Effectiveness of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on covid-19 related symptoms, hospital admissions, and mortality in older adults in England: test negative case-control study

  1. Jamie Lopez Bernal
  2. Nick Andrews
  3. Charlotte Gower
  4. Chris Robertson
  5. Julia Stowe
  6. Elise Tessier
  7. Ruth Simmons
  8. Simon Cottrell
  9. Richard Roberts
  10. Mark O’Doherty
  11. Kevin Brown
  12. Claire Cameron
  13. Diane Stockton
  14. Jim McMenamin
  15. Mary Ramsay

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Abstract

Objective

To estimate the real world effectiveness of the Pfizer-BioNTech BNT162b2 and Oxford-AstraZeneca ChAdOx1-S vaccines against confirmed covid-19 symptoms (including the UK variant of concern B.1.1.7), admissions to hospital, and deaths.

Design

Test negative case-control study.

Setting

Community testing for covid-19 in England.

Participants

156 930 adults aged 70 years and older who reported symptoms of covid-19 between 8 December 2020 and 19 February 2021 and were successfully linked to vaccination data in the National Immunisation Management System.

Interventions

Vaccination with BNT162b2 or ChAdOx1-S.

Main outcome measures

Primary outcomes were polymerase chain reaction confirmed symptomatic SARS-CoV-2 infections, admissions to hospital for covid-19, and deaths with covid-19.

Results

Participants aged 80 years and older vaccinated with BNT162b2 before 4 January 2021 had a higher odds of testing positive for covid-19 in the first nine days after vaccination (odds ratio up to 1.48, 95% confidence interval 1.23 to 1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore compared with the baseline post-vaccination period. Vaccine effects were noted 10 to 13 days after vaccination, reaching a vaccine effectiveness of 70% (95% confidence interval 59% to 78%), then plateauing. From 14 days after the second dose a vaccination effectiveness of 89% (85% to 93%) was found compared with the increased baseline risk. Participants aged 70 years and older vaccinated from 4 January (when ChAdOx1-S delivery commenced) had a similar underlying risk of covid-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (51% to 69%) from 28 to 34 days after vaccination, then plateaued. With ChAdOx1-S, effects were seen from 14 to 20 days after vaccination, reaching an effectiveness of 60% (41% to 73%) from 28 to 34 days, increasing to 73% (27% to 90%) from day 35 onwards. On top of the protection against symptomatic disease, a further 43% (33% to 52%) reduced risk of emergency hospital admission and 51% (37% to 62%) reduced risk of death was observed in those who had received one dose of BNT162b2. Participants who had received one dose of ChAdOx1-S had a further 37% (3% to 59%) reduced risk of emergency hospital admission. Follow-up was insufficient to assess the effect of ChAdOx1-S on mortality. Combined with the effect against symptomatic disease, a single dose of either vaccine was about 80% effective at preventing admission to hospital with covid-19 and a single dose of BNT162b2 was 85% effective at preventing death with covid-19.

Conclusion

Vaccination with either one dose of BNT162b2 or ChAdOx1-S was associated with a significant reduction in symptomatic covid-19 in older adults, and with further protection against severe disease. Both vaccines showed similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 was associated with further protection against symptomatic disease. A clear effect of the vaccines against the B.1.1.7 variant was found.

Article activity feed

  1. Version published to 10.1136/bmj.n1088
  2. ScreenIT

    SciScore for 10.1101/2021.03.01.21252652: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    RandomizationIndividuals contributed a maximum of three randomly chosen negative results in the follow-up period after excluding any taken within three weeks before a positive test result, or after a positive result, which are more likely to be false negatives, or taken within <7 days of a previous negative sample, again, because these could represent a single illness episode.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    No key resources detected.

    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:
    The observational nature of this analysis means that there are limitations and the results should be interpreted with caution. Some of the key confounding issues have been outlined above but there are others. Factors that could increase the risk of COVID-19 in vaccinees (and therefore result in underestimation of vaccine effects) include: individuals may have more risky behaviours after vaccination if they believe they are protected; also, presenting for vaccination may be a risk factor in itself (for example travelling to a vaccination centre with a friend or relative). Conversely, individuals who have been self-isolating may defer vaccination and may also be at lower risk of infection, this could underestimate vaccine effectiveness in the short period after vaccination. Misclassification is also likely to be a factor in this study. Symptoms are self-reported and may not be specific for COVID-19 without clinician diagnosis. Furthermore, individuals may falsely report symptoms in order to be tested – which will both include asymptomatic individuals in the symptomatic analysis and meant that symptom onset dates are incorrect. Low sensitivity or specificity of PCR testing may also mean that cases and controls are misclassified. Failure to exclude those with past infection because of low testing rates in wave 1 is another possibility. Lags in vaccination data could also lead to misclassification, however, we excluded the most recent two days from the analysis and a review of 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.

    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.

  3. Version published to 10.1101/2021.03.01.21252652 on medRxiv