Tag: review

ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature

Summary:

Some patients remain unwell for months after “recovering” from acute COVID-19. They develop persistent fatigue, cognitive problems, headaches, disrupted sleep, myalgias and arthralgias, post-exertional malaise, orthostatic intolerance and other symptoms that greatly interfere with their ability to function and that can leave some people housebound and disabled. The illness (Long COVID) is similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) as well as to persisting illnesses that can follow a wide variety of other infectious agents and following major traumatic injury. Together, these illnesses are projected to cost the U.S. trillions of dollars.

In this review, we first compare the symptoms of ME/CFS and Long COVID, noting the considerable similarities and the few differences. We then compare in extensive detail the underlying pathophysiology of these two conditions, focusing on abnormalities of the central and autonomic nervous system, lungs, heart, vasculature, immune system, gut microbiome, energy metabolism and redox balance. This comparison highlights how strong the evidence is for each abnormality, in each illness, and helps to set priorities for future investigation. The review provides a current road map to the extensive literature on the underlying biology of both illnesses.

Source: Anthony L. Komaroff and W. Ian Lipkin. ME/CFS and Long COVID share similar symptoms and biological abnormalities: road map to the literature. Front. Med., 02 June 2023. Sec. Infectious Diseases: Pathogenesis and Therapy. Volume 10 – 2023 | https://doi.org/10.3389/fmed.2023.1187163 (Full text)

Patient and clinician experiences of fibromyalgia, ME/CFS and medically unexplained symptoms: A meta-aggregative systematic review

Abstract:

Objectives: Fibromyalgia (FM), Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and other syndromes with medically unexplained symptoms (MUS) pose significant healthcare challenges. We aimed to synthesize qualitative evidence regarding the experiences of persons with these conditions (PwC) and their healthcare professionals (HCPs).

Methods & Measures: Databases were searched using terms relating to FM/ME/CFS/MUS, Experience and Qualitative research. Studies published between 2001-2021 concerning adult PwC or HCP perspectives were included and synthesized using Meta-Aggregation, with confidence established following the ConQual approach.

Results: 143 studies were included, with 708 findings aggregated into 82 categories and 13 synthesized findings. PwC narratives reflected a range of themes concerning: The experience of symptoms; The patient journey; Identity loss and change; Managing chronic illness; Understanding and legitimacy; Support needs and experiences; Healthcare needs and experiences; and Managing the healthcare encounters. HCPs perspective themes included: Beliefs and attitudes towards patients; Sensemaking at the limits of medical knowledge; Consultation and management; The patient-clinician relationship; and Barriers and facilitators to care.

Conclusion: Sensemaking challenges are at the core of the patient and clinician experience of MUS, FM and ME/CFS. While gaps in biomedical knowledge are clear, this review highlights the need to address the patient-clinician dynamic in the context of uncertainty.

Source: Duda N, Maguire R, Gitonga I, Corrigan S. Patient and clinician experiences of fibromyalgia, ME/CFS and medically unexplained symptoms: A meta-aggregative systematic review. PsyArXiv [Preprint], 28 Apr 2023  https://psyarxiv.com/5ct4k/ (Full text)

Whole-body cryotherapy as a treatment for chronic medical conditions?

Abstract:

Introduction: Whole-body cryotherapy (WBC) is a controlled exposure of the whole body to cold to gain health benefits. In recent years, data on potential applications of WBC in multiple clinical settings have emerged.

Sources of data: PubMed, EBSCO and Clinical Key search using keywords including terms ‘whole body’, ‘cryotherapy’ and ‘cryostimulation’.

Areas of agreement: WBC could be applied as adjuvant therapy in multiple conditions involving chronic inflammation because of its potent anti-inflammatory effects. Those might include systemic inflammation as in rheumatoid arthritis. In addition, WBC could serve as adjuvant therapy for chronic inflammation in some patients with obesity.

Areas of controversy: WBC probably might be applied as an adjuvant treatment in patients with chronic brain disorders including mild cognitive impairment and general anxiety disorder and in patients with depressive episodes and neuroinflammation reduction as in multiple sclerosis. WBC effects in metabolic disorder treatment are yet to be determined. WBC presumably exerts pleiotropic effects and therefore might serve as adjuvant therapy in multi-systemic disorders, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

Growing points: The quality of studies on the effects of WBC in the clinical setting is in general low; hence, randomized controlled trials with adequate sample size and longer follow-up periods are needed.

Areas are timely for developing research: Further studies should examine the mechanism underlying the clinical efficacy of WBC. Multiple conditions might involve chronic inflammation, which in turn could be a potential target of WBC. Further research on the application of WBC in neurodegenerative disorders, neuropsychiatric disorders and ME/CFS should be conducted.

