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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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Mobile Apps to Improve Medication Adherence in Cardiovascular Disease: Systematic Review and Meta-analysis.
Al-Arkee, S, Mason, J, Lane, DA, Fabritz, L, Chua, W, Haque, MS, Jalal, Z
Journal of medical Internet research. 2021;23(5):e24190
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A long-term use of cardiovascular medications significantly reduces the risk of morbidity and mortality, but their full therapeutic potential cannot be achieved if patients are nonadherent. Developing interventions to tackle medication nonadherence is important for improving health outcomes. The aim of this study was to evaluate the effectiveness of app-based interventions on medication adherence in patients with cardiovascular disease (CVD). This study is a systemic review and meta-analysis of 16 randomised controlled trials. The apps used were all different for each study and were developed by different organizations: 8 were academic or government institutions, whereas others were commercial organizations. Results show that a total of 9 trials showed a statistically significant improvement in medication adherence in the intervention arm. Furthermore, the apps used had mixed functionality, including reminders, education or both, however, overall, user engagement and usability were rated positively, demonstrating interest in the concept. Authors conclude that it is difficult to make strong, unrestricted recommendations for practice, especially with the methodological limitations of the trials included in this study. However, mobile apps may enhance medication adherence as part of a package of care.
Abstract
BACKGROUND Adherence rates of preventative medication for cardiovascular disease (CVD) have been reported as 57%, and approximately 9% of all CVD events in Europe are attributable to poor medication adherence. Mobile health technologies, particularly mobile apps, have the potential to improve medication adherence and clinical outcomes. OBJECTIVE The objective of this study is to assess the effects of mobile health care apps on medication adherence and health-related outcomes in patients with CVD. This study also evaluates apps' functionality and usability and the involvement of health care professionals in their use. METHODS Electronic databases (MEDLINE [Ovid], PubMed Central, Cochrane Library, CINAHL Plus, PsycINFO [Ovid], Embase [Ovid], and Google Scholar) were searched for randomized controlled trials (RCTs) to investigate app-based interventions aimed at improving medication adherence in patients with CVD. RCTs published in English from inception to January 2020 were reviewed. The Cochrane risk of bias tool was used to assess the included studies. Meta-analysis was performed for clinical outcomes and medication adherence, with meta-regression analysis used to evaluate the impact of app intervention duration on medication adherence. RESULTS This study included 16 RCTs published within the last 6 years. In total, 12 RCTs reported medication adherence as the primary outcome, which is the most commonly self-reported adherence. The duration of the interventions ranged from 1 to 12 months, and sample sizes ranged from 24 to 412. Medication adherence rates showed statistically significant improvements in 9 RCTs when compared with the control, and meta-analysis of the 6 RCTs reporting continuous data showed a significant overall effect in favor of the app intervention (mean difference 0.90, 95% CI 0.03-1.78) with a high statistical heterogeneity (I2=93.32%). Moreover, 9 RCTs assessed clinical outcomes and reported an improvement in systolic blood pressure, diastolic blood pressure, total cholesterol, and low-density lipoprotein cholesterol levels in the intervention arm. Meta-analysis of these clinical outcomes from 6 RCTs favored app interventions, but none were significant. In the 7 trials evaluating app usability, all were found to be acceptable. There was a great variation in the app characteristics. A total of 10 RCTs involved health care professionals, mainly physicians and nurses, in the app-based interventions. The apps had mixed functionality: 2 used education, 7 delivered reminders, and 7 provided reminders in combination with educational support. CONCLUSIONS Apps tended to increase medication adherence, but interventions varied widely in design, content, and delivery. Apps have an acceptable degree of usability; yet the app characteristics conferring usability and effectiveness are ill-defined. Future large-scale studies should focus on identifying the essential active components of successful apps. TRIAL REGISTRATION PROSPERO International Prospective Register of Systematic Reviews CRD42019121385; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=121385.
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Short- and potential long-term adverse health outcomes of COVID-19: a rapid review.
