Tag: review

Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A critical review of the literature

Abstract:

Introduction: Persistent debilitating fatigue is a frequent complaint in patients with systemic autoimmune rheumatic diseases (SARDs). Fatigue is, however, frequently overlooked in the clinic, and patients who successfully achieve remission of their disease, often still have a lowered quality of life due to its persistence. How similar is this fatigue to Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), what is this fatigue associated with, and what tools/approaches (if any), have resulted in the improvement of fatigue in these patients is poorly defined.

Areas covered: Similarities between the pathophysiology of ME/CFS, systemic sclerosis (SSc) and primary systemic vasculitides (PSV) are discussed, followed by an in-depth review of the prevalence and correlates of fatigue in these diseases. The authors reviewed literature from MEDLINE, APA PsycInfo, Embase, and CINAHL.

Expert opinion: Persistent fatigue is a prominent feature in SARDs and may not be associated with components commonly associated with disease activity and/or progression. Immune and metabolic commonalities exist between ME/CFS, SSc, and PSVs – suggesting that common pathways inherent to the diseases and fatigue may be present. We suggest that patients with features of ME/CFS need to be identified by treating physicians, as they may require alternative approaches to therapy to improve their quality of life.

Source: van Eeden C, Osman MS, Cohen Tervaert JW. Fatigue in ANCA-associated vasculitis (AAV) and systemic sclerosis (SSc): similarities with Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). A critical review of the literature. Expert Rev Clin Immunol. 2022 Aug 31:1-22. doi: 10.1080/1744666X.2022.2116002. Epub ahead of print. PMID: 36045606. https://pubmed.ncbi.nlm.nih.gov/36045606/

Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome

Abstract:

The pathophysiological mechanisms involved in chronic disorders such as complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome have not been clearly defined. The course of the pain in some of the syndromes, the absence of evident tissue damage, and the predominance of alterations in the autonomic nervous system are shared similarities between them.

The production of autoantibodies following a trigger in the syndromes was previously described, for instance, trauma in complex regional pain syndrome, infectious agents in fibromyalgia, chronic fatigue syndrome, and post-COVID syndrome, and the immune stimulation by silicone in women with breast implants. In fact, the autoantibodies produced were shown to be directed against the autonomic nervous system receptors, leading to the amplification of the perception of pain alongside various clinical symptoms seen during the clinical course of the syndromes. Therefore, we viewed autoantibodies targeting the autonomic nervous system resulting in autonomic dysfunction as likely the most comprehensive explanation of the pathophysiology of the disorders mentioned.

Based on this, we aimed to introduce a new concept uniting complex regional pain syndrome, fibromyalgia, chronic fatigue syndrome, silicone breast implant-related symptoms, and post-COVID syndrome, namely “autoimmune autonomic dysfunction syndromes”. Due to its etiological, pathophysiological, and clinical implications, the suggested term would be more precise in classifying the syndromes under one title. The new title would doubtlessly facilitate both laboratory and clinical studies aimed to improve diagnosis and make treatment options more directed and precise.

Source: Mahroum N, Shoenfeld Y. Autoimmune Autonomic Dysfunction Syndromes: Potential Involvement and Pathophysiology Related to Complex Regional Pain Syndrome, Fibromyalgia, Chronic Fatigue Syndrome, Silicone Breast Implant-Related Symptoms and Post-COVID Syndrome. Pathophysiology. 2022 Jul 28;29(3):414-425. doi: 10.3390/pathophysiology29030033. PMID: 35997389. https://www.mdpi.com/1873-149X/29/3/33/htm (Full text)

Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome

Abstract:

Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia syndrome. Implementations of mitochondrial nutrients (MNs) with diet are important for the clinical effects antioxidant. We examined if use of an association of coenzyme Q10 and alpha lipoic acid (Requpero®) could reduce chronic covid symptoms.

The Requpero study is a prospective observational study in which 174 patients, who had developed chronic-covid syndrome, were divided in two groups: The first one (116 patients) received coenzyme Q10 + alpha lipoic acid, and the second one (58 patients) did not receive any treatment. Primary outcome was reduction in Fatigue Severity Scale (FSS) in treatment group compared with control group. complete FSS response was reached most frequently in treatment group than in control group. A FSS complete response was reached in 62 (53.5%) patients in treatment group and in two (3.5%) patients in control group. A reduction in FSS core < 20% from baseline at T1 (non-response) was observed in 11 patients in the treatment group (9.5%) and in 15 patients in the control group (25.9%) (p < 0.0001).

To date, this is the first study that tests the efficacy of coenzyme Q10 and alpha lipoic acid in chronic Covid syndrome. Primary and secondary outcomes were met. These results have to be confirmed through a double blind placebo controlled trial of longer duration.

