Lack of antibodies against seasonal coronavirus OC43 nucleocapsid protein identifies patients at risk of critical COVID-19

  1. Martin Dugas
  2. Tanja Grote-Westrick
  3. Uta Merle
  4. Michaela Fontenay
  5. Andreas E. Kremer
  6. Frank Hanses
  7. Richard Vollenberg
  8. Eva Lorentzen
  9. Shilpa Tiwari-Heckler
  10. Jérôme Duchemin
  11. Syrine Ellouze
  12. Marcel Vetter
  13. Julia Fürst
  14. Philipp Schuster
  15. Tobias Brix
  16. Claudia M. Denkinger
  17. Carsten Müller-Tidow
  18. Hartmut Schmidt
  19. Phil-Robin Tepasse
  20. Joachim Kühn

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Abstract

No abstract available

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  1. Version published to 10.1016/j.jcv.2021.104847
  2. Version published to 10.1101/2020.12.07.20245241v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.12.07.20245241: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: In the pilot study, 60 patients were analyzed in the context of the Coronaplasma Project (local ethics committee approval: AZ 2020-220-f-S) and COVID-19 biomarker study (ethics committee approval: AZ 2020-210-f-S) at the University Hospital Münster.
    Consent: This study was approved by the local ethics committee (ethics committee approval: S-148/2020) and informed consent was obtained from study participants.
    Randomizationnot detected.
    BlindingLaboratory analyses were performed blinded regarding patient outcome.
    Power Analysisnot detected.
    Sex as a biological variableFigure 5 presents basic demographic information on the validation cohort comprising 296 COVID-19 patients (165 males, 131 females) treated at tertiary care referral centers in Heidelberg, Paris, Erlangen and Regensburg.

    Table 2: Resources

    Antibodies
    SentencesResources
    With respect to sHCoVs, this assay detects IgG antibodies directed against the nucleocapsid protein (NP) of HCoV 229E, NL63, OC43 and HKU1.
    NL63
    suggested: None
    HKU1
    suggested: None
    To test precision and reliability, internal negative and positive control sera with known antibody reactivity against sHCoVs and SARS-CoV-2, respectively, were included and analyzed as given below.
    SARS-CoV-2
    suggested: None
    In addition, S1-specific IgG antibodies were analyzed by ELISA (Euroimmun, Lübeck, Germany) according to the manufacturer’s instructions.
    S1-specific IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Relative antibody levels were quantitatively determined with ImageJ (version 153, 64bit-Version for windows) (18) using the signal intensity of the cutoff band as internal reference (ratio HCoV-specific band to cutoff band).
    ImageJ
    suggested: (ImageJ, RRID:SCR_003070)

    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:
    This study has limitations as it was a non-interventional, observational study. We analyzed patient cohorts from major tertiary care referral centers, which could explain the high overall proportion of critical COVID-19 cases. Clearly, a prospective, randomized trial would provide more robust evidence. However, in the current pandemic decisions about vaccination priority and therapy options for COVID-19 inpatients must be taken based on evidence available to date. We observed a consistent pattern in the data from pilot and validation study: HCoV OC43 is the seasonal coronavirus most similar to SARS-CoV-2 (14) and the association measures are stronger for HCoV OC43 than for all other HCoVs. It is widely accepted that individuals of high age should be vaccinated with priority. If absence of HCoV OC43-specific antibodies conveys more risk than high age, HCoV OC43 seronegative individuals will particularly profit from vaccination and should be vaccinated with priority. Approximately 90% of our inpatient cohort were aged 40 years and above, therefore our findings are valid for this age group. For the same reason we propose to determine HCoV OC43-specific IgG antibody levels upon admission of COVID-19 patients to the hospital for individual risk assessment. Table 2 and figure 3 can be used in this context.

    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.

    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 10.1101/2020.12.07.20245241v1 on medRxiv