A prospective observational study of post-COVID-19 chronic fatigue syndrome following the first pandemic wave in Germany and biomarkers associated with symptom severity

  1. Claudia Kedor
  2. Helma Freitag
  3. Lil Meyer-Arndt
  4. Kirsten Wittke
  5. Leif G. Hanitsch
  6. Thomas Zoller
  7. Fridolin Steinbeis
  8. Milan Haffke
  9. Gordon Rudolf
  10. Bettina Heidecker
  11. Thomas Bobbert
  12. Joachim Spranger
  13. Hans-Dieter Volk
  14. Carsten Skurk
  15. Frank Konietschke
  16. Friedemann Paul
  17. Uta Behrends
  18. Judith Bellmann-Strobl
  19. Carmen Scheibenbogen

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Abstract

A subset of patients has long-lasting symptoms after mild to moderate Coronavirus disease 2019 (COVID-19). In a prospective observational cohort study, we analyze clinical and laboratory parameters in 42 post-COVID-19 syndrome patients (29 female/13 male, median age 36.5 years) with persistent moderate to severe fatigue and exertion intolerance six months following COVID-19. Further we evaluate an age- and sex-matched postinfectious non-COVID-19 myalgic encephalomyelitis/chronic fatigue syndrome cohort comparatively. Most post-COVID-19 syndrome patients are moderately to severely impaired in daily live. 19 post-COVID-19 syndrome patients fulfill the 2003 Canadian Consensus Criteria for myalgic encephalomyelitis/chronic fatigue syndrome. Disease severity and symptom burden is similar in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome and non-COVID-19/myalgic encephalomyelitis/chronic fatigue syndrome patients. Hand grip strength is diminished in most patients compared to normal values in healthy. Association of hand grip strength with hemoglobin, interleukin 8 and C-reactive protein in post-COVID-19 syndrome/non-myalgic encephalomyelitis/chronic fatigue syndrome and with hemoglobin, N-terminal prohormone of brain natriuretic peptide, bilirubin, and ferritin in post-COVID-19 syndrome/myalgic encephalomyelitis/chronic fatigue syndrome may indicate low level inflammation and hypoperfusion as potential pathomechanisms.

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  1. Version published to 10.1038/s41467-022-32507-6
  2. Version published to 10.21203/rs.3.rs-384347/v1 on Research Square
  3. ScreenIT

    SciScore for 10.1101/2021.02.06.21249256: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: All patients signed informed consent before study assessment.
    IRB: This study is part of the Pa-COVID-19 study of Charité and approved by the Ethics Committee of Charité Universitätsmedizin Berlin in accordance with the 1964 Declaration of Helsinki and its later amendments (EA2/066/20).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableTo exclude sex-related differences in hand grip strength and blood pressure, here, we evaluated only female subjects.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Symptoms of autonomic dysfunction were assessed by the Composite Autonomic Symptom Score (COMPASS 31).17 Depression and sleepiness were assessed by Patient Health Questionnaire 9 (PHQ9) and Epworth Sleepiness Scale (ESS).
    COMPASS
    suggested: (COMPASS, RRID:SCR_015874)
    All data was recorded using a REDCap database.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Statistical analysis: We performed the statistical analysis with Excel GraphPad Prism 6.0.
    Excel GraphPad Prism
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations of this study: Our study has several limitations. Firstly, recruitment bias may have contributed to the severity of symptoms, thus this cohort is probably not representative for all COVID-19 patients with persistent fatigue. Secondly, it is unclear, if the distinction into subgroups based on the criterion of the length of PEM indicates differences in mechanisms or merely reflect the variance of the disease spectrum. Thirdly, the low number of patients precluded detailed comparisons of phenotypes with adequate statistical power.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from scite Reference Check: We found citations with errata. We recommend checking the errata to confirm that they do not impact the accuracy of your citation.

    DOIStatusTitle
    10.1186/s13054-019-2553-zHas correctionScreening for posttraumatic stress disorder in ARDS survivor…
    10.1371/journal.pone.0219663Has correctionHealth risks associated with social isolation in general and…

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  4. Version published to 10.1101/2021.02.06.21249256 on medRxiv