Estimated Effectiveness of COVID-19 Vaccines Against Omicron or Delta Symptomatic Infection and Severe Outcomes

  1. Sarah A. Buchan
  2. Hannah Chung
  3. Kevin A. Brown
  4. Peter C. Austin
  5. Deshayne B. Fell
  6. Jonathan B. Gubbay
  7. Sharifa Nasreen
  8. Kevin L. Schwartz
  9. Maria E. Sundaram
  10. Mina Tadrous
  11. Kumanan Wilson
  12. Sarah E. Wilson
  13. Jeffrey C. Kwong

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Abstract

The incidence of SARS-CoV-2 infection, including among individuals who have received 2 doses of COVID-19 vaccine, increased substantially following the emergence of the Omicron variant in Ontario, Canada. Understanding the estimated effectiveness of 2 or 3 doses of COVID-19 vaccine against outcomes associated with Omicron and Delta infections may aid decision-making at the individual and population levels.

Objective

To estimate vaccine effectiveness (VE) against symptomatic infections due to the Omicron and Delta variants and severe outcomes (hospitalization or death) associated with these infections.

Design, Setting, and Participants

This test-negative case-control study used linked provincial databases for SARS-CoV-2 laboratory testing, reportable disease, COVID-19 vaccination, and health administration in Ontario, Canada. Participants were individuals aged 18 years or older who had COVID-19 symptoms or severe outcomes (hospitalization or death) and were tested for SARS-CoV-2 between December 6 and 26, 2021.

Exposures

Receipt of 2 or 3 doses of the COVID-19 vaccine and time since last dose.

Main Outcomes and Measures

The main outcomes were symptomatic Omicron or Delta infection and severe outcomes (hospitalization or death) associated with infection. Multivariable logistic regression was used to estimate the effectiveness of 2 or 3 COVID-19 vaccine doses by time since the latest dose compared with no vaccination. Estimated VE was calculated using the formula VE = (1 – [adjusted odds ratio]) × 100%.

Results

Of 134 435 total participants, 16 087 were Omicron-positive cases (mean [SD] age, 36.0 [14.1] years; 8249 [51.3%] female), 4261 were Delta-positive cases (mean [SD] age, 44.2 [16.8] years; 2199 [51.6%] female), and 114 087 were test-negative controls (mean [SD] age, 42.0 [16.5] years; 67 884 [59.5%] female). Estimated VE against symptomatic Delta infection decreased from 89% (95% CI, 86%-92%) 7 to 59 days after a second dose to 80% (95% CI, 74%-84%) after 240 or more days but increased to 97% (95% CI, 96%-98%) 7 or more days after a third dose. Estimated VE against symptomatic Omicron infection was 36% (95% CI, 24%-45%) 7 to 59 days after a second dose and 1% (95% CI, –8% to 10%) after 180 days or longer, but 7 or more days after a third dose, it increased to 61% (95% CI, 56%-65%). Estimated VE against severe outcomes was high 7 or more days after a third dose for both Delta (99%; 95% CI, 98%-99%) and Omicron (95%; 95% CI, 87%-98%).

Conclusions and Relevance

In this study, in contrast to high estimated VE against symptomatic Delta infection and severe outcomes after 2 doses of COVID-19 vaccine, estimated VE was modest and short term against symptomatic Omicron infection but better maintained against severe outcomes. A third dose was associated with improved estimated VE against symptomatic infection and with high estimated VE against severe outcomes for both variants. Preventing infection due to Omicron and potential future variants may require tools beyond the currently available vaccines.

Article activity feed

  1. Version published to 10.1001/jamanetworkopen.2022.32760
  2. Version published to 10.1101/2021.12.30.21268565v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.12.30.21268565: (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 individuals who tested negative for SARS-CoV-2 during the study period and were considered as controls, we randomly selected one negative test to use as the index date.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    As of December 6, 2021, all specimens with a positive PCR result were re-tested using Thermofisher Taqpath™ COVID-19 PCR to identify SGTF.
    Thermofisher Taqpath™
    suggested: None
    In Ontario, the estimated sensitivity of SGTF relative to WGS for detecting Omicron among samples with Ct ≤30 was 99.5% and the specificity was 99.8%.
    WGS
    suggested: None
    All analyses were conducted using SAS Version 9.4 (SAS Institute Inc., Cary, NC).
    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:
    Our analysis has several limitations. First, we were unable to differentiate individuals who received a third dose as part of an extended primary series (i.e., severely or moderately immunocompromised individuals) as well as those who were eligible for a third dose earlier (e.g., residents of retirement homes). As such, the proportion of our sample with a third dose may reflect these highly vulnerable populations, and thus VE may be lower than for the general population due to underlying comorbidities, for example. Second, due to sample size constraints, we were unable to provide age-specific VE estimates. Third, we were unable to estimate effectiveness against severe outcomes, due to the lag between infection and hospitalization or death. Fourth, there may be residual confounding that was not accounted for in our analysis. This includes an inability to control for previous undocumented infections, which may be differential by vaccination status, as well as confounding due to behavioural patterns. For example, if vaccinated individuals have more exposure to SARS-CoV-2, our VE estimates are likely underestimated.21 Last, changes in testing patterns, including increased use of rapid antigen tests (which are not captured in our data) and decreased PCR testing availability, may have impacted our estimates, but the direction of any resulting bias is uncertain. Our findings have potentially important implications for proof of vaccination requirements. If the goal of these policies ...

    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

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  4. Version published to 10.1101/2021.12.30.21268565v1 on medRxiv