Nick K. Jones1,2*, Lucy Rivett1,2*,
Chris Workman3, Mark Ferris3, Ashley
Shaw1, Cambridge COVID-19
Collaboration1,4, Paul J. Lehner1,4,
Rob Howes5, Giles Wright3, Nicholas
J. Matheson1,4,6¶, Michael P.
Weekes1,7¶
1 Cambridge University NHS Hospitals Foundation Trust,
Cambridge, UK
2 Clinical Microbiology & Public Health Laboratory,
Public Health England, Cambridge, UK
3 Occupational Health and Wellbeing, Cambridge
Biomedical Campus, Cambridge, UK
4 Cambridge Institute of Therapeutic Immunology &
Infectious Disease, University of Cambridge, Cambridge, UK
5 Cambridge COVID-19 Testing Centre and AstraZeneca,
Anne Mclaren Building, Cambridge, UK
6 NHS Blood and Transplant, Cambridge, UK
7 Cambridge Institute for Medical Research, University
of Cambridge, Cambridge, UK
*Joint first authorship
¶Joint last authorship
Correspondence: mpw1001@cam.ac.uk
The UK has initiated mass COVID-19 immunisation, with healthcare workers
(HCWs) given early priority because of the potential for workplace
exposure and risk of onward transmission to patients. The UK’s Joint
Committee on Vaccination and Immunisation has recommended maximising the
number of people vaccinated with first doses at the expense of early
booster vaccinations, based on single dose efficacy against symptomatic
COVID-19 disease.1-3
At the time of writing, three COVID-19 vaccines have been granted
emergency use authorisation in the UK, including the BNT162b2 mRNA
COVID-19 vaccine (Pfizer-BioNTech). A vital outstanding question is
whether this vaccine prevents or promotes asymptomatic SARS-CoV-2
infection, rather than symptomatic COVID-19 disease, because
sub-clinical infection following vaccination could continue to drive
transmission. This is especially important because many UK HCWs have
received this vaccine, and nosocomial COVID-19 infection has been a
persistent problem.
Through the implementation of a 24 h-turnaround PCR-based comprehensive
HCW screening programme at Cambridge University Hospitals NHS Foundation
Trust (CUHNFT), we previously demonstrated the frequent presence of
pauci- and asymptomatic infection amongst HCWs during the UK’s first
wave of the COVID-19 pandemic.4 Here, we evaluate the
effect of first-dose BNT162b2 vaccination on test positivity rates and
cycle threshold (Ct) values in the asymptomatic arm of our programme,
which now offers weekly screening to all staff.
Vaccination of HCWs at CUHNFT began on 8th December
2020, with mass vaccination from 8th January 2021.
Here, we analyse data from the two weeks spanning 18thto 31st January 2021, during which: (a) the prevalence
of COVID-19 amongst HCWs remained approximately constant; and (b) we
screened comparable numbers of vaccinated and unvaccinated HCWs. Over
this period, 4,408 (week 1) and 4,411 (week 2) PCR tests were performed
from individuals reporting well to work. We stratified HCWs
<12 days or > 12 days post-vaccination
because this was the point at which protection against symptomatic
infection began to appear in phase III clinical
trial.2
26/3,252 (0·80%) tests from unvaccinated HCWs were positive
(Ct<36), compared to 13/3,535 (0·37%) from HCWs <12
days post-vaccination and 4/1,989 (0·20%) tests from HCWs ≥12 days
post-vaccination (p=0·023 and p=0·004, respectively; Fisher’s exact
test, Figure). This suggests a four-fold decrease in the risk of
asymptomatic SARS-CoV-2 infection amongst HCWs ≥12 days
post-vaccination, compared to unvaccinated HCWs, with an intermediate
effect amongst HCWs <12 days post-vaccination.
A marked reduction in infections was also seen when analyses were
repeated with: (a) inclusion of HCWs testing positive through both the
symptomatic and asymptomatic arms of the programme (56/3,282 (1·71%)
unvaccinated vs 8/1,997 (0·40%) ≥12 days post-vaccination, 4·3-fold
reduction, p=0·00001); (b) inclusion of PCR tests which were positive at
the limit of detection (Ct>36, 42/3,268 (1·29%) vs
15/2,000 (0·75%), 1·7-fold reduction, p=0·075); and (c) extension of
the period of analysis to include six weeks from December
28th to February 7th 2021
(113/14,083 (0·80%) vs 5/4,872 (0·10%), 7·8-fold reduction,
p=1x10-9). In addition, the median Ct value of
positive tests showed a non-significant trend towards increase between
unvaccinated HCWs and HCWs > 12 days post-vaccination
(23·3 to 30·3, Figure), suggesting that samples from vaccinated
individuals had lower viral loads.
We therefore provide real-world evidence for a high level of protection
against asymptomatic SARS-CoV-2 infection after a single dose of
BNT162b2 vaccine, at a time of predominant transmission of the UK
COVID-19 variant of concern 202012/01 (lineage B.1.1.7), and amongst a
population with a relatively low frequency of prior infection (7.2%
antibody positive).5
This work was funded by a Wellcome Senior Clinical Research Fellowship
to MPW (108070/Z/15/Z), a Wellcome Principal Research Fellowship to PJL
(210688/Z/18/Z), and an MRC Clinician Scientist Fellowship
(MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM. Funding was also
received from Addenbrooke’s Charitable Trust and the Cambridge
Biomedical Research Centre. We also acknowledge contributions from all
staff at CUHNFT Occupational Health and Wellbeing and the Cambridge
COVID-19 Testing Centre.