Tag: Tate

The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Abstract:

Long COVID is now well accepted as an ongoing post-viral syndrome resulting from infection of a single virus, the pandemic SARS-CoV-2. It mirrors the post-viral fatigue syndrome, Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, a global debilitating illness arising mainly from sporadic geographically-specific viral outbreaks, and from community endemic infections, but also from other stressors. Core symptoms of both syndromes are post-exertional malaise (a worsening of symptoms following mental or physical activity), pervasive fatigue, cognitive dysfunction (brain fog), and sleep disturbance. Long COVID patients frequently also suffer from shortness of breath, relating to the lung involvement of the SARS-CoV-2 virus.

There is no universally accepted pathophysiology, or recognized biomarkers yet for Long COVID or indeed for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Clinical case definitions with very similar characteristics for each have been defined. Chronic inflammation, immune dysfunction, and disrupted energy production in the peripheral system has been confirmed in Long COVID and has been well documented in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Neuroinflammation occurs in the brain in Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome as shown from a small number of positron emission tomography and magnetic resonance spectroscopy studies, and has now been demonstrated for Long COVID. Oxidative stress, an increase in reactive oxygen and reactive nitrogen species, and free radicals, has long been suggested as a potential cause for many of the symptoms seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, resulting from both activation of the brain’s immune system and dysregulation of mitochondrial function throughout the body. The brain as a high producer of energy may be particularly susceptible to oxidative stress. It has been shown in peripheral immune cells that the balanced production of proteins involved in regulation of the reactive oxygen species in mitochondria is disturbed in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Fluctuations in the chronic low level neuroinflammation during the ongoing course of Long COVID as well as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome have been proposed to cause the characteristic severe relapses in patients.

This review explores oxidative stress as a likely significant contributor to the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, and the mechanisms by which oxidative stress could cause the symptoms seen in both syndromes. Treatments that could mitigate oxidative stress and thereby lessen the debilitating symptoms to improve the life of patients are discussed.

Source: WALKER, Max Oliver Mackay et al. The significance of oxidative stress in the pathophysiology of Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Medical Research Archives, [S.l.], v. 10, n. 9, sep. 2022. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/3050>. Date accessed: 09 oct. 2022. doi: https://doi.org/10.18103/mra.v10i9.3050.

Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease now well-documented as having arisen commonly from a viral infection, but also from other external stressors, like exposure to agricultural chemicals, other types of infection, surgery, or other severe stress events. Research has shown these events produce a systemic molecular inflammatory response and chronic immune activation and dysregulation. What has been more difficult to establish is the hierarchy of the physiological responses that give rise to the myriad of symptoms that ME/CFS patients experience, and why they do not resolve and are generally life-long.

The severity of the symptoms frequently fluctuates through relapse recovery periods, with brain-centered symptoms of neuroinflammation, loss of homeostatic control, “brain fog” affecting cognitive ability, lack of refreshing sleep, and poor response to even small stresses. How these brain effects develop with ME/CFS from the initiating external effector, whether virus or other cause, is poorly understood and that is what our paper aims to address.

We propose the hypothesis that following the initial stressor event, the subsequent systemic pathology moves to the brain via neurovascular pathways or through a dysfunctional blood-brain barrier (BBB), resulting in chronic neuroinflammation and leading to a sustained illness with chronic relapse recovery cycles. Signaling through recognized pathways from the brain back to body physiology is likely part of the process by which the illness cycle in the peripheral system is sustained and why healing does not occur. By contrast, Long COVID (Post-COVID-19 condition) is a very recent ME/CFS-like illness arising from the single pandemic virus, SARS-CoV-2.

We believe the ME/CFS-like ongoing effects of Long COVID are arising by very similar mechanisms involving neuroinflammation, but likely with some unique signaling, resulting from the pathology of the initial SARS-CoV-2 infection. The fact that there are very similar symptoms in both ongoing diseases, despite the diversity in the nature of the initial stressors, supports the concept of a similar dysfunctional CNS component common to both.

Source: Tate W, Walker M, Sweetman E, Helliwell A, Peppercorn K, Edgar C, Blair A, Chatterjee A. Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses. Front Neurol. 2022 May 25;13:877772. doi: 10.3389/fneur.2022.877772. PMID: 35693009; PMCID: PMC9174654.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174654/ (Full text)