Tag: long covid vs ME/CFS

COVID-19 May Be a Trigger for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

ALBANY, N.Y. (July 25, 2022) – UAlbany researcher Roxana Moslehi from the Department of Epidemiology and Biostatistics is conducting important investigations on myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to better understand the illness, including its potential connection to cancer, auto-immune disease, and long-haul COVID-19.

According to the CDC, 1 in thirteen adults in the U.S. have COVID-19 symptoms lasting three or more months after contracting the virus—a condition often referred to as “long COVID.” However, research suggests that long COVID is complex, and in some instances may not be COVID-19 at all, but rather ME/CFS—triggered by COVID-19.

ME/CFS is a complex disabling disorder with no known treatment. Between 25 and 50 percent of those with the illness are bed or housebound for extended periods of time, with overwhelming fatigue that does not diminish after resting and difficulty performing daily tasks. Prior to the COVID-19 pandemic, it was estimated that up to 3.4 million people in the US suffered from the illness—the range is large due to the difficulty in diagnosing the disease as it is often dismissed or assumed to be another disorder.

Since ME/CFS is believed to be triggered by the onset of an infectious illness, research suggests that COVID-19 may be a trigger for ME/CFS. The chronic long-haul COVID-19 symptoms that some people report as following the resolution of their acute illness have similarities to symptoms of ME/CFS, such as persistent fatigue, sleep dysfunction, cognitive impairment, impaired memory, and more.

“It is estimated that in the wake of the COVID-19 pandemic, more than 10 million new ME/CFS cases may be triggered around the world,” Moslehi explains. “This makes it urgent to identify risk factors and underlying biologic mechanisms for this condition along with its potential connection to COVID-19.”

Moslehi conducted a molecular epidemiologic investigation of ME/CFS (funded by an NIH research grant awarded to her) to better understand the illness, providing the most compelling evidence to date that ME/CFS may be an auto-immune disorder. She compared people who developed ME/CFS after having an infectious illness with a group of individuals without ME/CFS (called the control group). She looked at various intrinsic factors related to the participants’ health, such as personal history of allergy and asthma, and extrinsic or environmental factors such as exposure to contaminants. She also assessed the prevalence of illnesses such as auto-immune diseases and cancer in their families, levels of serum immune system markers such as cytokines, and molecular evidence of viral reactivation such as mono flare-ups.

The study, published in the proceedings of the American Society of Human Genetics (ASHG), the International Genetic Epidemiology Society (IGES) and the American Association for Cancer Research (AACR), found that those with ME/CFS were five times more likely to have a family history of auto-immune diseases than the control group. ME/CFS was also associated with an increased risk of early-onset cancer (diagnosed before 60 years old) among the first-degree relatives. ME/CFS was associated with certain risk factors such as a history of allergies requiring medication and exposure to contaminants. The analysis by the Moslehi lab also identified a panel of cytokines that predict the risk of ME/CFS with high accuracy. A couple of the identified cytokines are involved in inflammatory processes and have been linked to other auto-immune diseases.

“Our multidimensional analysis of pedigree, epidemiologic, and molecular data not only provides the most objective evidence to date that ME/CFS may be an auto-immune disease— it provides etiologic clues and leads for prevention” says Moslehi. “In addition, our results may enable defining a subset of COVID-19 patients, who are at risk of developing long COVID or ME/CFS, for targeted monitoring and/or therapy.”

More recently, Moslehi, in collaboration with her colleagues at the NIH, obtained two additional NIH (intramural) grants to continue her research on ME/CFS. Through these grants, the DNA and RNA of ME/CFS cases and controls have been sequenced and will be analyzed to identify genes and genetic variations that are associated with ME/CFS.

“The ultimate goal is to conduct an integrative analysis of multi-omics (genomics, proteomics, transcriptomics) data to gain deeper insight into the biologic mechanisms of ME/CFS and identify druggable targets for ME/CFS therapy,” she says.

 

Chronic fatigue syndrome: an old public health issue highlighted by the COVID-19 pandemic

In some cases, C O VID-19 has been shown to cause both acute as well as prolonged neuropsychiatric manifestations, possibly due to CNS immune cell activation.13,14 Between 13 and 23% of hospitalized COVID-19 patients suffer from fatigue and PEM-like symptoms more than 6 months after the infection.15 These numbers, although alarming, are hardly surprising. Looking back at the 2002/03 SARS pandemic, a similar proportion of hospitalized patients with a severe course also developed CFS/ME (27% of survivors 4 years after hospitalisation).16Other common pathogens that can lead to CFS/ME include viruses like Epstein-Barr virus (EBV), cytomegalovirus (CMV) and enteroviruses, bacteria such as mycoplasma, Borrelia burgdorferi (Lyme disease), and Coxiella burnetii (Q fever).17 In fact, in 3 out of 4 cases of CFS/ME, the disease develops following an infectious episode.18 Interestingly, the innate immune response to infections is generally higher among women than men, which could perhaps also explain the higher prevalence of CFS/ME among women given the role that immunity plays in it. With an estimated prevalence of 0.1-0.7%, CFS/ME is far above the threshold value set by the European Union for classification as a rare disease (<5:10,000).

