Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection

  1. Nick K Jones
  2. Lucy Rivett
  3. Shaun Seaman
  4. Richard J Samworth
  5. Ben Warne
  6. Chris Workman
  7. Mark Ferris
  8. Jo Wright
  9. Natalie Quinnell
  10. Ashley Shaw
  11. Cambridge COVID-19 Collaboration
  12. Ian G Goodfellow
  13. Paul J Lehner
  14. Rob Howes
  15. Giles Wright
  16. Nicholas J Matheson
  17. Michael P Weekes  Is a corresponding author
  1. Cambridge University NHS Hospitals Foundation Trust, United Kingdom
  2. Clinical Microbiology & Public Health Laboratory, Public Health England, United Kingdom
  3. Medical Research Council Biostatistics Unit, University of Cambridge, United Kingdom
  4. Statistical Laboratory, Centre for Mathematical Sciences, University of Cambridge, United Kingdom
  5. Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, United Kingdom
  6. Department of Medicine, University of Cambridge, United Kingdom
  7. Occupational Health and Wellbeing, Cambridge Biomedical Campus, United Kingdom
  8. Division of Virology, Department of Pathology, University of Cambridge, United Kingdom
  9. Cambridge COVID-19 Testing Centre and AstraZeneca, Anne McLaren Building, United Kingdom
  10. NHS Blood and Transplant, United Kingdom
  11. Cambridge Institute for Medical Research, University of Cambridge, United Kingdom

Abstract

The BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioNTech) is being utilised internationally for mass COVID-19 vaccination. Evidence of single-dose protection against symptomatic disease has encouraged some countries to opt for delayed booster doses of BNT162b2, but the effect of this strategy on rates of asymptomatic SARS-CoV-2 infection remains unknown. We previously demonstrated frequent pauci- and asymptomatic SARS-CoV-2 infection amongst healthcare workers (HCWs) during the UK’s first wave of the COVID-19 pandemic, using a comprehensive PCR-based HCW screening programme (Rivett et al., 2020; Jones et al., 2020). Here, we evaluate the effect of first-dose BNT162b2 vaccination on test positivity rates and find a fourfold reduction in asymptomatic infection amongst HCWs ≥12 days post-vaccination. These data provide real-world evidence of short-term protection against asymptomatic SARS-CoV-2 infection following a single dose of BNT162b2 vaccine, suggesting that mass first-dose vaccination will reduce SARS-CoV-2 transmission, as well as the burden of COVID-19 disease.

Introduction

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 (Department of Health and Social Care, 2021; Polack et al., 2020; Voysey et al., 2021).

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 asymptomatic as well as symptomatic SARS-CoV-2 infection or merely converts infections from symptomatic to asymptomatic. 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 hour 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 (Rivett et al., 2020). 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.

Results and discussion

Vaccination of HCWs at CUHNFT began on 8 December 2020, with mass vaccination from 8 January 2021. Here, we analyse data from 2 weeks spanning 18–31 January 2021, during which (1) the prevalence of COVID-19 amongst HCWs remained approximately constant and (2) we screened comparable numbers of vaccinated and unvaccinated HCWs. During this period, 4408 (week 1) and 4411 (week 2) PCR tests were performed on individuals reporting well to work, from a weekly on-site HCW population of ~9000. 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 the phase III clinical trial (Polack et al., 2020). In the post-vaccination groups, the median number of days between vaccination and testing were 7 (interquartile range [IQR] 4–9; <12 day group) and 16 (14–18; ≥12 day group).

Twenty-six of 3252 (0.8%, Wilson’s interval 0.6–1.2%) tests from unvaccinated HCWs were positive (Ct < 36), compared to 13/3535 (0.4%, Wilson’s interval 0.2–0.6%) tests from HCWs <12 days post-vaccination and 4/1989 (0.2%, Wilson’s interval 0.1–0.5%) tests from HCWs ≥12 days post-vaccination (p=0.023 and p=0.004, respectively; Fisher’s exact test, Figure 1 and Table 1). This suggests a fourfold 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.

