Comparative effectiveness of different primary vaccination courses on mRNA-based booster vaccines against SARs-COV-2 infections: a time-varying cohort analysis using trial emulation in the Virus Watch community cohort
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Abstract
Background
The Omicron B.1.1.529 variant increased severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in doubly vaccinated individuals, particularly in the Oxford–AstraZeneca COVID-19 vaccine (ChAdOx1) recipients. To tackle infections, the UK’s booster vaccination programmes used messenger ribonucleic acid (mRNA) vaccines irrespective of an individual’s primary course vaccine type, and prioritized the clinically vulnerable. These mRNA vaccines included the Pfizer–BioNTech COVID-19 vaccine (BNT162b2) the Moderna COVID-19 vaccine (mRNA-1273). There is limited understanding of the effectiveness of different primary vaccination courses on mRNA booster vaccines against SARs-COV-2 infections and how time-varying confounders affect these evaluations.
Methods
Trial emulation was applied to a prospective community observational cohort in England and Wales to reduce time-varying confounding-by-indication driven by prioritizing vaccination based upon age, vulnerability and exposure. Trial emulation was conducted by meta-analysing eight adult cohort results whose booster vaccinations were staggered between 16 September 2021 and 05 January 2022 and followed until 23 January 2022. Time from booster vaccination until SARS-CoV-2 infection, loss of follow-up or end of study was modelled using Cox proportional hazard models and adjusted for age, sex, minority ethnic status, clinically vulnerability and deprivation.
Results
A total of 19 159 participants were analysed, with 11 709 ChAdOx1 primary courses and 7450 BNT162b2 primary courses. Median age, clinical vulnerability status and infection rates fluctuate through time. In mRNA-boosted adults, 7.4% (n = 863) of boosted adults with a ChAdOx1 primary course experienced a SARS-CoV-2 infection compared with 7.7% (n = 571) of those who had BNT162b2 as a primary course. The pooled adjusted hazard ratio (aHR) was 1.01 with a 95% confidence interval (CI) of: 0.90 to 1.13.
Conclusion
After an mRNA booster dose, we found no difference in protection comparing those with a primary course of BNT162b2 with those with a ChAdOx1 primary course. This contrasts with pre-booster findings where previous research shows greater effectiveness of BNT162b2 than ChAdOx1 in preventing infection.
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SciScore for 10.1101/2022.02.04.22270479: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: From Autumn 2020, Virus Watch also included a programme of nasopharyngeal swab sample collection and blood collection via venipuncture or finger prick sampling in a subset of 10,000 participants in research clinics.
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 variable not detected. Randomization This 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 confounding treatment, 2) use of an intention to … SciScore for 10.1101/2022.02.04.22270479: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: From Autumn 2020, Virus Watch also included a programme of nasopharyngeal swab sample collection and blood collection via venipuncture or finger prick sampling in a subset of 10,000 participants in research clinics.
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 variable not detected. Randomization This 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 confounding 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). Blinding not detected. Power Analysis not 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, our approach helps 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), mask usage, limitations on movement as well the emergence of new SARS-CoV-2 variants and their transition to becoming the dominant SARs-CoV-2 strain into England and Wales which we graphically demonstrated in Figure 3. Therefore our approach controls for measured time-varying confounders and to some extent, it goes some way to mitigating against the impact of unmeasured time-varying confounders (i.e. SARs-CoV-2 strain). 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 and NIMs to complement missing vaccination data. 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 a limitation of our study. Our use of observational data may mean that there is residual and uncontrolled confounding. Unlike test-negative designs our approach does not implicitly control for differences in testing behaviour between groups, but since we are comparing vaccine regimes rather than vaccinated and unvaccinated individuals we do not expect confounding by differential testing behav...
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.
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