Leung, TYM, Chan, AYL, Chan, EW, Chan, VKY, Chui, CSL, Cowling, BJ, Gao, L, Ge, MQ, Hung, IFN, Ip, MSM, et al
Emerging microbes & infections. 2020;9(1):2190-2199
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The Coronavirus pandemic (Covid-19) has infected millions of people worldwide and there is evidence that it affects many systems in the human body. This rapid review summarises the current evidence on short-term negative health outcomes of Covid-19. It also assesses the risk of potential long-term negative effects by looking at data from the other coronaviruses; Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). The burden for caring for Covid-19 survivors is likely to be huge and so policy makers need suitable data to put the appropriate care strategies in place. The review is divided into sections as per body system affected: Immune, respiratory, cardiovascular, gastrointestinal, hepatic and renal, neurological, dermatological, mental health, pregnancy and prenatal exposure. The evidence (short-term and long-term) is then reviewed by experts in those fields. Further large-scale studies are needed to monitor the adverse effects and to measure the long-term health consequences.
Abstract
The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of patients infected worldwide and indirectly affecting even more individuals through disruption of daily living. Long-term adverse outcomes have been reported with similar diseases from other coronaviruses, namely Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS). Emerging evidence suggests that COVID-19 adversely affects different systems in the human body. This review summarizes the current evidence on the short-term adverse health outcomes and assesses the risk of potential long-term adverse outcomes of COVID-19. Major adverse outcomes were found to affect different body systems: immune system (including but not limited to Guillain-Barré syndrome and paediatric inflammatory multisystem syndrome), respiratory system (lung fibrosis and pulmonary thromboembolism), cardiovascular system (cardiomyopathy and coagulopathy), neurological system (sensory dysfunction and stroke), as well as cutaneous and gastrointestinal manifestations, impaired hepatic and renal function. Mental health in patients with COVID-19 was also found to be adversely affected. The burden of caring for COVID-19 survivors is likely to be huge. Therefore, it is important for policy makers to develop comprehensive strategies in providing resources and capacity in the healthcare system. Future epidemiological studies are needed to further investigate the long-term impact on COVID-19 survivors.
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Comparison of dietary macronutrient patterns of 14 popular named dietary programmes for weight and cardiovascular risk factor reduction in adults: systematic review and network meta-analysis of randomised trials.
Ge, L, Sadeghirad, B, Ball, GDC, da Costa, BR, Hitchcock, CL, Svendrovski, A, Kiflen, R, Quadri, K, Kwon, HY, Karamouzian, M, et al
BMJ (Clinical research ed.). 2020;369:m696
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Dietary recommendations to combat obesity and its associated risk for heart disease are extensive. Many different diets and patterns of eating are being tried by millions of people, however no systematic review comparing their effectiveness has been performed. This systematic review and meta-analysis aimed to determine the effectiveness of 14 popular diets and diets which restrict certain nutrients on weight loss and heart disease risk. The results identified 121 studies with 21942 patients for inclusion. The Atkins diet, the Zone diet and the Dietary Approaches to Stop Hypertension (DASH) diet were the most effective for weight loss and for reducing blood pressure. Low carbohydrate and low-fat diets achieved similar weight loss when compared to a normal diet. Low carbohydrate diets had less effect on heart disease risk factors than low fat and moderate macronutrient diets. There were no improvements in good cholesterol with any of the diets. Interestingly any benefits on weight loss for any of the diets disappeared after 12 months and this was also observed for heart disease risk, except in those on the Mediterranean diet. It was concluded that most diets show improvements to weight loss and heart disease risk factors over 6 months, however these are largely unsustainable after 12 months. Differences between diets are small and healthcare practitioners could use this study to recommend any number of diets to achieve weight loss and the Mediterranean diet in particular to decrease heart disease risk. However, it is important to understand that this may be a short-term fix and at 12 months patients need to be assessed to ensure that weight loss is sustained.
