Magnitude and Kinetics of Anti–Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Responses and Their Relationship to Disease Severity

  1. Kara L Lynch
  2. Jeffrey D Whitman
  3. Noreen P Lacanienta
  4. Erica W Beckerdite
  5. Shannon A Kastner
  6. Brian R Shy
  7. Gregory M Goldgof
  8. Andrew G Levine
  9. Sagar P Bapat
  10. Susan L Stramer
  11. Jonathan H Esensten
  12. Allen W Hightower
  13. Caryn Bern
  14. Alan H B Wu

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Abstract

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can be detected indirectly by measuring the host immune response. For some viruses, antibody concentrations correlate with host protection and viral neutralization, but in rare cases, antiviral antibodies can promote disease progression. Elucidation of the kinetics and magnitude of the SARS-CoV-2 antibody response is essential to understand the pathogenesis of coronavirus disease 2019 (COVID-19) and identify potential therapeutic targets.

Methods

Sera (n = 533) from patients with real-time polymerase chain reaction–confirmed COVID-19 (n = 94 with acute infections and n = 59 convalescent patients) were tested using a high-throughput quantitative immunoglobulin M (IgM) and immunoglobulin G (IgG) assay that detects antibodies to the spike protein receptor binding domain and nucleocapsid protein. Individual and serial samples covered the time of initial diagnosis, during the disease course, and following recovery. We evaluated antibody kinetics and correlation between magnitude of the response and disease severity.

Results

Patterns of SARS-CoV-2 antibody production varied considerably. Among 52 patients with 3 or more serial specimens, 44 (84.6%) and 42 (80.8%) had observed IgM and IgG seroconversion at a median of 8 and 10 days, respectively. Compared to those with milder disease, peak measurements were significantly higher for patients admitted to the intensive care unit for all time intervals between 6 and 20 days for IgM, and all intervals after 5 days for IgG.

Conclusions

High-sensitivity assays with a robust dynamic range provide a comprehensive picture of host antibody response to SARS-CoV-2. IgM and IgG responses were significantly higher in patients with severe than mild disease. These differences may affect strategies for seroprevalence studies, therapeutics, and vaccine development.

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  1. Version published to 10.1093/cid/ciaa979
  2. ScreenIT

    SciScore for 10.1101/2020.06.03.20121525: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical review: Two separate protocols, one for Zuckerberg San Francisco General Hospital (ZSFG) remnant specimens (IRB #20-30387) and the other for convalescent plasma donor screening (IRB #20-30637), were approved by the Institutional Review Board of the University of California, San Francisco.
    Consent: The committee judged that written consent was not required for use of remnant specimens.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody measurement: Antibodies to SARS-CoV-2 (IgM and IgG) were measured using the Pylon 3D automated immunoassay system (ET Healthcare, Palo Alto, CA) as described previously.
    SARS-CoV-2 (IgM and IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Antibody measurement: Antibodies to SARS-CoV-2 (IgM and IgG) were measured using the Pylon 3D automated immunoassay system (ET Healthcare, Palo Alto, CA) as described previously.
    ET Healthcare
    suggested: None
    Analyses were performed in SAS version 9.4 (SAS Institute Inc., Cary, NC).
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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.

  3. Version published to 10.1101/2020.06.03.20121525v1 on medRxiv