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      Muscle abnormalities worsen after post-exertional malaise in long COVID

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          Abstract

          A subgroup of patients infected with SARS-CoV-2 remain symptomatic over three months after infection. A distinctive symptom of patients with long COVID is post-exertional malaise, which is associated with a worsening of fatigue- and pain-related symptoms after acute mental or physical exercise, but its underlying pathophysiology is unclear. With this longitudinal case-control study (NCT05225688), we provide new insights into the pathophysiology of post-exertional malaise in patients with long COVID. We show that skeletal muscle structure is associated with a lower exercise capacity in patients, and local and systemic metabolic disturbances, severe exercise-induced myopathy and tissue infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID worsen after induction of post-exertional malaise. This study highlights novel pathways that help to understand the pathophysiology of post-exertional malaise in patients suffering from long COVID and other post-infectious diseases.

          Abstract

          In this longitudinal, case-controlled, cohort design study, authors show that post-exertional malaise is associated with severe exercise-induced myopathy, local and systemic metabolic disturbances and infiltration of amyloid-containing deposits in skeletal muscles of patients with long COVID.

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          Most cited references65

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          Long COVID: major findings, mechanisms and recommendations

          Long COVID is an often debilitating illness that occurs in at least 10% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. More than 200 symptoms have been identified with impacts on multiple organ systems. At least 65 million individuals worldwide are estimated to have long COVID, with cases increasing daily. Biomedical research has made substantial progress in identifying various pathophysiological changes and risk factors and in characterizing the illness; further, similarities with other viral-onset illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome and postural orthostatic tachycardia syndrome have laid the groundwork for research in the field. In this Review, we explore the current literature and highlight key findings, the overlap with other conditions, the variable onset of symptoms, long COVID in children and the impact of vaccinations. Although these key findings are critical to understanding long COVID, current diagnostic and treatment options are insufficient, and clinical trials must be prioritized that address leading hypotheses. Additionally, to strengthen long COVID research, future studies must account for biases and SARS-CoV-2 testing issues, build on viral-onset research, be inclusive of marginalized populations and meaningfully engage patients throughout the research process. Long COVID is an often debilitating illness of severe symptoms that can develop during or following COVID-19. In this Review, Davis, McCorkell, Vogel and Topol explore our knowledge of long COVID and highlight key findings, including potential mechanisms, the overlap with other conditions and potential treatments. They also discuss challenges and recommendations for long COVID research and care.
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            Distribution Theory for Glass's Estimator of Effect size and Related Estimators

            L. Hedges (1981)
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              cocor: A Comprehensive Solution for the Statistical Comparison of Correlations

              A valid comparison of the magnitude of two correlations requires researchers to directly contrast the correlations using an appropriate statistical test. In many popular statistics packages, however, tests for the significance of the difference between correlations are missing. To close this gap, we introduce cocor, a free software package for the R programming language. The cocor package covers a broad range of tests including the comparisons of independent and dependent correlations with either overlapping or nonoverlapping variables. The package also includes an implementation of Zou’s confidence interval for all of these comparisons. The platform independent cocor package enhances the R statistical computing environment and is available for scripting. Two different graphical user interfaces—a plugin for RKWard and a web interface—make cocor a convenient and user-friendly tool.
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                Author and article information

                Contributors
                m.vanvugt@amsterdamumc.nl
                r.wust@vu.nl
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                4 January 2024
                4 January 2024
                2024
                : 15
                : 17
                Affiliations
                [1 ]GRID grid.509540.d, ISNI 0000 0004 6880 3010, Amsterdam UMC location University of Amsterdam, , Center for Experimental and Molecular Medicine, ; Meibergdreef 9, Amsterdam, the Netherlands
                [2 ]Amsterdam Institute for Infection and Immunity, Infectious diseases, Amsterdam, the Netherlands
                [3 ]Department of Human Movement Sciences, Faculty of Behavioral and Movement Sciences, Vrije Universiteit Amsterdam, ( https://ror.org/008xxew50) Amsterdam, the Netherlands
                [4 ]Amsterdam Movement Sciences, Amsterdam, the Netherlands
                [5 ]GRID grid.12380.38, ISNI 0000 0004 1754 9227, Department of Physiology, , Amsterdam UMC location Vrije Universiteit Amsterdam, ; De Boelelaan 1117, Amsterdam, the Netherlands
                [6 ]Amsterdam Cardiovascular Sciences, Amsterdam, the Netherlands
                [7 ]GRID grid.7177.6, ISNI 0000000084992262, Department of Trauma Surgery, , Amsterdam UMC location University of Amsterdam, ; Meibergdreef 9, Amsterdam, the Netherlands
                [8 ]Laboratory Genetic Metabolic Diseases, Core Facility Metabolomics, Amsterdam UMC location University of Amsterdam, ( https://ror.org/04dkp9463) Meibergdreef 9, Amsterdam, the Netherlands
                [9 ]Serviço de Neurologia, Departamento de Neurociências e Saúde Mental, Hospital de Santa Maria, CHULN, ( https://ror.org/05bz1tw26) Lisbon, Portugal
                [10 ]Faculdade de Medicina, Centro de Estudos Egas Moniz, University of Lisbon, ( https://ror.org/01c27hj86) Lisbon, Portugal
                [11 ]GRID grid.7177.6, ISNI 0000000084992262, Department of (Neuro)pathology, Amsterdam Neuroscience, , Amsterdam UMC location University of Amsterdam, ; Meibergdreef 9, Amsterdam, the Netherlands
                [12 ]Flevoziekenhuis, Division of Surgery, ( https://ror.org/02tqqrq23) Hospitaalweg 1, Almere, the Netherlands
                [13 ]GRID grid.7177.6, ISNI 0000000084992262, Division of Infectious Diseases, Department of Internal Medicine, , Amsterdam UMC location University of Amsterdam, ; Meibergdreef 9, Amsterdam, the Netherlands
                [14 ]GRID grid.7177.6, ISNI 0000000084992262, Division of Infectious Diseases, Tropical Medicine, Department of Medicine, , Amsterdam UMC location University of Amsterdam, ; Meibergdreef 9, Amsterdam, the Netherlands
                Author information
                http://orcid.org/0000-0002-4560-8410
                http://orcid.org/0000-0002-4242-3664
                http://orcid.org/0000-0002-4046-2504
                http://orcid.org/0009-0006-2516-0694
                http://orcid.org/0000-0002-4916-2866
                http://orcid.org/0000-0002-3542-3770
                http://orcid.org/0000-0003-2277-1343
                http://orcid.org/0000-0003-3781-5177
                Article
                44432
                10.1038/s41467-023-44432-3
                10766651
                38177128
                b0b6ca19-c591-415c-ad38-72c8887f0d32
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 21 March 2023
                : 13 December 2023
                Funding
                Funded by: FundRef https://doi.org/10.13039/501100001826, ZonMw (Netherlands Organisation for Health Research and Development);
                Funded by: the Patient-Led Research Collaborative for Long COVID the Talud Foundation for the Amsterdam UMC Corona Research Fund AMC Foundation VU Foundation ZonMw Onderzoeksprogramma ME/CVS 2022 Ramsay Grant Program
                Categories
                Article
                Custom metadata
                © Springer Nature Limited 2024

                Uncategorized
                viral infection,fatigue,metabolomics,energy metabolism,fluorescence imaging
                Uncategorized
                viral infection, fatigue, metabolomics, energy metabolism, fluorescence imaging

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