A Hemagglutination-Based Semiquantitative Test for Point-of-Care Determination of SARS-CoV-2 Antibody Levels

  1. Robert L. Kruse
  2. Yuting Huang
  3. Alyssa Lee
  4. Xianming Zhu
  5. Ruchee Shrestha
  6. Oliver Laeyendecker
  7. Kirsten Littlefield
  8. Andy Pekosz
  9. Evan M. Bloch
  10. Aaron A. R. Tobian
  11. Zack Z. Wang

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Abstract

Serologic point-of-care tests to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are an important tool in the COVID-19 pandemic. The majority of current point-of-care antibody tests developed for SARS-CoV-2 rely on lateral flow assays, but these do not offer quantitative information.

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  1. Version published to 10.1128/jcm.01186-21
  2. ScreenIT

    SciScore for 10.1101/2021.05.01.21256452: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Human subjects: The parent studies of the collected patient samples were approved by The Johns Hopkins University School of Medicine Institutional Review Board (IRB00247886, IRB00250798, and IRB00091667).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All statistical analyses were performed using GraphPad Prism 9.0.0 for Mac, GraphPad Software, San Diego, California USA, www.graphpad.com.
    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: We detected the following sentences addressing limitations in the study:
    This study had limitations. The specificity in our assay (95.5%) was lower than the 99% reported using the same fusion protein previously, and also lower than the aforementioned RBD-based ELISA tests (specificity of 100%17 and 99.3%18). The reason for lower specificity is uncertain but is likely multi-factorial. The manufacturing of a dried protein on the card may yield fusion protein clumping not seen in protein in solution in the prior report.11 Another consideration is that the prior study11 tested healthy donors as a control, while all negative control samples in our assay were patients with acute respiratory illness, including a subset with active seasonal coronavirus infection. While the sequence identity is only ∼20% shared between the viruses24 it’s possible that even weakly cross-reactive antibodies could achieve binding at high concentrations. Cross-reactivity has been suggested as a reason for significantly worse specificity of SARS-CoV-2 antibody ELISA assays (90-94% against spike protein)25 and CoronaChek lateral flow (96.5%)13 in African populations. An important distinction is that ELISA cutoff values for optical density can be optimized for maximal specificity,26 whereas the hemagglutination test relies on visual interpretation with more limited nuance. Soluble ACE2 and white blood cells expressing ACE2 may also contribute to false positives via binding to RBD fusion protein. Of note, specificity could be increased up to 98.5% if assay time was reduced to the ...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2021.05.01.21256452v1 on medRxiv