Abstract
OBJECTIVE To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement among adults who are overweight or obese. DESIGN Systematic review and network meta-analysis of randomised trials. DATA SOURCES Medline, Embase, CINAHL, AMED, and CENTRAL from database inception until September 2018, reference lists of eligible trials, and related reviews. STUDY SELECTION Randomised trials that enrolled adults (≥18 years) who were overweight (body mass index 25-29) or obese (≥30) to a popular named diet or an alternative diet. OUTCOMES AND MEASURES Change in body weight, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, systolic blood pressure, diastolic blood pressure, and C reactive protein at the six and 12 month follow-up. REVIEW METHODS Two reviewers independently extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. A bayesian framework informed a series of random effects network meta-analyses to estimate the relative effectiveness of the diets. RESULTS 121 eligible trials with 21 942 patients were included and reported on 14 named diets and three control diets. Compared with usual diet, low carbohydrate and low fat diets had a similar effect at six months on weight loss (4.63 v 4.37 kg, both moderate certainty) and reduction in systolic blood pressure (5.14 mm Hg, moderate certainty v 5.05 mm Hg, low certainty) and diastolic blood pressure (3.21 v 2.85 mm Hg, both low certainty). Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions. Low carbohydrate diets had less effect than low fat diets and moderate macronutrient diets on reduction in LDL cholesterol (1.01 mg/dL, low certainty v 7.08 mg/dL, moderate certainty v 5.22 mg/dL, moderate certainty, respectively) but an increase in HDL cholesterol (2.31 mg/dL, low certainty), whereas low fat (-1.88 mg/dL, moderate certainty) and moderate macronutrient (-0.89 mg/dL, moderate certainty) did not. Among popular named diets, those with the largest effect on weight reduction and blood pressure in comparison with usual diet were Atkins (weight 5.5 kg, systolic blood pressure 5.1 mm Hg, diastolic blood pressure 3.3 mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg, respectively), and Zone (4.1 kg, 3.5 mm Hg, 2.3 mm Hg, respectively) at six months (all moderate certainty). No diets significantly improved levels of HDL cholesterol or C reactive protein at six months. Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared. CONCLUSIONS Moderate certainty evidence shows that most macronutrient diets, over six months, result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure. At 12 months the effects on weight reduction and improvements in cardiovascular risk factors largely disappear. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42015027929.
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Non-Systematic Review of Diet and Nutritional Risk Factors of Cardiovascular Disease in Obesity.
Rychter, AM, Ratajczak, AE, Zawada, A, Dobrowolska, A, Krela-Kaźmierczak, I
Nutrients. 2020;12(3)
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Nutrition is a major factor influencing obesity associated heart disease risk, however many people with this disease do not follow nutritional recommendations. This review of 155 studies aimed to summarise dietary aspects of heart disease prevention. The paper began by outlining the role of obesity through the development of other disorders that contribute to heart disease, such as type 2 diabetes, high blood pressure and blood sugar imbalance. The quantity and distribution of fat tissue also can contribute to heart disease risk, especially if it is located within the heart or around the major organs of the body. Dietary factors which can increase heart disease risk were described as an increased intake of processed foods, sugar, salt and certain fats and low intakes of fruit, vegetables, fibre, whole grains, beans and nuts. The Mediterranean diet, the dietary approaches to stop hypertension (DASH) diet, plant-based diets, the portfolio dietary pattern and low carbohydrate diets were all reviewed and although mixed results were stated for low carbohydrate diets, most of the diets reviewed reported improved heart disease outcomes. The role of intestinal microbiota in heart disease were also reviewed and the influence of a poor diet was implicated in imbalanced gut microbiota and the development of heart disease. It was concluded that an unhealthy diet can contribute to heart disease and that dietary patterns such as the Mediterranean diet and plant-based diets may be favourable for its management. This study could be used by healthcare professionals to individualise dietary recommendations for patients with heart disease or who are at risk of it.
Abstract
Although cardiovascular disease and its risk factors have been widely studied and new methods of diagnosis and treatment have been developed and implemented, the morbidity and mortality levels are still rising-cardiovascular disease is responsible for more than four million deaths each year in Europe alone. Even though nutrition is classified as one of the main and changeable risk factors, the quality of the diet in the majority of people does not follow the recommendations essential for prevention of obesity and cardiovascular disease. It demonstrates the need for better nutritional education in cardiovascular disease prevention and treatment, and the need to emphasize dietary components most relevant in cardiovascular disease. In our non-systematic review, we summarize the most recent knowledge about nutritional risk and prevention in cardiovascular disease and obesity.
