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Efficacy and Safety of Curcumin and Curcuma longa Extract in the Treatment of Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.
Zeng, L, Yang, T, Yang, K, Yu, G, Li, J, Xiang, W, Chen, H
Frontiers in immunology. 2022;13:891822
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Arthritic disease is a chronic inflammatory condition affecting one or more joints. Over 100 different forms of arthritis have been identified. Despite their different causes (i.e. degenerative, autoimmune), they share common symptoms such as joint pain, swelling, stiffness, and reduced mobility, which can be disabling in many cases. Drug treatment focuses mainly on limiting the progression of the disease, reducing joint inflammation and managing pain. However, these drugs are associated with many side effects. The rhizome of Curcuma longa (CL), also known as turmeric, has longstanding use as an anti-inflammatory in traditional Asian medicines. Research has affirmed its anti-inflammatory and immunosuppressive properties. Evidence from multiple clinical trials suggests that curcumin, one of the active compounds of CL, can reduce the subjective experience of pain in some conditions and can also improve the symptoms and inflammation associated with arthritis. Hence this systematic review sought to evaluate the efficacy and safety of CL-extract in 5 types of arthritis (including Ankylosing Spondylitis, Rheumatoid Arthritis, Osteoarthritis, Juvenile idiopathic arthritis and gout). The review included 29 randomized controlled trials involving 2396 participants, with dosages ranging from 120 mg to 1500 mg for a period of 4-36 weeks. Overall, curcumin and CL extract appeared to improve inflammation and pain levels in arthritic subjects whilst demonstrating safety with no increases in adverse effects. CL and its active constituents appeared to favourably change immune and inflammatory responses, as well as serum uric acid levels in the reviewed forms of arthritis. However, due to the small sample numbers in the trials and some lower quality studies, the authors advocate to interpret the results with caution until more solid evidence is available.
Abstract
Background: Modern pharmacological research found that the chemical components of Curcuma longa L. are mainly curcumin and turmeric volatile oil. Several recent randomized controlled trials (RCT) have shown that curcumin improves symptoms and inflammation in patients with arthritis. Methods: Pubmed, Cochran Library, CNKI, and other databases were searched to collect the randomized controlled trials (RCTs). Then, the risk of bias of RCTs were assessed and data of RCTs were extracted. Finally, RevMan 5.3 was utilized for meta-analysis. Results: Twenty-nine (29) RCTs involving 2396 participants and 5 types of arthritis were included. The arthritis included Ankylosing Spondylitis (AS), Rheumatoid Arthritis (RA), Osteoarthritis (OA), Juvenile idiopathic arthritis (JIA) and gout/hyperuricemia. Curcumin and Curcuma longa Extract were administered in doses ranging from 120 mg to 1500 mg for a duration of 4-36 weeks. In general, Curcumin and Curcuma longa Extract showed safety in all studies and improved the severity of inflammation and pain levels in these arthritis patients. However, more RCTs are needed in the future to elucidate the effect of Curcumin and Curcuma longa Extract supplementation in patients with arthritis, including RA, OA, AS and JIA. Conclusion: Curcumin and Curcuma longa Extract may improve symptoms and inflammation levels in people with arthritis. However, due to the low quality and small quantity of RCTs, the conclusions need to be interpreted carefully.
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Dietary supplements in neurological diseases and brain aging.
Naureen, Z, Dhuli, K, Medori, MC, Caruso, P, Manganotti, P, Chiurazzi, P, Bertelli, M
Journal of preventive medicine and hygiene. 2022;63(2 Suppl 3):E174-E188
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The rate of neurodegenerative diseases (ND) is increasing at a concerning rate. The condition is characterized by the progressive decline of neuron function in the brain, eventually leading to cognitive impairment and motorneuron disorders. This process appears to be mediated by the complex interplay of factors. The brain is extremely sensitive to oxidative stress, and oxidative stress and inflammation of the nervous tissue appear to be a common denominator in all neurodegenerative diseases. One of the challenges of ND for prevention as well as treatment and treatment development, is that the initial disease progression usually goes unnoticed, with symptoms only becoming apparent in the more advanced stages when irreversible damage has occurred. Diet quality has a significant impact on brain health and hence can also influence ND development. For example, the Mediterranean diet (MedDiet) has demonstrated many valuable attributes that can reduce ND incidences and improve cognitive function. This review looked at dietary components, natural compounds and medicinal plants that have shown to be beneficial for brain health in ND. The authors discussed the MedDiet followed by a brief review of dietary supplements, including N-acetylcysteine (NAC), phospholipids (Phosphatidylserine, Phosphatidylcholine), Gamma-aminobutyric acid, melatonin, omega-3 fatty acids, neurotropic vitamin B (B1, B6 and B12), S-adenosyl methionine (SAMe), the amino acid tryptophan, magnesium and various polyphenols. Several medicinal plants are reviewed that have demonstrated positive effects on preventing or alleviating neurological diseases. This includes Withania somnifera (Ashwagandha), Baccopa monnieri (Brahmi), Acorus calamus (Calamus) and Hypericum perforatum (St. Johns Wort). The review concluded that many bioactive compounds and plant constituents that can be obtained from a qualitative diet, as well as certain medicinal plants and supplements, can help preserve and promote brain health and prevent the onset of ND. Large clinical trials are needed to assess their suitability for their wider use.
