Effectiveness of BNT162b2 and mRNA-1273 covid-19 vaccines against symptomatic SARS-CoV-2 infection and severe covid-19 outcomes in Ontario, Canada: test negative design study

  1. Hannah Chung
  2. Siyi He
  3. Sharifa Nasreen
  4. Maria E Sundaram
  5. Sarah A Buchan
  6. Sarah E Wilson
  7. Branson Chen
  8. Andrew Calzavara
  9. Deshayne B Fell
  10. Peter C Austin
  11. Kumanan Wilson
  12. Kevin L Schwartz
  13. Kevin A Brown
  14. Jonathan B Gubbay
  15. Nicole E Basta
  16. Salaheddin M Mahmud
  17. Christiaan H Righolt
  18. Lawrence W Svenson
  19. Shannon E MacDonald
  20. Naveed Z Janjua
  21. Mina Tadrous
  22. Jeffrey C Kwong

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Abstract

Objective

To estimate the effectiveness of mRNA covid-19 vaccines against symptomatic infection and severe outcomes (hospital admission or death).

Design

Test negative design study.

Setting

Ontario, Canada between 14 December 2020 and 19 April 2021.

Participants

324 033 community dwelling people aged ≥16 years who had symptoms of covid-19 and were tested for SARS-CoV-2.

Interventions

BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) vaccine.

Main outcome measures

Laboratory confirmed SARS-CoV-2 by reverse transcription polymerase chain reaction (RT-PCR) and hospital admissions and deaths associated with SARS-CoV-2 infection. Multivariable logistic regression was adjusted for personal and clinical characteristics associated with SARS-CoV-2 and vaccine receipt to estimate vaccine effectiveness against symptomatic infection and severe outcomes.

Results

Of 324 033 people with symptoms, 53 270 (16.4%) were positive for SARS-CoV-2 and 21 272 (6.6%) received at least one dose of vaccine. Among participants who tested positive, 2479 (4.7%) were admitted to hospital or died. Vaccine effectiveness against symptomatic infection observed ≥14 days after one dose was 60% (95% confidence interval 57% to 64%), increasing from 48% (41% to 54%) at 14-20 days after one dose to 71% (63% to 78%) at 35-41 days. Vaccine effectiveness observed ≥7 days after two doses was 91% (89% to 93%). Vaccine effectiveness against hospital admission or death observed ≥14 days after one dose was 70% (60% to 77%), increasing from 62% (44% to 75%) at 14-20 days to 91% (73% to 97%) at ≥35 days, whereas vaccine effectiveness observed ≥7 days after two doses was 98% (88% to 100%). For adults aged ≥70 years, vaccine effectiveness estimates were observed to be lower for intervals shortly after one dose but were comparable to those for younger people for all intervals after 28 days. After two doses, high vaccine effectiveness was observed against variants with the E484K mutation.

Conclusions

Two doses of mRNA covid-19 vaccines were observed to be highly effective against symptomatic infection and severe outcomes. Vaccine effectiveness of one dose was observed to be lower, particularly for older adults shortly after the first dose.

Article activity feed

  1. Version published to 10.1136/bmj.n1943
  2. Version published to 10.1101/2021.05.24.21257744v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.05.24.21257744: (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.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    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 study had some limitations. First, our study sample was limited to those with COVID-19 symptoms recorded in OLIS. Not all laboratories in Ontario currently have the information technology infrastructure to submit symptom information recorded on the SARS-CoV-2 laboratory requisition into OLIS. Thus, the generalizability of our findings to the broader population is uncertain. In addition, COVID-19 vaccination status is now collected on the laboratory requisition. This may introduce selection bias and underestimate the true VE estimate if symptoms were more likely to be documented on requisition forms for vaccinated individuals who ultimately test positive for SARS-CoV-2, for example. Traditional test-negative design studies collect vaccination status among all individuals with symptoms consistent with the pathogen under study, to minimize this selection bias. However, the congruence of our findings for fully vaccinated individuals with extant studies provides some reassurance that any under- or overestimation of VE is likely to be small. Second, because symptom onset date is largely unavailable in OLIS and CCM only has information on test-positive cases, we used specimen collection date as the index date. This may have led to classifying some individuals into an incorrect dose-to-index date interval, because their symptom onset would have been several days prior to getting tested, leading to underestimation of VE during earlier intervals. Furthermore, we could not limit the...

    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 10.1101/2021.05.24.21257744v1 on medRxiv