Tag: long covid vs ME/CFS

My experience with ME/CFS and implications: A personal narrative

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic, debilitating health condition characterized by overwhelming fatigue and post-exertional malaise, or exacerbation of symptoms following physical, mental, or emotional exertion. ME/CFS often impacts every aspect of an individual’s life, and one’s new reality may be much different from the daily life experienced before the onset of the condition. Though the long-term effects of COVID-19 have brought increased attention to chronic fatigue and related disorders, ME/CFS is still vastly understudied and frequently misunderstood.

People with ME/CFS are often passed between various healthcare providers as evidence-based treatments remain scarce. These patients are sometimes sent to rehabilitation professionals, who often lack appropriate education and experience with this patient population. This article describes the experience of a young woman and physical therapist with ME/CFS following COVID-19 infection, as well as potential implications for rehabilitation professionals and those who care for those with this condition.

Source: Sirotiak Z. My experience with ME/CFS and implications: A personal narrative. Work. 2023 Mar 9. doi: 10.3233/WOR-220487. Epub ahead of print. PMID: 36911961. https://content.iospress.com/articles/work/wor220487 (Full text)

Is exposure to Epstein-Barr virus a risk factor for long-covid?

Abstract:

Background: A viral etiology to chronic fatigue syndrome (CFS) has long been postulated, and Epstein-Barr Virus (EBV) was the first CFS associated virus. CFS and Long-COVID share features, potentially implicating a similar etiology. This study evaluated if EBV exposure is associated with post-COVID syndrome (Long-COVID)

Methods: Intermountain Healthcare electronic health records were queried to identify patients diagnosed with COVID-19 and tested for EBV between March 6, 2020 and April 13, 2022. A subsequent diagnosis of Long-COVID (ICD-10 U09.9) was evaluated using survival methods.

Results: Overall, 296,959 patients had COVID-19 and 590 had concurrent EBV test results [207 (35.1%) were EBV positive]. Subjects averaged 27.4±18.4 years of age (range: 0-86); 57.6% were female. Hospitalization occurred in 61 subjects (10.3%) within 30 days of COVID-19 diagnosis, with 17 (2.9%) requiring intensive care. Long-COVID was found in 29 (4.9%) subjects (just 10 were among the 61 hospitalized for COVID-19), with 15 (7.2%) EBV positive (Figure) and 14 (3.7%) EBV negative (HR=2.09, 95% CI=1.01, 4.34; p=0.042). EBV risk remained in multivariable analyses. Race, hyperlipidemia, and tobacco use also predicted Long-COVID, with histories of anticoagulant and vitamin D use were protective.

Conclusion: In a large prospectively-collected registry, EBV positivity was associated with an elevated risk of Long-COVID. This suggests that EBV may be a predisposing risk factor for or co-precipitant of Long-COVID.

Source: Horne B, Knowlton K, Le V, et al. IS EXPOSURE TO EPSTEIN-BARR VIRUS A RISK FACTOR FOR LONG-COVID?. J Am Coll Cardiol. 2023 Mar, 81 (8_Supplement) 1784. https://doi.org/10.1016/S0735-1097(23)02228-3 (Full text)

Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID patients have overlapping neurological, autonomic, pain, and post-exertional symptoms. We compared volumes of brainstem regions for 10 ME/CFS (CCC or ICC criteria), 8 long COVID (WHO Delphi consensus), and 10 healthy control (HC) subjects on 3D, T1-weighted MRI images acquired using sub-millimeter isotropic resolution using an ultra-high field strength of 7 Tesla.

Group comparisons with HC detected significantly larger volumes in ME/CFS for pons (p = 0.004) and whole brainstem (p = 0.01), and in long COVID for pons (p = 0.003), superior cerebellar peduncle (p = 0.009), and whole brainstem (p = 0.005). No significant differences were found between ME/CFS and long COVID volumes. In ME/CFS, we detected positive correlations between the pons and whole brainstem volumes with “pain” and negative correlations between the midbrain and whole brainstem volumes with “breathing difficulty.”

In long COVID patients a strong negative relationship was detected between midbrain volume and “breathing difficulty.” Our study demonstrated an abnormal brainstem volume in both ME/CFS and long COVID consistent with the overlapping symptoms.

Source: Thapaliya K, Marshall-Gradisnik S, Barth M, Eaton-Fitch N, Barnden L. Brainstem volume changes in myalgic encephalomyelitis/chronic fatigue syndrome and long COVID patients. Frontiers in Neuroscience, 2023 March 2; 17:1125208. https://www.frontiersin.org/articles/10.3389/fnins.2023.1125208/full (Full text)

A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level

Abstract:

COVID-19 afflicts patients with acute symptoms and longer term sequelae. One of the sequelae is myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), which is often difficult to diagnose, having no established tests. In this article, we synthesize information from literature reviews on patients with ME/CSF that developed after recovery from COVID-19.

