Severe COVID-19 patients display a back boost of seasonal coronavirus-specific antibodies

  1. Brenda M. Westerhuis
  2. Muriel Aguilar-Bretones
  3. Matthijs P. Raadsen
  4. Erwin de Bruin
  5. Nisreen M.A. Okba
  6. Bart L. Haagmans
  7. Thomas Langerak
  8. Henrik Endeman
  9. Johannes P.C. van den Akker
  10. Diederik A.M.P.J. Gommers
  11. Eric C.M. van Gorp
  12. Barry H.G. Rockx
  13. Marion P.G. Koopmans
  14. Gijsbert P. van Nierop

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Abstract

Severe acquired respiratory syndrome coronavirus-2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19). In severe COVID-19 cases, higher antibody titers against seasonal coronaviruses have been observed than in mild cases. To investigate antibody cross-reactivity as potential explanation for severe disease, we determined the kinetics, breadth, magnitude and level of cross-reactivity of IgG against SARS-CoV-2 and seasonal CoV nucleocapsid and spike from 17 severe COVID-19 cases at the clonal level. Although patients mounted a mostly type-specific SARS-CoV-2 response, B-cell clones directed against seasonal CoV dominated and strongly increased over time. Seasonal CoV IgG responses that did not neutralize SARS-CoV-2 were boosted well beyond detectable cross-reactivity, particularly for HCoV-OC43 spike. These findings support a back-boost of poorly protective coronavirus-specific antibodies in severe COVID-19 patients that may negatively impact de novo SARS-CoV-2 immunity, reminiscent of original antigenic sin.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.10.20210070: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Patient characteristics and clinical specimen: PCR-confirmed COVID-19 patients24 admitted to the ICU at the Erasmus Medical Center with acute respiratory distress syndrome (ARDS) were included in a biorepository study (MEC-2017-417) and samples were analyzed according to the SARS-CoV-2 protocol (MEC-2020-0222) with approval from the medical ethical committee of the Erasmus MC.
    Consent: Personal or deferred informed written consent was obtained after recovery or from a legal representative, partner or family member of the participant respectively, all in compliance with the Declaration of Helsinki. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from EDTA vacutainer blood collection tubes (BD biosciences) aliquoted and cryopreserved as described elsewhere25.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Oligoclonal B-cell cultures were stimulated using 1000 L-CD40L cells that were growth arrested by 40Gray γ-irradiation, 50 U/ml IL-2 (Novartis), 10 ng/ml IL-10 (Peprotech), 25 ng/ml IL-21 (Peprotech) and 1 µg/ml R848 (Invivogen) for 48 hours and subsequently cultured for 12 days in B-cell medium supplemented with 25ng/ml IL-21.
    L-CD40L
    suggested: None
    Software and Algorithms
    SentencesResources
    All analyses were performed using ‘R’ and Graphpad Prism 7 as previously described18,27.
    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

  2. Version published to 10.1101/2020.10.10.20210070 on medRxiv