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Source: Bonk JS, Khedkar PH. Chronic fatigue syndrome: an old public health issue highlighted by the COVID-19 pandemic. Acta Physiol (Oxf). 2022 Jul 30:e13863. doi: 10.1111/apha.13863. Epub ahead of print. PMID: 35906837. https://onlinelibrary.wiley.com/doi/epdf/10.1111/apha.13863 (Full text)

Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.

Methods: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.

Participants: People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.

Results: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).

Conclusions: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.

Source: Vernon SD, Funk S, Bateman L, Stoddard GJ, Hammer S, Sullivan K, Bell J, Abbaszadeh S, Lipkin WI, Komaroff AL. Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2022 Jun 23;9:917019. doi: 10.3389/fmed.2022.917019. PMID: 35847821; PMCID: PMC9285104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285104/ (Full text)

Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID

Abstract:

Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID.
Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022.
Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS.
Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.
Source: Tokumasu K, Honda H, Sunada N, Sakurada Y, Matsuda Y, Yamamoto K, Nakano Y, Hasegawa T, Yamamoto Y, Otsuka Y, Hagiya H, Kataoka H, Ueda K, Otsuka F. Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID. Medicina. 2022; 58(7):850. https://doi.org/10.3390/medicina58070850 https://www.mdpi.com/1648-9144/58/7/850/htm (Full text)

COVID-19 Pandemic-Revealed Consistencies and Inconsistencies in Healthcare: A Medical and Organizational View

Abstract:

The circumstances of the Coronavirus disease caused by the SARS-CoV-2 virus (COVID-19) pandemic have had a significant impact on global and national developments, affecting the existence of society in all its expressions, as well as the lives of people themselves. In the context of the pandemic, increased attention has been focused on acute measures, but the ending of the pandemic is expected as a resolution of the related healthcare problems. However, there are several indicators that the COVID-19 pandemic might induce long-term consequences for individual and public health. Some of the consequences are inferred and predictable, but there are also areas of medicine that have been indirectly affected by the pandemic, and these consequences have not yet been sufficiently explored.

This study is focused on drawing attention to some of the COVID-19 pandemic consistencies and the pandemic-revealed inconsistencies in healthcare. Content analysis and statistical analysis were applied to achieve the aim of the study. The main findings of the study address chronic disease burden (particularly, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)), healthcare governance and organizational issues, and the synergy between health policy perspectives and innovative solutions in practice.

The study provides insight into the particular healthcare issues affected by the COVID-19 pandemic, such as the increase in mortality in some diagnoses besides COVID-19 and the possible emergence of a new type of resistance-vaccine-resistance-contemporaneously supporting the identification of the tendencies and currently unnoticed indirect consistencies and inconsistencies revealed by the pandemic.

Source: Araja D, Berkis U, Murovska M. COVID-19 Pandemic-Revealed Consistencies and Inconsistencies in Healthcare: A Medical and Organizational View. Healthcare (Basel). 2022 May 31;10(6):1018. doi: 10.3390/healthcare10061018. PMID: 35742069. https://www.mdpi.com/2227-9032/10/6/1018/htm  (Full text)

Long COVID-19 and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: similarities and differences of two peas in a pod

Sr. Editor,

Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-COV-2). Prolonged recovery of COVID-19 symptoms, so-called Long COVID-19, has been described even in patients who have mild symptoms and did not required hospitalisation. Various studies showed that at least one out of ten COVID-19 symptomatic patients develop Long
COVID-19.

Although there is an absence of a evidence-based clinical practice guidelines neither a clear aetiopatogenesis, a clinical case definition of post-COVID-19 condition was proposed across the International Severe Respiratory and Emerging Infection Consortium (ISARIC) and the World Health Organization (WHO). Long COVID-19 occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis.

