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
Jamie Lopez Bernal
1,2,3
, Nick Andrews
1,2
, Charlotte Gower
1
, Julia Stowe
1
, Chris Robertson
4
, Elise
Tessier
1
, Ruth Simmons,
1
Simon Cottrell
5
, Richard Roberts
5
, Mark O’Doherty
6
, Kevin Brown
1
, Claire
Cameron
7
, Diane Stockton
7
, Jim McMenamin
7
, Mary Ramsay
1,2
1.
Public Health England, London, United Kingdom
2.
NIHR Health Protection Research Unit in Vaccines and Immunisation, London School of
Hygiene and Tropical Medicine, London, United Kingdom
3.
NIHR Health Protection Research Unit in Respiratory Infections, Imperial College London,
United Kingdom
4.
University of Strathclyde, Glasgow, United Kingdom.
5.
Public Health Wales, Cardiff, United Kingdom.
6.
Public Health Agency Northern Ireland, Belfast, United Kingdom.
7.
Public Health Scotland, Glasgow, United Kingdom.
Corresponding author: jamie.lopezbernal2@phe.gov.uk
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NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.
Abstract
Objectives
To estimate the real-world effectiveness of the Pfizer/BioNTech BNT162b2 vaccine and Astrazeneca
ChAdOx1 vaccine against Confirmed COVID-19, hospitalisations and deaths. To estimate
effectiveness on the UK variant of concern.
Design
Test negative case control design
Setting
Community COVID-19 PCR testing in England
Participants
All adults in England aged 70 years and older (over 7.5 million). All COVID-19 testing in the
community among eligible individuals who reported symptoms between 8
th
December 2020 and 19
th
February 2021 was included in the analysis.
Interventions
One and two doses of BNT162b2 vaccine . One dose of ChAd Ox1 vacci ne.
Main outcome measures
Symptomatic PCR confirmed SARS-CoV-2 infection, hospitalisations and deaths with COVID-19.
Results
Individuals aged >=80 years vaccinated with BNT162b2 prior to 4
th
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. Vaccine effectiveness
was therefore estimated relative to the baseline post-vaccination period. 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. From 14 days after the second dose a vaccine effectiveness of 89% (95%CI:
85-93%) was seen.
Individuals aged >=70 years vaccinated from 4
th
January had a similar underlying risk of COVID-19 to
unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (95%CI 51-69%) from
28-34 days after vaccination then plateaued. 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.
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. Cases who had been vaccinated with one
dose of ChAdOx1 had an additional 37% (95% CI 3-59%) lower risk of emergency hospitalisation.
There was insufficient follow-up to assess the effect of ChAdOx1 on mortality due to the later rollout
of this vaccine. 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.
Conclusion
Vaccina ti on with ei ther a single do se of BNT162b2 or ChAdOx1 COVID -19 vacc inat ion was associa ted
with a significant reduction in symptomatic SARS-CoV2 positive cases in older adults with even
greater protection against severe disease. Both vaccines show similar effects. Protection was
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
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maintaine d for the duration of follow -up (>6 week s) . A second d ose o f BNT162b2 provide s further
protection against symptomatic disease but second doses of ChAdOx1 have not yet been rolled out
in England. There is a clear effect of the vaccines against the UK variant of concern.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted March 2, 2021. ; https://doi.org/10.1101/2021.03.01.21252652doi: medRxiv preprint
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.(1) The programme has since expanded to include the AstraZeneca
adenovirus-vector vaccine, ChAdOx1 nCOV-19, and over 6.5 million individuals have now been
vacci nated. The burden of CO VID-19 in the UK remain s high and early evidence on the effec tiven e ss
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.(3) From the 18
th
of January, rollout was expanded to all
adults aged 70 years or older and those in clinically extremely vulnerable groups. Delivery was
initially through hospital trusts and care homes, where possible, subsequently also through primary
care providers and mass vaccination centres. 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.(4, 5) Data from the ChAdOx1 trial
suggests that protection may be greater with a longer dosing interval.(5) A reanalysis of the
BNT162b2 trial data suggests that a single dose of this vaccine has an efficacy of 92.6% in the early
post-vaccination period.(6) Furthermore, with other vaccines an extended interval between the
prime and booster doses typically provides a better immune response to the booster dose.(7, 8)
Based on this evidence, the increasing incidence of COVID-19 in the UK and the need to rapidly
vaccinate as many vulnerable people as possible, on the 20
th
December 2020, the Joint Committee
on Vaccination and Immunisation (JCVI) advised that the dose interval for both vaccines could be
extended to up to 12 weeks. A policy decision was subsequently made to prioritise vaccinating as
many people as possible with the first dose.
