Low SARS-CoV-2 sero-prevalence based on anonymized residual sero-survey before and after first wave measures in British Columbia, Canada, March-May 2020

  1. Danuta M Skowronski
  2. Inna Sekirov
  3. Suzana Sabaiduc
  4. Macy Zou
  5. Muhammad Morshed
  6. David Lawrence
  7. Kate Smolina
  8. May A Ahmed
  9. Eleni Galanis
  10. Mieke N Fraser
  11. Mayank Singal
  12. Monika Naus
  13. David M Patrick
  14. Samantha E Kaweski
  15. Christopher Mill
  16. Romina C Reyes
  17. Michael T Kelly
  18. Paul N Levett
  19. Martin Petric
  20. Bonnie Henry
  21. Mel Krajden

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Abstract

Background

The province of British Columbia (BC) has been recognized for successful SARS-CoV-2 control, with surveillance data showing amongst the lowest case and death rates in Canada. We estimate sero-prevalence for two periods flanking the start (March) and end (May) of first-wave mitigation measures in BC.

Methods

Serial cross-sectional sampling was conducted using anonymized residual sera obtained from an outpatient laboratory network, including children and adults in the Greater Vancouver Area (population ∼3 million) where community attack rates were expected to be highest. Screening used two chemiluminescent immuno-assays for spike (S1) and nucleocapsid antibodies. Samples sero-positive on either screening assay were assessed by a third assay targeting the S1 receptor binding domain plus a neutralization assay. Age-standardized sero-prevalence estimates were based on dual-assay positivity. The May sero-prevalence estimate was extrapolated to the source population to assess surveillance under-ascertainment, quantified as the ratio of estimated infections versus reported cases.

Results

Serum collection dates spanned March 5-13 and May 15-27, 2020. In March, two of 869 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.28% (95%CI=0.03-0.95). Neither specimen had detectable neutralizing antibodies. In May, four of 885 specimens were dual-assay positive, with age-standardized sero-prevalence of 0.55% (95%CI=0.15-1.37%). All four specimens had detectable neutralizing antibodies. We estimate ∼8 times more infections than reported cases.

Conclusions

Less than 1% of British Columbians had been infected with SARS-CoV-2 when first-wave mitigation measures were relaxed in May 2020. Our findings indicate successful suppression of community transmission in BC, but also substantial residual susceptibility. Further sero-survey snapshots are planned as the pandemic unfolds.

Key points

Cross-sectional sampling of anonymized residual sera at the start and end of first-wave mitigation measures in British Columbia, Canada shows SARS-CoV-2 sero-prevalence below 1% throughout the winter-spring 2020. Findings indicate successful suppression of community transmission but also substantial residual susceptibility.

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  1. ScreenIT

    SciScore for 10.1101/2020.07.13.20153148: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The sero-survey was authorized by the Provincial Health Officer and approved by the Clinical Research Ethics Board of the University of British Columbia (H20-00653)
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableConsistent with the WHO Unity protocol [19], sera were obtained from 100 patients within each of the following age groups (equally male and female): <5, 5-9, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, ≥ 80 years.

    Table 2: Resources

    No key resources detected.

    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:
    There are limitations to this analysis. Delay in generating an antibody response and uncertainty in the duration of antibody persistence, particularly among mild or asymptomatic cases and for neutralizing titres [27,29-31], may lead to under-estimation of sero-prevalence. Specimens were anonymized without accompanying clinical detail such as symptom history or testing indication. We restricted to outpatient specimens and show both snapshots to be generally representative of the source population for age and sex. However, residual clinical specimens are more likely to come from people with underlying comorbidity and may differ from the rest of the population in their exposure risk, immune response and healthcare seeking. We assume sampling within the Lower Mainland provides an upper range of community sero-prevalence for BC; however, this does not preclude discrete pockets experiencing higher attack rates. Given manifold uncertainties, our ratio of estimated infections versus reported cases is an imprecise approximation, meant only to gauge the likely order of magnitude of surveillance under-ascertainment. In addition to other considerations, reported surveillance tallies may include cases that were imported or accrued within care facilities or other settings under-represented in our community-based sero-sampling. Finally, with such low sero-prevalence, including just one infected child in 375 pediatric sera tested, we were limited in our ability to conduct subset comparisons....

