Serological Testing Reveals the Hidden COVID-19 Burden among Health Care Workers Experiencing a SARS-CoV-2 Nosocomial Outbreak

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Abstract

We describe the results of testing frontline health care workers, from a hospital in Japan that had experienced a COVID-19 outbreak, for SARS-CoV-2-specific antibodies. Antibody testing revealed that a surprising 42% of overlooked COVID-19 diagnoses occurred when case detection relied solely on PCR-based viral detection.

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  1. SciScore for 10.1101/2021.07.15.21260585: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Cohort and samples: A total 414 HCWs of St. Marianna University School of Medicine, Yokohama City Seibu Hospital, Kanagawa, Japan, who gave consent to participating in the study were recruited.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological testing: Two chemiluminescent immunoassays, the Abbott SARS-CoV-2 IgG and SARS-CoV-2 IgG II Quant (Abbott, Illinois, USA), designed to detect serum IgG antibodies targeting the nucleocapsid and the spike proteins of SARS-CoV-2, respectively, were performed in accordance with the manufacturer’s instructions.
    SARS-CoV-2 IgG
    suggested: None
    An orthogonal testing algorithm was adopted in order to idealize positive-predictivity and determine, with high specificity, the individuals who were truly sero-positive of SARS-CoV-2 specific antibodies (3).
    SARS-CoV-2 specific antibodies (3
    suggested: None
    In this algorithm the individuals who initially tested positive for anti-nucleocapsid antibodies were tested with a second test targeting the SARS-CoV-2 spike antigen.
    anti-nucleocapsid
    suggested: None
    SARS-CoV-2 spike antigen.
    suggested: None
    Software and Algorithms
    SentencesResources
    Serological testing: Two chemiluminescent immunoassays, the Abbott SARS-CoV-2 IgG and SARS-CoV-2 IgG II Quant (Abbott, Illinois, USA), designed to detect serum IgG antibodies targeting the nucleocapsid and the spike proteins of SARS-CoV-2, respectively, were performed in accordance with the manufacturer’s instructions.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Participants positive for both SARS-CoV-2 specific antibodies were finally confirmed of COVID-19 serological diagnosis by detecting neutralizing antibodies against SARS-CoV-2 using the Genscript SARS-CoV-2 sVNT (Genscript, Leiden, Netherlands), a competition ELISA-based surrogate virus neutralization assay.
    SARS-CoV-2
    suggested: (BioLegend Cat# 944703, RRID:AB_2890874)

    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:
    Against expectations, however, having been the sole first-tier diagnostic against this emerging infection, it is now increasingly recognized that NAT-based SARS-CoV-2 pathogen detection faces serious limitations. COVID-19 illness being primarily a lower respiratory tract infection, the probability of pathogen detection from upper respiratory tract specimens decrease rapidly and nearly halves within approximately two weeks from onset (7). Previous reports have suggested that a substantial fraction, as high as up to 54%, of COVID-19 patients may present with undetectable viral loads and show false-negative RT-PCR results (8–10). Our observation recapitulates such findings, by demonstrating the sensitivity of NAT to have remained as low as 61.7%. Missed diagnoses having occurred not only in the pauci-symptomatic and the asymptomatic populations but also in acutely ill cases of high suspicion, indefinite molecular testing results already have left behind a significant burden of those in need of a diagnosis. A well-defined diagnostic complementary to NAT is still in serious need. Since the host immune response lags behind viral invasion, the ability of antibody tests to detect an acute infection in its early phase is usually limited and considered inferior to NAT. However, in the case of COVID-19, NAT performance itself remains suboptimal and thus serological testing may well aid in early-phase case detection (11,12). While the present study targeted pre-exposed HCWs and was desig...

    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.

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


    About SciScore

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