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The neurological symptoms of COVID-19: a systematic overview of systematic reviews, comparison with other neurological conditions and implications for healthcare services.
Wildwing, T, Holt, N
Therapeutic advances in chronic disease. 2021;12:2040622320976979
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COVID-19 has been found to cause neurological manifestations in up to 50% of patients. The aim of this study was to inform future service provision for those who develop long-term neurological symptoms due to COVID-19, as well as exploring the effect of COVID-19 on health professionals’ perceptions towards those with symptoms of functional neurological disorder (FND). This study is a systematic overview of current systematic reviews which included 45 studies in qualitative synthesis. Results show that: - COVID-19 appears to be becoming chronic for some patients, presenting similar neurological symptoms to FND and to chronic fatigue syndrome; - the long-term neurological effects of COVID-19 may impact neurological and wider health care services; - the neurological symptoms seen in COVID-19 may affect health professionals’ perceptions of FND and chronic fatigue syndrome. Authors conclude that there is increasing evidence of the presence of long-COVID symptoms persisting beyond 3 months. Further research is recommended to explore whether the neurological symptoms of COVID-19 will improve acceptance and understanding of FND, or whether this will worsen the experience for those who suffer from FND.
Abstract
AIMS: In response to the rapid spread of COVID-19, this paper provides health professionals with better accessibility to available evidence, summarising findings from a systematic overview of systematic reviews of the neurological symptoms seen in patients with COVID-19. Implications of so-called 'Long Covid' on neurological services and primary care and similarities with other neurological disorders are discussed. METHODS Firstly, a systematic overview of current reviews of neurological symptoms of COVID-19 was conducted. Secondly, the implications of these findings are discussed in relation to the potential effect on neurological services and the similarities in the experience of patients with COVID-19 and those with other neurological disorders. A total of 45 systematic reviews were identified within seven databases, published between 11 April 2020 and 15 October 2020, following a search in June 2020, updated on 20 October 2020. RESULTS The results indicated that COVID-19 exhibits two types of neurological symptoms; life-threatening symptoms such as Guillain-Barre Syndrome (GBS) and encephalitis, and less devastating symptoms such as fatigue and myalgia. Many of these so-called lesser symptoms appear to be emerging as longer-term for some sufferers and have been recently labelled Long Covid. When compared, these less devastating symptoms are very similar to other neurological conditions such as chronic fatigue syndrome (CFS) and functional neurological disorder (FND). CONCLUSION Implications for neurological healthcare services in the United Kingdom (UK) may include longer waiting times and a need for more resources (including more qualified health professionals). There is also a possible change-effect on health professionals' perceptions of other neurological conditions such as CFS and FND. Future research is recommended to explore changes in health professionals' perceptions of neurological symptoms because of COVID-19.
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Long COVID: An overview.
Raveendran, AV, Jayadevan, R, Sashidharan, S
Diabetes & metabolic syndrome. 2021;15(3):869-875
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SARS-CoV-2 infection (COVID-19) is a major pandemic resulting in considerable mortality and morbidity worldwide. For some people who recover from COVID-19, symptoms persist or new ones develop for weeks or months after infection despite testing PCR negative. This is termed long-COVID or post-COVID syndrome and divided into two stages: post-acute-COVID with symptoms extending beyond three weeks, and chronic-COVID with symptoms extending beyond 12 weeks. Factors that increase the risk for long-COVID include being female, age, having more than five symptoms in the acute stage of infection and pre-existing health conditions. A mild disease course is not exclusive to long-COVID. Typically affected by long-COVID are the pulmonary or cardiovascular system, with neuropsychiatric presentations also being reported. Common symptoms are one or more of the following such as fatigue, breathlessness, cough, chest pain, heart racing, headache, joint pain, muscle pain and weakness, insomnia, pins and needles, diarrhoea, rash, hair loss, impaired balance, neurocognitive issues. Due to the novelty of the virus, the underline pathophysiology of long-COVID still requires further investigation. Contributing factors mentioned include: compromised body functions after illness and inactivity, organ damage, persistent inflammation, altered immune response and auto-antibody generation and viral persistence. The impact of medication, treatments, hospitalisation or associated post-traumatic stress is also urged to be accounted for. Diagnosis of long-COVID is made by thorough history taking, clinical examination and the exclusion of other conditions. For the management of long-COVID, the authors in this review suggest the sub-categorisation depending on the body system most affected to optimize treatment options. Furthermore, it is encouraged that medical treatment should also consider the monitoring for worsening of any pre-existing health conditions post-infection. This review yields a informative summary of the definition, symptom presentations, risk factors, diagnosis and medical treatment options relating to long-COVID.
