Effectiveness of a fourth dose of covid-19 mRNA vaccine against the omicron variant among long term care residents in Ontario, Canada: test negative design study

  1. Ramandip Grewal
  2. Sophie A Kitchen
  3. Lena Nguyen
  4. Sarah A Buchan
  5. Sarah E Wilson
  6. Andrew P Costa
  7. Jeffrey C Kwong

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Objectives

To estimate the marginal effectiveness of a fourth versus third dose and the vaccine effectiveness of mRNA covid-19 vaccines BNT162b2 and mRNA-1273 against any infection, symptomatic infection, and severe outcomes (hospital admission or death) related to the omicron variant.

Design

Test negative design.

Setting

Long term care facilities in Ontario, Canada, 30 December 2021 to 27 April 2022.

Participants

After exclusions, 61 344 residents aged 60 years or older across 626 long term care facilities in Ontario, Canada who were tested for SARS-CoV-2 were included.

Main outcome measures

Laboratory confirmed omicron SARS-CoV-2 infection (any and symptomatic) by reverse transcription polymerase chain reaction (RT-PCR), and hospital admission or death. Multivariable logistic regression was used to estimate marginal effectiveness (four versus three doses) and vaccine effectiveness (two, three, or four doses versus no doses) while adjusting for personal characteristics, comorbidities, week of test, and previous positive SARS-CoV-2 test result more than 90 days previously.

Results

13 654 residents who tested positive for omicron SARS-CoV-2 infection and 205 862 test negative controls were included. The marginal effectiveness of a fourth dose (95% of vaccine recipients received mRNA-1273 as the fourth dose) seven days or more after vaccination versus a third dose received 84 or more days previously was 19% (95% confidence interval 12% to 26%) against infection, 31% (20% to 41%) against symptomatic infection, and 40% (24% to 52%) against severe outcomes. Vaccine effectiveness in vaccine recipients (compared with unvaccinated) increased with each additional dose, and for a fourth dose was 49% (95% confidence interval 43% to 54%) against infection, 69% (61% to 76%) against symptomatic infection, and 86% (81% to 90%) against severe outcomes.

Conclusions

The findings suggest that compared with a third dose of mRNA covid-19 vaccine, a fourth dose improved protection against infection, symptomatic infection, and severe outcomes among long term care residents during an omicron dominant period. A fourth vaccine dose was associated with strong protection against severe outcomes in vaccinated residents compared with unvaccinated residents, although the duration of protection remains unknown.

Article activity feed

  1. Version published to 10.1136/bmj-2022-071502
  2. Version published to 10.1101/2022.04.15.22273846v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2022.04.15.22273846: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    RandomizationFor controls, we randomly selected 1 negative test during the study period.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    We excluded Delta cases that were identified based on WGS or SGTF.
    WGS
    suggested: None
    23 All analyses were conducted using SAS Version 9.4 (SAS Institute Inc.
    SAS Institute
    suggested: (Statistical Analysis System, RRID:SCR_008567)

    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:
    This study has some limitations. First, our symptomatic cohort was limited to individuals who had symptoms recorded in OLIS and therefore may be incomplete. Second, Ontario laboratories discontinued routine SGTF screening of all positive samples on December 30, 2021, therefore there may be some misclassification of Delta cases as Omicron, potentially inflating VE. Nonetheless, it is unlikely this would significantly impact our estimates since the prevalence of Delta in Ontario was very low during our study period. Third, we classified outbreaks at the facility level since we did not have data on whether the outbreak was on a resident’s floor or if it was more contained, therefore we may have overestimated the impact of outbreaks at the person level. Finally, we did not have access to LTC staff vaccination records. Staff vaccination strongly influences SARS-CoV-2 transmission in LTC facilities.32 At the time of this study, all LTC staff in Ontario were required to be vaccinated with 2 doses,33 but 2-dose VE against Omicron infection is low.13,27,34 Although a mandate for required third doses was also implemented, staff had until March 14, 2022 (past our study period) to comply (though this may not have been enforced since the province shifted from a provincial LTC vaccination mandate to supporting employer-led policies on the same day).33

    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.

    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.

  4. Version published to 10.1101/2022.04.15.22273846v1 on medRxiv