Comparative effectiveness of ChAdOx1 versus BNT162b2 vaccines against SARS-CoV-2 infections in England and Wales: A cohort analysis using trial emulation in the Virus Watch community data

  1. Vincent Grigori Nguyen
  2. Alexei Yavlinsky
  3. Sarah Beale
  4. Susan Hoskins
  5. Vasileios Lampos
  6. Isobel Braithwaite
  7. Thomas E Byrne
  8. Wing Lam Erica Fong
  9. Ellen Fragaszy
  10. Cyril Geismar
  11. Jana Kovar
  12. Annalan M D Navaratnam
  13. Parth Patel
  14. Madhumita Shrotri
  15. Sophie Weber
  16. Andrew C Hayward
  17. Robert W Aldridge

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Introduction

Infections of SARS-CoV-2 in vaccinated individuals have been increasing globally. Understanding the associations between vaccine type and a post-vaccination infection could help prevent further COVID-19 waves. In this paper, we use trial emulation to understand the impact of a phased introduction of the vaccine in the UK driven by vulnerability and exposure status. We estimate the comparative effectiveness of COVID-19 vaccines (ChAdOx1 versus BNT162b2) against post-vaccination infections of SARS-CoV-2 in a community setting in England and Wales.

Method

Trial emulation was conducted by pooling results from six cohorts whose recruitment was staggered between 1st January 2021 and 31st March 2021 and followed until 12th November 2021. Eligibility for each trial was based upon age (18+ at the time of vaccination), without prior signs of infection or an infection within the first 14 days of the first dose. Time from vaccination of ChAdOx1 or BNT162b2 until SARS-CoV-2 infection (positive polymerase chain reaction or lateral flow test after 14 of the vaccination) was modelled using Cox proportional hazards model for each cohort and adjusted for age at vaccination, gender, minority ethnic status, clinically vulnerable status and index of multiple deprivation quintile. For those without SARS-CoV-2 infection during the study period, follow-up was until loss-of-follow-up or end of study (12th November 2021). Pooled hazard ratios were generated using random-effects meta-analysis.

Results

Across six cohorts, there were a total of 21,283 participants who were eligible and vaccinated with either ChAdOx1 (n = 13,813) or BNT162b2 (n = 7,470) with a median follow-up time of 266 days (IQR: 235 - 282). By November 12th 2021, 750 (5.4%) adults who had ChAdOx1 as their vaccine experienced a SARS-CoV-2 infection, compared to 296 (4.0%) who had BNT162b2. We found that people who received ChAdOx1 vaccinations had 10.54 per 1000 people higher cumulative incidence for SARS-CoV-2 infection compared to BNT162b2 for infections during a maximum of 315 days of follow-up. When adjusted for age at vaccination, sex, minority ethnic status, index of multiple deprivation, and clinical vulnerability status, we found a pooled adjusted hazard ratio of 1.35 [HR: 1.35, 95%CI: 1.15 - 1.58], demonstrating a 35% increase in SARS-CoV-2 infections in people who received ChAdOx1 compared to BNT162b2.

Discussion

We found evidence of greater effectiveness of receiving BNT162b2 compared to ChAdOx1 vaccines against SARS-CoV-2 infection in England and Wales during a time period when Delta became the most prevalent variant of concern. Our findings demonstrate the importance of booster (third) doses to maintain protection and suggest that these should be prioritised to those who received ChAdOx1 as their primary course.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.12.21.21268214: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: From Autumn 2020, Virus Watch also included a programme of nasopharyngeal swab sample collection and blood collection via venepuncture or finger prick sampling in a subset of 10,000 participants in clinics who are part of the National Institute for Health Research’s Clinical Research Network.
    IRB: Statistical analysis was conducted using R version 4.0.3, Ethical approval: This study has been approved by the Hampstead NHS Health Research Authority Ethics Committee.
    Sex as a biological variablenot detected.
    RandomizationThis approach includes three primary components 1) excluding prevalent users of an intervention to estimate the impact of treatment initiation without the lingering effect of previous treatment, 2) use of an intention to treat analysis as this is the common estimand in randomised controlled trials, and 3) the use of multiple staggered cohorts to appropriately account for “time zero” (or the start of follow-up).
    Blindingnot detected.
    Power Analysisnot 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:
    Second, it can help control for changes in SARS-CoV-2 transmission rates driven by changes in public health policy such as the vaccination efforts (e.g., prioritised distribution and booster campaigns), mask usage, limitations on movement as well the introduction of new SARS-CoV-2 variants into England and Wales(14). Due to the reliance on self-reported observational studies, there is a risk of inconsistent and inaccurate data recording; however, this was mitigated through linkage to external data sources such as SGSS to complement missing incidence SARS-CoV-2 infections. We measured the risk of SARS-CoV-2 infection as our primary outcome, and whilst this precedes hospitalisation or death, we were not able to look at these more severe outcomes, which is an important limitation of our study. Our use of observational data may mean that there is residual and uncontrolled confounding. Using multiple staggered cohorts reduces the cohort size, and as a result, we had difficulties with analysing certain covariates such as geographical region and ethnicity, which we had to combine into an aggregated category. We did not include occupation or geographical risk in our analyses, and these may result in imbalances in the comparison arms as both risk of exposure to SARS-CoV-2 infection and access to BNT162b2 varied geographically (due to its cold storage requirements) and by occupation (e.g., health and social care workers). Our findings add to previous analyses which used test negative d...

    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.

  2. Version published to 10.1101/2021.12.21.21268214 on medRxiv