Abstract
BACKGROUND AND AIMS Long COVID is the collective term to denote persistence of symptoms in those who have recovered from SARS-CoV-2 infection. METHODS WE searched the pubmed and scopus databases for original articles and reviews. Based on the search result, in this review article we are analyzing various aspects of Long COVID. RESULTS Fatigue, cough, chest tightness, breathlessness, palpitations, myalgia and difficulty to focus are symptoms reported in long COVID. It could be related to organ damage, post viral syndrome, post-critical care syndrome and others. Clinical evaluation should focus on identifying the pathophysiology, followed by appropriate remedial measures. In people with symptoms suggestive of long COVID but without known history of previous SARS-CoV-2 infection, serology may help confirm the diagnosis. CONCLUSIONS This review will helps the clinicians to manage various aspects of Long COVID.
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Management of post-acute covid-19 in primary care
The British Medical Journal (BMJ) is a global healthcare knowledge provider with a vision for a healthier world. It shares knowledge and expertise to improve healthcare outcomes. They publish more than 70 medical and allied science journals.
2021
Abstract
The article offers a thorough analysis of post-acute COVID-19, relating to those patients who have experienced a delayed recovery from the infection. These patients can be divided into two categories: those who have serious thromboembolic complications, and those with a non-specific clinical picture, mainly characterised by breathlessness and fatigue. Based on the UK COVID Symptom Study, in which people enter their ongoing symptoms on a smartphone app, around 10% of patients who tested positive remain unwell beyond three weeks, and a smaller proportion for months. A recent study in the US also found that only 65% of people had returned to their previous health level 14-21 days after a positive test. The authors discuss further the urge for clinical management of long-COVID to revolve around a whole-patient perspective, highlighting that no evidence-based recommendations for the management of post-acute covid-19 exist yet.
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The Effect of Nutritional Therapy for Yeast Infection (Candidiasis) in Cases of Chronic Fatigue Syndrome
The Journal of Orthomolecular Medicine has led the way for a quarter century in presenting new health concerns and treatments including: Candidiasis; Mercury Amalgam Toxicity; Niacin Therapy for Schizophrenia and Coronary Disease; Chronic Fatigue Syndrome; Vitamin C and Cancer; Allergies and Behavioural Disorders; Drug and Alcohol Abuse; Tissue and Mineral Analysis; and Orthomolecular Treatment for AIDS and Cardiovascular Disease.
2021
Abstract
The objective of this study was to evaluate the effectiveness of nutritional therapy for yeast infection in cases of medically diagnosed Chronic Fatigue Syndrome/ME. Forty participants received individual nutritional advice for treating yeast infection (candidiasis) over the course of one year. Whilst there were numerous confounding variables (stress, glucose tolerance, use of steroid treatments/ HRT/ contraceptive pill and age) and the drop-out rate was high (18 subjects completed the year), analysis indicated a relatively strong positive correlation between candida and CFS/ME at the start of the study. The average fall in CFS/ME symptom scores throughout the year was 30.5%, with one participant achieving a 100% reduction in symptoms. 83% of participants experienced some reduction in CFS/ME symptoms scores. Higher than average stress scores and use of steroids/HRT/contraceptive pill all negatively impacted CFS/ME scores despite following an anti-candida protocol. Nutrition practitioners may want to consider dietary strategies for candida when working with clients with CFS/ME.
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Will COVID-19 Lead to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome?
Komaroff, AL, Bateman, L
Frontiers in medicine. 2020;7:606824
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In people who have contracted COVID-19, many do not return to full health. Some may develop permanent dysfunction of damaged organs such as the brain, heart and kidney. Others report ongoing lingering symptoms despite tests no longer detecting the virus. This condition is being called ‘long covid.’ Patients post-COVID-19 can develop a post-viral syndrome that is very similar to Myalgic Encephalomyelitis/Chronic Fatigue syndrome, (ME/CFS). This short review looks at how common a post covid illness is and what implications this has for the U.S. and globally. The review concludes that the U.S. and the world will see a substantial growth in the number of people with ME/CFS. We can’t predict at this stage how long lasting that will be.