Proportion of positive screening tests for SARS-CoV-2 amongst HCWs from the CUHNHFT asymptomatic screening programme (grey bars; week 1, 18–24 January 2021; week 2, 25–31 January 2021) and Ct values of positive tests (Ct < 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 of positive screening tests, p-values for pair-wise comparisons of unvaccinated HCWs with HCWs <12 days or ≥12 days post-vaccination are shown (Fisher’s exact test; both weeks). For Ct values, medians ± interquartile ranges are shown.

Figure 1—source data 1

Proportions of positive asymptomatic SARS-CoV-2 screens and distributions of Ct values.

https://cdn.elifesciences.org/articles/68808/elife-68808-fig1-data1-v2.xlsx
Table 1
Weekly numbers and proportions of positive SARS-CoV-2 test results spanning 6 weeks around the main study period (indicated in grey).
Unvaccinated<12 Days since vaccination≥12 Days since vaccination
Week startTotal testsPositive tests%Total testsPositive tests%Total testsPositive tests%
28 December 20202097160.8%800.0%600.0%
4 January 20214762430.9%9300.0%2200.0%
11 January 20213273270.8%97860.6%3000.0%
18 January 20212183170.8%171680.5%48310.2%
25 January 2021106990.8%181950.3%150630.2%
1 February 202169910.1%75810.1%282510.0%

A marked reduction in infections was also seen when analyses were repeated with (1) inclusion of HCWs testing positive through both the symptomatic and asymptomatic arms of the programme (56/3370 [1.7%, Wilson’s interval 1.3–2.2%] unvaccinated vs 8/2018 [0.4%, Wilson’s interval 0.2–0.8%] ≥12 days post-vaccination, 4.2-fold reduction, p<0.0001) and (2) inclusion of PCR tests that were positive at the limit of detection (Ct > 36, 42/3268 [1.3%, Wilson’s interval 1.0–1.7%] vs 15/2000 [0.7%, Wilson’s interval 0.5–1.2%], 1.7-fold reduction, p=0.07). 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 [IQR 13.5–33.0] to 30.3 [IQR 25.5–35.1], Figure 1), raising the possibility that vaccinated individuals who do go on to develop infection may have lower viral loads.

HCWs working in COVID-19 clinical areas were prioritised for vaccination, and a small number of clinically vulnerable HCWs were also given priority. Otherwise, vaccine allocation was arbitrary. Since asymptomatic infection was examined, the date of infection could have been earlier than the test date. These factors would all tend to lead to an underestimate of the vaccine’s effect (bias towards the null). Because of the rapid decline in the incidence of SARS-CoV-2 infection in the Cambridge community, this study could only examine the short-term impact of single-dose BNT162b2 vaccination. The frequency of prior SARS-CoV-2 infection (Cooper et al., 2020) was similar in all groups (seroprevalence 7.1%, unvaccinated; 5.6%, <12 days post-vaccination; 5.7%, ≥12 days post-vaccination), suggesting that this did not confound our observations.

Taken together, our findings provide real-world evidence of short-term protection against asymptomatic SARS-CoV-2 infection after a single dose of BNT162b2 vaccine, at a time when the UK COVID-19 variant of concern 202012/01 (lineage B.1.1.7) accounted for the great majority of infections (24/29 sequenced isolates from asymptomatic HCWs). A fourfold reduction from 0.8% to 0.2% in asymptomatic infection is likely to be crucial in controlling nosocomial SARS-CoV-2 transmission. Nonetheless, protection is incomplete, suggesting that continuing asymptomatic HCW screening, social distancing, mask-wearing, and strict hand hygiene remain vital.

Materials and methods

HCW screening programme

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We previously described protocols for staff screening, sample collection, and results reporting in detail (Rivett et al., 2020; Jones et al., 2020). In general, these methods remained unchanged throughout this study period. Two parallel streams of entry into the testing programme included (1) HCW symptomatic and HCW symptomatic household contact screening arms and (2) an HCW asymptomatic screening arm. Since our prior description of the screening programme, weekly asymptomatic testing is now offered to all CUHNFT staff. Testing was performed (1) at temporary on-site ‘Pods’ and (2) via self-swabbing kits collected by HCWs. Individuals performed a self-swab of the oropharynx and anterior nasal cavity. Samples were subjected to RNA extraction and amplification using real-time RT-PCR, with all sample processing and analysis undertaken at the Cambridge COVID-19 Testing Centre (Lighthouse Laboratory).