Source: Jinushi R, Nishiguchi S, Masuda S, Sasaki A, Koizumi K, Ryozawa S. A case of post-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome characterized by post-exertional malaise and low serum acylcarnitine level. Clin Case Rep. 2023 Feb 10;11(2):e6930. doi: 10.1002/ccr3.6930. PMID: 36789311; PMCID: PMC9913186. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9913186/ (Full text)

No Causal Effects Detected in COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two Sample Mendelian Randomization Study

Abstract

New clinical observational studies suggest that Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a sequela of COVID-19 infection, but whether there is an exact causal relationship between COVID-19 and ME/CFS remains to be verified. To investigate whether infection with COVID-19 actually causes ME/CFS, this paper obtained pooled data from the Genome Wide Association Study (GWAS) and analyzed the relationship between COVID susceptibility, hospitalization and severity of COVID and ME/CFS, respectively, using two-sample Mendelian randomization (TSMR).
TSMR analysis was performed by inverse variance weighting (IVW), weighted median method, MR-Egger regression and weighted mode and simple mode methods, respectively, and then the causal relationship between COVID-19 and ME/CFS was further evaluated by odds ratio (OR). Eventually, we found that COVID-19 severity, hospitalization and susceptibility were all not significantly correlated with ME/CFS (OR:1.000,1.000,1.000; 95% CI:0.999–1.000, 0.999–1.001, 0.998–1.002; p = 0.333, 0.862, 0.998, respectively). We found the results to be reliable after sensitivity analysis.
These results suggested that SARS-CoV-2 infection may not significantly contribute to the elevated risk of developing CFS, and therefore ME/CFS may not be a sequela of COVID-19, but may simply present with symptoms similar to those of CFS after COVID-19 infection, and thus should be judged and differentiated by physicians when diagnosing and treating the disease in clinical practice.
Source: Xu W, Cao Y, Wu L. No Causal Effects Detected in COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Two Sample Mendelian Randomization Study. International Journal of Environmental Research and Public Health. 2023; 20(3):2437. https://doi.org/10.3390/ijerph20032437 https://www.mdpi.com/1660-4601/20/3/2437 (Full text)

Improvement of Long COVID symptoms over one year

Abstract:

Importance: Early and accurate diagnosis and treatment of Long COVID, clinically known as post-acute sequelae of COVID-19 (PASC), may mitigate progression to chronic diseases such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Our objective was to determine the utility of the DePaul Symptom Questionnaire (DSQ) to assess the frequency and severity of common symptoms of ME/CFS, to diagnose and monitor symptoms in patients with PASC.

Methods: This prospective, observational cohort study enrolled 185 people that included 34 patients with PASC that had positive COVID-19 test and persistent symptoms of >3 months and 151 patients diagnosed with ME/CFS. PASC patients were followed over 1 year and responded to the DSQ at baseline and 12 months. ME/CFS patients responded to the DSQ at baseline and 1 year later. Changes in symptoms over time were analyzed using a fixed-effects model to compute difference-in-differences estimates between baseline and 1-year follow-up assessments.

Participants: Patients were defined as having PASC if they had a previous positive COVID-19 test, were experiencing symptoms of fatigue, post-exertional malaise, or other unwellness for at least 3 months, were not hospitalized for COVID-19, had no documented major medical or psychiatric diseases prior to COVID-19, and had no other active and untreated disease processes that could explain their symptoms. PASC patients were recruited in 2021. ME/CFS patients were recruited in 2017.

Results: At baseline, patients with PASC had similar symptom severity and frequency as patients with ME/CFS and satisfied ME/CFS diagnostic criteria. ME/CFS patients experienced significantly more severe unrefreshing sleep and flu-like symptoms. Five symptoms improved significantly over the course of 1 year for PASC patients including fatigue, post-exertional malaise, brain fog, irritable bowel symptoms and feeling unsteady. In contrast, there were no significant symptom improvements for ME/CFS patients.

Conclusion and relevance: There were considerable similarities between patients with PASC and ME/CFS at baseline. However, symptoms improved for PASC patients over the course of a year but not for ME/CFS patients. PASC patients with significant symptom improvement no longer met ME/CFS clinical diagnostic criteria. These findings indicate that the DSQ can be used to reliably assess and monitor PASC symptoms.

