Waning effectiveness of BNT162b2 and ChAdOx1 covid-19 vaccines over six months since second dose: OpenSAFELY cohort study using linked electronic health records
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (ScreenIT)
Abstract
Objective
To estimate waning of covid-19 vaccine effectiveness over six months after second dose.
Design
Cohort study, approved by NHS England.
Setting
Linked primary care, hospital, and covid-19 records within the OpenSAFELY-TPP database.
Participants
Adults without previous SARS-CoV-2 infection were eligible, excluding care home residents and healthcare professionals.
Exposures
People who had received two doses of BNT162b2 or ChAdOx1 (administered during the national vaccine rollout) were compared with unvaccinated people during six consecutive comparison periods, each of four weeks.
Main outcome measures
Adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, positive SARS-CoV-2 test, and non-covid-19 related death comparing vaccinated with unvaccinated people. Waning vaccine effectiveness was quantified as ratios of adjusted hazard ratios per four week period, separately for subgroups aged ≥65 years, 18-64 years and clinically vulnerable, 40-64 years, and 18-39 years.
Results
1 951 866 and 3 219 349 eligible adults received two doses of BNT162b2 and ChAdOx1, respectively, and 2 422 980 remained unvaccinated. Waning of vaccine effectiveness was estimated to be similar across outcomes and vaccine brands. In the ≥65 years subgroup, ratios of adjusted hazard ratios for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test ranged from 1.19 (95% confidence interval 1.14 to 1.24) to 1.34 (1.09 to 1.64) per four weeks. Despite waning vaccine effectiveness, rates of covid-19 related hospital admission and death were substantially lower among vaccinated than unvaccinated adults up to 26 weeks after the second dose, with estimated vaccine effectiveness ≥80% for BNT162b2, and ≥75% for ChAdOx1. By weeks 23-26, rates of positive SARS-CoV-2 test in vaccinated people were similar to or higher than in unvaccinated people (adjusted hazard ratios up to 1.72 (1.11 to 2.68) for BNT162b2 and 1.86 (1.79 to 1.93) for ChAdOx1).
Conclusions
The rate at which estimated vaccine effectiveness waned was consistent for covid-19 related hospital admission, covid-19 related death, and positive SARS-CoV-2 test and was similar across subgroups defined by age and clinical vulnerability. If sustained to outcomes of infection with the omicron variant and to booster vaccination, these findings will facilitate scheduling of booster vaccination.
Article activity feed
-
-
SciScore for 10.1101/2022.03.23.22272804: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable Potential confounding factors: The following potential confounders were defined at a single time (typically the day before the start of comparison period 1; full details in Supplementary Table 3): age; sex (male or female); English Index of Multiple Deprivation (IMD, grouped by quintiles); ethnicity (Black, Mixed, South Asian, White, Other, as per the UK census); number of SARS-CoV-2 tests between 18 May 2020 (when widespread testing became available) and eligibility for first vaccine dose; and receipt of one or more flu vaccines in the five years prior to COVID-19 vaccine eligibility. Randomization not detected. Blinding not detected. Power Analysis not … SciScore for 10.1101/2022.03.23.22272804: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable Potential confounding factors: The following potential confounders were defined at a single time (typically the day before the start of comparison period 1; full details in Supplementary Table 3): age; sex (male or female); English Index of Multiple Deprivation (IMD, grouped by quintiles); ethnicity (Black, Mixed, South Asian, White, Other, as per the UK census); number of SARS-CoV-2 tests between 18 May 2020 (when widespread testing became available) and eligibility for first vaccine dose; and receipt of one or more flu vaccines in the five years prior to COVID-19 vaccine eligibility. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: Thank you for sharing your code.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study has several limitations. First, as in any observational study, our estimates could be affected by confounding by unmeasured factors. However, the detailed linked data analysed permitted adjustment for a wide range of potential confounding factors. Second, patients registered with a GP who have moved or emigrated (or whose death was not recorded)25 may contribute person-time but not events. Because the BNT162b2 and ChAdOx1 groups are defined by recent vaccination, these “ghost” patients are more likely to be present in the unvaccinated group, leading to bias in estimates of waning. Also, healthcare workers could be identified and excluded from the vaccinated groups because this information was recorded at the time of vaccination, but not from the unvaccinated group. This limitation should not affect results for the 65+ subgroup, most of whom are retired, or comparisons between BNT162b2 and ChAdOx1. Third, consistent with an Australian survey,24 we found that unvaccinated individuals had tested less frequently than vaccinated individuals during the pre-vaccine rollout period when widespread testing was available, and were considerably less likely to be tested during follow-up. Fourth, differential depletion of susceptible people in the unvaccinated groups over time may lead to attenuation of HRs even when true vaccine effectiveness does not change. However, such bias is likely to be minimal when vaccine effectiveness is high.27 Our results have immediate implications ...
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.
-
