Prevalence and determinants of serum antibodies to SARS-CoV-2 in the general population of the Gardena Valley

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Abstract

Background

Community-based studies are essential to quantify the spread of SARS-CoV-2 infection and for unbiased characterization of its determinants and outcomes. We conducted a cross-sectional study in the Gardena valley, a major Alpine touristic destination which was struck in the expansion phase of the COVID-19 pandemic over the winter 2020.

Methods

We surveyed 2244 representative study participants who underwent swab and serum antibody tests. We made multiple comparisons among the Abbott and Diasorin bioassays and serum neutralization titers. Seroprevalence accounted for the stratified design, non-response and test accuracy. Determinants and symptoms predictive of infection were analyzed by weighted multiple logistic regression.

Results

SARS-CoV-2 seroprevalence was 26.9% (95% confidence interval: 25.2%, 28.6%) by June 2020. The serum antibody bioassays had modest agreement with each other. Receiver operating characteristic curve analysis on the serum neutralizing capacity showed better performance of the Abbott test at lower than the canonical threshold. Socio-demographic characteristics showed no clear evidence of association with seropositivity, which was instead associated with place of residence and economic activity. Loss of taste or smell, fever, difficulty in breathing, pain in the limbs, and weakness were the most predictive symptoms of positive antibody test results. Fever and weakness associations were age-dependent.

Conclusion

The Gardena valley had one of the highest SARS-CoV-2 infection prevalence in Europe. The age-dependent risk associated with COVID-19 related symptoms implies targeted strategies for screening and prophylaxis planning.

Article activity feed

  1. SciScore for 10.1101/2021.03.19.21253883: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The Ethics Committee of the Healthcare System of the Autonomous Province of Bolzano/Bozen authorized the study.
    Consent: Each participant gave written informed consent.
    RandomizationIn the latter approach, we randomly split the sample set into 80% and 20% training and test sets, respectively, corresponding to 239 and 60 observations, repeatedly 5000 times.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variable(StataCorp LLC) and were restricted to 6+ year old individuals and non-pregnant women using the ‘subpop’ option.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibody response was tested using the Abbott SARS-CoV-2 IgG assay (Sligo, Ireland), designed to detect immunoglobulin class G (IgG) antibodies to the nucleocapsid (N) protein of SARS-CoV-2.
    immunoglobulin class G (IgG
    suggested: None
    Cells were fixed for 5 minutes with 96% ethanol and subsequently stained using the serum from a SARS-CoV-2 recovered patient and a horse radish peroxidase-conjugated anti-human secondary antibody (Dianova).
    anti-human secondary antibody ( Dianova) .
    suggested: None
    Prevalence of serum antibodies to SARS-CoV-2 (seroprevalence) in the overall sample was also estimated using the Rogan and Gladen formula to account for the serological test inaccuracy.[12] Statistical analyses were run with the ‘svyset’ suite of commands in Stata software v16.1
    SARS-CoV-2
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Serum/virus mixes were incubated for 1 hour at 37°C and subsequently transferred to 96-wells containing 90% confluent Vero cells expressing TMPRSS2 seeded one day before.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    Software and Algorithms
    SentencesResources
    Participants were selected with known extraction probability from the municipality registries, excluding nursing homes, using the ‘surveyselect’ program in SAS v9.2.
    SAS
    suggested: (SASqPCR, RRID:SCR_003056)
    Antibody response was tested using the Abbott SARS-CoV-2 IgG assay (Sligo, Ireland), designed to detect immunoglobulin class G (IgG) antibodies to the nucleocapsid (N) protein of SARS-CoV-2.
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Within 6 hours from collection, assessment of IgG antibodies to SARS-CoV-2 was performed using the Abbott Architect i2000SR system, which implements a two-step chemiluminescent microparticle immunoassay, at Laboratory of Clinical Pathology of the Bressanone/Brixen Hospital,
    Abbott Architect
    suggested: (Abbott ARCHITECT i1000sr System, RRID:SCR_019328)
    Prevalence of serum antibodies to SARS-CoV-2 (seroprevalence) in the overall sample was also estimated using the Rogan and Gladen formula to account for the serological test inaccuracy.[12] Statistical analyses were run with the ‘svyset’ suite of commands in Stata software v16.1
    Stata
    suggested: (Stata, RRID:SCR_012763)
    (StataCorp LLC) and were restricted to 6+ year old individuals and non-pregnant women using the ‘subpop’ option.
    StataCorp
    suggested: (Stata, RRID:SCR_012763)

    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:
    Our study also comes with several limitations. First, antibody testing methods have imperfect accuracy. We corrected seroprevalence analyses for the test sensitivity and specificity to overcome this limitation. Second, certain social groups such as, for instance, non-Italian residents might have been underrepresented. While we corrected all analyses for differential participation in known groups, we could not prevent participation bias of unknown sources such as, for example, COVID-19-related mortality and possible self-selection of severely ill individuals. A third limitation is the questionnaire self-administration: while this was the only way to collect essential information, response bias might affect some analyses. For instance, symptom onset estimation might not be totally accurate as the question was not specific to each possible symptom. Similarly, we cannot exclude that symptoms were due to competitive seasonal diseases such as flu or allergies. A nearly 30% seroprevalence is a large figure compared to other studies.[4] This estimate aligns with those of nearby Italian regions.[13, 14] However, the Manaus case shows that it might still result in a non-negligible underestimation of the true infection rate.[15] Several reasons suggest that our estimate should be considered as a lower bound of the real seroprevalence. First, the survey had missed people who already died. In 2020, the raw excess all-cause mortality rate over the previous five years was between +32.8% and...

    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.