Safety and Efficacy of Preventative COVID Vaccines: The StopCoV Study

  1. Sharon Walmsley
  2. Leah Szadkowski
  3. Bradly Wouters
  4. Rosemarie Clarke
  5. Karen Colwill
  6. Paula Rochon
  7. Michael Brudno
  8. Rizani Ravindran
  9. Janet Raboud
  10. Allison McGeer
  11. Amit Oza
  12. Christopher Graham
  13. Amanda Silva
  14. Dorin Manase
  15. Laura Parente
  16. Jacqueline Simpson
  17. Roaya Monica Dayam
  18. Adrian Pasculescu
  19. Anne-Claude Gingras

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Abstract

Background

To partially immunize more persons against COVID-19 during a time of limited vaccine availability, Canadian public health officials recommended extending the vaccine dose interval and brand mixing. Impact on the antibody response among the older ambulatory population was unclear.

Methods

Decentralized prospective cohort study with self-report of adverse events and collection of dried blood spots. Data is presented for 1193 (93%) of the 911 older (aged >70 years) and 375 younger (30-50 years) recruits.

Findings

Local and systemic reactivity rates were high but short-lived, particularly in the younger cohort and with mRNA-1273 vaccine. After a single COVID-19 vaccine, 84% younger but only 46% older participants had positive IgG antibodies to both spike protein and receptor binding domain (RBD) antigens, increasing to 100/98% with the second dose respectively. In multivariable linear regression model, lower normalized IgG RBD antibody ratios two weeks after the second dose were statistically associated with older age, male gender, cancer diagnosis, lower body weight, BNT162b2 relative to mRNA-1273 and longer dose intervals. Antibody ratios in both cohorts declined 12 weeks post second vaccine dose.

Interpretation

We report success of a decentralized serology study. Antibody responses were higher in the younger than older cohort and were greater for those with at least one mRNA-1273 dose. The immunity threshold is unknown but correlations between binding and neutralizing antibodies are strongly positive. Trends with time and at breakthrough infection will inform vaccine booster strategies.

Funding

Supported by the Public Health Agency of Canada and the University Health Network Foundation.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2022.02.09.22270734: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: The study and electronic consent process were approved by the University Health Network (UHN) Ethics Review Committee.
    IRB: The study and electronic consent process were approved by the University Health Network (UHN) Ethics Review Committee.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    We selected to profile total IgG antibodies to the indicated antigens since our results and others [11] show a strong correlation especially between anti-RBD IgG levels and neutralization titers, enabling us to infer neutralization changes across groups.
    total IgG
    suggested: None
    Calibration of these assays to WHO standard was previously described. [12] Data management and Statistical Analysis: Sample Size Considerations: A sample size of 768 older and 192 younger participants was planned to enable detection of differences in normalized ratios of anti-spike and anti-RBD IgG antibodies of ·092 and ·124 at two weeks post second vaccination, with 80% power and a significance level of ·05, assuming SDs of ·406 and ·55 respectively[11].
    anti-RBD IgG
    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:
    It may be necessary to have other strategies to overcome possible age-related limitations to COVID-vaccination such as the use of adjuvents, increased amounts or multiple doses, or more frequent boosters. In our study the vaccines were safe and well tolerated. Although 95% of participants reported at least one adverse event, they tended to be mild and short lived. Adverse events were reported more commonly in our younger cohort and those receiving mRNA-1273. Our rates appeared to be higher than that previously reported [26-28], which may reflect real time symptom recording or the misinterpretation of symptoms related to underlying disease. However, by seven days after the second dose few participants reported residual symptoms. Our unique and nimble study included electronic consent, questionnaires, symptom diaries and serial self-collected specimens. Our decentralized protocol and recruitment strategy enabled province-wide enrollment, including smaller communities without access to hospital-based research centers. The cohort is less diverse than planned reflecting the need for English and grasp of web-based technology. Additional strengths include the cohort size and retention and our ability to quickly adapt to changing vaccine dose and interval recommendations. Other population-based serology studies evaluating vaccine responses through DBS[29, 30] have small population sizes, infrequent testing and younger individuals. Returning individual and group results through the pl...

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

    IdentifierStatusTitle
    NCT05208983Active, not recruitingSafeTy and Efficacy of Preventative CoVID Vaccines

    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.
    • Thank you for including a protocol registration statement.

    Results from scite Reference Check: We found no unreliable references.

    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. Version published to 10.1101/2022.02.09.22270734 on medRxiv