Seroprevalence of Antibodies to SARS-CoV-2 in Healthcare Workers in Non-epidemic Region: A Hospital Report in Iwate Prefecture, Japan

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Abstract

Background

As of June 18, 2020, Iwate is the only one of 47 prefectures in Japan with no confirmed coronavirus disease 2019 (COVID-19) cases. S erological survey for COVID-19 antibodies is crucial in area with low prevalence as well as epidemic area when addressing health and social issues caused by COVID-19.

Methods

Serum samples from healthcare workers (n = 1,000, mean 40 ± 11 years) of Iwate Prefectural Central Hospital, Iwate, Japan were tested for the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Two laboratory-based quantitative tests (Abbott’s and Roche’s immunoassays) and one point-of-care (POC) qualitative test performed simultaneously. Sensitivity and specificity were 100%, 99.6% in Abbott’s immunoassay; 100%, 99.8% in Roche’s immunoassay; 97.8%, 94.6% in Alfa POC test, respectively.

Results

The laboratory-based quantitative tests showed positive in 4 of 1,000 samples (0.4%) (95% CI: 0.01 to 0.79): 4/1,000 (0.4%) (95% CI: 0.01 to 0.79) in Abbott; 0/1,000 (0%) in Roche. Positive samples were not detected for both Abbott’s and Roche’s immunoassays. The POC qualitative test showed positive in 33 of 1,000 samples (3.3%) (95% CI: 2.19 to 4.41). There were no samples with simultaneous positive reaction for two quantitative tests and a POC test.

Conclusions

Infected COVID-2 cases were not confirmed by a retrospective serological study in healthcare workers of our hospital. The POC qualitative tests with lower specificity have the potential for higher false positive reactions than the laboratory-based quantitative tests in areas with very low prevalence of COVID-19.

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  1. SciScore for 10.1101/2020.06.15.20132316: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Informed consent was obtained from all participants.
    IRB: The study protocol was approved by the ethics committee of the Iwate Prefectural Central Hospital (Approval Number. 343), and carried out according to the principles of the Declaration of Helsinki.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The laboratory-based quantitative tests were performed using Abbott ARCHITECT® SARS-CoV-2 IgG Assay (chemiluminescence microparticle immunoassay; sensitivity: 100%, specificity: 99.6%) (Abbott Laboratories, Abbott Park, IL);7 Roche Elecsys® Anti-SARS-CoV-2 RUO Assay (electro chemiluminescence immunoassay; sensitivity: 100%, specificity: 99.8%) (Roche Diagnostics, Basel, Switzerland).
    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: We detected the following sentences addressing limitations in the study:
    This study has several limitations. First, it was a survey from a single medical institution with a relatively small blood samples. Moreover, the participants in this study were limited to healthcare workers in our hospital, so younger or older people were not enrolled. Second, positive and negative control tests are significant for the full validation of COVID-19 antibodies and the assessment of non-specific binding. In this study, attempts to use the positive or negative control test have presented difficulties because of no identified infected cases and the stay-at-home order. Third, there is still a problem in reliability of antibody tests for COVID-19 and development of accurate tests should be needed. However, they are essential as an epidemiologic tool even in a given population with low prevalence to track progression towards herd immunity for a long time In conclusion, the positive rate of SARS-CoV-2 antibodies in healthcare workers of our hospital was 0%. Our results suggest the presence of no COVID-19 cases in Iwate Prefecture and the necessity of the antibody tests with high specificity in the areas with very low prevalence.

    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.