Source: Barletta MA, Marino G, Spagnolo B, Bianchi FP, Falappone PCF, Spagnolo L, Gatti P. Coenzyme Q10 + alpha lipoic acid for chronic COVID syndrome. Clin Exp Med. 2022 Aug 22. doi: 10.1007/s10238-022-00871-8. Epub ahead of print. PMID: 35994177.  https://link.springer.com/article/10.1007/s10238-022-00871-8 (Full text)

Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis

Abstract:

Prolonged symptoms after the clearance of acute coronavirus disease 2019 (COVID-19) infection, termed long COVID, are an emerging threat to the post-COVID-19 era. Complementary and alternative medicine (CAM) interventions may play a significant role in the management of long COVID. The present study aimed to identify published studies on the use of CAM interventions for long COVID and provide an overview of the research status using bibliometric analysis.

The present scoping review searched MEDLINE, Embase, and Cochrane Library from inception until November 2021 and identified published studies on CAM interventions for long COVID. A narrative analysis of the study types and effectiveness and safety of the CAM interventions are presented and a bibliometric analysis of citation information and references of the included publications were analyzed using the Bibliometrix package for R. An electronic database search identified 16 publications (2 clinical studies and 14 study protocols of systematic reviews or clinical studies) that were included in the present study. Dyspnea or pulmonary dysfunction, quality of life, olfactory dysfunction, and psychological symptoms after COVID-19 infection were assessed in the included publications.

The two clinical studies suggested that Chinese herbal medications were effective in relieving symptoms of pulmonary dysfunction. Bibliometric analysis revealed the current trend of research publication in this area was driven by study protocols written by Chinese, Korean, and Indian authors. Thus, the present scoping review and bibliometric analysis revealed that there are few studies published about the use of CAM for long COVID and long-term management for COVID-19 survivors. Original studies on CAM interventions, including randomized controlled trials and systematic reviews, are required to actively support evidence for their use in the management of long COVID. PROSPERO registration: this trial is registered with CRD42021281526.

Source: Tae-Hun Kim, Sae-Rom Jeon, Jung Won Kang, Sunoh Kwon, “Complementary and Alternative Medicine for Long COVID: Scoping Review and Bibliometric Analysis“, Evidence-Based Complementary and Alternative Medicine, vol. 2022, Article ID 7303393, 7 pages, 2022. https://doi.org/10.1155/2022/7303393 https://www.hindawi.com/journals/ecam/2022/7303393/ (Full text)

A Review of Respiratory Post-Acute Sequelae of COVID-19 (PASC) and the Potential Benefits of Pulmonary Rehabilitation

Abstract:

With the SARS-CoV-2 pandemic continuing into its third year, the number of patients who survive acute COVID-19 infection but go on to develop long-term symptoms is increasing daily. Those individuals who experience one or more of a variety of persistent symptoms post-COVID-19 are now diagnosed with the syndrome called post-acute sequelae of COVID-19 (PASC), often colloquially called “Long COVID.” This article discusses relevant research and current hypotheses regarding the pathophysiology and management of respiratory symptoms of PASC, in order to provide primary care physicians with context for management of this heterogeneous population. We focus on the growing body of research that supports the use of pulmonary rehabilitation for patients with PASC to improve symptoms and quality of life.

Source: Simon M, Simmons JE. A Review of Respiratory Post-Acute Sequelae of COVID-19 (PASC) and the Potential Benefits of Pulmonary Rehabilitation. R I Med J (2013). 2022 Sep 1;105(7):11-15. PMID: 35930484.  https://pubmed.ncbi.nlm.nih.gov/35930484/ http://rimed.org/rimedicaljournal/2022/09/2022-09-11-covid-simon.pdf (Full text available as PDF file)

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)

At the Root of 3 “Long” Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome

Abstract:

Several foreign antigens such as those derived from viruses and bacteria have been linked to long-term deleterious effects on the brain and other organs; yet, health outcomes subsequent to foreign antigen exposure vary depending in large part on the host’s immune system, in general, and on human leukocyte antigen (HLA) composition, in particular.

Here we first provide a brief description of 3 conditions characterized by persistent long-term symptoms, namely long-COVID-19, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and Gulf War Illness (GWI), followed by a brief overview of the role of HLA in the immune response to foreign antigens. We then discuss our Persistent Antigen (PA) hypothesis and highlight associations between antigen persistence due to HLA-antigen incongruence and chronic health conditions in general and the 3 “long” diseases above in particular. This review is not intended to cover the breadth and depth of symptomatology of those diseases but is specifically focused on the hypothesis that the presence of persistent antigens underlies their pathogenesis.

