SARS-CoV-2 Antibody Responses Correlate with Resolution of RNAemia But Are Short-Lived in Patients with Mild Illness

  1. Katharina Röltgen
  2. Oliver F. Wirz
  3. Bryan A. Stevens
  4. Abigail E. Powell
  5. Catherine A. Hogan
  6. Javaria Najeeb
  7. Molly Hunter
  8. Malaya K. Sahoo
  9. ChunHong Huang
  10. Fumiko Yamamoto
  11. Justin Manalac
  12. Ana R. Otrelo-Cardoso
  13. Tho D. Pham
  14. Arjun Rustagi
  15. Angela J. Rogers
  16. Nigam H. Shah
  17. Catherine A. Blish
  18. Jennifer R. Cochran
  19. Kari C. Nadeau
  20. Theodore S. Jardetzky
  21. James L. Zehnder
  22. Taia T. Wang
  23. Peter S. Kim
  24. Saurabh Gombar
  25. Robert Tibshiran
  26. Benjamin A. Pinsky
  27. Scott D. Boyd

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Abstract

SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, could offer protective immunity, and may affect clinical outcomes of COVID-19 patients. We analyzed 625 serial plasma samples from 40 hospitalized COVID-19 patients and 170 SARS-CoV-2-infected outpatients and asymptomatic individuals. Severely ill patients developed significantly higher SARS-CoV-2-specific antibody responses than outpatients and asymptomatic individuals. The development of plasma antibodies was correlated with decreases in viral RNAemia, consistent with potential humoral immune clearance of virus. Using a novel competition ELISA, we detected antibodies blocking RBD-ACE2 interactions in 68% of inpatients and 40% of outpatients tested. Cross-reactive antibodies recognizing SARS-CoV RBD were found almost exclusively in hospitalized patients. Outpatient and asymptomatic individuals’ serological responses to SARS-CoV-2 decreased within 2 months, suggesting that humoral protection may be short-lived.

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  1. ScreenIT

    SciScore for 10.1101/2020.08.15.20175794: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: This study was approved by the Stanford University Institutional Review Board (protocol # 48973).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Study design and participants: The objective of this study was to investigate correlations between humoral immune responses to SARS-CoV-2, antibodies blocking binding of RBD to the human ACE2 receptor, and viral RNAemia in different COVID-19 patient groups and individual patients.
    SARS-CoV-2,
    suggested: None
    ELISA to detect anti-SARS-CoV-2 Spike RBD antibodies in plasma samples: The ELISA procedure in this study was modified from a protocol published by Stadlbauer (30).
    anti-SARS-CoV-2 Spike RBD
    suggested: None
    The p-values for the correlation between the slopes of anti-RBD antibodies and ACE2 were estimated using 1000 permutations of the ACE2 values within each patient time course.
    ACE2
    suggested: None
    The p-values for the difference in slopes of anti-RBD antibody decreases (after they peaked) between outpatients/asymptomatic individuals and inpatients were estimated using 1000 permutations of the group labels for each patient.
    anti-RBD
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 S1 (spike residues 1–682) and ACE2-mFc, expressed in HEK293 cells, and the N protein, expressed in E.coli were produced by the CRO Atum.
    HEK293
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    Software and Algorithms
    SentencesResources
    Statistics: ELISA data were analyzed using GraphPad Prism version 8.0 (GraphPad Software, San Diego, California, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    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 10.1101/2020.08.15.20175794v1 on medRxiv