Antibodies to SARS-CoV-2 and risk of past or future sick leave

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Abstract

The extent that antibodies to SARS-CoV-2 may protect against future virus-associated disease is unknown. We invited all employees (n = 15,300) at work at the Karolinska University Hospital, Stockholm, Sweden to participate in a study examining SARS-Cov-2 antibodies in relation to registered sick leave. For consenting 12,928 healthy hospital employees antibodies to SARS-CoV-2 could be determined and compared to participant sick leave records. Subjects with viral serum antibodies were not at excess risk for future sick leave (adjusted odds ratio (OR) controlling for age and sex: 0.85 [95% confidence interval (CI) (0.85 (0.43–1.68)]. By contrast, subjects with antibodies had an excess risk for sick leave in the weeks prior to testing [adjusted OR in multivariate analysis: 3.34 (2.98–3.74)]. Thus, presence of viral antibodies marks past disease and protection against excess risk of future disease. Knowledge of whether exposed subjects have had disease in the past or are at risk for future disease is essential for planning of control measures.

Trial registration: First registered on 02/06/20, ClinicalTrials.gov NCT04411576.

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  1. SciScore for 10.1101/2020.09.14.20194308: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: We enrolled 14,057 participants who all signed a written informed consent that also included permission to extract data from the employer’s administrative databases that contain data on sick leave.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisData analyses: With conventional statistical power and two-sided tests of significance, and assuming a cumulative proportion of sick leave among non-exposed persons of 30% and that 10% of the cohort might be exposed, at least 3800 subjects would need to be enrolled to be able to detect associations of 1.4 or greater, a level which was considered to be medically meaningful.
    Sex as a biological variableMost participants were between 30-59 years old and 79% were females (Supplementary Table 1).
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serum IgG bound to antigen coated beads was detected by F(ab’)2-Goat anti-Human IgG Fc Secondary Antibody, PEfluorescent anti-hIgG (Invitrogen, H10104.
    anti-Human IgG Fc Secondary Antibody, PEfluorescent anti-hIgG
    suggested: None
    H10104
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    The evaluation of different production hosts was based on degree of concordance in antibody reactivity of the alternative hosts with the virus proteins produced in the HEK cells.
    HEK
    suggested: CLS Cat# 300192/p777_HEK293, RRID:CVCL_0045)
    Consequently, antigen reactivity was measured towards three different virus protein-variants, (i) Spike trimers comprising the prefusion-stabilized spike glycoprotein ectodomain [7] expressed in HEK cells and purified using a C-terminal Strep II tag), (ii) Spike S1 domain, expressed in CHO cells and purified using C- terminal HPC4-tag, and (iii) Nucleocapsid protein, expressed in E.coli and purified using a C-terminal His-tag.
    CHO
    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:
    A limitation is that we were not able to study infections occurring more than six to seven weeks before enrollment, as community transmission of SARS-CoV-2 in the region started only about six to seven weeks before the study. Participants were not questioned about present or prior symptoms, but the hospital rules were clear that employees with symptoms should not be at work and we had, by design, decided to use only sick leave data to avoid possible recall bias. Hospital rules state that also employees working from home that develop COVID-19 symptoms must report this as sick leave. We conclude that antibody testing is a powerful tool for identification of subjects who have had prior virus exposure and are protected against future disease. Although it is commonly assumed that antibodies mark immunity, it is important that it has now been shown in a large cohort study that seropositive subjects have no excess risk for future sick leave. We would like to caution that there is a large number of serology tests currently on the market and the extent of their validation may vary. Also, none of these tests have been specifically validated for the indication proposed here (to separate exposed subjects who are protected from future disease from exposed subjects at risk to develop disease in the future). In summary, the present study has found that validated antibody testing may be helpful in SARS-CoV-2 screening strategies as antibody-positive subjects were found to have no excess risk...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04411576RecruitingCurrent and Past SARS-CoV-2 Infection and COVID-19 in Health…


    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

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