Abstract
A healthy diet shapes a healthy mind. Diet quality has a strong association with brain health. Diet influences the onset and consequences of neurological diseases, and dietary factors may influence mental health at individual and population level. The link between unhealthy diet, impaired cognitive function and neurodegenerative diseases indicates that adopting a healthy diet would ultimately afford prevention and management of neurological diseases and brain aging. Neurodegenerative diseases are of multifactorial origin and result in progressive loss of neuronal function in the brain, leading to cognitive impairment and motoneuron disorders. The so-called Mediterranean diet (MedDiet) with its healthy ingredients rich in antioxidant, anti-inflammatory, immune, neuroprotective, antidepressant, antistress and senolytic activity plays an essential role in the prevention and management of neurological diseases and inhibits cognitive decline in neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's diseases. The MedDiet also modulates the gut-brain axis by promoting a diversity of gut microbiota. In view of the importance of diet in neurological diseases management, this review focuses on the dietary components, natural compounds and medicinal plants that have proven beneficial in neurological diseases and for brain health. Among them, polyphenols, omega-3 fatty acids, B vitamins and several ayurvedic herbs have promising beneficial effects.
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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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Clinical applications of detecting IgG, IgM or IgA antibody for the diagnosis of COVID-19: A meta-analysis and systematic review.
Chen, M, Qin, R, Jiang, M, Yang, Z, Wen, W, Li, J
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases. 2021;104:415-422
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The rapidly spreading nature of COVID-19 has put an emphasis on the importance of fast diagnosis. Gold standard diagnosis is through reverse transcription polymerase chain reaction (RT-PCR) tests, which aims to detect the presence of COVID-19. However, challenges with collection techniques and when in the disease lifecycle these tests are taken, can affect their reliability, highlighting a need for alternative methods of testing. Other testing methods exist, which involve testing the body’s own immune response to the presence of COVID-19, however these may also have their limitations. This systematic review and meta-analysis aimed to determine the effectiveness of testing the body’s own immune reaction for the presence of COVID-19. The results showed that testing the body’s immune reaction was effective, however if the person being tested is at an early stage in the disease, then it may be misdiagnosed. This study could be used by healthcare professionals to understand that the use of any type of COVID-19 testing may have its limitations, and although a person may test negative, there is still a possibility that they have the infection if symptoms exist
Abstract
BACKGROUND The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. METHODS A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG-); (2) IgG-positive but IgM-negative (IgG+IgM-); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/-); (5) IgG-positive without IgM information (IgG+IgM+/-); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). RESULTS Sixty-eight studies were included. Pooled sensitivities for IgM+IgG-, IgG+IgM-, IgM+IgG+, IgM+IgG+/-, IgG+IgM+/-, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. DISCUSSION These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.
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Contribution of Lactobacillus iners to Vaginal Health and Diseases: A Systematic Review.