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Clinical symptoms and markers of disease mechanisms in adolescent chronic fatigue following Epstein-Barr virus infection: An exploratory cross-sectional study.
Kristiansen, MS, Stabursvik, J, O'Leary, EC, Pedersen, M, Asprusten, TT, Leegaard, T, Osnes, LT, Tjade, T, Skovlund, E, Godang, K, et al
Brain, behavior, and immunity. 2019;80:551-563
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Epstein-Barr virus (EBV) can trigger chronic fatigue (CF) and chronic fatigue syndrome (CFS) in individuals who are predisposed. However, how fatigue develops and how infections may trigger this is not fully understood. This exploratory cross-sectional study of 200 fatigued and non-fatigued adolescents 6 months after EBV aimed to understand symptoms and potential markers for disease. The results showed that all symptoms (not just fatigue) were more pronounced in those individuals suffering from fatigue, despite no increases in viral load. Those with fatigue only had slight changes in immune, nerve and hormonal markers and none correlated with severity of symptoms. It was concluded that there is a discrepancy between symptoms and viral load and alterations to several markers were only marginal. This study could be used by healthcare professionals to understand the possible limitations of using several biomarkers as a diagnostic tool for CF and CFS.
Abstract
INTRODUCTION Acute Epstein-Barr virus (EBV) infection is a trigger of chronic fatigue (CF) and Chronic Fatigue Syndrome (CFS). The aim of this cross-sectional study was to explore clinical symptoms as well as markers of disease mechanisms in fatigued and non-fatigued adolescents 6 months after EBV-infection, and in healthy controls. MATERIALS AND METHODS A total of 200 adolescents (12-20 years old) with acute EBV infection were assessed 6 months after the initial infectious event and divided into fatigued (EBV CF+) and non-fatigued (EBV CF-) cases based on questionnaire score. The EBV CF+ cases were further sub-divided according to case definitions of CFS. In addition, a group of 70 healthy controls with similar distribution of sex and age was included. Symptoms were mapped with a questionnaire. Laboratory assays included EBV PCR and serology; detailed blood leukocyte phenotyping and serum high-sensitive C-reactive protein; and plasma and urine cortisol and catecholamines. Assessment of autonomic activity was performed with continuous, non-invasive monitoring of cardiovascular variables during supine rest, controlled breathing and upright standing. Differences between EBV CF+ and EBV CF- were assessed by simple and multiple linear regression adjusting for sex as well as symptoms of depression and anxiety. A p-value ≤ 0.05 was considered statistically significant. This study is part of the CEBA-project (Chronic fatigue following acute Epstein-Barr virus infection in adolescents). RESULTS The EBV CF+ group had significantly higher scores for all clinical symptoms. All markers of infection and most immune, neuroendocrine and autonomic markers were similar across the EBV CF+ and EBV CF- group. However, the EBV CF+ group had slightly higher serum C-reactive protein (0.48 vs 0.43 mg/L, p = 0.031, high-sensitive assay), total T cell (CD3+) count (median 1573 vs 1481 × 106 cells/L, p = 0.012), plasma norepinephrine (1420 vs 1113 pmol/L, p = 0.01) and plasma epinephrine (363 vs 237 nmol/L, p = 0.032); lower low-frequency:high frequency (LF/HF) ratio of heart rate variability at supine rest (0.63 vs 0.76, p = 0.008); and an attenuated decline in LF/HF ratio during controlled breathing (-0.11 vs -0.25, p = 0.002). Subgrouping according to different CFS diagnostic criteria did not significantly alter the results. Within the EBV CF+ group, there were no strong correlations between clinical symptoms and markers of disease mechanisms. In a multiple regression analysis, serum CRP levels were independently associated with serum cortisol (B = 4.5 × 10-4, p < 0.001), urine norepinephrine (B = 9.6 × 10-2, p = 0.044) and high-frequency power of heart rate variability (B = -3.7 × 10-2, p = 0.024). CONCLUSIONS In adolescents, CF and CFS 6 months after acute EBV infection are associated with high symptom burden, but no signs of increased viral load and only subtle alterations of immune, autonomic, and neuroendocrine markers of which no one is strongly correlated with symptom scores. A slight sympathetic over parasympathetic predominance is evident in CF and might explain slightly increased CRP levels.