Source: Oliveira CR, Jason LA, Unutmaz D, Bateman L, Vernon SD. Improvement of Long COVID symptoms over one year. Front Med (Lausanne). 2023 Jan 9;9:1065620. doi: 10.3389/fmed.2022.1065620. PMID: 36698810; PMCID: PMC9868805. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9868805/ (Full text)

Long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Potential neurophysiological biomarkers for these enigmatic entities

Since early in the pandemic, fatigue has been recognized as one of the most common persistent complaints in individuals infected with SARS-CoV-2, and constitutes one main symptom of the so-called long-COVID syndrome. The term fatigue refers to a sustained feeling of tiredness, which can be present at rest; it is not directly related to physical activity, but can be exacerbated disproportionally by exertion.

Survivors of other recent coronavirus outbreaks, such as severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012 also developed chronic fatigue. These ‘post-infectious’ fatigue syndromes, including long-COVID, resemble myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a chronic disorder of unknown physiopathology characterized by fatigue, post-exertional malaise, chronic muscle or skeletal pain, and cognitive impairment (‘brain fog’).

Despite it being an extremely disabling symptom, the results of routine examinations are often normal in patients complaining of lingering fatigue, a phenomenon that has also led the medical-scientific community to view this condition with skepticism.

In physiology, fatigue is defined as a decrease in the maximal force-generating capacity of a muscle during exercise. It may result from peripheral processes distal to the neuromuscular junction and from central processes controlling the discharge rate of motoneurons.

Physical fatigue related to both central and peripheral nervous system dysfunction can be assessed with neurophysiological techniques including transcranial magnetic stimulation (TMS) of the motor cortex, electrical stimulation of nerve trunks or intramuscular nerve fibers, and electromyography (EMG) recordings.

In August 2021, the first study showing myopathic changes in quantitative EMG (qEMG) in long-COVID patients with musculoskeletal symptoms was published (). The same authors demonstrated myopathic qEMG features and histopathological changes in skeletal muscle biopsies in 16 patients with complaints of fatigue, myalgia, and/or weakness persisting for up to 14 months after mild to moderate COVID-19 (). The wide variety of histological changes in this study, including muscle fiber atrophy, mitochondrial changes, subsarcolemmal accumulation, inflammation, capillaries alteration, suggests that skeletal muscle may be a major target of SARS-CoV-2.

On the opposite side of the neuroaxis, dysfunction in the activity of the primary motor cortex and reduced corticomotor output may underlie fatigue.

The first TMS study on motor cortex physiology was conducted on 12 patients with long-term fatigue and ‘brain fog’ after severe COVID-19 (). It showed disruption of the physiological mechanism of post-contraction depression, i.e., the transient decrease in the amplitude of motor evoked potentials and prolongation of the cortical silent period after a fatiguing motor task, which depends on cortical inhibitory mechanisms and has the protective purpose of preventing muscle overload. Impairment of intracortical GABAergic activity, as indicated by disrupted long-interval intracortical inhibition, together with reduced excitability of the primary motor cortex was subsequently demonstrated in 67 patients with fatigue and cognitive difficulties after mild COVID-19 (). These patients also presented selective deficits in executive functions. Based on these findings, the authors proposed that fatigue depends on altered excitability and neurotransmission within the motor cortex at rest, and on abnormal reactivity to muscular exercise. In addition, reduced executive control may contribute to exacerbating poor physical performance and fatigue tolerance ().

These objective neurophysiological and histopathological findings showed for the first time that fatigue may due both to pathological processes in the muscle (the effector of the motor command) and/or at the site of motor command processing. The mechanisms of chronic dysfunction of neural and muscle cells may be sustained by inflammation or dysimmunity, triggered by SARS-COV-2 in predisposed individuals.

Immune-inflammatory and neuroendocrine mechanisms have also been implicated in ME/CFS. In particular, increased production of autoantibodies against CNS and autonomic nervous system targets, such as the ß2 adrenergic receptor (ß2AdR), have been documented (). As ß2AdR are important vasodilators, their functional disturbance may result in vasoconstriction and hypoxemia with chronic muscular and cerebral hypoperfusion.

The COVID-19 pandemic is likely to greatly increase the incidence of ME/CFS, so that the intense research on the pathophysiological mechanisms of fatigue in long-COVID can help to shed light on a poorly understood and underestimated syndrome.

