COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which has been at the forefront of people’s minds since its emergence in late 2019. It is fair to say that the pandemic it unleashed throughout the world will resonate with us for many years. The arrival of successful vaccines has tilted the pandemic in our favour, but there is a sinister side to this story.
Not long after COVID-19 became synonymous with the collapse of tourism, businesses and overburdened health systems, reports of people surfaced who suffered from a condition that became known as Long Covid. In essence, Long Covid is a lingering illness in people who have contracted COVID-19 and then presumably recovered because the virus was no longer detectable. Regardless of how severe the initial onset of COVID-19 manifested itself, a significant proportion of patients report debilitating symptoms long after the virus has been eliminated from their body [1].
An Irish study found that over 50% of patients with COVID-19 reported persistent fatigue more than 10 weeks after initial symptoms [2]. Likewise, researchers in Italy confirmed troublesome symptoms sixty days after initial onset [3]. The US Centers for Disease Control and Prevention similarly concluded ongoing symptoms such as fatigue and cough. They found this to be more prevalent in older people or those suffering from chronic diseases.
But is this a hallmark of SARS-CoV-2 and entirely unexpected? The short answer is no, because there is a range of viruses that cause post-infectious fatigue syndrome. Similar conditions have been reported for Ross River virus, Ebola virus, Dengue Fever virus and SARS coronavirus [1], just to name a few. Although the progression of disease and the organ damage they cause is quite different, chronic fatigue is a lingering condition they all share. Interestingly, the symptoms of post-infectious chronic fatigue are remarkably similar to those experienced by people who have Myalgic Encephalomyelitis, commonly known as Chronic Fatigue Syndrome . In fact, Dr Anthony Fauci, the Director of the National Institute for Allergy and Infectious Diseases, reported that patients who had COVID-19 often develop a post-viral syndrome that is remarkably like Chronic Fatigue Syndrome [4]. It is too early to tell how long this condition will last post-COVID-19.
The indirect cost of Chronic Fatigue Syndrome is staggering, up to 836 000 and 2.5 million individuals are affected in the United States alone before COVID-19 struck [5]. It remains to be seen how many additional cases will be added as a result of this pandemic.
So, what causes post-infectious chronic fatigue? We know that viruses such as SARS-CoV-2 can damage the heart, lungs or kidneys, and the impaired function of these organs would be sufficient to produce chronic fatigue. Also, patients who have been on ventilators can suffer from post-traumatic stress disorder. Others may develop depression due to their reduced quality of life post-infection. It is highly likely that these psychiatric disorders also lead to chronic fatigue. However, many patients do not present with either physiological symptoms, such as organ damage, or psychiatric conditions and still suffer from post-infectious chronic fatigue [1].
To study this further, we can look at earlier research conducted on sufferers of Chronic Fatigue Syndrome. Even back in 1999, it was suspected that Chronic Fatigue Syndrome may have its roots in oxidative stress [6]. That lead to the conclusion that acute glutathione depletion may be involved. Some studies have revealed that glutathione is chronically depleted in some sufferers [7].
The role of glutathione in preventing oxidative stress is well understood. As an antioxidant, it performs many vital functions inside the cell. In the case of chronic fatigue, there appears to be a tug of war for this critical molecule. The immune system places great demands on glutathione when challenged, as is the case in Chronic Fatigue Syndrome. This can lead to competition for glutathione precursors since the muscular system also relies on glutathione for aerobic muscular contraction [8]. As the immune system takes priority in survival, insufficient glutathione may express itself as fatigue since skeletal muscles cannot sustain normal aerobic metabolism.
Time will tell how post-infectious chronic fatigue will progress in COVID-19 patients. It is hoped that further research will identify specific causes that lead to effective treatments. This may ultimately also relieve the symptoms of Chronic Fatigue Syndrome. Glutathione will most likely play a significant role in these studies, and an effective way to supplement cellular glutathione will be needed. Supplementation with gamma-glutamylcysteine has been demonstrated in a human clinical trial to increase cellular glutathione levels regardless of its initial (basal) concentration. And, most importantly, this increase occurred rapidly (within hours) [9]. With other supplements, a slight increase in glutathione (GSH) could only be observed after many months of daily supplementation. The recent commercial availability of gamma-glutamylcysteine means that researchers are now able to successfully test the effectiveness of increasing cellular glutathione (GSH) in treating the symptoms of Long Covid and Chronic Fatigue Syndrome.
References
- Komaroff, A.L. and L. Bateman, Will COVID-19 Lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome? Frontiers in Medicine, 2021. 7(1132)
https://www.frontiersin.org/article/10.3389/fmed.2020.606824 - Townsend, L., A.H. Dyer, K. Jones, J. Dunne, A. Mooney, F. Gaffney, L. O’Connor, D. Leavy, K. O’Brien, J. Dowds, J.A. Sugrue, D. Hopkins, I. Martin-Loeches, C. Ni Cheallaigh, P. Nadarajan, A.M. McLaughlin, N.M. Bourke, C. Bergin, C. O’Farrelly, C. Bannan, and N. Conlon, Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. PLoS One, 2020. 15(11): p. e0240784.
https://doi.org/10.1371/journal.pone.0240784 - Carfì, A., R. Bernabei, and F. Landi, Persistent Symptoms in Patients After Acute COVID-19. Jama, 2020. 324(6): p. 603-605. 10.1001/jama.2020.12603.
- Topol, E. and A. Verghese, Fauci to Medscape:‘We’re All In It Together and We’re Gonna Get Through It’. 2020, Medscape.
- Clayton, E.W., Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An IOM Report on Redefining an Illness. JAMA, 2015. 313(11): p. 1101-1102.
https://doi.org/10.1001/jama.2015.1346 - Bounous, G. and J. Molson, Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome. Med Hypotheses, 1999. 53(4): p. 347-9. 10.1054/mehy.1998.0780
- Shungu, D.C., N. Weiduschat, J.W. Murrough, X. Mao, S. Pillemer, J.P. Dyke, M.S. Medow, B.H. Natelson, J.M. Stewart, and S.J. Mathew, Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology. NMR Biomed, 2012. 25(9): p. 1073-87. 10.1002/nbm.2772
- JAMMES, Y., J.G. STEINBERG, O. MAMBRINI, F. BRÉGEON, and S. DELLIAUX, Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise. Journal of Internal Medicine, 2005. 257(3): p. 299-310.
https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2796.2005.01452.x - Zarka, M.H. and W.J. Bridge, Oral administration of γ-glutamylcysteine increases intracellular glutathione levels above homeostasis in a randomised human trial pilot study. Redox Biology, 2017. 11: p. 631-636.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5284489/pdf/main.pdf