Source: James LM, Georgopoulos AP. At the Root of 3 “Long” Diseases: Persistent Antigens Inflicting Chronic Damage on the Brain and Other Organs in Gulf War Illness, Long-COVID-19, and Chronic Fatigue Syndrome. Neurosci Insights. 2022 Jul 22;17:26331055221114817. doi: 10.1177/26331055221114817. PMID: 35910083; PMCID: PMC9335483. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9335483/ (Full text)

Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome

Abstract:

Many acute COVID-19 convalescents experience a persistent sequelae of infection, called post-acute COVID-19 syndrome (PACS). With incidence ranging between 31% and 69%, PACS is becoming increasingly acknowledged as a new disease state in the context of SARS-CoV-2 infection. As SARS-CoV-2 infection can affect several organ systems to varying degrees and durations, the cellular and molecular abnormalities contributing to PACS pathogenesis remain unclear.

Despite our limited understanding of how SARS-CoV-2 infection promotes this persistent disease state, mitochondrial dysfunction has been increasingly recognized as a contributing factor to acute SARS-CoV-2 infection and, more recently, to PACS pathogenesis. The biological mechanisms contributing to this phenomena have not been well established in previous literature; however, in this review, we summarize the evidence that NAD+ metabolome disruption and subsequent mitochondrial dysfunction following SARS-CoV-2 genome integration may contribute to PACS biological pathogenesis.

We also briefly examine the coordinated and complex relationship between increased oxidative stress, inflammation, and mitochondrial dysfunction and speculate as to how SARS-CoV-2-mediated NAD+ depletion may be causing these abnormalities in PACS. As such, we present evidence supporting the therapeutic potential of intravenous administration of NAD+ as a novel treatment intervention for PACS symptom management.

Source: Block T, Kuo J. Rationale for Nicotinamide Adenine Dinucleotide (NAD+) Metabolome Disruption as a Pathogenic Mechanism of Post-Acute COVID-19 Syndrome. Clin Pathol. 2022 Jun 24;15:2632010X221106986. doi: 10.1177/2632010X221106986. PMID: 35769168; PMCID: PMC9234841. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234841/ (Full text)

Disorders of gut-brain interaction in post-acute COVID-19 syndrome

Abstract:

The novel coronavirus SARS-CoV-2 is responsible for the devastating pandemic which has caused more than 5 million deaths across the world until today. Apart from causing acute respiratory illness and multiorgan dysfunction, there can be long-term multiorgan sequalae after recovery, which is termed ‘long COVID-19’ or ‘post-acute COVID-19 syndrome’. Little is known about long-term gastrointestinal (GI) consequences, occurrence of post-infection functional gastrointestinal disorders and impact the virus may have on overall intestinal health.

In this review, we put forth the various mechanisms which may lead to this entity and possible ways to diagnose and manage this disorder. Hence, making physicians aware of this spectrum of disease is of utmost importance in the present pandemic and this review will help clinicians understand and suspect the occurrence of functional GI disease post recovery from COVID-19 and manage it accordingly, avoiding unnecessary misconceptions and delay in treatment.

Source: Golla R, Vuyyuru SK, Kante B, Kedia S, Ahuja V. Disorders of gut-brain interaction in post-acute COVID-19 syndrome. Postgrad Med J. 2022 Jul 1:postgradmedj-2022-141749. doi: 10.1136/pmj-2022-141749. Epub ahead of print. PMID: 35777934. https://pmj.bmj.com/content/early/2022/07/01/pmj-2022-141749 (Full text)

Animal Models for Neuroinflammation and Potential Treatment Methods

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic disease of unknown etiology and without effective treatment options. The onset of ME/CFS is often associated with neuroinflammation following bacterial or viral infection.

A positron emission tomography imaging study revealed that the degree of neuroinflammation was correlated with the severity of several symptoms in patients with ME/CFS. In animal studies, lipopolysaccharide- and polyinosinic-polycytidylic acid-induced models are thought to mimic the pathological features of ME/CFS and provoke neuroinflammation, characterized by increased levels of proinflammatory cytokines and activation of microglia.

In this review, we described the anti-inflammatory effects of three compounds on neuroinflammatory responses utilizing animal models. The findings of the included studies suggest that anti-inflammatory substances may be used as effective therapies to ameliorate disease symptoms in patients with ME/CFS.

Source: Tamura Y, Yamato M, Kataoka Y. Animal Models for Neuroinflammation and Potential Treatment Methods. Front Neurol. 2022 Jun 27;13:890217. doi: 10.3389/fneur.2022.890217. PMID: 35832182; PMCID: PMC9271866. https://pubmed.ncbi.nlm.nih.gov/35832182/  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9271866/ (Full study)