  2. SciScore for 10.1101/2020.06.15.20132316: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementInformed consent was obtained from all participants .Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibodies , COVID-19 , Iwate , SARS-CoV-2 , Seroprevalence Total word count: 1,871; 1 figures; 1 tables Abstract Methods Serum samples from healthcare workers ( n = 1,000 , mean 40 ± 11 years ) of Iwate Prefectural Central Hospital , Iwate , Japan were tested for the prevalence of the severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) antibodies .
    SARS-CoV-2
    suggested: None
    The POC qualitative tests with lower specificity have the potential for higher false positive reactions than the laboratory-based quantitative tests in areas with very low prevalence of COVID-19 . ( Abstract: 285 words ) Abbreviations and acronyms CMIA = chemiluminescence microparticle immunoassay COVID-19 = coronavirus disease 2019 ECLIA = electro chemiluminescence immunoassay Ig = immunoglobins POC = point-of-care RT-PCR = real-time reverse transcriptase polymerase chain reaction SARS-CoV-2 = acute respiratory syndrome coronavirus 2 Materials and methods Study design This was a retrospective study evaluating the prevalence of COVID-19 antibodies in healthcare workers in Iwate Prefecture Central Hospital using currently available immunoassays for detection of antibodies specific to the SARS-CoV-2 virus .
    RT-PCR
    suggested: (Amparo Estepa Lab University Miguel Hernandez; Spain Cat# om-BD1, AB_2716268)
    Presence of COVID-19 cases, which were defined as positive reaction to SARS-CoV-2 IgG antibodies using Abbott and Roche quantitative assays, was not confirmed.
    SARS-CoV-2 IgG
    suggested: None
    With flattening of epidemic curve as a result of the nation adhering to staying at home and social distancing, the focus has been shifted to widespread testing for COVID-19 antibodies from the RT-PCR test for diagnosis of SARS-CoV-2 infection.
    COVID-19
    suggested: None
    In Japan, the positive rate of SARS-CoV-2 specific IgG antibodies was 3.3% in 1,000 outpatients visited Kobe City Medical Center General Hospital, Kobe (11); 5.9% in 202 blood samples obtained from two community clinics in Tokyo (12).
    SARS-CoV-2 specific IgG
    suggested: None
    Software and Algorithms
    SentencesResources
    Two laboratory-based quantitative tests ( Abbott Architect® SARS-CoV-2 IgG and Roche Elecsys® Anti-SARS-CoV-2 assays ) and one point-of-care ( POC ) qualitative test ( Alfa Instant-view® plus COVID-19 Test ) were performed simultaneously .
    Abbott Architect®
    suggested: (Abbott ARCHITECT i1000sr System, SCR_018371)
    The laboratory-based quantitative tests were performed using Abbott ARCHITECT® SARS-CoV-2 IgG Assay ( chemiluminescence microparticle immunoassay; sensitivity: 100 % , specificity: 99.6 % ) ( Abbott Laboratories , Abbott Park , IL ) ( 7); Roche Elecsys®
    Abbott Laboratories
    suggested: None
    In this study, a serum sample showing positive for both Abbott and Roche quantitative assays was considered an infected COVID-19 case.
    Abbott
    suggested: (Abbott, SCR_010477)

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:

    • This study has several limitations.
    • First, it was a survey from a single medical institution with a relatively small blood samples.
    • Moreover, the participants in this study were limited to healthcare workers in our hospital, so younger or older people were not enrolled in this study.
    • Second, positive and negative control tests are significant for the full validation of COVID-19 antibodies and the assessment of non-specific binding.
    • In this study, attempts to use the positive or negative control test have presented difficulties because of no identified infected cases and the stay-at-home order.
    • Third, there is still a problem in reliability of antibody tests for COVID-19 and development of accurate tests should be needed.
    • However, they are essential as an epidemiologic tool even in a given population with low prevalence to track progression towards herd immunity for a long time In conclusion, the positive rate of SARS-CoV-2 antibodies in healthcare workers of our hospital was 0%.
    • Our results suggest the presence of no COVID-19 cases in Iwate Prefecture and the necessity of the antibody tests with high specificity in the areas with very low prevalence.


    Results from OddPub: We did not find a statement about open data. We also did not find a statement about open code. Researchers are encouraged to share open data when possible (see Nature blog).


    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 is not a substitute for expert review. SciScore checks for the presence and correctness of RRIDs (research resource identifiers) in the manuscript, and detects sentences that appear to be missing RRIDs. SciScore also checks to make sure that rigor criteria are addressed by authors. It does this by detecting sentences that discuss criteria such as blinding or power analysis. SciScore does not guarantee that the rigor criteria that it detects are appropriate for the particular study. Instead it assists authors, editors, and reviewers by drawing attention to sections of the manuscript that contain or should contain various rigor criteria and key resources. For details on the results shown here, including references cited, please follow this link.