Zheng, N, Guo, R, Wang, J, Zhou, W, Ling, Z
Frontiers in cellular and infection microbiology. 2021;11:792787
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The vaginal microbiome is an important contributor to vaginal health. Here the dominance of Lactobacilli species, alongside their antimicrobial compounds play a critical role in contributing and protecting the vaginal milieu. Conversely the disruption or absence of Lactobacilli dominance is frequently associated with vaginal disease and infections. One of the Lactobacilli species prevalent in the vaginal microbiome is Lactobacillus iners. It was long overlooked in research due to it being so difficult to culture, and it was first identified in 1999 thanks to DNA sequencing. Researchers since discovered that the relationship between L. iners and vaginal health is far more complicated and ambiguous compared to the other Lactobacilli species. This systematic review explores the current knowledge of the characteristics of L. iners and its role in vaginal health and disease. The article discusses L. iners identification, genetic make up and differences to other Lactobacilli species and how they relate to vaginal health. The article also summarizes L. iners nutrient requirements and its role in diseases like dysbiosis, bacterial vaginosis, sexually transmitted infections and biofilm formation. Furthermore the authors look at the relation between L. iners and premature birthing, fertility and menstrual cycles. A final section in discusses the antimicrobial and immune sytem activating qualities of L. iners. In light of all these findings the authors describe L . iners as a very unique Lactobacilli due to its unusual characteristics. Whether L. iners is beneficial or pathogenic for the host remains controversial, as it can adapt to high and low pH environment and is seen in health and equally dysbiotic states of infection. Hence some describe it as a transitional species that colonizes the vagina after disturbances. It may be a risk factor for infections by contributing to the onset and maintenance of dysbiotic disturbances. Further studies are needed to clarify the role of L. iners and its role on vaginal health and whether it could serve as a biomarker for vaginal inflammation. This article is a useful summary about the characteristics and role of L. iners in vaginal health in disease.
Abstract
Lactobacillus iners, first described in 1999, is a prevalent bacterial species of the vaginal microbiome. As L. iners does not easily grow on de Man-Rogosa-Sharpe agar, but can grow anaerobically on blood agar, it has been initially overlooked by traditional culture methods. It was not until the wide application of molecular biology techniques that the function of L. iners in the vaginal microbiome was carefully explored. L. iners has the smallest genome among known Lactobacilli and it has many probiotic characteristics, but is partly different from other major vaginal Lactobacillus species, such as L. crispatus, in contributing to the maintenance of a healthy vaginal microbiome. It is not only commonly present in the healthy vagina but quite often recovered in high numbers in bacterial vaginosis (BV). Increasing evidence suggests that L. iners is a transitional species that colonizes after the vaginal environment is disturbed and offers overall less protection against vaginal dysbiosis and, subsequently, leads to BV, sexually transmitted infections, and adverse pregnancy outcomes. Accordingly, under certain conditions, L. iners is a genuine vaginal symbiont, but it also seems to be an opportunistic pathogen. Further studies are necessary to identify the exact role of this intriguing species in vaginal health and diseases.
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Potential Anti-SARS-CoV-2 Therapeutics That Target the Post-Entry Stages of the Viral Life Cycle: A Comprehensive Review.
Al-Horani, RA, Kar, S
Viruses. 2020;12(10)
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The covid-19 pandemic has required the identification of therapies to prevent infection and limit severity. A previous paper by the same authors reviewed therapies that block the virus in the early stages of its lifecycle. This very large review of over 300 papers aimed to summarise therapeutics which are aimed at blocking the lifecycle of the virus after it has entered the body’s cells. The authors began by reviewing the lifecycle of the covid-19 virus explaining how it enters the body’s cells, replicates inside and then is released to infect new cells. Several antivirals, antimalarials and natural products were then reviewed. Of note, Remdesivir is being trialled in covid-19 patients, with mixed results, however, is being recommended in the US for the treatment of hospitalised covid-19 patients with severe disease. Ribavirin, which is being trialled in combination with other antivirals is also showing promising results in shortening hospitalisation times in covid-19 patients. It was concluded that any stage of the covid-19 lifecycle could be a target for therapeutics and combining therapies is likely to be more successful than monotherapy. This paper could be used by health care professionals to understand the most recent therapeutic research for covid-19.