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Source: Qanneta R, COVID-19 persistente y Encefalomielitis Mialgica /Sındrome de Fatiga Cronica: similitudes y diferencias,  Reumatologia Clinica (2022), doi: https://doi.org/10.1016/j.reuma.2022.05.003 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167847/pdf/main.pdf (Full text available in English as PDF file)

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)

Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19) triggers the development of numerous pathologies and infection-linked complications and exacerbates existing pathologies in nearly all body systems. Aside from the primarily targeted respiratory organs, adverse SARS-CoV-2 effects were observed in nervous, cardiovascular, gastrointestinal/metabolic, immune, and other systems in COVID-19 survivors. Long-term effects of this viral infection have been recently observed and represent distressing sequelae recognised by the World Health Organisation (WHO) as a distinct clinical entity defined as post-COVID-19 condition. Considering the pandemic is still ongoing, more time is required to confirm post COVID-19 condition diagnosis in the COVID-19 infected cohorts, although many reported post COVID-19 symptoms overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Aims of Review: In this study, COVID-19 clinical presentation and associated post-infection sequelae (post-COVID-19 condition) were reviewed and compared with ME/CFS symptomatology.

Key Scientific Concepts of Review: The onset, progression, and symptom profile of post COVID-19 condition patients have considerable overlap with ME/CFS. Considering the large scope and range of pro-inflammatory effects of this virus, it is reasonable to expect development of post COVID-19 clinical complications in a proportion of the affected population. There are reports of a later debilitating syndrome onset three months post COVID-19 infection (often described as long-COVID-19), marked by the presence of fatigue, headache, cognitive dysfunction, post-exertional malaise, orthostatic intolerance, and dyspnoea. Acute inflammation, oxidative stress, and increased levels of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα), have been reported in SARS-CoV-2 infected patients. Longitudinal monitoring of post COVID-19 patients is warranted to understand the long-term effects of SARS-CoV-2 infection and the pathomechanism of post COVID-19 condition.

Source: Sukocheva OA, Maksoud R, Beeraka NM, Madhunapantula SV, Sinelnikov M, Nikolenko VN, …. and Marshall-Gradisnik S. Analysis of post COVID-19 condition and its overlap with myalgic encephalomyelitis/chronic fatigue syndrome.  Journal of Advanced Research, Available online 26 November 2021. https://www.sciencedirect.com/science/article/pii/S2090123221002320  (Full text)

Long-term outcomes of pediatric infections: from traditional infectious diseases to long covid

Abstract:

There is limited evidence available on the long-term impact of SARS-CoV-2 infection in children. In this article, the authors analyze the recent evidence on pediatric long covid and lessons learnt from a pediatric post-covid unit in Rome, Italy. To gain a better understanding of the concerns raised by parents and physicians in relation to the potential long-term consequences of this novel infection, it is important to recognize that long-term effect of a post-infectious disease is not a new phenomenon.

Source: Buonsenso D, Di Gennaro L, Rose C, Morello R, D’Ilario F, Zampino G, Piazza M, Boner AL, Iraci C, O’Connell S, Cohen VB, Esposito S, Munblit D, Reena J, Sigfrid L, Valentini P. Long-term outcomes of pediatric infections: from traditional infectious diseases to long covid. Future Microbiol. 2022 Mar 10:10.2217/fmb-2022-0031. doi: 10.2217/fmb-2022-0031. Epub ahead of print. PMID: 35264003; PMCID: PMC8910780.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910780/ (Full text)

Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS

Abstract

Purpose of Review: To discuss emerging understandings of adolescent long COVID or post-COVID-19 conditions, including proposed clinical definitions, common symptoms, epidemiology, overlaps with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and orthostatic intolerance, and preliminary guidance on management.

Recent Findings: The recent World Health Organization clinical case definition of post-COVID-19 condition requires a history of probable or confirmed SARS-CoV-2 infection, with symptoms starting within 3 months of the onset of COVID-19. Symptoms must last for at least 2 months and cannot be explained by an alternative diagnosis.

Common symptoms of the post-COVID-19 condition include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction. These symptoms generally have an impact on everyday functioning.

The incidence of prolonged symptoms following SARS-CoV-2 infection has proven challenging to define, but it is now clear that those with relatively mild initial infections, without severe initial respiratory disease or end-organ injury, can still develop chronic impairments, with symptoms that overlap with conditions like ME/CFS (profound fatigue, unrefreshing sleep, post-exertional malaise, cognitive dysfunction, and orthostatic intolerance).

Summary: We do not yet have a clear understanding of the mechanisms by which individuals develop post-COVID-19 conditions. There may be several distinct types of long COVID that require different treatments.

At this point, there is no single pharmacologic agent to effectively treat all symptoms. Because some presentations of post-COVID-19 conditions mimic disorders such as ME/CFS, treatment guidelines for this and related conditions can be helpful for managing post-COVID-19 symptoms.

Source: Morrow, A.K., Malone, L.A., Kokorelis, C. et al. Long-Term COVID 19 Sequelae in Adolescents: the Overlap with Orthostatic Intolerance and ME/CFS. Curr Pediatr Rep (2022). https://doi.org/10.1007/s40124-022-00261-4  (Full text)