Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2

  1. Kanika Vanshylla
  2. Veronica Di Cristanziano
  3. Franziska Kleipass
  4. Felix Dewald
  5. Philipp Schommers
  6. Lutz Gieselmann
  7. Henning Gruell
  8. Maike Schlotz
  9. Meryem S Ercanoglu
  10. Ricarda Stumpf
  11. Petra Mayer
  12. Eva Heger
  13. Wibke Johannis
  14. Carola Horn
  15. Isabelle Suárez
  16. Norma Jung
  17. Susanne Salomon
  18. Kirsten Alexandra Eberhardt
  19. Gerd Fätkenheuer
  20. Nico Pfeifer
  21. Ralf Eggeling
  22. Max Augustin
  23. Clara Lehmann
  24. Florian Klein

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Abstract

A detailed understanding of antibody-based SARS-CoV-2 immunity has critical implications for overcoming the COVID-19 pandemic and for informing on vaccination strategies. In this study, we evaluated the dynamics of the SARS-CoV-2 antibody response in a cohort of 963 recovered individuals over a period of 10 months. Investigating a total of 2,146 samples, we detected an initial SARS-CoV-2 antibody response in 94.4% of individuals, with 82% and 79% exhibiting serum and IgG neutralization, respectively. Approximately 3% of recovered patients demonstrated exceptional SARS-CoV-2 neutralizing activity, defining them as ‘elite neutralizers’. These individuals also possessed effective cross-neutralizing IgG antibodies to SARS-CoV-1 without any known prior exposure to this virus. By applying multivariate statistical modeling, we found that sero-reactivity, age, time since disease onset, and fever are key factors predicting SARS-CoV-2 neutralizing activity in mild courses of COVID-19. Investigating longevity of the antibody response, we detected loss of anti-spike reactivity in 13% of individuals 10 months after infection. Moreover, neutralizing activity had an initial half-life of 6.7 weeks in serum versus 30.8 weeks in purified IgG samples indicating the presence of a more stable and long-term memory IgG B cell repertoire in the majority of individuals recovered from COVID-19. Our results demonstrate a broad spectrum of the initial SARS-CoV-2 neutralizing antibody response depending on clinical characteristics, with antibodies being maintained in the majority of individuals for the first 10 months after mild course of COVID-19.

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  1. ScreenIT

    SciScore for 10.1101/2021.01.26.428207: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Enrollment of participants and study design: Blood samples were collected from donors who gave their written consent under the protocols 20-1187 and 16-054, approved by the Institutional Review Board (IRB) of the University Hospital Cologne.
    IRB: Enrollment of participants and study design: Blood samples were collected from donors who gave their written consent under the protocols 20-1187 and 16-054, approved by the Institutional Review Board (IRB) of the University Hospital Cologne.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detection of anti-SARS-CoV-2 spike IgG and IgA by ELISA: For assessing IgA and IgG antibody titers, the Euroimmun anti-SARS-CoV-2 ELISA using the S1 domain of the spike protein as antigen was used (Euroimmun Diagnostik, Lübeck, Germany).
    anti-SARS-CoV-2 spike IgG
    suggested: None
    IgG
    suggested: None
    anti-SARS-CoV-2
    suggested: None
    Additional commercial kits used for antibody measurements were also used as per manufacturer’s recommendations; Anti-S1/S2 IgG was measured using DiaSorin’s LIAISON® SARS-CoV-2 ELISA kit with the following cut-off values: negative <12.0 AU/ml, equivocal ≥12.0- < 15.0 AU/ml and positive ≥15.0 AU/ml.
    Anti-S1/S2 IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    In brief, HEK 293T cells were transfected with the pseudovirus encoding plasmids using FuGENE 6 Transfection Reagent (Promega).
    HEK 293T
    suggested: NCBI_Iran Cat# C498, RRID:CVCL_0063)
    Pseudovirus assay to determine IgG/plasma/serum SARS-CoV-2 neutralizing activity: For testing SARS-CoV-2 neutralizing activity of IgG or serum/plasma samples, serial dilutions of IgG or serum/plasma (heat inactivated at 56°C for 45 min) were co-incubated with pseudovirus supernatants for 1 h at 37°C prior to addition of 293T cells engineered to express ACE263.
    293T
    suggested: None
    SARS-CoV-2 live virus isolation from nasopharyngeal swabs: For outgrowth cultures of authentic SARS-CoV-2 from nasopharyngeal swabs, 1×106 VeroE6 cells were seeded onto a T25 flask (Sarstedt) on the previous day DMEM (Gibco) containing 10% FBS, 1% PS, 1mM L-Glutamine and 1mM Sodium pyruvate.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Software and Algorithms
    SentencesResources
    IC50 and ID50 values were calculated in GraphPad Prism 7.0 by plotting a dose response curve.
    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 10.1101/2021.01.26.428207v1 on bioRxiv