Tag: long covid vs ME/CFS

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic

Summary:

Background The global prevalence of PASC is estimated to be present in 0·43 and based on the WHO estimation of 470 million worldwide COVID-19 infections, corresponds to around 200 million people experiencing long COVID symptoms. Despite this, its clinical features are not well defined.

Methods We collected retrospective data from 140 patients with PASC in a post-COVID-19 clinic on demographics, risk factors, illness severity (graded as one-mild to five-severe), functional status, and 29 symptoms and principal component symptoms cluster analysis. The Institute of Medicine (IOM) 2015 criteria were used to determine the ME/CFS phenotype.

Findings The median age was 47 years, 59·0% were female; 49·3% White, 17·2% Hispanic, 14·9% Asian, and 6·7% Black. Only 12·7% required hospitalization. Seventy-two (53·5%) patients had no known comorbid conditions. Forty-five (33·9%) were significantly debilitated. The median duration of symptoms was 285·5 days, and the number of symptoms was 12. The most common symptoms were fatigue (86·5%), post-exertional malaise (82·8%), brain fog (81·2%), unrefreshing sleep (76·7%), and lethargy (74·6%). Forty-three percent fit the criteria for ME/CFS.

Interpretations Most PASC patients evaluated at our clinic had no comorbid condition and were not hospitalized for acute COVID-19. One-third of patients experienced a severe decline in their functional status. About 43% had the ME/CFS subtype.

Source:  H Bonilla, TC Quach, A Tiwari, AE Bonilla, M Miglis, P Yang, L Eggert, H Sharifi, A Horomanski, A Subramanian, L Smirnoff, N Simpson, H Halawi, O Sum-Ping, A Kalinowski, Z Patel, R Shafer, L. Geng. Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is common in post-acute sequelae of SARS-CoV-2 infection (PASC): Results from a post-COVID-19 multidisciplinary clinic. medRxiv 2022.08.03.22278363; doi: https://doi.org/10.1101/2022.08.03.22278363

Post-COVID syndrome with fatigue and exercise intolerance: myalgic encephalomyelitis/chronic fatigue syndrome

Abstract:

in English, German

Background: A sizable part of post-COVID syndrome meets the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). A doubling of cases of ME/CFS within the next years is therefore projected.

Objectives: Presentation of the current state of knowledge on ME/CFS.

Materials and methods: Unsystematic review of the literature and of own contributions in research and patient care.

Results and conclusions: ME/CFS is a neuroimmunological disease, mostly infection-induced, usually persisting throughout life. Clinically it is characterized by fatigue lasting at least 6 months and the defining core feature of exercise intolerance (post-exertional malaise, PEM). Exercise intolerance is defined as a worsening of symptoms after (even mild) everyday exertion, which usually begins after several hours or on the following day, is still noticeable at least 14 h after exertion, and often lasts for several days (up to weeks or longer). Furthermore, ME/CFS is characterized by pain, disturbances of sleep, thinking and memory, and dysregulation of the circulatory, endocrine, and immune systems.

As a separate clinical entity, ME/CFS should be distinguished from chronic fatigue, which occurs as a symptom of a range of very different diseases. The diagnosis of ME/CFS is made clinically using established international diagnostic criteria and requires careful stepwise diagnosis to exclude other diagnoses. A causal therapy for ME/CFS has not been established; the focus is on symptoms relief, treatment of the often accompanying orthostatic intolerance, and assistance with anticipatory energy management (pacing).

Source: Renz-Polster H, Scheibenbogen C. Post-COVID-Syndrom mit Fatigue und Belastungsintoleranz: Myalgische Enzephalomyelitis bzw. Chronisches Fatigue-Syndrom [Post-COVID syndrome with fatigue and exercise intolerance: myalgic encephalomyelitis/chronic fatigue syndrome]. Inn Med (Heidelb). 2022 Aug;63(8):830-839. German. doi: 10.1007/s00108-022-01369-x. Epub 2022 Jul 13. PMID: 35925074. https://pubmed.ncbi.nlm.nih.gov/35925074/  https://link.springer.com/article/10.1007/s00108-022-01369-x (Full text in German)

Serum of Post-COVID-19 Syndrome patients with or without ME/CFS differentially affects endothelial cell function in vitro

Abstract:

A proportion of COVID-19 reconvalescent patients develop post-COVID-19 syndrome (PCS) including a subgroup fulfilling diagnostic criteria of Myalgic encephalomyelitis/Chronic Fatigue Syndrome (PCS/CFS). Recently, endothelial dysfunction (ED) has been demonstrated in these patients, but the mechanisms remain elusive. Therefore, we investigated the effects of patients’ sera on endothelia cells (ECs) in vitro.
PCS (n = 17), PCS/CFS (n = 13), and healthy controls (HC, n = 14) were screened for serum anti-endothelial cell autoantibodies (AECAs) and dysregulated cytokines. Serum-treated ECs were analysed for the induction of activation markers and the release of small molecules by flow cytometry. Moreover, the angiogenic potential of sera was measured in a tube formation assay.
While only marginal differences between patient groups were observed for serum cytokines, AECA binding to ECs was significantly increased in PCS/CFS patients. Surprisingly, PCS and PCS/CFS sera reduced surface levels of several EC activation markers. PCS sera enhanced the release of molecules associated with vascular remodelling and significantly promoted angiogenesis in vitro compared to the PCS/CFS and HC groups. Additionally, sera from both patient cohorts induced the release of molecules involved in inhibition of nitric oxide-mediated endothelial relaxation.
Overall, PCS and PCS/CFS patients′ sera differed in their AECA content and their functional effects on ECs, i.e., secretion profiles and angiogenic potential. We hypothesise a pro-angiogenic effect of PCS sera as a compensatory mechanism to ED which is absent in PCS/CFS patients.
Source: Flaskamp L, Roubal C, Uddin S, Sotzny F, Kedor C, Bauer S, Scheibenbogen C, Seifert M. Serum of Post-COVID-19 Syndrome Patients with or without ME/CFS Differentially Affects Endothelial Cell Function In Vitro. Cells. 2022; 11(15):2376. https://doi.org/10.3390/cells11152376  https://www.mdpi.com/2073-4409/11/15/2376/htm (Full text)

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).

Read the rest of this article HERE. 

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.

Read the rest of this article HERE.

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)