Long COVID and Post-infective Fatigue Syndrome: A Review.
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ABSTRACT:
SUBMITTER: Sandler CX
PROVIDER: S-EPMC8496765 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
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Long COVID and Post-infective Fatigue Syndrome: A Review.
Sandler Carolina X CX Wyller Vegard B B VBB Moss-Morris Rona R Buchwald Dedra D Crawley Esther E Hautvast Jeannine J Katz Ben Z BZ Knoop Hans H Little Paul P Taylor Renee R Wensaas Knut-Arne KA Lloyd Andrew R AR
Open forum infectious diseases 20210909 10
Fatigue is a dominant feature of both acute and convalescent coronavirus disease 2019 (COVID-19) (sometimes termed "long-COVID"), with up to 46% of patients reporting fatigue that lasts from weeks to months. The investigators of the international Collaborative on Fatigue Following Infection (COFFI) conducted a systematic review of post-COVID fatigue and a narrative review on fatigue after other infections, and made recommendations for clinical and research approaches to assessing fatigue after C ...[more]
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Project description:Fatigue is one of the most disabling symptoms in several neurological disorders and has an important cognitive component. However, the relationship between self-reported cognitive fatigue and objective cognitive assessment results remains elusive. Patients with post-COVID syndrome often report fatigue and cognitive issues several months after the acute infection. We aimed to develop predictive models of fatigue using neuropsychological assessments to evaluate the relationship between cognitive fatigue and objective neuropsychological assessment results. We conducted a cross-sectional study of 113 patients with post-COVID syndrome, assessing them with the Modified Fatigue Impact Scale (MFIS) and a comprehensive neuropsychological battery including standardized and computerized cognitive tests. Several machine learning algorithms were developed to predict MFIS scores (total score and cognitive fatigue score) based on neuropsychological test scores. MFIS showed moderate correlations only with the Stroop Color-Word Interference Test. Classification models obtained modest F1-scores for classification between fatigue and non-fatigued or between 3 or 4 degrees of fatigue severity. Regression models to estimate the MFIS score did not achieve adequate R2 metrics. Our study did not find reliable neuropsychological predictors of cognitive fatigue in the post-COVID syndrome. This has important implications for the interpretation of fatigue and cognitive assessment. Specifically, MFIS cognitive domain could not properly capture actual cognitive fatigue. In addition, our findings suggest different pathophysiological mechanisms of fatigue and cognitive dysfunction in post-COVID syndrome.
| S-EPMC9267301 | biostudies-literature
Project description:Fatigue is recognized as one of the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. This systematic review was performed to describe symptoms, etiology, possible risk factors related to post-COVID-19 fatigue and the therapeutic approaches used for the treatment of post-COVID-19 fatigue. For the systematic literature search the databases PubMed, Web of Science, Cochrane Library, and PsycInfo were used. All articles that met the inclusion criteria were analyzed for demographics, clinical data and treatment. Included were studies which focused on an adult population (18-65 years old); elderly patients and patients with chronic somatic diseases which can also cause fatigue were excluded. We identified 2,851, screened 2,193 and finally included 20 studies with moderate to high methodological quality, encompassing 5,629 participants. Potential risk factors for post-COVID-19 fatigue were old age, female sex, severe clinical status in the acute phase of infection, a high number of comorbidities, and a prediagnosis of depression/anxiety. Lastly, a possible autoimmune etiology was suspected. Several treatment approaches have been tested mostly in small and uncontrolled studies so far: a Chinese herbal formulation improved breathlessness and fatigue. Moreover, molecular hydrogen (H2) inhalation had beneficial health effects in terms of improved physical (6-min walking test) and respiratory function in patients with post-COVID-19. Patients also noticed improvement in fatigue after undergoing hyperbaric oxygen therapy (HBOT) and enhanced external counterpulsation (EECP). Lastly. muscle strength and physical function were improved after undergoing an 8-weeks biweekly physical therapy course including aerobic training, strengthening exercises, diaphragmatic breathing techniques, and mindfulness training. However, larger and controlled studies e.g., investigating the effect of physical and / or psychotherapy for patients with post-COVID-19 fatigue are urgently warranted.Systematic review registrationUnique Identifier: CRD42022320676, https://www.crd.york.ac.uk/PROSPERO/.
| S-EPMC9403611 | biostudies-literature
Project description:ImportanceCOVID-19 is associated with clinically significant symptoms despite resolution of the acute infection (i.e., post-COVID-19 syndrome). Fatigue and cognitive impairment are amongst the most common and debilitating symptoms of post-COVID-19 syndrome.ObjectiveTo quantify the proportion of individuals experiencing fatigue and cognitive impairment 12 or more weeks following COVID-19 diagnosis, and to characterize the inflammatory correlates and functional consequences of post-COVID-19 syndrome.Data sourcesSystematic searches were conducted without language restrictions from database inception to June 8, 2021 on PubMed/MEDLINE, The Cochrane Library, PsycInfo, Embase, Web of Science, Google/Google Scholar, and select reference lists.Study selectionPrimary research articles which evaluated individuals at least 12 weeks after confirmed COVID-19 diagnosis and specifically reported on fatigue, cognitive impairment, inflammatory parameters, and/or functional outcomes were selected.Data extraction & synthesisTwo reviewers independently extracted published summary data and assessed methodological quality and risk of bias. A meta-analysis of proportions was conducted to pool Freeman-Tukey double arcsine transformed proportions using the random-effects restricted maximum-likelihood model.Main outcomes & measuresThe co-primary outcomes were the proportions of individuals reporting fatigue and cognitive impairment, respectively, 12 or more weeks following COVID-19 infection. The secondary outcomes were inflammatory correlates and functional consequences associated with post-COVID-19 syndrome.ResultsThe literature search yielded 10,979 studies, and 81 studies were selected for inclusion. The fatigue meta-analysis comprised 68 studies, the cognitive impairment meta-analysis comprised 43 studies, and 48 studies were included in the narrative synthesis. Meta-analysis revealed that the proportion of individuals experiencing fatigue 12 or more weeks following COVID-19 diagnosis was 0.32 (95% CI, 0.27, 0.37; p < 0.001; n = 25,268; I2 = 99.1%). The proportion of individuals exhibiting cognitive impairment was 0.22 (95% CI, 0.17, 0.28; p < 0.001; n = 13,232; I2 = 98.0). Moreover, narrative synthesis revealed elevations in proinflammatory markers and considerable functional impairment in a subset of individuals.Conclusions & relevanceA significant proportion of individuals experience persistent fatigue and/or cognitive impairment following resolution of acute COVID-19. The frequency and debilitating nature of the foregoing symptoms provides the impetus to characterize the underlying neurobiological substrates and how to best treat these phenomena.Study registrationPROSPERO (CRD42021256965).
| S-EPMC8715665 | biostudies-literature
Project description: Not available
| S-EPMC8447548 | biostudies-literature
Project description:ObjectivesFatigue syndromes have been widely observed following post-viral infection and are being recognised because of Covid19. Interventions used to treat and manage fatigue have been widely researched and this study aims to synthesise the literature associated with fatigue interventions to investigate the outcomes that may be applicable to 'long Covid'.MethodThe study was registered with PROSPERO (CRD42020214209) in October 2020 and five electronic databases were searched. Papers were screened, critically appraised and data extracted from studies that reported outcomes of fatigue interventions for post-viral syndromes. The narrative synthesis includes statistical analysis associated with effectiveness and then identifies the characteristics of the interventions, including identification of transferable learning for the treatment of fatigue in long Covid. An expert panel supported critical appraisal and data synthesis.ResultsOver 7,000 research papers revealed a diverse range of interventions and fatigue outcome measures. Forty papers were selected for data extraction after final screening. The effectiveness of all interventions was assessed according to mean differences (MD) in measured fatigue severity between each experimental group and a control following the intervention, as well as standardised mean differences as an overall measure of effect size. Analyses identified a range of effects-from most effective MD -39.0 [95% CI -51.8 to -26.2] to least effective MD 42.28 [95% CI 33.23 to 51.34]-across a range of interventions implemented with people suffering varying levels of fatigue severity. Interventions were multimodal with a range of supportive therapeutic methods and varied in intensity and requirements of the participants. Those in western medical systems tended to be based on self- management and education principles (i.e., group cognitive behavioural therapy (CBT).ConclusionFindings suggest that the research is highly focussed on a narrow participant demographic and relatively few methods are effective in managing fatigue symptoms. Selected literature reported complex interventions using self-rating fatigue scales that report effect. Synthesis suggests that long Covid fatigue management may be beneficial when a) physical and psychological support, is delivered in groups where people can plan their functional response to fatigue; and b) where strengthening rather than endurance is used to prevent deconditioning; and c) where fatigue is regarded in the context of an individual's lifestyle and home-based activities are used.
| S-EPMC8577752 | biostudies-literature
Project description:PurposePost-Covid-19 syndrome is defined as the persistence of symptoms beyond 3 months after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The most common symptoms include reduced exercise tolerance and capacity, fatigue, neurocognitive problems, muscle pain and dyspnea. The aim of our work was to investigate exercise capacity and markers of subjective wellbeing and their independent relation to post-COVID-19 syndrome.Patients and methodsWe examined a total of 69 patients with post-COVID-19 syndrome (23 male/46 female; age 46±12 years; BMI 28.9±6.6 kg/m2) with fatigue and a score ≥22 in the Fatigue Assessment Scale (FAS). We assessed exercise capacity on a cycle ergometer, a 6-minute walk test, the extent of fatigue (FAS), markers of health-related quality of life (SF-36 questionnaire) and mental health (HADS).ResultsOn average the Fatigue Assessment Scale was 35.0±7.4 points. Compared with normative values the VO2max/kg was reduced by 8.6±5.8 ml/min/kg (27.7%), the 6MWT by 71±96 m (11.9%), the health-related quality of life physical component score by 15.0±9.0 points (29.9%) and the mental component score by 10.6±12.8 points (20.6%). Subdivided into mild fatigue (FAS score 22-34) and severe fatigue (FAS score ≥35), patients with severe fatigue showed a significant reduction of the 6-minute walk test by 64±165 m (p<0.01) and the health-related quality of life physical component score by 5.8±17.2 points (p = 0.01). In multiple regression analysis age (β = -0.24, p = 0.02), sex (β = 0.22, p = 0.03), mental (β = -0.51, p<0.01) and physical (β = -0.44, p<0.01) health-related quality of life and by trend the 6-minute walk test (β = -0.22, p = 0.07) were associated with the FAS.ConclusionPatients with post-COVID-19 syndrome show reduced maximal and submaximal physical performance as well as limitations in quality of life, particularly pronounced in the physical components. These results are essentially influenced by the severity of fatigue and implicating the need for targeted treatments.
| S-EPMC10593222 | biostudies-literature
Project description:ObjectiveLong COVID encompasses a range of symptoms in which fatigue is one of the most prevalents. It is clear from other conditions that the definition and measurement of fatigue can be complex, but it is not clear how fatigue is defined and measured in long COVID. To advance our understanding, this review summarises the definitions and measures of long COVID fatigue being used by researchers.DesignScoping review following JBI methodology and reports using the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for scoping reviews.Data sourcesMedline, Scopus, CINAHL, PsycINFO, EMCARE, Web of Science, Epistemonikos, Cochrane Central Register of Controlled Trials, Dimensions, Overton and ProQuest Dissertation & Theses Database were searched from January 2020 to May 2023.Eligibility criteriaThis review included quantitative and qualitative studies that included any definition of long COVID and/or measurement tool that purported to quantify either the impact, severity or symptoms of long COVID fatigue.Data extraction and synthesisTwo independent reviewers screened the title, abstracts and full texts of the selected studies based on the inclusion criteria. Data extraction was performed by two independent reviewers. The data were summarised in tabular format and a narrative summary.ResultsThe search retrieved 9839 studies, of which 57 met the inclusion criteria. Only 21 (37%) provided a definition of fatigue. Definitions ranged across physical, mental, cognitive, emotional, psychosocial, central, peripheral, postexertional symptom exacerbation and general dimensions of fatigue. Fifty-five (96%) used a measurement or assessment of fatigue. Twenty-six measures of fatigue were identified: 21 self-report measures (eg, Fatigue Assessment Scale) and five fatigability measures that purport to reflect changes in physiological processes that contribute to or reflect fatigue (eg, change in force generating capacity of a muscle).ConclusionsThe definitions identified demonstrate considerable diversity, each highlighting different dimensions of long COVID fatigue. Long COVID fatigue was predominantly measured through self-report methods, which were problematic. There is an urgent need to better understand long COVID fatigue and to identify the different mechanisms involved. In order to do this, we need consistency with the language around fatigue and its measurement within research and across disciplines.Review registrationThe protocol has been registered on open science framework (https://doi.org/10.17605/OSF.IO/HNF8Z).
