Abstract

Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.

Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.

Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.

Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.

Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.

Data availability

Ab-C data will be made available publicly through the COVID-19 Immunity Task Force (CITF) Databank. To access the data, please create an account on the CITF Databank portal and submit an application to use the data. Your application will be reviewed by the CITF Databank team. The data access procedure is described in detail at https://www.covid19immunitytaskforce.ca/wp-content/uploads/2022/11/data-access-diagram-en.pdf. This process is free of charge.Analytical code will be available on request in accordance with the Ab-C study's data governance plan. Please email the corresponding author, Dr. Jha at prabhat.jha@utoronto.ca to request the code. The CITF data team harmonizes data from multiple studies funded by CITF, including the Ab-C study. As a result, variable names and labels may change after the harmonization. To minimize confusion when using the code, it's best to have some contact with us when using the harmonized data.

The following data sets were generated

Article and author information

Author details

  1. Patrick E Brown

    Centre for Global Health Research, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  2. Sze Hang Fu

    Centre for Global Health Research, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  3. Leslie Newcombe

    Centre for Global Health Research, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  4. Xuyang Tang

    Centre for Global Health Research, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  5. Nico Nagelkerke

    Centre for Global Health Research, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  6. H Chaim Birnboim

    Centre for Global Health Research, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  7. Aiyush Bansal

    Centre for Global Health Research, University of Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  8. Karen Colwill

    Sinai Health, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
    Competing interests
    No competing interests declared.
  9. Geneviève Mailhot

    Sinai Health, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
    Competing interests
    No competing interests declared.
  10. Melanie Delgado-Brand

    Sinai Health, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
    Competing interests
    No competing interests declared.
  11. Tulunay Tursun

    Sinai Health, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
    Competing interests
    No competing interests declared.
  12. Freda Qi

    Sinai Health, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
    Competing interests
    No competing interests declared.
  13. Anne-Claude Gingras

    Sinai Health, Lunenfeld-Tanenbaum Research Institute, Toronto, Canada
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6090-4437
  14. Arthur S Slutsky

    Unity Health Toronto, Toronto, Canada
    Competing interests
    Arthur S Slutsky, Has received consulting fees from Apeiron Biologics, Cellenkos, Diffusion Pharmaceuticals, and GlaxoSmithKline outside the submitted work..
  15. Maria D Pasic

    Unity Health Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  16. Jeffrey Companion

    Unity Health Toronto, Toronto, Canada
    Competing interests
    No competing interests declared.
  17. Isaac I Bogoch

    General Internal Medicine and Infectious Diseases, Toronto General Hospital, Toronto, Canada
    Competing interests
    Isaac I Bogoch, Has served as a consultant for BlueDot and the National Hockey League Players' Association outside the submitted work..
  18. Ed Morawski

    Angus Reid Institute, Vancouver, Canada
    Competing interests
    No competing interests declared.
  19. Teresa Lam

    Angus Reid Institute, Vancouver, Canada
    Competing interests
    No competing interests declared.
  20. Angus Reid

    Angus Reid Institute, Vancouver, Canada
    Competing interests
    No competing interests declared.
  21. Prabhat Jha

    Centre for Global Health Research, University of Toronto, Toronto, Canada
    For correspondence
    Prabhat.jha@utoronto.ca
    Competing interests
    Prabhat Jha, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7067-8341
  22. Ab-C Study Collaborators

Funding

COVID-19 Immunity Task Force (2021-HQ-000139)

  • Anne-Claude Gingras
  • Prabhat Jha

Canadian Institutes of Health Research (EG2-179433)

  • Prabhat Jha

Pfizer Global Medical Grants (61608943)

  • Prabhat Jha

St. Michael's Hospital Foundation

  • Prabhat Jha

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Eduardo L Franco, McGill University, Canada

Ethics

Human subjects: The Ab-C study was approved by the Unity Health Toronto Research Ethics Board (REB # 20-107 and 21-213). All participants provided informed consent to be included in the study.

Version history

  1. Received: October 23, 2023
  2. Accepted: June 20, 2024
  3. Accepted Manuscript published: June 25, 2024 (version 1)

Copyright

© 2024, Brown et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Patrick E Brown
  2. Sze Hang Fu
  3. Leslie Newcombe
  4. Xuyang Tang
  5. Nico Nagelkerke
  6. H Chaim Birnboim
  7. Aiyush Bansal
  8. Karen Colwill
  9. Geneviève Mailhot
  10. Melanie Delgado-Brand
  11. Tulunay Tursun
  12. Freda Qi
  13. Anne-Claude Gingras
  14. Arthur S Slutsky
  15. Maria D Pasic
  16. Jeffrey Companion
  17. Isaac I Bogoch
  18. Ed Morawski
  19. Teresa Lam
  20. Angus Reid
  21. Prabhat Jha
  22. Ab-C Study Collaborators
(2024)
Hybrid immunity from SARS-CoV-2 infection and vaccination in Canadian adults: cohort study
eLife 13:e89961.
https://doi.org/10.7554/eLife.89961

Share this article

https://doi.org/10.7554/eLife.89961

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