Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in England
Summary (2 min read)
Introduction
- On the 8 th December 2020 the UK became the first country to implement a COVID-19 vaccination programme following the approval of the Pfizer-BioNtech messenger RNA (mRNA) vaccine, BNT162b2, for emergency use.
- The burden of COVID-19 in the UK remains high and early evidence on the effectiveness of vaccines is essential for informing policy decisions on the ongoing rollout of the programme and the use of other non-pharmaceutical interventions.
- (2) During these first few weeks of the programme, the priority groups for vaccination included: (i) residents in a care home for older adults and their carers; and (ii) all those 80 years of age and over and frontline health and social care workers.
- Interim results from phase 3 clinical trials have found the BNT162b2 and ChAdOx1 vaccines to be highly effective using a two-dose schedule with a target interval of 3 weeks and 4 weeks respectively between doses.
- (10, 11) The variant is characterised by 23 mutations, including mutations to genes encoding the spike protein, the target in the two vaccines currently in use, as well as the majority of vaccine candidates.
Covariates
- These include demographic factors, such as age, gender, index of multiple deprivation and ethnicity; geography and period (incidence of COVID-19 varied by region and by week over the study period, as did vaccine rollout); and care home status, care homes have been high exposure settings during the course of the pandemic.
- Age, gender, DOB, ethnicity and address were extracted from the testing data and the NIMS.
- Addresses were used to determine index of multiple deprivation quintile and were also linked to Care Quality Commission (CQC) registered care homes using the Unique Property Reference Number.
Statistical methods
- Logistic regression was used to estimate the odds of vaccination in PCR confirmed cases compared to those testing negative .
- Individuals 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.
- Proportional hazards survival analyses were also conducted for these outcomes, adjusting for age, care home status, gender and period.
- Ethics and Governance Group and was found to be fully compliant with all regulatory requirements.
Ethics
- As no regulatory issues were identified, and ethical review is not a requirement for this type of work, it was decided that a full ethical review would not be necessary.
- Differences in characteristics in linked and unlinked tests are shown in supplementary table 1.
- During the first few days after vaccination (before an immune response would be anticipated), vaccinated individuals had a higher odds of testing positive, suggesting that vaccination was being targeted at those at higher risk of disease.
- A stratified approach was therefore considered more appropriate for the primary analysis.
Vaccine coverage by vaccine brand at
- This was due to confounding by age and care home status, likely because few care home residents were vaccinated in the early period and this period was restricted to a smaller age group (>=80 years).
- When using the comparison to the 4-9 day period to account for differences in baseline risk in those vaccinated, the results are similar with and without SGTF.
Discussion
- This study provides the first real world evidence of COVID-19 vaccine effectiveness against symptomatic COVID-19 in older people in the UK.
- (4, 23) This effect appears to lessen as roll-out vaccination programme progresses suggesting that access to vaccine was initially focussed on those at higher risk, although this bias may still affect the longer follow-up periods (to which those vaccinated earliest will contribute) more than the earlier follow-up periods.
- Dagan et al found a vaccine effectiveness against symptomatic disease of 57% in the 14-20 day period and 66% in the 21-27 day period which is similar to their estimates.
- The initial phase 3 trial found a two-dose efficacy against symptomatic disease of 70.4% (all ages).(.
- Failure to exclude those with past infection because of low testing rates in wave 1 is another possibility.
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Frequently Asked Questions (10)
Q2. What are the future works in "Early effectiveness of covid-19 vaccination with bnt162b2 mrna vaccine and chadox1 adenovirus vector vaccine on symptomatic disease, hospitalisations and mortality in older adults in england" ?
Further evidence is needed on the duration of any effect and the effect against asymptomatic infection and transmission and the four UK nations will work closely to develop and share evidence on this as it becomes available. What this study adds: • A single dose of either vaccine provides significant protection against COVID-19 and further protection against severe disease lasting at least 6 weeks, including against the UK variant of concern.
Q3. How long after vaccination did the effectiveness of the ChAdOx1 vaccine increase?
With the ChAdOx1 vaccine, vaccine effects were seen from 14-20 days after vaccination reaching an effectiveness of 60% (95%CI 41-73%) from 28-34 days and further increasing to 73% (95%CI 27-90%) from day 35 onwards.
Q4. What was the effect of the BNT162b2 vaccine on the symptomatic ?
On top of the protection against symptomatic disease, cases who had been vaccinated with one dose of BNT162b2 had an additional 43% (95%CI 33-52%) lower risk of emergency hospitalisation and an additional 51% (95%CI 37-62%) lower risk of death.
Q5. What is the effect of the vaccines against symptomatic disease?
Vaccination with either a single dose of BNT162b2 or ChAdOx1 COVID-19 vaccination was associated with a significant reduction in symptomatic SARS-CoV2 positive cases in older adults with even greater protection against severe disease.
Q6. how effective is a single dose of bnt162b2?
Combined with the effect against symptomatic disease, this indicates that a single dose of either vaccine is approximately 80% effective at preventing hospitalisation and a single dose of BNT162b2 is 85% effective at preventing death with COVID-19.
Q7. How long after vaccination did the effectiveness of the vaccine reach 70%?
Vaccine effects were noted from 10-13 days after vaccination, reaching an effectiveness of 70% (95% CI 59-78%) from 28-34 days, then plateauing.
Q8. How many adults in England have been tested for COVID-19?
Test negative case control designCommunity COVID-19 PCR testing in EnglandAll adults in England aged 70 years and older (over 7.5 million).
Q9. What is the effect of the second dose of BNT162b2 on symptomatic?
A second dose of BNT162b2 provides further protection against symptomatic disease but second doses of ChAdOx1 have not yet been rolled out in England.
Q10. How did the PCR test confirm the risk of COVID-19?
Individuals aged >=80 years vaccinated with BNT162b2 prior to 4th January, had a higher odds of testing positive in the first 9 days after vaccination (odds ratio up to 1.48, 95%CI 1.23-1.77), indicating that those initially targeted had a higher underlying risk of infection.