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Project description:[This corrects the article DOI: 10.1371/journal.pone.0292928.].
| S-EPMC11925273 | biostudies-literature
Project description:Patients suffering from chronic fatigue syndrome (CFS) or post-COVID syndrome (PCS) exhibit a reduced physiological performance capability. Impaired mitochondrial function and morphology may play a pivotal role. Thus, we aimed to measure the muscle mitochondrial oxidative phosphorylation (OXPHOS) capacity and assess mitochondrial morphology in CFS and PCS patients in comparison to healthy controls (HCs). Mitochondrial OXPHOS capacity was measured in permeabilized muscle fibers using high-resolution respirometry. Mitochondrial morphology (subsarcolemmal/intermyofibrillar mitochondrial form/cristae/diameter/circumference/area) and content (number and proportion/cell) were assessed via electron microscopy. Analyses included differences in OXPHOS between HC, CFS, and PCS, whereas comparisons in morphology/content were made for CFS vs. PCS. OXPHOS capacity of complex I, which was reduced in PCS compared to HC. While the subsarcolemmal area, volume/cell, diameter, and perimeter were higher in PCS vs. CFS, no difference was observed for these variables in intermyofibrillar mitochondria. Both the intermyofibrillar and subsarcolemmal cristae integrity was higher in PCS compared to CFS. Both CFS and PCS exhibit increased fatigue and impaired mitochondrial function, but the progressed pathological morphological changes in CFS suggest structural changes due to prolonged inactivity or unknown molecular causes. Instead, the significantly lower complex I activity in PCS suggests probably direct virus-induced alterations.
| S-EPMC10855807 | biostudies-literature
Project description:BackgroundPost-COVID-19 syndrome (PCS) is characterised by a wide range of symptoms, primarily fatigue and exertion intolerance. While disease courses in the early months post-infection have been well-described, the long-term health consequences for patients with PCS with disabling fatigue remain unclear.MethodsIn this prospective observational cohort study, we evaluated symptom severity and various biomarkers, including hand grip strength (HGS), cardiovascular function, and laboratory parameters, in 106 patients with PCS with moderate to severe fatigue and exertion intolerance at three time points after infection (3-8, 9-16, and 17-20 months). The study was conducted at the Charité's Fatigue Centre and the Charité's outpatient clinic for neuroimmunology at Berlin, Germany from July 16, 2020, to February 18, 2022. A subset of patients (PCS-ME/CFS) met the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome according to the Canadian Consensus Criteria (CCC). The aim was to determine differences in the disease course between the two patient groups (i.e., PCS vs PCS-ME/CFS) and identify correlating biomarkers.FindingsPatients with PCS-ME/CFS reported persistently high severity of most symptoms up to 20 months after infection, while patients with PCS showed overall health improvement. Although fatigue and post-exertional malaise (PEM), hallmarks of post-infectious fatigue syndromes, were still evident in both groups, they remained more pronounced in PCS-ME/CFS. Inflammatory biomarkers decreased in both groups, but not antinuclear antibodies. Lower HGS at onset correlated with symptom persistence, particularly in patients with PCS-ME/CFS.InterpretationOur findings suggest that PCS can persist beyond 20 months post-infection and encompass the full scope of post-infectious ME/CFS as defined by the CCC. Sub-classifying patients with PCS based on the CCC can assist in the management and monitoring of patients with PCS-ME/CFS due to their persistently higher symptom severity.FundingC. S. was supported by a grant from the Weidenhammer-Zoebele Foundation. F. K. was supported by the Volkswagen Foundation.
| S-EPMC10469383 | biostudies-literature