Source: Tabisz H, Modlinska A, Kujawski S, Słomko J, Zalewski P. Whole-body cryotherapy as a treatment for chronic medical conditions? Br Med Bull. 2023 May 12:ldad007. doi: 10.1093/bmb/ldad007. Epub ahead of print. PMID: 37170956. https://pubmed.ncbi.nlm.nih.gov/37170956/

Can we Reduce the Symptoms of Chronic Fatigue Syndrome by Regulating Micronutrients? A Review

Abstract:

Introduction: Deficiencies of some micronutrients have been observed in chronic fatigue syndrome patients, but the underlying cause has not been fully understood. The aim of this study was to investigate whether there is a relationship between CFS and micronutrients.

Methods: Related articles searched the combinations of the following terms which were used for the search in the Web of Science database: “Chronic Fatigue Syndrome” OR “Chronic Fatigue- Fibromyalgia Syndrome” OR “Postviral Fatigue Syndrome” AND “vitamins” OR “minerals” OR “micronutrients”. Articles that met the inclusion criteria were included.

Results: The initial search resulted in 225 studies, with 11 studies fully meeting the inclusion criteria. In these studies, it has been shown that micronutrients may play a role in the etiology of CFS, and that supplemented micronutrients can positively affect the symptoms of CFS.

Conclusion: Although there seems to be a close relationship between CFS-related syndromes and nutritional status, the literature on this subject remains limited. The results of the studies were not compatible with each other due to differences in the studies. Therefore, new studies are needed to fully explain the relationship between CFS and micronutrients.

Source: Akduman, GUl; Kurtbeyoglu, Emine; Gunes, Fatma E. Can we Reduce the Symptoms of Chronic Fatigue Syndrome by Regulating Micronutrients? A Review. Current Nutrition & Food Science, Volume 19, Number 5, 2023, pp. 509-518(10). https://www.ingentaconnect.com/content/ben/cnf/2023/00000019/00000005/art00005

Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review

Long COVID disproportionately affects premenopausal women, but relatively few studies have examined Long COVID’s impact on female reproductive health. We conduct a review of the literature documenting the female reproductive health impacts of Long COVID which may include disruptions to the menstrual cycle, gonadal function, ovarian sufficiency, menopause, and fertility, as well as symptom exacerbation around menstruation.

Given limited research, we also review the reproductive health impacts of overlapping and associated illnesses including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), postural orthostatic tachycardia syndrome (POTS), connective tissue disorders like Ehlers-Danlos syndrome (EDS), and endometriosis, as these illnesses may help to elucidate reproductive health conditions in Long COVID.

These associated illnesses, whose patients are 70%–80% women, have increased rates of dysmenorrhea, amenorrhea, oligomenorrhea, dyspareunia, endometriosis, infertility, vulvodynia, intermenstrual bleeding, ovarian cysts, uterine fibroids and bleeding, pelvic congestion syndrome, gynecological surgeries, and adverse pregnancy complications such as preeclampsia, maternal mortality, and premature birth. Additionally, in Long COVID and associated illnesses, symptoms can be impacted by the menstrual cycle, pregnancy, and menopause.

We propose priorities for future research and reproductive healthcare in Long COVID based on a review of the literature. These include screening Long COVID patients for comorbid and associated conditions; studying the impacts of the menstrual cycle, pregnancy, and menopause on symptoms and illness progression; uncovering the role of sex differences and sex hormones in Long COVID and associated illnesses; and addressing historical research and healthcare inequities that have contributed to detrimental knowledge gaps for this patient population.

Source: Pollack Beth, von Saltza Emelia, McCorkell Lisa, Santos Lucia, Hultman Ashley, Cohen Alison K., Soares Letícia. Female reproductive health impacts of Long COVID and associated illnesses including ME/CFS, POTS, and connective tissue disorders: a literature review. Frontiers in Rehabilitation Sciences, Vol 4, 2023, ISSN=2673-6861. DOI: 10.3389/fresc.2023.1122673 https://www.frontiersin.org/articles/10.3389/fresc.2023.1122673 (Full text)

A review of cytokine-based pathophysiology of Long COVID symptoms

Abstract:

The Long COVID/Post Acute Sequelae of COVID-19 (PASC) group includes patients with initial mild-to-moderate symptoms during the acute phase of the illness, in whom recovery is prolonged, or new symptoms are developed over months. Here, we propose a description of the pathophysiology of the Long COVID presentation based on inflammatory cytokine cascades and the p38 MAP kinase signaling pathways that regulate cytokine production.