Abstract
The coronavirus disease-2019 (COVID-19) pandemic continues to challenge health care systems around the world. Scientists and pharmaceutical companies have promptly responded by advancing potential therapeutics into clinical trials at an exponential rate. Initial encouraging results have been realized using remdesivir and dexamethasone. Yet, the research continues so as to identify better clinically relevant therapeutics that act either as prophylactics to prevent the infection or as treatments to limit the severity of COVID-19 and substantially decrease the mortality rate. Previously, we reviewed the potential therapeutics in clinical trials that block the early stage of the viral life cycle. In this review, we summarize potential anti-COVID-19 therapeutics that block/inhibit the post-entry stages of the viral life cycle. The review presents not only the chemical structures and mechanisms of the potential therapeutics under clinical investigation, i.e., listed in clinicaltrials.gov, but it also describes the relevant results of clinical trials. Their anti-inflammatory/immune-modulatory effects are also described. The reviewed therapeutics include small molecules, polypeptides, and monoclonal antibodies. At the molecular level, the therapeutics target viral proteins or processes that facilitate the post-entry stages of the viral infection. Frequent targets are the viral RNA-dependent RNA polymerase (RdRp) and the viral proteases such as papain-like protease (PLpro) and main protease (Mpro). Overall, we aim at presenting up-to-date details of anti-COVID-19 therapeutics so as to catalyze their potential effective use in fighting the pandemic.
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Harnessing the immune system to overcome cytokine storm and reduce viral load in COVID-19: a review of the phases of illness and therapeutic agents.
Khadke, S, Ahmed, N, Ahmed, N, Ratts, R, Raju, S, Gallogly, M, de Lima, M, Sohail, MR
Virology journal. 2020;17(1):154
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Severe manifestations of COVID-19 infection and mortality are associated with a cytokine storm. This is an excessive inflammatory response to the infection leading to an overproduction of pro-inflammatory signalling molecules, which consequently contributes to tissue and organ damage. This literature review summarised current knowledge, as of June 2020, about virus-associated cytokine storm, virus-host interactions and immunological mechanism, to gain a better understanding of the phenomena observed in COVID-19 infections and devise better treatment strategies. The review briefly outlines the epidemiology of COVID-19, predictors of severity of disease, mode of transmission, testing, viral structure, mechanism of invasion of the host cell, replication and immune invasion and the progression of the four stages of the cytokine storm. The second part of the review discusses antiviral therapeutics of interest with a table summarising drugs, mechanism and available data. This article may be of interest to those who like to delve further into the mechanisms and immune components involved in a cytokine storm and gain an oversight of the pathways targeted by allopathic agents that have been put forward as treatment options.
Abstract
BACKGROUND Coronavirus disease 2019 (COVID-19) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, previously named 2019-nCov), a novel coronavirus that emerged in China in December 2019 and was declared a global pandemic by World Health Organization by March 11th, 2020. Severe manifestations of COVID-19 are caused by a combination of direct tissue injury by viral replication and associated cytokine storm resulting in progressive organ damage. DISCUSSION We reviewed published literature between January 1st, 2000 and June 30th, 2020, excluding articles focusing on pediatric or obstetric population, with a focus on virus-host interactions and immunological mechanisms responsible for virus associated cytokine release syndrome (CRS). COVID-19 illness encompasses three main phases. In phase 1, SARS-CoV-2 binds with angiotensin converting enzyme (ACE)2 receptor on alveolar macrophages and epithelial cells, triggering toll like receptor (TLR) mediated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ƙB) signaling. It effectively blunts an early (IFN) response allowing unchecked viral replication. Phase 2 is characterized by hypoxia and innate immunity mediated pneumocyte damage as well as capillary leak. Some patients further progress to phase 3 characterized by cytokine storm with worsening respiratory symptoms, persistent fever, and hemodynamic instability. Important cytokines involved in this phase are interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α. This is typically followed by a recovery phase with production of antibodies against the virus. We summarize published data regarding virus-host interactions, key immunological mechanisms responsible for virus-associated CRS, and potential opportunities for therapeutic interventions. CONCLUSION Evidence regarding SARS-CoV-2 epidemiology and pathogenesis is rapidly evolving. A better understanding of the pathophysiology and immune system dysregulation associated with CRS and acute respiratory distress syndrome in severe COVID-19 is imperative to identify novel drug targets and other therapeutic interventions.
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Dissecting the interaction between COVID-19 and diabetes mellitus.
