Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection

  1. Chansavath Phetsouphanh
  2. David R. Darley
  3. Daniel B. Wilson
  4. Annett Howe
  5. C. Mee Ling Munier
  6. Sheila K. Patel
  7. Jennifer A. Juno
  8. Louise M. Burrell
  9. Stephen J. Kent
  10. Gregory J. Dore
  11. Anthony D. Kelleher
  12. Gail V. Matthews

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Abstract

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  1. Version published to 10.1038/s41590-021-01113-x
  2. Version published to 10.1101/2021.06.01.21257759v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.06.01.21257759: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics: The ADAPT study was approved by the St Vincent’s Hospital Research Ethics Committee (2020/ETH00964) and is a registered trial (ACTRN12620000554965).
    Consent: All participants gave written informed consent.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The aims of ADAPT are to evaluate a number of outcomes after COVID-19 relating to pathophysiology, immunology and clinical sequalae.
    ADAPT
    suggested: (ADAPT, RRID:SCR_006769)
    All data were stored using REDCap electronic data capture tools.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    For unsupervised analysis, the following FlowJo plugins were used: DownSample (v.3), TriMap (v.0.2), Phenograph (v.3.0) and ClusterExplorer (v.1.5.9) (all FlowJo LLC).
    TriMap
    suggested: None
    ClusterExplorer
    suggested: None
    FlowJo
    suggested: (FlowJo, RRID:SCR_008520)
    Phenograph plugin was then used to determine clusters of phenotypically related cells.
    Phenograph
    suggested: (Phenograph, RRID:SCR_016919)
    Wilcoxon paired t test was used to analyse statistical data employing Prism 9.0 (GraphicPad, La Jolla, CA, USA) software.
    Prism
    suggested: (PRISM, RRID:SCR_005375)
    RStudio version 1.2.1335 was used to generate correlograms utilizing corrplot package and Spearman’s rank-order correlation coefficient with an adjusted FDR <0.05. p values <0.05 were considered significant (*<0.05, **<0.01, ***<0.001, and ****<0.0001).
    RStudio
    suggested: (RStudio, RRID:SCR_000432)

    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:
    Our data does have some limitations. Firstly, although our long COVID ‘cases’ and controls were matched for two major characteristics (age and gender) it is possible that the differences observed reflect other key demographic or other factors between the groups. Secondly, although 7 of the 29 analytes were observed to be abnormally elevated, 22 of 29 were not (including key cytokines often implicated in chronic fatigue syndromes such as Pentraxin- 3(PTX3), TGF-β1, and IL-13)62,63. This suggests long COVID may be differentiated from other post viral fatigue syndromes, however, our results require validation in other cohorts of long COVID to ensure their replicability. Finally, our definition of ‘long COVID’ cases was internally set given the lack of international consensus regarding this and thus is not definitive. Nevertheless, the inclusion of three of the commonest persisting symptoms and the blinding of cases and controls from the laboratory scientists has helped to ensure the validity of our findings. Additional strengths of our study include the prospective protocol defined collection of samples and data and the establishment of an ADAPT–C cohort of individuals affected contemporaneously with other human coronaviruses to act as controls. In summary, taken together our data identifies a distinct but diffuse profile of elevated inflammatory cytokines in people with persisting symptoms post COVID-19 infection, the majority of whom had initial mild-moderate illness. This inf...

    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 rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.06.01.21257759v1 on medRxiv