Also in December 2020, a new COVID-19 variant of concern (labelled VOC 202012/01) was found to
be associated with increasing case numbers in Kent in South East England.(9) Recent analyses
suggest that this variant has increased transmissibility and it has since become the dominant strain
in large parts of the UK.(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.(9) Concerns have been raised on the possible impact of the new
variant on vaccine effectiveness.(12)
Public Health England have undertaken their first analysis of the early effect of COVID-19 vaccination
using routine testing and vaccination data. The aims of this analysis were: (i) to estimate the effect
of vaccination on confirmed COVID-19 in adults aged >=70 years with one and two doses; (ii) to
estimate vaccine effectiveness against the new variant of concern, VOC 202012/01; (iii) to estimate
case hospitalisation and case fatality rates among vaccinated and unvaccinated cases.
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
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Methods
This study estimates the effect of vaccination with the BNT162b2 and ChAdOx1 COVID-19 vaccines
on laboratory confirmed symptomatic disease in individuals aged 70 years or older in England.
All individuals aged 70 years or older in England (over 7.5 million individuals) were eligible for
inclusion.
A test negative case control design was used to estimate odds ratios for testing positive for SARS-
CoV-2 in all vaccinated compared to unvaccinated individuals with compatible symptoms who were
tested using PCR. Test negative case control designs are considered powerful study designs for
estimating vaccine effectiveness and are used extensively for estimating effectiveness of influenza
vaccines and vaccines against other respiratory viruses.(13-15) They have been found to have high
concordance with randomised controlled trials.(16, 17) Vaccination status is compared in individuals
testing positive for the target organism compared to those testing negative. Comparing to other
individuals presenting for testing but testing negative helps to control for factors that are typically
difficult to estimate in observational studies including differences in health seeking behaviour,
access to testing and case ascertainment.
Data sources
Outcome assessment
Testing for COVID-19 in the UK is conducted through hospital and public health laboratories for
those with a clinical need as well as some healthcare workers (referred to as Pillar 1) and through
community testing (referred to as Pillar 2).(18) Anybody can access a Pillar 2 test if they have
coronavirus symptoms (high temperature, new continuous cough, loss or change in sense of smell or
taste), or if they are part of a local or national mass testing programme. For this analysis, PCR testing
data from Pillar 2 in individuals who reported having symptoms were included, data were extracted
for all te sts between 26
th
of October 2020 and the 21
st
of February 2021.
The mutations to the Spike (S) gene in VOC 202012/01 cause a reproducible S gene target failure
(SGTF) in laboratories using a three target from Thermo Fisher (TaqPath) PCR assay.(9) Between
week commencing 7
th
of December 2020 and week commencing 25
th
of January 2021, VOC
202012/01 accounted for be twe en 98 and 100% of SGTF in England.(19) SGTF therefo re provide s a
good proxy for identification of VOC 202012/01 without relying on sequencing. An analysis of the
vacci ne effects again s t COVID -19 de tecti ons with SGTF was under taken restric ted to data from
laboratories using the TaqPath assay.
Exposure assessment
Testing data were linked to individual vaccination histories from the national vaccination register
(the National Immunisation Management System, NIMS) using NHS number, date of birth, surname,
forename and postcode. All COVID-19 vaccines administered in England are recorded in the NIMS by
clinici ans through point of care applications. The NIMS data were ext ract ed on February 22
nd
2021
with immunisations to February 21
st
2021. To allow for delayed entry of data into NIMS only samples
taken from February 19
th
2021 were included in analyses.
Secondary outcomes
The data were also linked to hospitalisation data from the Emergency Care Dataset (ECDS), which
includes hospital admissions via emergency departments but not elective admissions, and to deaths
data from NHS records.(20)
. CC-BY-NC-ND 4.0 International licenseIt is made available under a
is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)
The copyright holder for this preprint this version posted March 2, 2021. ; https://doi.org/10.1101/2021.03.01.21252652doi: medRxiv preprint