Chee, YJ, Tan, SK, Yeoh, E
Journal of diabetes investigation. 2020;11(5):1104-1114
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Several countries have reported higher death rates and more severe cases of covid-19 amongst individuals with chronic diseases such as type 2 diabetes. This review of 100 papers aimed to investigate the interconnecting factors which may contribute to poorer prognosis in individuals with covid-19 and type 2 diabetes. Although the evidence suggests that patients with type 2 diabetes have poorer outcomes after contracting covid-19, they are not more susceptible to infection. The paper reported that mechanisms which may increase severity in type 2 diabetics are abnormal immune function, increased susceptibility to inflammation, the increased adherence of the virus to target cells and reduced ability to fight infection. It is important to manage blood sugars when suffering from covid-19. The paper reviewed the use of several medications such as metformin, dipeptidyl peptidase-4 inhibitors (DPP4), glucagon-like peptide-1 agonists and insulin in the context of individuals suffering from covid-19, with insulin being the treatment of choice in the acutely ill patient. Current treatments of covid-19 were also reviewed such as chloroquine and hydroxychloroquine, Lopinavir-ritonavir, IL-6 receptor agonists, type 1 interferon and remdesivir. It was concluded that clinicians should be aware of the risks in patients with type 2 diabetes and covid-19. However as new data is made available, the chronic and long-term implications will become clearer. This study could be used by health care professionals to ensure that patients with type 2 diabetes do everything they can to avoid covid-19 infection and that if contracted these patients are closely monitored for severe disease.
Abstract
Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2. Data from several countries have shown higher morbidity and mortality among individuals with chronic metabolic diseases, such as diabetes mellitus. In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have diabetes mellitus, this adds another layer of complexity to their management. We explore potential interactions between antidiabetic medications and renin-angiotensin-aldosterone system inhibitors with COVID-19. Suggested recommendations for the use of antidiabetic medications for COVID-19 patients with diabetes mellitus are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in COVID-19 patients. In addition, we aim to increase clinicians' awareness of the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with diabetes mellitus.
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Viruses belonging to Anelloviridae or Circoviridae as a possible cause of chronic fatigue.
Grinde, B
Journal of translational medicine. 2020;18(1):485
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Chronic fatigue syndrome (CFS) is often triggered by a virus. This review argues that viruses already present in the body may be the cause of this condition and identifies two groups of viruses the anello and circoviruses as potential causes. The paper explains that both viruses are already present in many individuals, and only become a problem when the immune system is supressed by a secondary infection. When this happens the anello and circoviruses can penetrate the brain resulting in CFS. Therapies that inhibit these viruses are required and recently certain antimalarials have reported to be potential candidates. Further research is required. This study could be used by healthcare professionals to extend research into the role of viruses that are already present within the body on CFS.
Abstract
Chronic fatigue often starts with an acute viral infection-as witnessed in the case of SARS-CoV-2-but indirect consequences of these infections are presumably the actual cause of the condition. As recently reviewed in this journal, the culprit could be a virus already present in the patient. The review covers several types of viruses, but concludes that the question is still open. The focus is on well known, pathogenic viruses for which there are ample diagnostic tools. I argue that there is one lesser-known group of viruses, the related anello- and circoviruses, which ought to be investigated. More or less everyone harbours at least one strain of these viruses in the blood, while not in the spinal fluid. They normally replicate at a low level, but their activity increases in an immune suppressed host; and there are cases where they do reach the brain. The initial infection could facilitate their access to the brain.
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COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status.
Thomas, T, Stefanoni, D, Reisz, JA, Nemkov, T, Bertolone, L, Francis, RO, Hudson, KE, Zimring, JC, Hansen, KC, Hod, EA, et al
JCI insight. 2020;5(14)
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There is increasing urgency for the development of Covid-19 therapies. Treatments preventing infection and decreasing the amount of virus in the body have largely been unsuccessful and so the focus has turned to host biological pathways, which may be altered by Covid-19 infection. This observational study of forty-nine Covid-19 positive and negative individuals aimed to determine alterations in the hosts metabolism. The results showed that Covid-19 infection was associated with disrupted host inflammatory and immune pathways. Markers for kidney dysfunction were also increased alongside raised blood sugar levels and fatty acids in the blood. It was concluded that inflammatory markers may be an indicator for disease severity and a target for Covid-19 therapy. Dietary therapy could be used to target blood fatty acid changes brought about by Covid-19 infection. This study could be used by healthcare professionals to understand that inflammation is increased in Covid-19 patients and in lieu of approved therapies, dietary intervention may be of benefit.
Abstract
BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODSTo investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n = 33; diagnosed by nucleic acid testing), as compared with COVID-19-negative controls (n = 16).RESULTSTargeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).CONCLUSIONIn conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.FUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH.