Tag: 2022

Cognitive impairments in chronic fatigue syndrome patients: choice reaction time, encoding of new information, response organisation and selective attention

ABSTRACT:

Background: One of the features of Chronic Fatigue Syndrome (CFS) is the reporting of cognitive impairment. Prior research has confirmed this using cognitive performance test batteries. Psychomotor slowing and episodic memory impairments appear to be robust, but little is known about selective attention or the stages of processing leading to slower reaction times. The present study addressed these gaps in the literature.

Methods: CFS patients were recruited from a health service clinic. Sixty-seven patients agreed to carry out cognitive tasks measuring aspects of focused attention and categoric search and the components (encoding and response organisation) of choice reaction time. They were compared with 126 healthy controls. As well as carrying out the performance tasks, the participants also completed symptom checklists and questionnaires measuring fatigue, mental health and cognitive failures.

Results: The questionnaires revealed the typical profile of symptoms of CFS patients. With regards to the objective performance tasks, the CFS patients had significantly slower choice reaction times on both tasks. This is likely to be due to slower motor responses as neither of the measures of stimulus encoding or response organisation showed differences between the groups. There was also little evidence for the groups differing in aspects of selective attention.

Conclusions: CFS patients report greater fatigue, more somatic symptoms, greater mental health issues and more cognitive difficulties. Objective testing revealed slower choice reaction times which probably reflect motor slowing. These measures can now be used to assess the efficacy of the management of CFS.

Source: Smith AP. Cognitive impairments in chronic fatigue syndrome patients: choice reaction time, encoding of new information, response organisation and selective attention. World Journal of Pharmaceutical and Medical Research 8(4): 27-36 https://www.wjpmr.com/home/article_abstract/4110 (Full text available as PDF file)

Reducing fatigue-related symptoms in Long COVID-19: a preliminary report of a lymphatic drainage intervention

Abstract:

In the early days of the first global wave of the COVID-19 pandemic, the potential for a postviral syndrome to manifest following COVID-19 infection was first recognized. Here, we present an analysis of a case series of the first 20 patients’ data collected in clinical practice to evaluate the potential of a possible alternative treatment for Long COVID.

Methods: Face-to-face treatment sessions with Perrin technique practitioners occurred weekly involving effleurage/other manual articulatory techniques. The individuals being treated also undertook daily self-massage along with gentle mobility exercises. Patients recorded symptom severity using the self-report 54-item profile of fatigue-related states (PFRS) before and after treatment.

Results: The mean age of male patients was 41.8 years (range, 29-53 years), and for female patients, 39.3 years (range, 28-50 years). None of the participants had a prior diagnosis of chronic fatigue syndrome, and all were new attendees to the clinics at the time of initial assessment. The average number of treatment sessions was 9.7 in men and 9.4 in women. The reduction in PFRS scores was 45% in men and 52% in women. The highest subscale scores on average were for fatigue, with the lowest for somatic symptoms. All subscale scores showed, on average, a similar reduction of approximately 50% postintervention, with the reduction in score relating to a decrease in the severity of symptoms.

Conclusion: Our findings suggest that a specific manual lymphatic drainage intervention may help to reduce fatigue symptoms related to Long COVID. Perhaps preventing acute symptoms through early intervention.

Source: H Heald A, Perrin R, Walther A, Stedman M, Hann M, Mukherjee A, Riste L. Reducing fatigue-related symptoms in Long COVID-19: a preliminary report of a lymphatic drainage intervention. Cardiovasc Endocrinol Metab. 2022 Apr 12;11(2):e0261. doi: 10.1097/XCE.0000000000000261. PMID: 35441129; PMCID: PMC9010124. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9010124/ (Full text)

The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome

Abstract:

Introduction: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) is a complex multisystem disease characterised by severe and disabling new-onset symptoms of post-exertional malaise (PEM), fatigue, brain fog, and sleep dysfunction that lasts for at least six months. Accumulating evidence suggests that sex and endocrine events have a significant influence on symptom onset and moderation of ME/CFS, with female sex being one of the most consistent and credible predictive risk factors associated with diagnosis. Such sex differences suggest sex chromosomes and sex steroids may play a part in the development of the condition or moderation of symptoms, although this has yet to be explored in detail.

Methods/aims: This narrative review outlines sex differences in ME/CFS in terms of vulnerability factors and clinical phenotype and explores the known sex differences in neuroendocrine systems affected in ME/CFS and how this may relate to disease risk, onset, pathophysiology, and potential treatment avenues.

Conclusions: There is clear evidence of a sex dimorphism with regards to prevalence (3:1 female preponderance), clinical phenotypes, and aetiological triggers prior to symptom onset of ME/CFS. Endocrinological events, particularly those throughout the female lifespan, are associated with ME/CFS and include reproductive menstrual cycle fluctuations, pregnancy, post-partum and perimenopause. Further, there is evidence for gonadal sex, adrenal stress and renal neuroendocrine systems as implicated in ME/CFS, including changes in estrogen, progesterone compounds, aldosterone, and cortisol levels, of which there are established sex differences. The broad effects of steroid hormones on the physiological systems may also speak to the diversity of ME/CFS symptomatology observed in patients. Further attention must be paid to sex, age, and steroid biology in ME/CFS.

Source: Thomas N, Gurvich C, Huang K, Gooley PR, Armstrong CW. The underlying sex differences in neuroendocrine adaptations relevant to Myalgic Encephalomyelitis Chronic Fatigue Syndrome. Front Neuroendocrinol. 2022 Apr 11:100995. doi: 10.1016/j.yfrne.2022.100995. Epub ahead of print. PMID: 35421511. https://www.sciencedirect.com/science/article/abs/pii/S0091302222000188?via%3Dihub  (Full text)

Non-improvement in chronic fatigue syndrome: relation to activity patterns, uplifts and hassles, and autonomic dysfunction

Abstract:

Objective: To test a model of non-improvement in chronic fatigue syndrome (CFS) utilizing self-report activity patterns (e.g., “push-crash”), uplifts and hassles, and a biological measure of cardiac autonomic function. Activity pattern impacts on symptoms and objective measures of autonomic and physical activity were also examined.

Methods: This prospective study in CFS collected all data remotely, including six months of weekly web diaries that recorded symptom ratings, activity patterns, and hassles and uplifts. In addition, six months of weekly heart monitoring and three months of daily waking actigraphy data were collected. Improvement or non-improvement status was assessed using semi-structured interviews at 6 months follow-up.

Results: 148 individuals (87.2% female) were enrolled and 12.2% were lost to follow-up. Participants reporting non-improvement (n = 92), as compared to improvement (n = 38) showed greater autonomic dysfunction (lower heart rate variability [HRV], group difference = 5.93 (SE = 2.73) ms; p = .032) and lower mean intensity of behavioral uplifts (group difference = 0.14 (SE = 0.16); p = .043), but no significant differences in any activity pattern, including push-crash, limiting activity, and healthy pacing.

Conclusions: This study provided evidence for linking patient-reported non-improvement to a biological variable indexing autonomic dysfunction and a behavioral measure indicating a deficit in psychological uplifts. These findings suggest a possible marker of illness trajectory that could potentially advance the biomedical underpinnings of CFS.

Source: Friedberg F, Adamowicz JL, Bruckenthal P, Milazzo M, Ramjan S, Quintana D. Non-improvement in chronic fatigue syndrome: relation to activity patterns, uplifts and hassles, and autonomic dysfunction. Psychosom Med. 2022 Apr 15. doi: 10.1097/PSY.0000000000001082. Epub ahead of print. PMID: 35420586. https://pubmed.ncbi.nlm.nih.gov/35420586/

COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study

Abstract:

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been often characterized as a respiratory disease. However, it is increasingly being understood as an infection that impacts multiple systems, and many patients report neurological symptoms. Indeed, there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere. There are several mechanisms by which the COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and cognitive problems are one of the most commonly reported symptoms in those experiencing Long COVID – the chronic illness following the COVID-19 infection that affects between 10 and 25% of patients. However, there is yet little research testing cognition in Long COVID.

The COVID and Cognition Study is a cross-sectional/longitudinal study aiming to understand cognitive problems in Long COVID. The first paper from the study explored the characteristics of our sample of 181 individuals who had experienced the COVID-19 infection, and 185 who had not, and the factors that predicted ongoing symptoms and self-reported cognitive deficits.

In this second paper from the study, we assess this sample on tests of memory, language, and executive function. We hypothesize that performance on “objective” cognitive tests will reflect self-reported cognitive symptoms. We further hypothesize that some symptom profiles may be more predictive of cognitive performance than others, perhaps giving some information about the mechanism. We found a consistent pattern of memory deficits in those that had experienced the COVID-19 infection, with deficits increasing with the severity of self-reported ongoing symptoms. Fatigue/Mixed symptoms during the initial illness and ongoing neurological symptoms were predictive of cognitive performance.

Source: Guo P, Benito Ballesteros A, Yeung SP, Liu R, Saha A, Curtis L, Kaser M, Haggard MP, Cheke LG. COVCOG 2: Cognitive and Memory Deficits in Long COVID: A Second Publication From the COVID and Cognition Study. Front Aging Neurosci. 2022 Mar 17;14:804937. doi: 10.3389/fnagi.2022.804937. PMID: 35370620; PMCID: PMC8967943. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967943/ (Full study)

COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study

Abstract:

Since its first emergence in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has evolved into a global pandemic. Whilst often considered a respiratory disease, a large proportion of COVID-19 patients report neurological symptoms, and there is accumulating evidence for neural damage in some individuals, with recent studies suggesting loss of gray matter in multiple regions, particularly in the left hemisphere.

There are a number of mechanisms by which COVID-19 infection may lead to neurological symptoms and structural and functional changes in the brain, and it is reasonable to expect that many of these may translate into cognitive problems. Indeed, cognitive problems are one of the most commonly reported symptoms in those experiencing “Long COVID”-the chronic illness following COVID-19 infection that affects between 10 and 25% of patients. The COVID and Cognition Study is a part cross-sectional, part longitudinal, study documenting and aiming to understand the cognitive problems in Long COVID. In this first paper from the study, we document the characteristics of our sample of 181 individuals who had experienced COVID-19 infection, and 185 who had not.

We explore which factors may be predictive of ongoing symptoms and their severity, as well as conducting an in-depth analysis of symptom profiles. Finally, we explore which factors predict the presence and severity of cognitive symptoms, both throughout the ongoing illness and at the time of testing. The main finding from this first analysis is that that severity of initial illness is a significant predictor of the presence and severity of ongoing symptoms, and that some symptoms during the initial illness-particularly limb weakness-may be more common in those that have more severe ongoing symptoms. Symptom profiles can be well described in terms of 5 or 6 factors, reflecting the variety of this highly heterogenous condition experienced by the individual. Specifically, we found that neurological/psychiatric and fatigue/mixed symptoms during the initial illness, and that neurological, gastrointestinal, and cardiopulmonary/fatigue symptoms during the ongoing illness, predicted experience of cognitive symptoms.

Source: Guo P, Benito Ballesteros A, Yeung SP, Liu R, Saha A, Curtis L, Kaser M, Haggard MP, Cheke LG. COVCOG 1: Factors Predicting Physical, Neurological and Cognitive Symptoms in Long COVID in a Community Sample. A First Publication From the COVID and Cognition Study. Front Aging Neurosci. 2022 Mar 17;14:804922. doi: 10.3389/fnagi.2022.804922. PMID: 35370617; PMCID: PMC8968323. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968323/ (Full text)

Obesity and lipid metabolism disorders determine the risk for development of long COVID syndrome: a cross-sectional study from 50,402 COVID-19 patients

Abstract:

Purpose: Metabolic disorders have been identified as major risk factors for severe acute courses of COVID-19. With decreasing numbers of infections in many countries, the long COVID syndrome (LCS) represents the next major challenge in pandemic management, warranting the precise definition of risk factors for LCS development.

Methods: We identified 50,402 COVID-19 patients in the Disease Analyzer database (IQVIA) featuring data from 1056 general practices in Germany. Multivariate logistic regression analysis was used to identify risk factors for the development of LCS.

Results: Of the 50,402 COVID-19 patients included into this analysis, 1,708 (3.4%) were diagnosed with LCS. In a multivariate regression analysis, we identified lipid metabolism disorders (OR 1.46, 95% CI 1.28-1.65, p < 0.001) and obesity (OR 1.25, 95% CI 1.08-1.44, p = 0.003) as strong risk factors for the development of LCS. Besides these metabolic factors, patients’ age between 46 and 60 years (compared to age ≤ 30, (OR 1.81 95% CI 1.54-2.13, p < 0.001), female sex (OR 1.33, 95% CI 1.20-1.47, p < 0.001) as well as pre-existing asthma (OR 1.67, 95% CI 1.39-2.00, p < 0.001) and depression (OR 1.27, 95% CI 1.09-1.47, p = < 0.002) in women, and cancer (OR 1.4, 95% CI 1.09-1.95, p = < 0.012) in men were associated with an increased likelihood of developing LCS.

Conclusion: Lipid metabolism disorders and obesity represent age-independent risk factors for the development of LCS, suggesting that metabolic alterations determine the risk for unfavorable disease courses along all phases of COVID-19.

Source: Loosen SH, Jensen BO, Tanislav C, Luedde T, Roderburg C, Kostev K. Obesity and lipid metabolism disorders determine the risk for development of long COVID syndrome: a cross-sectional study from 50,402 COVID-19 patients. Infection. 2022 Mar 30:1–6. doi: 10.1007/s15010-022-01784-0. Epub ahead of print. PMID: 35355237; PMCID: PMC8966865. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966865/ (Full text)

Long COVID (post-COVID-19 condition) in children: a modified Delphi process

Abstract:

Objective: The aim of this study was to derive a research definition for ‘Long COVID (post-COVID-19 condition)’ in children and young people (CYP) to allow comparisons between research studies.

Design: A three-phase online Delphi process was used, followed by a consensus meeting. Participants were presented with 49 statements in each phase and scored them from 1 to 9 based on how important they were for inclusion in the research definition of Long COVID in CYP. The consensus meeting was held to achieve representation across the stakeholder groups. Statements agreed at the consensus meeting were reviewed by participants in the Patient and Public Involvement (PPI) Research Advisory Group.

Setting: The study was conducted remotely using online surveys and a virtual consensus meeting.

Participants: 120 people with relevant expertise were divided into three panels according to their area of expertise: Service Delivery, Research (or combination of research and service delivery) and Lived Experience. The PPI Research Advisory group consisted of CYP aged 11-17 years.

Main outcome measures: Consensus was defined using existing guidelines. If consensus was achieved in two or more panels or was on the border between one and two panels, those statements were discussed and voted on at the consensus meeting.

Results: Ten statements were taken forward for discussion in the consensus meeting and five statements met threshold to be included in the research definition of Long COVID among CYP. The research definition, aligned to the clinical case definition of the WHO, is proposed as follows: Post-COVID-19 condition occurs in young people with a history of confirmed SARS-CoV-2 infection, with at least one persisting physical symptom for a minimum duration of 12 weeks after initial testing that cannot be explained by an alternative diagnosis. The symptoms have an impact on everyday functioning, may continue or develop after COVID infection, and may fluctuate or relapse over time. The positive COVID-19 test referred to in this definition can be a lateral flow antigen test, a PCR test or an antibody test.

Conclusions: This is the first research definition of Long COVID (post-COVID-19 condition) in CYP and complements the clinical case definition in adults proposed by the WHO.

Source: Stephenson T, Allin B, Nugawela MD, Rojas N, Dalrymple E, Pinto Pereira S, Soni M, Knight M, Cheung EY, Heyman I; CLoCk Consortium, Shafran R. Long COVID (post-COVID-19 condition) in children: a modified Delphi process. Arch Dis Child. 2022 Apr 1:archdischild-2021-323624. doi: 10.1136/archdischild-2021-323624. Epub ahead of print. PMID: 35365499; PMCID: PMC8983414. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983414/ (Full text)

Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates

Abstract:

Neurological manifestations are a significant complication of coronavirus disease (COVID-19), but underlying mechanisms aren’t well understood. The development of animal models that recapitulate the neuropathological findings of autopsied brain tissue from patients who died from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are critical for elucidating the neuropathogenesis of infection and disease.

Here, we show neuroinflammation, microhemorrhages, brain hypoxia, and neuropathology that is consistent with hypoxic-ischemic injury in SARS-CoV-2 infected non-human primates (NHPs), including evidence of neuron degeneration and apoptosis. Importantly, this is seen among infected animals that do not develop severe respiratory disease, which may provide insight into neurological symptoms associated with “long COVID”. Sparse virus is detected in brain endothelial cells but does not associate with the severity of central nervous system (CNS) injury.

We anticipate our findings will advance our current understanding of the neuropathogenesis of SARS-CoV-2 infection and demonstrate SARS-CoV-2 infected NHPs are a highly relevant animal model for investigating COVID-19 neuropathogenesis among human subjects.

Source: Rutkai I, Mayer MG, Hellmers LM, Ning B, Huang Z, Monjure CJ, Coyne C, Silvestri R, Golden N, Hensley K, Chandler K, Lehmicke G, Bix GJ, Maness NJ, Russell-Lodrigue K, Hu TY, Roy CJ, Blair RV, Bohm R, Doyle-Meyers LA, Rappaport J, Fischer T. Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates. Nat Commun. 2022 Apr 1;13(1):1745. doi: 10.1038/s41467-022-29440-z. PMID: 35365631. https://www.nature.com/articles/s41467-022-29440-z (Full text)

Histopathology of Persistent Long COVID Toe: A Case Report

Abstract:

During the 2020 coronavirus (SARS-CoV-2) pandemic, several cutaneous lesions were identified, including: pseudo-chilblain, vesicular, urticarial, maculopapular, and livedo/necrosis. A 59-year-old obese man with probable COVID-19 developed painful cyanosis with histopathologic capillary thrombosis of toes, and the cyanosis persisted for nearly 22 months. Shortly after initial exposure to family members with documented SARS-CoV-2, he developed upper respiratory symptoms, yet his anti-SARS-CoV-2 antibody and nasal swab RT-PCR tests were repeatedly negative. Two family members were hospitalized and one of them succumbed with documented SARS-CoV-2 pneumonia within ten days of exposure. Biopsy of the distal toe 16 weeks after initial exposure demonstrated papillary dermal capillary thrombosis with endothelial swelling, telangiectasia, and peri-eccrine lymphocytic infiltrates resembling pernio. Overall, this is the first case of biopsy of “long COVID toe” following presumed SARS-Cov-2 exposure, with demonstration of thrombotic vasculopathy, toe cyanosis, and pernio-like pathology.

Source: Nirenberg MS, Requena L, Santonja C, Smith GT, McClain SA. Histopathology of Persistent Long COVID Toe: A Case Report. J Cutan Pathol. 2022 Apr 2. doi: 10.1111/cup.14240. Epub ahead of print. PMID: 35366017.  https://pubmed.ncbi.nlm.nih.gov/35366017/