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Comorbid Chronic Diseases are Strongly Correlated with Disease Severity among COVID-19 Patients: A Systematic Review and Meta-Analysis.
Liu, H, Chen, S, Liu, M, Nie, H, Lu, H
Aging and disease. 2020;11(3):668-678
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Symptomatic COVID-19 infection is accompanied by a cluster of flu-like symptoms and life-threatening severe illnesses including acute respiratory distress syndrome, acute kidney injury, myocarditis, and organ failure. The aim of this study was to provide a systematic evaluation and detailed estimate on the prevalence and effects of pre-existing chronic conditions in COVID-19 patients. This study is a systemic review and meta-analysis of 24 studies (with a total of 10948 COVID-19 patients) for qualitative and quantitative synthesis. Results show that: - male participants were more susceptible to COVID-19. - both sexes exhibited clinical presentations similar in symptomatology. - diabetes and coronary artery disease/cardiovascular disease were prevalent in 10.0% and 8.0% of the patients, respectively. - pre-existing chronic diseases were strongly correlated with the increased disease severity and increased admittance to ICU. Authors conclude that patients with pre-existing chronic diseases may have a higher risk for developing severe COVID-19 and should be given close attention.
Abstract
Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. In order to explore the effects of comorbid chronic diseases on clinical outcomes of COVID-19, a search was conducted in PubMed, Ovid MEDLINE, EMBASE, CDC, and NIH databases to April 25, 2020. A total of 24 peer-reviewed articles, including 10948 COVID-19 cases were selected. We found diabetes was present in 10.0%, coronary artery disease/cardiovascular disease (CAD/CVD) was in 8.0%, and hypertension was in 20.0%, which were much higher than that of chronic pulmonary disease (3.0%). Specifically, preexisting chronic conditions are strongly correlated with disease severity [Odds ratio (OR) 3.50, 95% CI 1.78 to 6.90], and being admitted to intensive care unit (ICU) (OR 3.36, 95% CI 1.67 to 6.76); in addition, compared to COVID-19 patients with no preexisting chronic diseases, COVID-19 patients who present with either diabetes, hypertension, CAD/CVD, or chronic pulmonary disease have a higher risk of developing severe disease, with an OR of 2.61 (95% CI 1.93 to 3.52), 2.84 (95% CI 2.22 to 3.63), 4.18 (95% CI 2.87 to 6.09) and 3.83 (95% CI 2.15 to 6.80), respectively. Surprisingly, we found no correlation between chronic conditions and increased risk of mortality (OR 2.09, 95% CI 0.26 to16.67). Taken together, cardio-metabolic diseases, such as diabetes, hypertension and CAD/CVD were more common than chronic pulmonary disease in COVID-19 patients, however, each comorbid disease was correlated with increased disease severity. After active treatment, increased risk of mortality in patients with preexisting chronic diseases may reduce.
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Role of gut microbiota in cardiovascular diseases.
Novakovic, M, Rout, A, Kingsley, T, Kirchoff, R, Singh, A, Verma, V, Kant, R, Chaudhary, R
World journal of cardiology. 2020;12(4):110-122
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Cardiovascular disease (CVD) is the leading cause of death globally. CVD risk factors such as aging, obesity, dietary patterns and a sedentary lifestyle induce changes in the gut microbiota. The resulting dysbiosis is associated with intestinal inflammation leading to reduced integrity of the gut barrier. When this happens, certain components enter the circulation which may facilitate the development of CVD. Looking at the gut microbiota as a locus of intervention is therefore a novel and relevant avenue for future research. This article reviews the normal function and composition of the gut microbiome, the mechanisms leading to reduced gut barrier integrity (leaky gut syndrome), its link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. The alteration of the gut microbiome is a potential therapeutic target in managing CVD. However, further experiments are needed to see if the effects observed in animal studies can be translated to humans.
