Will COVID-19 lead to myalgic encephalomyelitis/chronic fatigue syndrome? Frontiers in Medicine. 2021;7. 
  5. Mayo Clinic Staff. Covid-19: Long-term effects [Internet]. Mayo Clinic. Mayo Foundation for Medical Education and Research; 2022 [cited 2022 Nov 28]. Available from: https://www.mayoclinic.org/diseases-conditions/coronavirus/in-depth/coronavirus-long-term-effects/art-20490351
  6. Public Health Agency of Canada. Government of Canada [Internet]. Post-COVID-19 condition (long COVID) – Canada.ca. / Gouvernement du Canada; 2022 [cited 2022 Nov 28]. Available from: https://www.canada.ca/en/public-health/services/diseases/2019-novel-coronavirus-infection/symptoms/post-covid-19-condition.html#s
  7. Is long covid really chronic fatigue syndrome by another name? [Internet]. Columbia University Mailman School of Public Health. Columbia University Irving Medical Center; 2021 [cited 2022 Nov 28]. Available from: https://www.publichealth.columbia.edu/public-health-now/news/long-covid-really-chronic-fatigue-syndrome-another-name
  8. Chronic fatigue syndrome [Internet]. Mayo Clinic. Mayo Foundation for Medical Education and Research; 2022 [cited 2022 Nov 28]. Available from: https://www.mayoclinic.org/diseases-conditions/chronic-fatigue-syndrome/diagnosis-treatment/drc-20360510
  9. Ledford H. Long-Covid Treatments: Why the world is still waiting [Internet]. Nature News. Nature Publishing Group; 2022 [cited 2022 Nov 28]. Available from: https://www.nature.com/articles/d41586-022-02140-w
Categories
Sleep

Exploring the Latest Advances in Narcolepsy Research

Zahra Alam—McMaster University Life Sciences 2024

Narcolepsy is a chronic and neurological sleep disorder, where the brain is unable to control the sleep-wake cycle. This results in excessive daytime drowsiness, sudden and recurring attacks of sleep, hallucinations, sleep paralysis, and disturbed sleep [1]. Narcolepsy is deemed to be a rare condition, as less than 2% of the worldwide population is affected [2]. However, the percentage is estimated to be higher since many cases are either undiagnosed or misdiagnosed. The unpredictability of narcolepsy consisting of uncontrollable urges to fall asleep spontaneously and chronic fatigue drastically affects an individual’s quality of life [2].  

There are two types of narcolepsy: Type 1 (NT1) and Type 2 (NT2). NT1 presents itself to be the more common form. It is characterized by the presence of a symptom called cataplexy, which is the loss of muscle tone, resulting in involuntary muscle weakness and temporary paralysis in response to strong emotions, such as fear or excitement [3]. This is caused by a lack of a brain chemical called hypocretin (or orexin) present in cerebrospinal fluid which is responsible for activating arousal and regulating sleep-wake patterns [2]. 

SOURCE: SLEEPOLIS

Low hypocretin levels are the defining feature of NT1 in narcoleptics (individuals with narcolepsy), and although the true cause of the loss of hypocretin-producing cells remains unknown, research suggests that it is due to an autoimmune reaction. It is suspected that the immune system mistakenly attacks the small group of neurons in the hypothalamus that are responsible for producing this chemical due to variations in the HLA-DQB1 gene or environmental factors such as influenza A virus [1]. There is not much research pertaining to NT2, however, it is known that NT2 differs from NT1 narcoleptics as they do not have cataplexy and have normal levels of hypocretin [1]. Both types of narcolepsy can also occur along with conditions of the central nervous system and brain injuries, specifically to the hypothalamus [1]. 

Despite copious amounts of research, the exact mechanisms of narcolepsy are unknown. As of now, there is still no cure, however, treatments and therapies are being investigated to treat the symptoms. There has been significant evolution in the treatment of narcolepsy within the last year in which mouse models have been used to mitigate the pathogenetic mechanisms of narcolepsy more accurately than ever before. Researchers were able to follow and track T-cells (immune system cells) to determine how the Pandermix influenza vaccination triggers an autoimmune response against orexinergic neurons (hypocretin-producing cells) [4]. This study provides more evidence of narcolepsy being an immune disorder, which has been the focal point of research in this field for decades [4]. Mouse models have also been the vessel through which treatments have been tested. A new breakthrough drug, Danavorexton, is an example of a drug being heavily researched. This drug reduced cataplexy-like episodes and sleep disturbance in mice [5]. This new drug was then administered intravenously in humans in a phase 1 clinical trial, proving to be well  tolerated and have an association with better sleep latency in both NT1 and NT2 patients [5].  

SOURCE: Winship Cancer Institute

This shows promising potential as a therapeutic agent and shows that more clinical trials need to be investigated. Stem cell transplantation and immunotherapy have demonstrated to be new and successful medical initiatives and treatments. For the first time, both hypothalamic stem cell transplantation and immunotherapy are being tested together to treat sleep disorders, with the goal of replacing  the damaged neurons that are unable to produce hypocretin in NT1 cases [6]. 

Overall, there has been significant growth in the field of narcolepsy research. However, in order to fully understand its implications, pathways, and causes, further research is required. Many promising studies have shown great treatment potential, and thus presents hope for success in the future towards combating narcolepsy.  

References

  1. Bassetti CLA, Adamantidis A, Burdakov D, Han F, Gay S, Kallweit U, et al. Narcolepsy — clinical spectrum, aetiopathophysiology, diagnosis and treatment. Nature Reviews Neurology [Internet]. 2019 Jul 19;15(9):519–39. Available from: https://www.nature.com/articles/s41582-019-0226-9 
  1. Rahman T, Farook O, Heyat BB, Siddiqui MM. An overview of narcolepsy. IARJSET. 2016 Mar;3:85-7. 
  1. Dauvilliers Y, Siegel JM, Lopez R, Torontali ZA, Peever JH. Cataplexy—clinical aspects, pathophysiology and management strategy. Nature Reviews Neurology. 2014 Jun 3;10(7):386–95. 
  1. Bernard-Valnet R, Frieser D, Nguyen XH, Khajavi L, Quériault C, Arthaud S, et al. Influenza vaccination induces autoimmunity against orexinergic neurons in a mouse model for narcolepsy. Brain [Internet]. 2022 May 13 [cited 2022 Nov 29];145(6):2018–30. Available from: https://academic.oup.com/brain/article-abstract/145/6/2018/6581499
  1. Evans R, Kimura H, Alexander R, Davies CH, Faessel H, Hartman DS, et al. Orexin 2 receptor–selective agonist danavorexton improves narcolepsy phenotype in a mouse model and in human patients. Proceedings of the National Academy of Sciences. 2022 Aug 22;119(35). 
  1. José Ortega-Albás J, López García R, Martínez Martínez A, Carratalá Monfort S, Antonio Royo Prats J, Albiol Varela L, et al. Narcolepsy Treatment: Present and Future. Sleep Medicine and the Evolution of Contemporary Sleep Pharmacotherapy. 2022 Jan 7