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The Microbiota-Gut-Brain Axis in Neuropsychiatric Disorders: Pathophysiological Mechanisms and Novel Treatments.
Kim, YK, Shin, C
Current neuropharmacology. 2018;16(5):559-573
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The connection between the microbiome in the gut and the brain is known as the gut-brain axis and may have implications in the development and treatment of brain disorders. This narrative review paper aimed to summarise the gut-brain axis and studies surrounding the use of gut microbiota in treatment for brain disorders. The authors first highlighted that the gut microbiota is individual and varies depending on the age of the host, with full development around the age of 3 years old. Diet, infections, the use of antibiotics and stress can all affect the gut-microbiota in what is termed dysbiosis. Studies in animals indicate that the gut-brain axis may be bidirectional with either aspect affecting the other. Stress may cause dysbiosis, affecting both digestion and the immune system. In turn the gut microbiota may affect the brain through the immune system, modulation of nerves, and through the production of signalling molecules. Several diseases of the brain may be influenced by the gut microbiota. Mood disorders, brain degeneration and childhood brain development disorders were all highlighted as having potential relationships with dysbiosis. The use of probiotics in chronic fatigue syndrome, schizophrenia, brain function and autism spectrum disorder were reviewed with positive results in chronic fatigue syndrome and brain function, however studies are lacking. It was concluded that gut microbiota may directly or indirectly affect brain disorders, however the role of probiotics as a treatment needs more research. This study could be used by healthcare professionals to understand the potential role of the gut microbiota in brain disorders.
Abstract
BACKGROUND The human gut microbiome comprise a huge number of microorganisms with co-evolutionary associations with humans. It has been repeatedly revealed that bidirectional communication exists between the brain and the gut and involves neural, hormonal, and immunological pathways. Evidences from neuroscience researches over the past few years suggest that microbiota is essential for the development and maturation of brain systems that are associated to stress responses. METHOD This review provides that the summarization of the communication among microbiota, gut and brain and the results of preclinical and clinical studies on gut microbiota used in treatments for neuropsychiatric disorders. RESULT Recent studies have reported that diverse forms of neuropsychiatric disorders (such as autism, depression, anxiety, and schizophrenia) are associated with or modulated by variations in the microbiome, by microbial substrates, and by exogenous prebiotics, antibiotics, and probiotics. CONCLUSION The microbiota-gut-brain axis might provide novel targets for prevention and treatment of neuropsychiatric disorders. However, further studies are required to substantiate the clinical use of probiotics, prebiotics and FMT.
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From good health to illness with post-infectious fatigue syndrome: a qualitative study of adults' experiences of the illness trajectory.
Stormorken, E, Jason, LA, Kirkevold, M
BMC family practice. 2017;18(1):49
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In 2004, the parasite Giardia lamblia [parasitic microorganism] contaminated the municipal drinking water reservoir in Bergen, Norway, which caused an outbreak of gastrointestinal infection. The aim of this study was to explore the evolvement of illness trajectory from the onset of the Giardia l. enteritis [inflammation of the small intestine] and identify any concomitant disabilities over the subsequent four years. This study had a retrospective explorative qualitative design. In-depth qualitative interviews were done in order to gain access to the participants’ experiences and conducted an inductive qualitative content analysis. Findings show five distinct progressive phases of the illness and disability trajectory. The time to develop post-infectious fatigue syndrome varied from one participant to the other. None of the participants experienced full remission, pre-illness functional level, or experienced a good outcome. Authors conclude that comparison of the functional trajectory in post-infectious fatigue syndrome cases and cases with an unknown trigger mechanism would be helpful to identify any differences in trajectories.
