Long-Haul COVID
Abstract
Modern medicine has faced its biggest challenge from the smallest of organisms. It is becoming increasingly apparent that many patients who recovered from the acute phase of the SARS-CoV-2 infection have persistent symptoms. This includes clouding of mentation, sleep disturbances, exercise intolerance and autonomic symptoms (table 1). Some also complain of persistent low grade fever and lymphadenopathy. Although there are no peer reviewed papers at the moment on these patients, many news articles have been written about this phenomenon1–4 and there are Facebook groups with several thousand patients describing these symptoms. They call the illness, “Long-Haul COVID” or “Long-tail COVID.” Many of these patients are health care workers who had massive exposure to the virus early in the pandemic and describe having symptoms for “100+ days.”5
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References
1.
Reddy S. Three months in, these patients are still ravaged by Covid’s fallout. The Wall Street Journal. July 1, 2020. Available at: wsj.com/articles/three-months-in-these-patients-are-still-ravaged-by-covids-fallout-11593612004. Accessed August 11, 2020.
2.
Vastag B, Mazur B. Researchers warn covid-19 could cause debilitating long-term illness in some patients. The Washington Post. May 30, 2020. Available at: washingtonpost.com/health/could-covid-19-cause-long-term-chronic-fatigue-and-illness-in-some-patients/2020/05/29/bcd5edb2-a02c-11ea-b5c9-570a91917d8d_story.html. Accessed August 11, 2020.
3.
The lingering symptoms of Covid-19. Bloomberg. June 10, 2020. Accessed Available at: bloomberg.com/news/videos/2020-06-10/the-lingering-symptoms-of-covid-19-video. Accessed August 11, 2020.
4.
Cha AE, Bernstein L. These people have been sick with Coronavirus for more than 60 days: doctors aren’t sure why. The Washington Post. June 11, 2020. Available at: washingtonpost.com/health/2020/06/11/coronavirus-chronic/?arc404=true. Accessed August 11, 2020.
5.
Kleinman Z. Coronavirus: thousands say debilitating symptoms last 'for weeks'. BBC News. July 7, 2020. Available at: bbc.com/news/health-53269391. Accessed August 11, 2020.
6.
Zimmer K. Could COVID-19 Trigger Chronic Disease in Some People? The Scientist. July 17, 2020. Available at: the-scientist.com/news-opinion/could-covid-19-trigger-chronic-disease-in-some-people-67749. Accessed August 11, 2020.
7.
Berlinger J, McKeehan B, Kottasová I, Upright E, Wagner M, Macaya M. July 9 coronavirus news. CNN July 9, 2020. Available at: edition.cnn.com/world/live-news/coronavirus-pandemic-07-09-20-intl/h_5125152a01f8c98d362cf15d6860ab37. Accessed August 11, 2020.
8.
Rasa S, Nora-Krukle Z, Henning N, et al. Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Transl Med 2018;16:268.
9.
Moriguchi T, Harii N, Goto J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55–58.
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© 2020 American Academy of Neurology.
Publication History
Published online: August 11, 2020
Published in print: September 29, 2020
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The author reports no disclosures relevant to the manuscript. Please contact [email protected] for full disclosures.
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Supported by funding from the intramural program of the National Institute of Neurologic Disorders and Stroke at the NIH, Bethesda, Maryland.
