Humoral Immune Response to SARS-CoV-2

  1. Pauline H Herroelen
  2. Geert A Martens
  3. Dieter De Smet
  4. Koen Swaerts
  5. An-Sofie Decavele

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Abstract

Objectives

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology tests are clinically useful to document prior SARS-CoV-2 infections. Data are urgently needed to select assays with optimal sensitivity at acceptable specificity for antibody detection.

Methods

A comparative evaluation was performed of 7 commercial SARS-CoV-2 serology assays on 171 sera from 135 subjects with polymerase chain reaction–confirmed SARS-CoV-2 infection (71 hospitalized patients and 64 paucisymptomatic individuals). Kinetics of IgA/IgM/IgG seroconversion to viral N and S protein epitopes were studied from 0 to 54 days after onset of symptoms. Cross-reactivity was verified on 57 prepandemic samples.

Results

Wantai SARS-COV-2 Ab ELISA and Orient Gene COVID-19 IgG/IgM Rapid Test showed superior overall sensitivity for detection of SARS-CoV-2 antibodies. Elecsys Anti-SARS-CoV-2 assay and EUROIMMUN Anti-SARS-CoV-2 combined IgG/IgA showed acceptable sensitivity (>95%) vs the consensus result of all assays from 10 days post onset of symptoms. Wantai SARS-COV-2 Ab ELISA, Elecsys Anti-SARS-CoV-2 assay, and Innovita 2019-nCoV Ab rapid test showed least cross-reactivity, resulting in an optimal analytical specificity greater than 98%.

Conclusions

Wantai SARS-COV-2 Ab ELISA and Elecsys Anti-SARS-CoV-2 assays are suitable for sensitive and specific detection of SARS-CoV-2 antibodies from 10 days after onset of symptoms.

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  1. Version published to 10.1093/ajcp/aqaa140
  2. ScreenIT

    SciScore for 10.1101/2020.06.09.20124719: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The study was approved by the AZ Delta ethical committee with a waiver of informed consent from the hospitalized COVID-19 patients (Clinical Trial Number IRB B1172020000009) and with written informed consent from participants with paucisymptomatic and suspected SARS-CoV-2 infections (Clinical Trial Number B1172020000006).
    Consent: The study was approved by the AZ Delta ethical committee with a waiver of informed consent from the hospitalized COVID-19 patients (Clinical Trial Number IRB B1172020000009) and with written informed consent from participants with paucisymptomatic and suspected SARS-CoV-2 infections (Clinical Trial Number B1172020000006).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Rapid tests: The COVID-19 IgG/IgM Rapid Test (Zhejiang Orient Gene Biotech Co., Ltd., Zhejiang, China) is a solid phase immunochromatographic assay for the qualitative detection of IgM and IgG antibodies to recombinant N- and S-proteins.
    IgG
    suggested: None
    Three indirect ELISAs from EUROIMMUN AG (a PerkinElmer Company, Luebeck, Germany) were tested: the Anti-SARS-CoV-2 IgG and IgA assays for semiquantitative detection of IgA and IgG antibodies against the S1 protein and Anti-SARS-CoV-2-NCP(IgG) assay for semiquantitative detection of IgG to the N protein.
    Anti-SARS-CoV-2 IgG
    suggested: None
    Electrochemiluminescence immunoassays (CLIA): The Elecsys Anti-SARS-CoV-2 assay for Cobas e601 module (Roche Diagnostics, Basel, Switzerland) is a double-antigen sandwich assay for the qualitative detection of all antibody isotypes (IgM, IgA, IgG) against the N protein (cutoff = 1 Cutoff Index) LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin, Saluggia, Italy) is an indirect CLIA for the quantitative detection of IgG antibodies against S1/S2 proteins (cutoff = 12 AU/mL, classifying gray zone results between 12 and 15 AU/mL as positive).
    IgM, IgA, IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    All ELISAs were tested using the PhD™ system (Version EIA 0_16, Bio-Rad Laboratories, Inc., Hercules, California).
    Bio-Rad Laboratories
    suggested: (Bio-Rad Laboratories, RRID:SCR_008426)
    Statistical analysis: Statistical analyses were performed using MedCalc (version 12.2.1, Belgium).
    MedCalc
    suggested: (MedCalc, RRID:SCR_015044)
    Figure 2 was created in Python 3.7.7.
    Python
    suggested: (IPython, RRID:SCR_001658)
    The packages numpy (1.18.4), pandas (1.0.3) and matplotlib (3.2.1) were used to process the data and generate the plot.
    numpy
    suggested: (NumPy, RRID:SCR_008633)
    matplotlib
    suggested: (MatPlotLib, RRID:SCR_008624)

    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: We detected the following sentences addressing limitations in the study:
    The limitations of our study are that the specificity analysis requires further extension, particularly with time series analyzing false positive seroconversion triggered by other HCoV (229E/HKU1/OC43/NL63) during the common cold season, and that our study did not include a sizeable cohort of fully asymptomatic SARS-CoV-2 infections. Our study also focused on qualitative analysis and did not investigate differences in assays’ performance for quantification of antibody titers. In critically ill COVID-19 patients, SARS-CoV-2 antibody levels were reported to correlate to disease severity (4) by triggering bradykinin and complement activation pathways. The assays evaluated here show large variations in their dynamic range (raw data in Supplementary Information), ranging from a good linearity for the LIAISON SARS-CoV-2 S1/S2 IgG (12) to a limited dynamic range with rapid signal saturation for the most sensitive: with a sample volume input of 100 µL that is 10-20 times higher than the other evaluated assays, the Wantai SARS-COV-2 Ab ELISA is clearly designed towards high sensitivity by maximal antibody capture. Caution is thus warranted when comparing (semi)quantitative estimates of antibody titers across platforms before certified standards with known titers become available. Our data are compatible with other cross-platform evaluations (13) indicating superior performance of the Wantai SARS-COV-2 Ab ELISA as compared to EUROIMMUN Anti-SARS-CoV-2 IgG and IgA. Our data are, however...

    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 10.1101/2020.06.09.20124719v2 on medRxiv
  4. Version published to 10.1101/2020.06.09.20124719v1 on medRxiv