Prospective observational study and serosurvey of SARS-CoV-2 infection in asymptomatic healthcare workers at a Canadian tertiary care center

  1. Victor H. Ferreira
  2. Andrzej Chruscinski
  3. Vathany Kulasingam
  4. Trevor J. Pugh
  5. Tamara Dus
  6. Brad Wouters
  7. Amit Oza
  8. Matthew Ierullo
  9. Terrance Ku
  10. Beata Majchrzak-Kita
  11. Sonika T. Humar
  12. Ilona Bahinskaya
  13. Natalia Pinzon
  14. Jianhua Zhang
  15. Lawrence E. Heisler
  16. Paul M. Krzyzanowski
  17. Bernard Lam
  18. Ilinca M. Lungu
  19. Dorin Manase
  20. Krista M. Pace
  21. Pouria Mashouri
  22. Michael Brudno
  23. Michael Garrels
  24. Tony Mazzulli
  25. Myron Cybulsky
  26. Atul Humar
  27. Deepali Kumar

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Abstract

Health care workers (HCWs) are at higher risk for SARS-CoV-2 infection and may play a role in transmitting the infection to vulnerable patients and members of the community. This is particularly worrisome in the context of asymptomatic infection. We performed a cross-sectional study looking at asymptomatic SARS-CoV-2 infection in HCWs. We screened asymptomatic HCWs for SARS-CoV-2 via PCR. Complementary viral genome sequencing was performed on positive swab specimens. A seroprevalence analysis was also performed using multiple assays. Asymptomatic health care worker cohorts had a combined swab positivity rate of 29/5776 (0.50%, 95%CI 0.32–0.75) relative to a comparative cohort of symptomatic HCWs, where 54/1597 (3.4%) tested positive for SARS-CoV-2 (ratio of symptomatic to asymptomatic 6.8:1). SARS-CoV-2 seroprevalence among 996 asymptomatic HCWs with no prior known exposure to SARS-CoV-2 was 1.4–3.4%, depending on assay. A novel in-house Coronavirus protein microarray showed differing SARS-CoV-2 protein reactivities and helped define likely true positives vs. suspected false positives. Our study demonstrates the utility of routine screening of asymptomatic HCWs, which may help to identify a significant proportion of infections.

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  1. Version published to 10.1371/journal.pone.0247258
  2. Version published to 10.1101/2020.07.21.20159053v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2020.07.21.20159053: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The study was approved by the institutional research ethics board.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serology testing: Serologic testing for anti-SARS-CoV-2 IgG antibody was performed on a subset of consenting individuals.
    anti-SARS-CoV-2 IgG
    suggested: None
    Serology was performed using two commercially available IgG assays, one that tests anti-nucleoprotein (NP) antibodies by CMIA (Abbott Diagnostics, Health Canada approved assay) and the other for anti-spike (S) antibodies (EuroImmun, Germany) followed by a further assessment using a custom in-house protein microarray platform.
    anti-nucleoprotein (NP
    suggested: None
    anti-spike (S)
    suggested: None
    To confirm antibody specificities a custom microarray was performed using 45 commercially available coronavirus recombinant proteins corresponding to SARS-CoV-2, SARS-CoV, MERS-CoV and community coronaviruses (CoV-NL63, -HKU1, - 229E and -OC43) (Sino Biological and ProSci) 6,7. [See Supplementary methods and Supplementary Table 1]
    -OC43
    suggested: None
    To detect the bound antibodies, a second incubation is carried out using an enzyme-labelled anti-human IgG and substrate catalyzing a colorimetric reaction.
    anti-human IgG
    suggested: None
    Antigen Microarray: The Coronavirus antigen microarray was generated using previously published protocols for generation of antigen microarrays to screen for autoantibodies in heart failure and transplantation 6,7. Human IgA, IgM, IgG and viral antigens were spotted in triplicate onto two-pad FAST nitrocellulose-coated slides (GVS North America, Sanford, ME, USA) using a Chipwriter Pro microarrayer (Virtek
    Human IgA , IgM , IgG
    suggested: None
    After washing, the slides were incubated for 45 minutes at 4°C with a pair of secondary antibodies consisting of Cy3-labeled goat anti-human IgG (Jackson ImmunoResearch, West Grove, PA, USA) and Alexa Fluor 647-labeled goat anti-human IgM (Jackson ImmunoResearch, West Grove, PA, USA).
    anti-human IgM
    suggested: None
    Software and Algorithms
    SentencesResources
    The Abbott SARS-CoV-2 IgG 16 assay is a chemiluminescent microparticle immunoassay (CMIA) run on the fully automated ARCHITECT instrument (Abbott Laboratories, Chicago, IL, USA).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Abbott Laboratories
    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

    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.

  4. Version published to 10.1101/2020.07.21.20159053v1 on medRxiv