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Cited By
- Long-term clinical outcomes and prognosis, COVID-19 and the Cardiovascular System, (199-232), (2025).https://doi.org/10.1016/B978-0-443-14001-3.00012-1
- Pathogenetic and clinical-neurological features of post-COVID syndrome, Vestnik nevrologii, psihiatrii i nejrohirurgii (Bulletin of Neurology, Psychiatry and Neurosurgery), 6, (688-696), (2024).https://doi.org/10.33920/med-01-2406-01
- Neuropsychiatric Burden of SARS-CoV-2: A Review of Its Physiopathology, Underlying Mechanisms, and Management Strategies, Viruses, 16, 12, (1811), (2024).https://doi.org/10.3390/v16121811
- Exploring the Pathophysiology of Long COVID: The Central Role of Low-Grade Inflammation and Multisystem Involvement, International Journal of Molecular Sciences, 25, 12, (6389), (2024).https://doi.org/10.3390/ijms25126389
- Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome, Frontiers in Immunology, 15, (2024).https://doi.org/10.3389/fimmu.2024.1341843
- Prevalence of long COVID in India and its impact on morbidity in terms of Years Lived with Disability: A semi-systematic review, THE FIFTH SCIENTIFIC CONFERENCE FOR ELECTRICAL ENGINEERING TECHNIQUES RESEARCH (EETR2024), (070002), (2024).https://doi.org/10.1063/5.0228037
- Long COVID in India and its impact on mental health: A comprehensive review, THE FIFTH SCIENTIFIC CONFERENCE FOR ELECTRICAL ENGINEERING TECHNIQUES RESEARCH (EETR2024), (070003), (2024).https://doi.org/10.1063/5.0228034
- Deep phenotyping of post-infectious myalgic encephalomyelitis/chronic fatigue syndrome, Nature Communications, 15, 1, (2024).https://doi.org/10.1038/s41467-024-45107-3
- The persistence of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) after SARS-CoV-2 infection: A systematic review and meta-analysis, Journal of Infection, 89, 6, (106297), (2024).https://doi.org/10.1016/j.jinf.2024.106297
- Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome, Journal of Autoimmunity, 147, (103267), (2024).https://doi.org/10.1016/j.jaut.2024.103267
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Since Dr. Nath’s Special Editorial on Long-Haul COVID1 in the September issue of Neurology, there has been increasing media coverage of athletes, or previously very fit individuals, struggling with the exhaustion of long-haul COVID. The difficulties faced by runners, cyclists, even children who attended ballet classes 4 days/week or dancing and aikido lessons 5 days/week2 have been reported in sports and athletic magazines, newspapers, and news shows.
Long-haul COVID resembles, to some degree, “overtraining syndrome”, in that disordered metabolism or energy utilization may be common to both. Overtraining syndrome is the maladaptive response to excessive exercise training characterized by under- or impaired sport performance, persistent fatigue, mood alterations, disturbed sleep, neuroendocrine changes.3 Could mitochondria have a role in pathogenesis of long-haul COVID? Mitochondrial DNA (mtDNA) stress is also a cell-intrinsic stimulus for antiviral signaling. Humans have a DNA sensing and defense system to cytosolic DNA exposure, such that virus-derived cytosolic DNA as well as self-DNA can trigger immune responses.4
A common feature of + strand RNA viruses is that virus replication takes place on host intracellular membranes. For coronaviruses it is on mitochondria, as shown by localization of SARS-COV-2 open reading frame proteins to mitochondria.5 Mitochondria, upon viral infection, would leak mtDNA into cytoplasm and extracellular space. Systems for monitoring mtDNA homeostasis, for example, the integrity of intracellular and extracellular mtDNA, work together with canonical virus sensing systems to generate an mtDNA inflammasome and stimulation of interferon genes.4
Although mitochondrial cytopathy does not explain how acute becomes long-term illness, mitochondria—fundamental to life—may present new paradigms for disease understanding. Mitochondrial mechanisms related to striatal muscle may generalize to smooth and cardiac muscle and capture some of the autonomic features of long-haul COVID. Mechanisms generalizable to the brain may further elucidate cognitive and attention features of long-haul COVID.
Disclosure
The author reports no relevant disclosures. Contact [email protected] for full disclosures.
References
Avindra Nath’s article1 makes a welcome “call to arms” for neurologists to be interested in “long-haul COVID,” noting that many sufferers are “concerned that they could be stigmatized” as having a functional disorder. Research over the last 20 years has shown that functional disorders have their own neurobiology, they are commonly precipitated by physical experiences such as injury and (any kind of) infection, and they can affect anyone regardless of education or prior medical history.2 Functional disorders are genuine conditions, not synonyms for “nothing wrong” or “nothing biological.” The investigation of long-haul COVID should not be polarized at the outset by a false dichotomy between “biology” and “functional disorders.” We now have positive diagnostic features for functional neurological disorders involving motor and seizure symptoms, and increasingly for cognitive symptoms.3 Including these in phenotypic studies—especially as comorbidities—may help improve our understanding of long-haul covid and other post-viral syndromes.
Disclosure
The authors report no relevant disclosures. Contact [email protected] for full disclosures.
References