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\begin{document}

\title{Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection}



\author[1]{Michael Weekes}%
\author[2]{Nick K Jones}%
\author[2]{Lucy Rivett}%
\author[3]{Chris Workman}%
\author[3]{Mark Ferris}%
\author[4]{Ashley Shaw}%
\author[5]{Cambridge Covid-19 Collaboration}%
\author[5]{Paul J Lehner}%
\author[6]{Rob Howes}%
\author[3]{Giles Wright}%
\author[5,7]{Nicholas J Matheson}%
\author[8]{Michael P Weekes}%
\affil[1]{Affiliation not available}%
\affil[2]{Clinical Microbiology \& Public Health Laboratory, Public Health England}%
\affil[3]{Cambridge University Hospitals Occupational Health and Wellbeing}%
\affil[4]{Cambridge University Hospitals}%
\affil[5]{Cambridge Institute of Therapeutic Immunology \& Infectious Disease, University of Cambridge}%
\affil[6]{Cambridge COVID-19 Testing Centre}%
\affil[7]{NHS Blood and Transplant}%
\affil[8]{Cambridge Institute for Medical Research, University of Cambridge}%


\vspace{-1em}



  
  \date{March 13, 2024}


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Nick K. Jones\textsuperscript{1,2*}, Lucy Rivett\textsuperscript{1,2*},
Chris Workman\textsuperscript{3}, Mark Ferris\textsuperscript{3}, Ashley
Shaw\textsuperscript{1}, Cambridge COVID-19
Collaboration\textsuperscript{1,4}, Paul J. Lehner\textsuperscript{1,4},
Rob Howes\textsuperscript{5}, Giles Wright\textsuperscript{3}, Nicholas
J. Matheson\selectlanguage{ngerman}\textsuperscript{1,4,6¶}, Michael P.
Weekes\textsuperscript{1,7¶}

\textsuperscript{1} Cambridge University NHS Hospitals Foundation Trust,
Cambridge, UK

\textsuperscript{2} Clinical Microbiology \& Public Health Laboratory,
Public Health England, Cambridge, UK

\textsuperscript{3} Occupational Health and Wellbeing, Cambridge
Biomedical Campus, Cambridge, UK

\textsuperscript{4} Cambridge Institute of Therapeutic Immunology \&
Infectious Disease, University of Cambridge, Cambridge, UK

\textsuperscript{5} Cambridge COVID-19 Testing Centre and AstraZeneca,
Anne Mclaren Building, Cambridge, UK

\textsuperscript{6} NHS Blood and Transplant, Cambridge, UK

\textsuperscript{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.\textsuperscript{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.\textsuperscript{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 8\textsuperscript{th} December
2020, with mass vaccination from 8\textsuperscript{th} January 2021.
Here, we analyse data from the two weeks spanning
18\textsuperscript{th}to 31\textsuperscript{st} 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 \textless{}12 days or \emph{\textgreater{}}
12 days post-vaccination because this was the point at which protection
against symptomatic infection began to appear in phase III clinical
trial.\textsuperscript{2}

26/3,252 (0·80\%) tests from unvaccinated HCWs were positive
(Ct\textless{}36), compared to 13/3,535 (0·37\%) from HCWs \textless{}12
days post-vaccination and 4/1,989 (0·20\%) tests from HCWs \selectlanguage{english}[?]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 \selectlanguage{english}[?]12 days
post-vaccination, compared to unvaccinated HCWs, with an intermediate
effect amongst HCWs \textless{}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\%) \selectlanguage{english}[?]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\textgreater{}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
28\textsuperscript{th} to February 7\textsuperscript{th} 2021
(113/14,083 (0*80\%) vs 5/4,872 (0*10\%), 7*8-fold reduction,
p=1x10\textsuperscript{-9}). In addition, the median Ct value of
positive tests showed a non-significant trend towards increase between
unvaccinated HCWs and HCWs \emph{\textgreater{}} 12 days
post-vaccination (23*3 to 30*3, Figure), suggesting that samples from
vaccinated individuals had \emph{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).\textsuperscript{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.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

Figure : Proportion of HCWs testing positive for SARS-CoV-2 in the
CUHNHFT asymptomatic screening programme (grey bars; week 1,
18/01/2021-24/01/2021; week 2, 25/01/2021-31/01/2021) and Ct values of
positive tests (CT\textless{}36; blue dots; both weeks). RT-PCR
targeting the SARS-CoV-2 ORF1ab genes was conducted at the Cambridge
COVID-19 Testing Centre (part of the UK Lighthouse Labs Network). For
proportions testing positive, p values for pair-wise comparisons of
unvaccinated HCWs with HCWs \textless{}12 days or\emph{\textgreater{}}
12 days post-vaccination are shown (Fisher's exact test; both weeks).
For Ct values, medians \selectlanguage{ngerman}± interquartile ranges are shown.

\textbf{References}

1. Department of Health and Social Care. Optimising the COVID-19
vaccination programme for maximum short-term
impact\emph{\url{https://www.gov.uk/government/publications/prioritising-the-first-covid-19-vaccine-dose-jcvi-statement/optimising-the-covid-19-vaccination-programme-for-maximum-short-term-impact}}

2. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the
BNT162b2 mRNA Covid-19 Vaccine.~\emph{N Engl J
Med}2020;\textbf{383}(27):2603--15. DOI: 10.1056/NEJMoa2034577

3. Voysey M, Clemens SAC, Madhi SA, et al. Safety and efficacy of the
ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim
analysis of four randomised controlled trials in Brazil, South Africa,
and the UK.~\emph{Lancet} 2021;\textbf{397}(10269):99--111.
DOI:\emph{\url{https://doi.org/10.1016/S0140-6736(20)32661-1}}

4. Rivett L, Sridhar S, Sparkes D, et al. Screening of healthcare
workers for SARS-CoV-2 highlights the role of asymptomatic carriage in
COVID-19 transmission.~\emph{eLlife} 2020;\textbf{9}. DOI:
10.7554/eLife.58728

5. Cooper DJ, Lear S, Watson L, et al. A prospective study of risk
factors associated with seroprevalence of SARS-CoV-2 antibodies in
healthcare workers at a large UK teaching hospital.~\emph{medRxiv} 2020.
DOI:~\emph{\href{https://doi.org/10.1101/2020.11.03.20220699Cambridge}{https://doi.org/10.1101/2020.11.03.20220699}}

\emph{Cambridge COVID-19 Collaboration}

Amy Amory, Steve Baker, Emma Bateman, Aklima Begum, Moushima Begum, John
Bradley, Michael Brennan, Helen Burn, Caroline Crofts, Sharon Dawson,
Gordon Dougan, Renny Feather, Louise Free, Katie Friel, Claire Gildea,
Ian Goodfellow, Lizz Grimwade, Ravi Gupta, Susan Hall, Sophie Hannan,
James Hayes, Aleksandra Hosaja, Lidia James, Jill Jardin, Nathalie
Kingston, Paul A. Lyons, Patrick H. Maxwell, Sue Mott, Sarah Mugavin,
Joyce Mwiya, Ravi Prakash Nallattil, Willem H. Ouwehand, Elle Page,
Marina Perez, Natalie Quinnell, Caroline Saunders, Kenneth G.C. Smith,
Maria Stafford, Charlotte Summers, Despiona Tatsi, James E.D.
Thaventhiran, Sharon Thomas Johnson, Mark Toshner, Lesley Turner, Kate
Wall, Ben Warne, Karis Watson, Jo Wright

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