Refining “Long-COVID” by a Prospective Multimodal Evaluation of Patients with Long-Term Symptoms Attributed to SARS-CoV-2 Infection

  1. Marc Scherlinger
  2. Renaud Felten
  3. Floriane Gallais
  4. Charlotte Nazon
  5. Emmanuel Chatelus
  6. Luc Pijnenburg
  7. Amaury Mengin
  8. Adrien Gras
  9. Pierre Vidailhet
  10. Rachel Arnould-Michel
  11. Sabrina Bibi-Triki
  12. Raphaël Carapito
  13. Sophie Trouillet-Assant
  14. Magali Perret
  15. Alexandre Belot
  16. Seiamak Bahram
  17. Laurent Arnaud
  18. Jacques-Eric Gottenberg
  19. Samira Fafi-Kremer
  20. Jean Sibilia

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Abstract

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  1. Version published to 10.1007/s40121-021-00484-w
  2. ScreenIT

    SciScore for 10.1101/2021.04.08.21255167: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All patients provided written informed consent.
    IRB: This study is part of the “COVID-HUS” study, which was approved by the ethics committee of the University Hospital of Strasbourg (NCE–2020– 51).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    One lateral flow assay tested for the receptor binding 2 (RBD) of the spike protein as an antigenic source (Biosynex BSS IgM/IgG assay), and two enzyme-linked immunosorbent assays (ELISA) targeted the RBD (Wantai total antibody) and the S1 domain (Euroimmun IgG).
    S1 domain ( Euroimmun IgG
    suggested: None
    Anti–IFN-γ antibody-coated wells (UCytech) were seeded with 200,000 CD3+ cells per well.
    Anti–IFN-γ antibody-coated wells ( UCytech )
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses involved using GraphPad Prism 7.0.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Indeed, both groups had high pain/fatigue indexes and limitations in several components of the SF-36 scale (Supplemental Figures 1 and 3). Only half of the patient had objective cellular (IFN-γ ELISPOT-based) and humoral immunity for SARS-CoV-2 (Figure 2B). There are three possible (and non-exclusive) explanations for this result. First, some patients may have been infected with SARS-CoV-2, without detectable immunity. As already described (22), one of our patients with RT-PCR– proven SARS-CoV-2 infection had a negative SARS-CoV-2 serology result at several times (36, 85 and 140 days after initial symptoms) as well as on IFN-γ ELISPOT (after 140 days). Second, immunity may have developed in some patients but subsequently waned over time, although such reports are discordant (23,24). In our cohort, one patient with PCR/ELISPOT-confirmed infection showed IgG serology findings between days 133 and 251, both on anti-N (from equivocal to negative) and anti-S (from positive to equivocal) ELISA. Additionally, patients with cellular immunity might have negative serology, particularly anti-N IgG (Figure 2A). Finally, some patients may have presented a non-specific viral illness and subsequent symptoms, which were falsely attributed to SARS-CoV-2. In fact, the period of the first pandemic wave was highly anxiogenic and may have exacerbated pre-existing psychological conditions and induced a nocebo effect in some patients (25). The high prevalence of probable anxiety and depression diso...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

    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.

  3. Version published to 10.1101/2021.04.08.21255167v1 on medRxiv