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Long COVID and Post-infective Fatigue Syndrome: A Review

ABSTRACT: Abstract 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 COVID-19. In the majority of COVID-19 cohort studies, persistent fatigue was reported by a significant minority of patients, ranging from 13% to 33% at 16–20 weeks post-symptom onset. Data from the prospective cohort studies in COFFI and others indicate that fatigue is also a prevalent outcome from many acute systemic infections, notably infectious mononucleosis, with a case rate for clinically significant Post-infective fatigue after exclusion of recognized medical and psychiatric causes, ranging from 10%–35% at 6 months. To better characterize post-COVID fatigue, the COFFI investigators recommend the following: application of validated screening questionnaires for case detection; standardized interviews encompassing fatigue, mood, and other symptoms; and investigative approaches to identify end-organ damage and mental health conditions. Fatigue after COVID-19 is common but generally resolves over months, like other postinfective fatigue states. Post-COVID fatigue results from end-organ injury, mental health conditions, or idiopathic post-COVID fatigue. Post-COVID fatigue should be assessed with validated questionnaires, interviews, and protocolized investigations.

SUBMITTER: Sandler C

PROVIDER: S-EPMC8496765 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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).

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.

Project description:Introduction Il est désormais admis que les « orteils COVID » sont associés à la pathogenèse du SARS-CoV-2. Les descriptions sont concordantes dans le monde entier, mais le suivi est peu décrit. Nous présentons 4 cas « d’orteils COVID » avec un suivi de plusieurs mois. Matériel et méthodes Entre février 2020 et avril 2021, 4 cas de plus de 3 mois ont été suivis rétrospectivement dans notre clinique dermatologique. Résultats Le premier patient était une femme de 19 ans sans antécédent médical. Deux mois après l’apparition des symptômes de la COVID-19, des lésions acrales de type engelures apparaissaient sur les orteils. Elle se plaignait de démangeaisons. Il n’y avait pas d’aggravation avec le froid. La sérologie SARS-CoV-2 était positive, et la recherche d’anticorps antinucléaires, de cryoglobuline, de cryofibrinogène, d’agglutinines froides était négative. Les engelures étaient encore visibles à 4 mois. Le deuxième patient était une femme de 18 ans en bonne santé. Deux semaines après l’apparition des signes de la COVID-19, des engelures asymptomatiques apparaissaient sur les orteils et les doigts. L’infection par le SARS-Cov-2 était confirmée par PCR nasopharyngée. En outre, on observait une éruption urticarienne transitoire et indolore du tronc, des genoux et des mains, exacerbée par la chaleur et disparaissant avec le froid. La biologie montrait des anticorps antinucléaires positifs avec une fluorescence nucléolaire, et un facteur rhumatoïde. Les engelures étaient encore visibles à 3 mois. Le troisième patient était une femme de 60 ans en bonne santé. Peu après les signes de la COVID-19 avec des symptômes typiques légers, apparaissaient des engelures indolores des orteils. Elle notait une exacerbation par la chaleur, mais pas d’aggravation par le froid. Un épisode de nécrose digitale fut observé et les engelures disparaissaient après cinq mois. Le 4e cas était une femme de 20 ans qui souffrait de symptômes compatibles avec la COVID-19. Cependant, aucune PCR nasopharyngée n’était réalisée et la sérologie était négative. Deux mois plus tard, des engelures et une érythromélalgie apparaissaient sur les orteils. Aucune autre cause n’était trouvée. Les symptômes persistaient après 10 mois, avec à certains endroits une évolution nécrotique superficielle. Discussion Notre petite série de cas montre une durée d’évolution des engelures de 3 à 10 mois. La symptomatologie varie de l’absence de douleur à l’incapacité fonctionnelle, avec parfois une évolution nécrotique. Nos données montrent une longue durée de ces symptômes. À ce jour, les « orteils COVID » n’ont pas été intégrés dans le concept de « long COVID » représentant les complications persistantes de la COVID-19 ; et aucun syndrome acral aigu pédiatrique n’a eu cette durée d’évolution. Nous suggérons de définir les orteils chroniques de la COVID-19 comme une entité distincte des formes aiguës survenant au cours de l’infection.

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Long COVID and Post-infective Fatigue Syndrome: A Review

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