COVID-19 serological survey using micro blood sampling

  1. Melissa M. Matthews
  2. Tae Gyun Kim
  3. Satoshi Shibata
  4. Noriko Shibata
  5. Christian Butcher
  6. Jaekyung Hyun
  7. Keon Young Kim
  8. Theodore Robb
  9. Siang Sheng Jheng
  10. Masashi Narita
  11. Tomoari Mori
  12. Mary Collins
  13. Matthias Wolf

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Abstract

During August 2020, we carried out a serological survey among students and employees at the Okinawa Institute of Science and Technology Graduate University (OIST), Japan, testing for the presence of antibodies against SARS-CoV-2, the causative agent of COVID-19. We used a FDA-authorized 2-step ELISA protocol in combination with at-home self-collection of blood samples using a custom low-cost finger prick-based capillary blood collection kit. Although our survey did not find any COVID-19 seropositive individuals among the OIST cohort, it reliably detected all positive control samples obtained from a local hospital and excluded all negatives controls. We found that high serum antibody titers can persist for more than 9 months post infection. Among our controls, we found strong cross-reactivity of antibodies in samples from a serum pool from two MERS patients in the anti-SARS-CoV-2-S ELISA. Here we show that a centralized ELISA in combination with patient-based capillary blood collection using as little as one drop of blood can reliably assess the seroprevalence among communities. Anonymous sample tracking and an integrated website created a stream-lined procedure. Major parts of the workflow were automated on a liquid handler, demonstrating scalability. We anticipate this concept to serve as a prototype for reliable serological testing among larger populations.

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  1. Version published to 10.1038/s41598-021-88850-z
  2. ScreenIT

    SciScore for 10.1101/2020.10.09.20209858: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationThe sample IDs were composed of six characters generated randomly from the set of alphanumeric characters (a-zA-Z0-9) (random string generator https://www.random.org/strings/), excluding letters O, I, l, Z, Q and numbers 0, 1, 2, 9 to minimize human read errors.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableNegative controls taken from patients prior to November 2019 were obtained from Naha Municipal Hospital from intravenous blood, and from a commercial serum pool (Human Serum from human male AB plasma, Sigma Aldrich H4522-100ML

    Table 2: Resources

    Antibodies
    SentencesResources
    Protein purity was verified by SDS-PAGE and confirmed by Western blot with MonoRab™ Anti-His Tag (C-term) Antibody (Nr. 25B6E11, GenScript,
    Anti-His Tag (C-term
    suggested: None
    Therefore, another threshold, calculated as 4-times the average blank, which has been demonstrated to be valid for identifying anti-SARS-CoV-2 antibody-positive samples was used instead (6).
    anti-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Contrast transfer function (CTF) estimation, particle picking and 2D classification were performed with RELION 3.1 (5)
    RELION
    suggested: (RELION, RRID:SCR_016274)
    Sequence alignments: The full-length sequences of SARS-CoV, MERS-CoV S protein (UniProt ID: P59594 and K9N5Q8, respectively) were aligned pairwise using ClustalW2 (8), against the SΔcs sequence (3)
    ClustalW2
    suggested: (ClustalW2, RRID:SCR_002909)
    Figure preparation and digital processing: Images of protein gel and Western blot in Figure 1A were acquired by smartphone camera, cropped and adjusted for intensity level in Adobe Photoshop 2020 (Adobe Inc, USA)
    Adobe Photoshop
    suggested: (Adobe Photoshop, RRID:SCR_014199)
    Graphs in Figures 2-5 were plotted with GraphPad Prism v8.4.3 (
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    (GraphPad Software, USA), using the scatter plot function (Figure 2).
    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: 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 10.1101/2020.10.09.20209858v2 on medRxiv
  4. Version published to 10.1101/2020.10.09.20209858v1 on medRxiv