    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. ScreenIT

    SciScore for 10.1101/2020.07.13.20153148: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementThe sero-survey was authorized by the Provincial Health Officer and approved by the Clinical Research Ethics Board of the University of British Columbia (H20-00653).Randomizationnot detected.Blindingnot detected.Power Analysisnot detected.Sex as a biological variableConsistent with the WHO Unity protocol [19], sera were obtained from 100 patients within each of the following age groups (equally male and female): <5, 5-9, 10-19, 20-29, 30-39, 40-49, 50-59, 60-69, 70-79, ≥ 80 years.Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detection of total antibody (IgA, IgG and IgM) to recombinant spike (S1) protein using the Vitros XT 7600 analyzer
    IgA , IgG
    suggested: None
    Public Health England reports overall sensitivity of 85% (95% confidence interval (CI)=76.5-91.4) for this assay, 91.8% (95%CI=83.8-96.6) at ≥14 days and 93.5% (95%CI=85.5-97.9) at ≥21 days after symptom onset, with specificity of 99.5% (95%CI=98.2-99.9) [22]. 2. Detection of IgG antibody to nucleocapsid using the ARCHITECT i2000SR analyzer (Abbott Laboratories, Diagnostic Division, Abbott Park, Illinois) [21].
    CI=98.2-99.9 ) [ 22] . 2 . Detection of IgG
    suggested: None
    Detection of total (IgG, IgM) antibodies to the S1 receptor-binding domain (S1-RBD) by the ADVIA Centaur XPT system (Siemens Healthineers, Erlangen, Germany) [21].
    total ( IgG
    suggested: None
          <div style="margin-bottom:8px">
        <div><b>IgM </b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">In fact, just two of 869 March specimens were sero-positive to both S1 and S1-RBD, but none were sero-positive on both S1 and nucleocapsid screening assays and none had detectable neutralizing antibodies.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>S1-RBD</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Furthermore, all sera that were positive for S1-RBD were also positive for S1 antibodies; and all sera that were positive for S1 and that had a neutralizing antibody response were also nucleocapsid sero-positive.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>S1</b></div>
        <div>suggested: None</div>
      </div>
    
      <div style="margin-bottom:8px">
        <div><b>antibodies</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Experimental Models: Cell Lines</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Each serum specimen was heat inactivated at 56°C for 30min and duplicate serial 2-fold dilutions from 1:8 to 1:4096 were each incubated with 100 TCID50 of SARS-CoV-2 for 2h, then added to monolayers of Vero-E6 cells.</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Vero-E6</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr><tr><td style="min-width:100px;text-align:center; padding-top:4px;" colspan="2"><b>Software and Algorithms</b></td></tr><tr><td style="min-width:100px;text=align:center"><i>Sentences</i></td><td style="min-width:100px;text-align:center"><i>Resources</i></td></tr><tr><td style="min-width:100px;vertical-align:top;border-bottom:1px solid lightgray">Public Health England reports overall sensitivity of 85% (95% confidence interval (CI)=76.5-91.4) for this assay, 91.8% (95%CI=83.8-96.6) at ≥14 days and 93.5% (95%CI=85.5-97.9) at ≥21 days after symptom onset, with specificity of 99.5% (95%CI=98.2-99.9) [22]. 2. Detection of IgG antibody to nucleocapsid using the ARCHITECT i2000SR analyzer (Abbott Laboratories, Diagnostic Division, Abbott Park, Illinois) [21].</td><td style="min-width:100px;border-bottom:1px solid lightgray">
      <div style="margin-bottom:8px">
        <div><b>Abbott Laboratories</b></div>
        <div>suggested: None</div>
      </div>
    </td></tr></table>

    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.

  3. Version published to 10.1101/2020.07.13.20153148v1 on medRxiv