A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity

  1. Vincent Legros
  2. Solène Denolly
  3. Manon Vogrig
  4. Bertrand Boson
  5. Eglantine Siret
  6. Josselin Rigaill
  7. Sylvie Pillet
  8. Florence Grattard
  9. Sylvie Gonzalo
  10. Paul Verhoeven
  11. Omran Allatif
  12. Philippe Berthelot
  13. Carole Pélissier
  14. Guillaume Thiery
  15. Elisabeth Botelho-Nevers
  16. Guillaume Millet
  17. Jérôme Morel
  18. Stéphane Paul
  19. Thierry Walzer
  20. François-Loïc Cosset
  21. Thomas Bourlet
  22. Bruno Pozzetto

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and, thus, for public health policy and vaccine development for COVID-19. In this study, using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein (Spike), we studied the neutralizing antibody (nAb) response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections, including patients with mild symptoms and also more severe forms, including those that required intensive care. We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels. Indeed, patients from intensive care units exhibited high nAb titers; conversely, patients with milder disease symptoms had heterogeneous nAb titers, and asymptomatic or exclusive outpatient-care patients had no or low nAbs. We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses. Moreover, we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2, indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2. Finally, we found that the D614G mutation in the spike protein, which has recently been identified as the current major variant in Europe, does not allow neutralization escape. Altogether, our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease, and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2020.08.27.20182493: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethics: This study was approved by the Ethical Committee of the University Hospital of Saint-Etienne (reference number IRBN512020/CHUSTE).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-Spike RBD SARS-CoV2 (Sino Biological) and anti-gp70 RD114 (79S914, ViroMed Biosafety Labs) were used as positive and negative control neutralizing antibodies, respectively.
    Anti-Spike RBD SARS-CoV2
    suggested: None
    anti-gp70
    suggested: None
    Commercial kits for measuring IgG antibodies against SARS-CoV-2: Two commercially-available kits were used for measuring the anti-SARS-CoV-2 IgG antibodies.
    anti-SARS-CoV-2 IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Seroneutralization assay using wild type SARS-CoV-2: The viral strain (RoBo strain) used this assay was a clinical isolate cultured on Vero-E6 cells (kind gift from Pr. B. La Scola, IHU Méditerranée, Marseille, France) from a nasopharyngeal aspirate of a patient hospitalized at the University Hospital of Saint-Étienne for severe COVID-19 infection; it was diluted in DMEM containing 2% FCS so that to obtain 100 to 500 tissue culture infectious doses 50% (TCID50) per ml.
    Vero-E6
    suggested: None
    After gentle shaking and a contact of 30 minutes at room temperature, 150 µl of the mixt was transferred to 96-well microplates covered with VeroE6 cells.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Briefly, HEK293T cells (ATCC CRL-1573) were transfected with constructs expressing MLV Gag-Pol, the green fluorescent protein (GFP) reporter, and the SARS-CoV-2 Spike (kind gift from D. Lavillette).
    HEK293T
    suggested: None
    Software and Algorithms
    SentencesResources
    The LIAISON® SARS-CoV-2 S1/S2 kit (Diasorin) measures antibodies against S1-S2 proteins whereas the ARCHITECT SARS-CoV-2 IgG kit (Abbott Laboratories) measures antibodies to the viral nucleoprotein.
    Abbott Laboratories
    suggested: None
    Statistical analysis: Analysis were performed using the GraphPad Prism 6 software.
    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 10.1038/s41423-020-00588-2
  3. Version published to 10.1101/2020.08.27.20182493 on medRxiv