In this model, the SARS-CoV-2 viral infection is hypothesized to trigger a dysregulated peripheral immune system activation with subsequent cytokine release. Chronic low-grade inflammation leads to dysregulated brain microglia with an exaggerated release of central cytokines, producing neuroinflammation. Immunothrombosis linked to chronic inflammation with microclot formation leads to decreased tissue perfusion and ischemia. Intermittent fatigue, Post Exertional Malaise (PEM), CNS symptoms with “brain fog,” arthralgias, paresthesias, dysautonomia, and GI and ophthalmic problems can consequently arise as result of the elevated peripheral and central cytokines.

There are abundant similarities between symptoms in Long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). DNA polymorphisms and viral-induced epigenetic changes to cytokine gene expression may lead to chronic inflammation in Long COVID patients, predisposing some to develop autoimmunity, which may be the gateway to ME/CFS.

Source: Low RN, Low RJ, Akrami A. A review of cytokine-based pathophysiology of Long COVID symptoms. Front Med (Lausanne). 2023 Mar 31;10:1011936. doi: 10.3389/fmed.2023.1011936. PMID: 37064029; PMCID: PMC10103649. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10103649/ (Full text)

Exercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-Acute Sequelae of SARS-CoV-2: More in Common Than Not?

Abstract:

Topic importance: Post-Acute Sequelae of SARS-CoV-2 (PASC) is a long-term consequence of acute infection from coronavirus disease 2019 (COVID-19). Clinical overlap between PASC and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) has been observed, with shared symptoms including intractable fatigue, postexertional malaise, and orthostatic intolerance. The mechanistic underpinnings of such symptoms are poorly understood.

Review findings: Early studies suggest deconditioning as the primary explanation for exertional intolerance in PASC. Cardiopulmonary exercise testing (CPET) reveals perturbations related to systemic blood flow and ventilatory control associated with acute exercise intolerance in PASC, which are not typical of simple detraining. Hemodynamic and gas exchange derangements in PASC have substantial overlap with those observed with ME/CFS, suggestive of shared mechanisms.

Summary: This review aims to illustrate exercise pathophysiologic commonalities between PASC and ME/CFS that will help guide future diagnostics and treatment.

Source: Joseph P, Singh I, Oliveira R, Capone CA, Mullen MP, Cook DB, Stovall MC, Squires J, Madsen K, Waxman AB, Systrom DM. Exercise Pathophysiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome and Post-Acute Sequelae of SARS-CoV-2: More in Common Than Not? Chest. 2023 Apr 11:S0012-3692(23)00502-0. doi: 10.1016/j.chest.2023.03.049. Epub ahead of print. PMID: 37054777; PMCID: PMC10088277. https://pubmed.ncbi.nlm.nih.gov/37054777/

Therapeutical interventions for myalgic encephalomyelitis/chronic fatigue syndrome; A review of phase IV Clinical trials

Abstract:

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disabling and complex illness with multifactorial etiology. Current clinical trials were examined to understand the characteristics of ME/CFS as well as possible therapeutical interventions.

Aim: To identify features of clinical trials related to ME/CFS registered at ClinicalTrials.gov, specifically, the therapeutical interventions used to manage the syndrome in phase IV.

Method: Analysis of all clinical trials registered at ClinicalTrials.gov for ME/CFS. Those clinical trials that employed a targeted therapy were included. The analysis identified a selection of clinical trials examining a targeted therapy for ME/CFS, providing a platform for further exploration of potential treatments.

Results: By November 19th, 2022, 151 clinical trials related to ME/CFS had been found. Interventional studies were the most prevalent type. However, the trials were restricted to specific continents and were not extensively conducted in pediatric patients. Micronutrients were the most commonly used intervention. Phase IV studies had fewer clinical trials with limited interventional measures. Only three out of nine studies completed pharmacological interventional studies, and of these, sodium oxybate was being used most frequently.

Conclusion: Among the clinical trials identified through this paper, there were few related to ME/CFS treatment. The interventions in the completed phase IV studies involved drugs that mainly interacted with the CNS, and more rarely that had an effect on blood vessels and blood perfusion. The limited number of phase IV clinical trials meant that the results were inconclusive.

Source: Alorfi, N. (2023). Therapeutical interventions for myalgic encephalomyelitis/chronic fatigue syndrome; A review of phase IV Clinical trials. Bulletin of Pharmaceutical Sciences. Assiut, (), -. doi: 10.21608/bfsa.2023.199974.1690 https://bpsa.journals.ekb.eg/article_294098.html

Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses

Abstract:

ME/CFS is a debilitating chronic condition that often develops after viral or bacterial infection. Insight from the study of Long COVID/Post Acute Sequelae of COVID-19 (PASC), the post-viral syndrome associated with SARS-CoV-2 infection, might prove to be useful for understanding pathophysiological mechanisms of ME/CFS. Disease presentation is similar between the two conditions, and a subset of Long COVID patients meet the diagnostic criteria for ME/CFS.