Abstract
The human gut is colonized by a community of microbiota, primarily bacteria, that exist in a symbiotic relationship with the host. Intestinal microbiota-host interactions play a critical role in the regulation of human physiology. Deleterious changes to the composition of gut microbiota, referred to as gut dysbiosis, has been linked to the development and progression of numerous diseases, including cardiovascular disease (CVD). Imbalances in host-microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Most CVD risk factors, including aging, obesity, dietary patterns, and a sedentary lifestyle, have been shown to induce gut dysbiosis. Dysbiosis is associated with intestinal inflammation and reduced integrity of the gut barrier, which in turn increases circulating levels of bacterial structural components and microbial metabolites, including trimethylamine-N-oxide and short-chain fatty acids, that may facilitate the development of CVD. This article reviews the normal function and composition of the gut microbiome, mechanisms leading to the leaky gut syndrome, its mechanistic link to CVD and potential novel therapeutic approaches aimed towards restoring gut microbiome and CVD prevention. As CVD is the leading cause of deaths globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research.
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Recent Advances in Psoriasis Research; the Clue to Mysterious Relation to Gut Microbiome.
Komine, M
International journal of molecular sciences. 2020;21(7)
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Psoriasis is a chronic inflammatory disease where the skin forms bumpy red patches covered with white scales. There is no cure, but medications have focused on supressing the immune response. There is a link between the gut microbiome and psoriasis but it is poorly understood. This review includes the current understanding of how psoriasis develops and discusses the recent findings to support further research in this area. The composition of the gut microbiome affects inflammation in the whole body. This inflammation is associated with cardiovascular disease, diabetes mellitus and other inflammatory disorders. Recent studies have linked cardiovascular disease, insulin resistance, and metabolic syndrome to an imbalance in the gut microbiome. Psoriasis is often found alongside these conditions with similar abnormalities in gut bacteria. An imbalance in gut microbiome could cause certain people to develop psoriasis. The role of the gut microbiome needs to be further clarified but mounting evidence for this gut/skin link means that other therapeutic options may be available for treatment in the future.
Abstract
Psoriasis is a chronic inflammatory cutaneous disease, characterized by activated plasmacytoid dendritic cells, myeloid dendritic cells, Th17 cells, and hyperproliferating keratinocytes. Recent studies revealed skin-resident cells have pivotal roles in developing psoriatic skin lesions. The balance in effector T cells and regulatory T cells is disturbed, leading Foxp3-positive regulatory T cells to produce proinflammatory IL-17. Not only acquired but also innate immunity is important in psoriasis pathogenesis, especially in triggering the disease. Group 3 innate lymphoid cell are considered one of IL-17-producing cells in psoriasis. Short chain fatty acids produced by gut microbiota stabilize expression of Foxp3 in regulatory T cells, thereby stabilizing their function. The composition of gut microbiota influences the systemic inflammatory status, and associations been shown with diabetes mellitus, cardiovascular diseases, psychomotor diseases, and other systemic inflammatory disorders. Psoriasis has been shown to frequently comorbid with diabetes mellitus, cardiovascular diseases, psychomotor disease and obesity, and recent report suggested the similar abnormality in gut microbiota as the above comorbid diseases. However, the precise mechanism and relation between psoriasis pathogenesis and gut microbiota needs further investigation. This review introduces the recent advances in psoriasis research and tries to provide clues to solve the mysterious relation of psoriasis and gut microbiota.
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Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults.
Ludvigsson, JF
Acta paediatrica (Oslo, Norway : 1992). 2020;109(6):1088-1095
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Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was also previously known as 2019-nCoV. This study is a systematic literature review which summarises the findings on the current knowledge of COVID-19 in children. The review includes 45 scientific papers and letters. Results showed that children have so far accounted for 1%-5% of diagnosed cases. Children often are asymptomatic, have milder disease than adults, and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent. Authors conclude that the disease course in paediatric COVID-19 was milder than in adults, children had a better prognosis and deaths were extremely rare.
Abstract
AIM: The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS A systematic literature review was carried out to identify papers on COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%-5% of diagnosed COVID-19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.
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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.
keywords:"Cardiovascular Diseases" OR (Cardiovascular AND Diseases) OR "Cardiovascular Diseases" OR (cardiovascular AND disease) OR "cardiovascular disease"