Source: Versace V, Tankisi H. Long-COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): Potential neurophysiological biomarkers for these enigmatic entities. Clin Neurophysiol. 2023 Jan 13;147:58-59. doi: 10.1016/j.clinph.2023.01.001. Epub ahead of print. PMID: 36657309; PMCID: PMC9838078. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9838078/ (Full text)

Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis

Abstract:

The purpose of this article is to review the evidence of similar symptomatology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-acute sequelae of SARS-CoV-2 infection (PASC).
Reanalysis of data from a study by Jason comparing symptom reports from two groups of ME/CFS and PASC patients shows a notably similar symptomatology. Symptom scores of the PASC group and the ME/CFS group correlated 0.902 (p < 0.0001) across items. The hypothesis is presented that ME/CFS and PASC are caused by a chronic state of multisystemic disequilibrium including endocrinological, immunological, and/or metabolic changes.
The hypothesis holds that a changed set point persistently pushes the organism towards a pathological dysfunctional state which fails to reset. To use an analogy of a thermostat, if the ‘off switch’ of a thermostat intermittently stops working, for periods the house would become warmer and warmer without limit. The hypothesis draws on recent investigations of the Central Homeostasis Network showing multiple interconnections between the autonomic system, central nervous system, and brain stem.
The hypothesis helps to explain the shared symptomatology of ME/CFS and PASC and the unpredictable, intermittent, and fluctuating pattern of symptoms of ME/CFS and PASC. The current theoretical approach remains speculative and requires in-depth investigation before any definite conclusions can be drawn.
Source: Marks DF. Converging Evidence of Similar Symptomatology of ME/CFS and PASC Indicating Multisystemic Dyshomeostasis. Biomedicines. 2023; 11(1):180. https://doi.org/10.3390/biomedicines11010180 https://www.mdpi.com/2227-9059/11/1/180 (Full text)

Orthostatic Intolerance after COVID-19 Infection: Is Disturbed Microcirculation of the Vasa Vasorum of Capacitance Vessels the Primary Defect?

Abstract:

Following COVID-19 infection, a substantial proportion of patients suffer from persistent symptoms known as Long COVID. Among the main symptoms are fatigue, cognitive dysfunction, muscle weakness and orthostatic intolerance (OI). These symptoms also occur in myalgic encephalomyelitis/chronic fatigue (ME/CFS).
OI is highly prevalent in ME/CFS and develops early during or after acute COVID-19 infection. The causes for OI are unknown and autonomic dysfunction is hypothetically assumed to be the primary cause, presumably as a consequence of neuroinflammation. Here, we propose an alternative, primary vascular mechanism as the underlying cause of OI in Long COVID.
We assume that the capacitance vessel system, which plays a key role in physiologic orthostatic regulation, becomes dysfunctional due to a disturbance of the microvessels and the vasa vasorum, which supply large parts of the wall of those large vessels. We assume that the known microcirculatory disturbance found after COVID-19 infection, resulting from endothelial dysfunction, microthrombus formation and rheological disturbances of blood cells (altered deformability ), also affects the vasa vasorum to impair the function of the capacitance vessels.
In an attempt to compensate for the vascular deficit, sympathetic activity overshoots to further worsen OI, resulting in a vicious circle that maintains OI. The resulting orthostatic stress, in turn, plays a key role in autonomic dysfunction and the pathophysiology of ME/CFS.
Source: Wirth KJ, Löhn M. Orthostatic Intolerance after COVID-19 Infection: Is Disturbed Microcirculation of the Vasa Vasorum of Capacitance Vessels the Primary Defect? Medicina. 2022; 58(12):1807. https://doi.org/10.3390/medicina58121807 https://www.mdpi.com/1648-9144/58/12/1807 (Full text)

ME/CFS and Post-Exertional Malaise among Patients with Long COVID

Abstract:

This study sought to ascertain the prevalence of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) among a sample of 465 patients with Long COVID. The participants completed three questionnaires: (1) a new questionnaire measuring both the frequency and severity of 38 common symptoms of COVID and Long COVID, (2) a validated short form questionnaire assessing ME/CFS, and (3) a validated questionnaire measuring post-exertional malaise.
The population was predominantly white, female, and living in North America. The mean duration since the onset of COVID-19 symptoms was 70.5 weeks. Among the 465 participants, 58% met a ME/CFS case definition. Of respondents who reported that they had ME/CFS only 70.57% met criteria for ME/CFS and of those who did not report they had ME/CFS, 29.43% nevertheless did meet criteria for the disease: both over-diagnosis and under-diagnosis were evident on self-report. This study supports prior findings that ME/CFS occurs with high prevalence among those who have persistent COVID-19 symptoms.
Source: Jason LA, Dorri JA. ME/CFS and Post-Exertional Malaise among Patients with Long COVID. Neurology International. 2023; 15(1):1-11. https://doi.org/10.3390/neurolint15010001 https://www.mdpi.com/2035-8377/15/1/1 (Full text)