Longitudinal detection of SARS‐CoV‐2‐specific antibody responses with different serological methods

  1. Petra Emmerich
  2. Ronald von Possel
  3. Christoph Josef Hemmer
  4. Carlos Fritzsche
  5. Hilte Geerdes‐Fenge
  6. Babett Menge
  7. Claudia Messing
  8. Viola Borchardt‐Lohölter
  9. Christina Deschermeier
  10. Katja Steinhagen

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Abstract

Serological testing for anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antibodies is used to detect ongoing or past SARS‐CoV‐2 infections. To study the kinetics of anti‐SARS‐CoV‐2 antibodies and to assess the diagnostic performances of eight serological assays, we used 129 serum samples collected on known days post symptom onset (dpso) from 42 patients with polymerase chain reaction‐confirmed coronavirus disease 2019 (COVID‐19) and 54 serum samples from healthy blood donors, and children infected with seasonal coronaviruses. The sera were analyzed for the presence of immunoglobulin G (IgG), immunoglobulin M (IgM), and immunoglobulin A (IgA) antibodies using indirect immunofluorescence testing (IIFT) based on SARS‐CoV‐2‐infected cells. They were further tested for antibodies against the S1 domain of the SARS‐CoV‐2 spike protein (IgG, IgA) and against the viral nucleocapsid protein (IgG, IgM) using enzyme‐linked immunosorbent assays. The assay specificities were 94.4%–100%. The sensitivities varied largely between assays, reflecting their respective purposes. The sensitivities of IgA and IgM assays were the highest between 11 and 20 dpso, whereas the sensitivities of IgG assays peaked between 20 and 60 dpso. IIFT showed the highest sensitivities due to the use of the whole SARS‐CoV‐2 as substrate and provided information on whether or not the individual has been infected with SARS‐CoV‐2. Enzyme‐linked immunosorbent assays provided further information about both the prevalence and concentration of specific antibodies against selected antigens of SARS‐CoV‐2.

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  1. Version published to 10.1002/jmv.27113
  2. ScreenIT

    SciScore for 10.1101/2021.04.16.21255608: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    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 antibodies: The detection of the antibodies against SARS-CoV-2 (genus: Betacoronavirus, family: Coronaviridae) using IIFT was performed with anti-IgG-, anti-IgA- and anti-IgM-FITC-labelled secondary antibodies on infected Vero E6 cells fixed in acetone-methanol16,17.
    SARS-CoV-2
    suggested: None
    anti-IgG-,
    suggested: None
    anti-IgA-
    suggested: None
    anti-IgM-FITC-labelled
    suggested: None
    The Anti-SARS-CoV-2 ELISA (IgG) and Anti-SARS-CoV-2 ELISA (IgA) are based on the S1 domain of the spike protein of SARS-CoV-2 as antigen, including the immunologically relevant receptor binding domain (RBD), to detect anti-SARS-CoV-2 IgG and IgA antibodies, respectively.
    Anti-SARS-CoV-2 ELISA (IgG
    suggested: None
    Anti-SARS-CoV-2 ELISA (IgA
    suggested: None
    IgA
    suggested: None
    The Anti-SARS-CoV-2 QuantiVac ELISA (IgG) was used for quantitative detection of anti-SARS-CoV-2 IgG antibodies by means of a 6-point calibration curve.
    Anti-SARS-CoV-2 QuantiVac ELISA (IgG
    suggested: None
    anti-SARS-CoV-2 IgG
    suggested: None
    The Anti-SARS-CoV-2 NCP ELISA (IgG) and Anti-SARS-CoV-2 NCP ELISA (IgM) are based on a modified nucleocapsid protein (NCP) as antigen to detect anti-SARS-CoV-2 IgG and IgM antibodies, respectively.
    Anti-SARS-CoV-2 NCP ELISA (IgG
    suggested: None
    Anti-SARS-CoV-2 NCP ELISA (IgM
    suggested: None
    IgM
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Detection of anti-SARS-CoV-2 antibodies: The detection of the antibodies against SARS-CoV-2 (genus: Betacoronavirus, family: Coronaviridae) using IIFT was performed with anti-IgG-, anti-IgA- and anti-IgM-FITC-labelled secondary antibodies on infected Vero E6 cells fixed in acetone-methanol16,17.
    Vero E6
    suggested: None

    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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  3. Version published to 10.1101/2021.04.16.21255608v1 on medRxiv