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September 29, 2020; 95 (13) Special Editorial

Long-Haul COVID

View ORCID ProfileAvindra Nath
First published August 11, 2020, DOI: https://doi.org/10.1212/WNL.0000000000010640
Avindra Nath
From the National Institutes of Health, Bethesda, MD.
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Long-Haul COVID
Avindra Nath
Neurology Sep 2020, 95 (13) 559-560; DOI: 10.1212/WNL.0000000000010640

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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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Table 1

Autonomic symptoms in Long-Haul COVID

A 26-year-old high school teacher from Georgia described the symptoms as such:My chest hurts and head poundsThe body aches and heart racesI can hardly move, it's extreme fatigueBrain's in a fog, can't remember the name of my dogLost my sleep and my appetiteFeet are tingling and ears are ringingIt's the Long-Haul COVID

Most of these patients were in excellent health prior to getting infected with SARS-CoV-2. They all had a myriad of symptoms during the acute phase. However as the fever and respiratory symptoms improved, they are left with persistent systemic symptoms some of which are gradually improving but not all are following that course. Still others feel they had nearly recovered from the acute illness and then a few days later, developed a plethora of symptoms that are now persisting. Some describe a cyclical nature to their symptoms where they improve and then worsen every few days. While some were admitted to the hospital due to pulmonary symptoms, the majority were isolated at home. Access to testing and medical care has been limited and most appointments with physicians are being done via telemedicine which has its limitations. Some patients have had extensive testing by internists, infectious disease specialists, cardiologists and pulmonary medicine experts but nothing has been found to explain the symptoms.5 These patients, some of whom are physicians themselves are concerned that they could be stigmatized as being “functional.” Many of these symptoms overlap with those of patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).6,7 However one needs to be careful not jump to the conclusion that they have ME/CFS unless other possible causes of their symptoms have been investigated (table 2).

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Table 2

Possible etiopathogenesis of Long-Haul COVID

The cause of ME/CFS remains unknown despite decades of research on the syndrome. Many patients with ME/CFS similarly report a viral infection as a trigger but since they come to our attention often years after symptom onset, it is impossible to know what may have triggered the symptoms.8 Long-Haul COVID thus represents an excellent opportunity to study the pathophysiology of ME/CFS and in doing so may have broader implications.

Even at this early stage, it might be important to determine what the potential pathophysiologic mechanisms might be. So far there is no convincing evidence for wide spread infection of the brain with the virus. Virus has been detected in CSF and brain of very rare cases9 however, there is evidence for wide spread glial cell activation which may be related to metabolic dysfunction or to the massive immune activation in the periphery. Other possibilities include specific immune responses targeted against specific regions of the brain and autonomic nervous system. Depending on the predominant underlying pathophysiologic mechanism at play, targeted treatment might be possible.

Unfortunately, it looks like this pandemic is out of control. It is spreading rapidly across the globe and even if we have an effective vaccine, we might never have enough dosages to vaccinate the 8 billion inhabitants on this planet. Not insignificantly, there is also a population that is opposed to any kind of vaccination. So COVID-19 is here for the long haul and neurologists are going to play a critical role in the management of these Long-Haulers! Many of their symptoms are neurologic in nature. It is important for us to carefully document the clinical manifestations, to investigate them and treat them. As necessary, we need to conduct research to determine the biological basis of this illness. We discovered the biological basis of diseases such as epilepsy and dystonia, to name a few, which had been called “hysteria” for centuries. Long-Haul COVID is our calling and we should take the lead. In fact, several efforts are underway to prospectively follow these patients with persistent symptoms, including studies at the intramural program at the NIH in Bethesda. As we put these efforts in place, it is equally important for us to remember that we should study and treat not the disease that affects patient but rather the patient that is affected by the disease. Only then can we hope to find solace for these patients in a timely manner.

Study funding

Supported by funding from the intramural program of the National Institute of Neurologic Disorders and Stroke at the NIH, Bethesda, Maryland.

Disclosure

The author reports no disclosures relevant to the manuscript. Please contact journal@neurology.org for full disclosures.https://n.neurology.org/lookup/doi/10.1212/WNL.0000000000010640

Footnotes

  • Please contact journal@neurology.org for full disclosures.https://n.neurology.org/lookup/doi/10.1212/WNL.0000000000010640 Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • © 2020 American Academy of Neurology

References

  1. 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. 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. 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. 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. 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. 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. 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. 8.↵
    1. Rasa S,
    2. Nora-Krukle Z,
    3. Henning N, et al
    . Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Transl Med 2018;16:268.
    OpenUrl
  9. 9.↵
    1. Moriguchi T,
    2. Harii N,
    3. Goto J, et al
    . A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis 2020;94:55–58.
    OpenUrlCrossRefPubMed

Letters: Rapid online correspondence

  • Reader Response: Long-Haul COVID
    • Marylou V Solbrig, Professor of Medicine (Neurology) and Medical Microbiology (retired), University of Manitoba
    Submitted November 30, 2020
  • Reader response: Long-Haul COVID
    • Jon Stone, Professor of Neurology, Centre of Clinical Brain Sciences, University of Edinburgh (Edinburgh, UK)
    • Alan Carson, Professor of Neuropsychiatry, Centre of Clinical Brain Sciences, University of Edinburgh (Edinburgh, UK)
    Submitted September 29, 2020
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