Abstract
BACKGROUND Municipal drinking water contaminated with the parasite Giardia lamblia in Bergen, Norway, in 2004 caused an outbreak of gastrointestinal infection in 2500 people, according to the Norwegian Prescription Database. In the aftermath a minor group subsequently developed post-infectious fatigue syndrome (PIFS). Persons in this minor group had laboratory-confirmed parasites in their stool samples, and their enteritis had been cured by one or more courses of antibiotic treatment. The study's purpose was to explore how the affected persons experienced the illness trajectory and various PIFS disabilities. METHODS A qualitative design with in-depth interviews was used to obtain first-hand experiences of PIFS. To get an overall understanding of their perceived illness trajectory, the participants were asked to retrospectively rate their functional level at different points in time. A maximum variation sample of adults diagnosed with PIFS according to the international 1994 criteria was recruited from a cohort of persons diagnosed with PIFS at a tertiary Neurology Outpatient Clinic in Western Norway. The sample comprised 19 women and seven men (mean age 41 years, range 26-59). The interviews were fully transcribed and subjected to a qualitative content analysis. RESULTS All participants had been living healthy lives pre-illness. The time to develop PIFS varied. Multiple disabilities in the physical, cognitive, emotional, neurological, sleep and intolerance domains were described. Everyone more or less dropped out from studies or work, and few needed to be taken care of during the worst period. The severity of these disabilities varied among the participants and during the illness phases. Despite individual variations, an overall pattern of illness trajectory emerged. Five phases were identified: prodromal, downward, turning, upward and chronic phase. All reached a nadir followed by varying degrees of improvement in their functional ability. None regained pre-illness health or personal and professional abilities. CONCLUSIONS The needs of persons with this condition are not met. Early diagnosis and interdisciplinary rehabilitation could be beneficial in altering the downward trajectory at an earlier stage, avoiding the most severe disability and optimising improvement. Enhanced knowledge among health professionals, tailored treatment, rest as needed, financial support and practical help would likely improve prognosis.
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Dietary and nutrition interventions for the therapeutic treatment of chronic fatigue syndrome/myalgic encephalomyelitis: a systematic review.
Campagnolo, N, Johnston, S, Collatz, A, Staines, D, Marshall-Gradisnik, S
Journal of human nutrition and dietetics : the official journal of the British Dietetic Association. 2017;30(3):247-259
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This systematic review evaluated the evidence available for dietary and nutritional interventions for chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). 17 studies met the inclusion criteria the authors used. Notably, studies that used multi-treatments were excluded from this review. The quality of the studies varied, but two thirds were considered to be of high quality. None of the trials reported a dietary intake method at start and end of the trial period, so dietary changes alongside the intervention may have influenced the results. A variety of scales were used to measure improvement of symptoms, making it difficult to compare studies, and study designs limited recruitment to those CFS/ME sufferers who were well enough to attend a clinic/hospital. Positive results were found for nicotinamide adenine dinucleotide hydride (NADH), with and without Co-enzyme Q10, polyphenol rich chocolate and probiotics, however, studies were either of short duration or had small samples sizes, and for most interventions there was only one study. The authors conclude that, whilst there is insufficient evidence for the general prescription of supplements or elimination diets for CFS/ME patients, such interventions may be considered on an individual basis.
Abstract
BACKGROUND Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of symptoms. Diet modification and nutritional supplements could be used to improve patient outcomes, such fatigue and quality of life. We reviewed and discussed the evidence for nutritional interventions that may assist in alleviating symptoms of CFS/ME. METHODS Medline, Cinahl and Scopus were systematically searched from 1994 to May 2016. All studies on nutrition intervention were included where CFS/ME patients modified their diet or supplemented their habitual diet on patient-centred outcomes (fatigue, quality of life, physical activity and/or psychological wellbeing). RESULTS Seventeen studies were included that meet the inclusion criteria. Of these, 14 different interventions were investigated on study outcomes. Many studies did not show therapeutic benefit on CFS/ME. Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol rich chocolate, and a combination of NADH and coenzyme Q10. CONCLUSIONS This review identified insufficient evidence for the use of nutritional supplements and elimination or modified diets to relieve CFS/ME symptoms. Studies were limited by the number of studies investigating the interventions, small sample sizes, study duration, variety of instruments used, and studies not reporting dietary intake method. Further research is warranted in homogeneous CFS/ME populations.