Since Long COVID is characterized by significant vascular pathology – including endothelial dysfunction, coagulopathy, and vascular dysregulation – the question of whether or not the same biological abnormalities are of significance in ME/CFS arises.

Cardiac abnormalities have for a while now been documented in ME/CFS cohorts, with recent studies demonstrating major deficits in cerebral blood flow, and hence vascular dysregulation. A growing body of research is demonstrating that ME/CFS is accompanied by platelet hyperactivation, anomalous clotting, a procoagulant phenotype, and endothelial dysfunction. Endothelial damage and dysregulated clotting can impair substance exchange between blood and tissues, and result in hypoperfusion, which may contribute to the manifestation of certain ME/CFS symptoms.

Here we review the ME/CFS literature to summarize cardiovascular and haematological findings documented in patients with the condition, and, in this context, briefly discuss the potential role of previously-implicated pathogens.

Overall, cardiac and haematological abnormalities are present within ME/CFS cohorts. While atherosclerotic heart disease is not significantly associated with ME/CFS, suboptimal cardiovascular function defined by reduced cardiac output, impaired cerebral blood flow, and vascular dysregulation are, and these abnormalities do not appear to be influenced by deconditioning. Rather, these cardiac abnormalities may result from dysfunction in the (autonomic) nervous system.

Plenty of recently published studies are demonstrating significant platelet hyperactivity and endothelial dysfunction in ME/CFS, as well as anomalous clotting processes. It is of particular importance to determine to what extent these cardiovascular and haematological abnormalities contribute to symptom severity, and if these two systems can be targeted for therapeutic purposes.

Viral reservoirs of herpesviruses exist in ME/CFS, and most likely contribute to cardiovascular and haematological dysfunction directly or indirectly. This review highlights the potential of studying cardiac functioning, the vasculature, and coagulation system in ME/CFS.

Source: Jean M. Nunes, Douglas B. Kell, Etheresia Pretorius. Cardiovascular and haematological pathology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS): A role for viruses. Blood reviews, 20 March 2023, 101075 [Epub ahead of print]  https://www.sciencedirect.com/science/article/pii/S0268960X2300036X (Full text)

Neuropathology and Neurological Manifestations in ME/CFS and Long COVID with focus on Post-Exertional Symptom Exacerbation: a Literature Review

Summary:

Many of the people that get infected with the Coronavirus develop long-lasting complaints and are diagnosed with Long COVID after the acute infection is gone. These complains can last several months or years and include fatigue, cognitive impairment, sleeping problems and post-exertional symptom exacerbation (PESE). Research shows that COVID-19 patients with an acute infection have abnormalities in their brain, which could potentially lead to long-lasting neurological problems and symptoms. However, although many researchers are trying to uncover the underlying mechanisms, Long COVID is still very new.
The underlying mechanisms causing and maintaining the disease are therefore unclear. A large group of Long COVID patients resembles patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in terms of symptoms and, in many cases, the viral trigger of the disease. A core symptom of ME/CFS is PESE, which is uncommon in other fatiguing illnesses, but frequently seen in Long COVID patients. PESE involves an abnormal worsening of symptoms and cognitive and physical functions after any type of normal activity. Because of the large symptom overlap and lack of knowledge regarding PESE, underlying brain-mechanisms associated with Long COVID and ME/CFS in general as well as after physical exertion were investigated.
The findings of this review indicate that ME/CFS is associated with several abnormalities in the brain which are also proposed to be present in Long COVID patients. Such abnormalities include inflammation of the brain, shrinkage of the brain and less blood flow to the brain. After physical exertion, these abnormalities might be exacerbated in ME/CFS patients. This results in a brain that needs to work harder than the healthy brain to complete a task. It is demonstrated by increased brain activity in several brain regions after physical exertion and general symptom exacerbation. Since the two diseases seem to have a large overlap in symptoms and underlying brain-mechanisms, this finding might apply to patients with long COVID as well. Importantly, Long COVID seems to consist of different subgroups of which a large part fulfills the criteria for ME/CFS.
Treatment and therapy for ME/CFS patients is therefore likely transferable to this subgroup of Long COVID patients, with explicit attention towards the PESE phenomenon. More research is needed to uncover the underlying mechanisms as well as correct treatment approach of these diseases. Future research should take subgroups of Long COVID into account.
Source: Rodenburg, Sanne. Neuropathology and Neurological Manifestations in ME/CFS and Long COVID with focus on Post-Exertional Symptom Exacerbation: a Literature Review. Master Thesis, Utrecht University. March 14, 2023. https://studenttheses.uu.nl/bitstream/handle/20.500.12932/43647/Rodenburg_7433050_Neuropathology%20and%20neurological%20manifestations%20in%20MECFS%20and%20Long%20COVID%20with%20focus%20on%20PESE.pdf (Full text)