Longitudinal Serological Analysis and Neutralizing Antibody Levels in Coronavirus Disease 2019 Convalescent Patients

  1. Frauke Muecksch
  2. Helen Wise
  3. Becky Batchelor
  4. Maria Squires
  5. Elizabeth Semple
  6. Claire Richardson
  7. Jacqueline McGuire
  8. Sarah Clearly
  9. Elizabeth Furrie
  10. Neil Greig
  11. Gordon Hay
  12. Kate Templeton
  13. Julio C C Lorenzi
  14. Theodora Hatziioannou
  15. Sara Jenks
  16. Paul D Bieniasz

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Abstract

Background

Understanding the longitudinal trajectory of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies is crucial for diagnosis of prior infection and predicting future immunity.

Methods

We conducted a longitudinal analysis of coronavirus disease 2019 convalescent patients, with neutralizing antibody assays and SARS-CoV-2 serological assay platforms using SARS-CoV-2 spike (S) or nucleocapsid (N) antigens.

Results

Sensitivities of serological assays in diagnosing prior SARS-CoV-2 infection changed with time. One widely used commercial platform that had an initial sensitivity of >95% declined to 71% at 81–100 days after diagnosis. The trajectories of median binding antibody titers measured over approximately 3–4 months were not dependent on the use of SARS-CoV-2 N or S proteins as antigen. The median neutralization titer decreased by approximately 45% per month. Each serological assay gave quantitative antibody titers that were correlated with SARS-CoV-2 neutralization titers, but S-based serological assay measurements better predicted neutralization potency. Correlation between S-binding and neutralization titers deteriorated with time, and decreases in neutralization titers were not predicted by changes in S-binding antibody titers.

Conclusions

Different SARS-CoV-2 serological assays are more or less well suited for surveillance versus prediction of serum neutralization potency. Extended follow-up should facilitate the establishment of appropriate serological correlates of protection against SARS-CoV-2 reinfection.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.05.20169128: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All recruits gave written and informed consent for serial blood sample collection.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableThe mean age of the participants was 44.2 years (21 – 65 y), with 70 female (72% of cohort) participants.

    Table 2: Resources

    Antibodies
    SentencesResources
    The Roche Anti-SARS-CoV total antibody assay is a two-step bridging electrochemiluminesent immunoassay (ECLIA) using ruthenium-labelled and biotin conjugated N protein.
    Anti-SARS-CoV
    suggested: None
    Software and Algorithms
    SentencesResources
    Assays were performed on the Abbott Architect and Diasorin Liason platforms (NHS Lothian), and the Roche Elecsys (NHS Lanarkshire) and Siemens Atellica (NHS Tayside) platforms.
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)

    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

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  2. Version published to 10.1093/infdis/jiaa659
  3. Version published to 10.1101/2020.08.05.20169128v1 on medRxiv