A longitudinal comparison of spike and nucleocapsid SARS-CoV-2 antibody responses in a tertiary hospital’s laboratory workers with validation of DBS specimen analysis

  1. I Murrell
  2. D Forde
  3. L Tyson
  4. L Chichester
  5. A Garratt
  6. O Vineall
  7. N Palmer
  8. R Jones
  9. C Moore

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Abstract

There is a requirement for easily accessible, high throughput serological testing as part of the SARS-CoV-2 pandemic response. Whilst of limited diagnostic use in an acute individual setting, its use on a population level is key to informing a coherent public health response. As experience of commercial assays increases, so too does knowledge of their precision and limitations. Here we present our experience of these systems thus far. We perform a spot sero-prevalence study amongst staff in a tertiary hospital’s clinical microbiology laboratory, before undertaking validation of DBS serological testing as an alternate specimen for analysis. Finally, we characterise the spike and nucleocapsid antibody response over 160 days post a positive PCR test in nine non-hospitalised staff members.

Amongst a cohort of 195 staff, 17 tested positive for SARS-CoV-2 antibodies (8.7%). Self-reporting of SARS-CoV2 infection (P=<0.0001) and testing of a household contact (P = 0.027) were significant variables amongst the positive and negative sub-groups. Testing of 28 matched serum and DBS samples demonstrated 96% accuracy between the sample types. A differential rate of decline of SARS-CoV-2 antibodies against nucleocapsid or spike protein was observed. At 4 months post a positive PCR test 7/9 (78%) individuals had detectable antibodies against spike protein, but only 2/9 (22%) had detectable antibodies against nucleocapsid protein. This study reveals a broad agreement amongst commercial platforms tested and suggests the use of DBS as an alternate specimen option to enable widespread population testing for SARS-CoV-2 antibodies. These results suggest potential limitations of these platforms in estimating historical infection. By setting this temporal point of reference for this cohort of non-patient facing laboratory staff, future exposure risks and mitigation strategies can be evaluated more fully.

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  1. ScreenIT

    SciScore for 10.1101/2020.10.29.20219931: (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.

    Table 2: Resources

    Antibodies
    SentencesResources
    Three were performed on random access high-throughput platforms; the Anti-SARS-CoV-2 total antibody assay (Ortho Clinical Diagnostics) and the Anti-SARS-CoV-2 IgG assay (Ortho Clinical Diagnostics) which both target the spike protein were performed on the Vitros 3600 and the Abbott SARS-CoV-2 IgG assay (Abbott) which targets the nucleocapsid protein which was performed on the Abbott Architect.
    Anti-SARS-CoV-2
    suggested: None
    Anti-SARS-CoV-2 IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Three were performed on random access high-throughput platforms; the Anti-SARS-CoV-2 total antibody assay (Ortho Clinical Diagnostics) and the Anti-SARS-CoV-2 IgG assay (Ortho Clinical Diagnostics) which both target the spike protein were performed on the Vitros 3600 and the Abbott SARS-CoV-2 IgG assay (Abbott) which targets the nucleocapsid protein which was performed on the Abbott Architect.
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    The antibody response of both nucleocapsid and spike protein was evaluated by using the SARS-CoV-2 IgG assay by Abbott and the SARS-CoV-2 IgG ELISA by Euroimmun respectively.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Statistical analysis was performed using Prism V7 where a P value of <0.05 is considered significant.
    Prism
    suggested: (PRISM, RRID:SCR_005375)

    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:
    Mass serological testing could be facilitated by DBS sampling but we must be mindful of their limitations due to antibody kinetics (Thevis et al., 2020).

    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 10.1101/2020.10.29.20219931v1 on medRxiv