Vaccination

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HCW vaccination began at CUHNFT on 8 December 2020, with appointments made by invitation only for all high-risk HCWs working on-site. This was followed by self-booked appointments for HCWs working in designated COVID-19 clinical areas, from 8 January 2021 onwards. From 18 January 2021, vaccination was offered to all HCWs, with appointments made via a booking website and latterly using the hospital’s electronic patient record system ‘MyChart’. All vials of Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) were stored at −74°C, before being transferred to storage at 2–8°C. From the moment the vials were removed from the freezer, they were given a 120 hr expiration date, of which 3 hr were dedicated to thawing the vaccines. All vaccine doses were administered intramuscularly by trained vaccinators, in accordance with the manufacturer’s instructions. Vaccination was undertaken exclusively at an on-site vaccination centre, with mandatory mask-wearing and social distancing in place. HCWs remained at the on-site vaccination centre for a minimum observation period of 15 min after vaccination.

Data extraction and analysis

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Swab result, vaccination details, and serology data for HCWs were extracted directly from the hospital-laboratory interface software, Epic (Verona, WI). Data were collated using Microsoft Excel and the figure produced with GraphPad Prism (GraphPad Software, La Jolla, CA). Fisher’s exact test was used for the comparison of positive rates between groups, defined in the main text. Additionally, 95% confidence intervals were calculated using Wilson’s method.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data file has been provided for Figure 1.

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Article and author information

Author details

  1. Nick K Jones

    1. Cambridge University NHS Hospitals Foundation Trust, Cambridge, United Kingdom
    2. Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, United Kingdom
    Contribution
    Data curation, Formal analysis, Investigation, Methodology, Writing - original draft, Project administration
    Contributed equally with
    Lucy Rivett
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4475-7761
  2. Lucy Rivett

    1. Cambridge University NHS Hospitals Foundation Trust, Cambridge, United Kingdom
    2. Clinical Microbiology & Public Health Laboratory, Public Health England, Cambridge, United Kingdom
    Contribution
    Data curation, Formal analysis, Investigation, Methodology, Writing - original draft, Project administration
    Contributed equally with
    Nick K Jones
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2781-9345
  3. Shaun Seaman

    Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom
    Contribution
    Investigation, Methodology, Writing - review and editing
    Competing interests
    No competing interests declared
  4. Richard J Samworth

    Statistical Laboratory, Centre for Mathematical Sciences, University of Cambridge, Cambridge, United Kingdom
    Contribution
    Investigation, Methodology, Writing - review and editing
    Competing interests
    No competing interests declared
  5. Ben Warne

    1. Cambridge University NHS Hospitals Foundation Trust, Cambridge, United Kingdom
    2. Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, United Kingdom
    3. Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    Contribution
    Formal analysis, Investigation, Writing - review and editing
    Competing interests
    No competing interests declared
  6. Chris Workman

    Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, United Kingdom
    Contribution
    Data curation, Formal analysis, Project administration, Writing - review and editing
    Competing interests
    No competing interests declared
  7. Mark Ferris

    Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, United Kingdom
    Contribution
    Investigation, Methodology, Project administration, Writing - review and editing
    Competing interests
    No competing interests declared
  8. Jo Wright

    Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, United Kingdom
    Contribution
    Data curation, Investigation, Project administration, Writing - review and editing
    Competing interests
    No competing interests declared
  9. Natalie Quinnell

    Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, United Kingdom
    Contribution
    Data curation, Investigation, Project administration, Writing - review and editing
    Competing interests
    No competing interests declared
  10. Ashley Shaw

    Cambridge University NHS Hospitals Foundation Trust, Cambridge, United Kingdom
    Contribution
    Supervision, Project administration, Writing - review and editing
    Competing interests
    No competing interests declared
  11. Cambridge COVID-19 Collaboration

    1. Cambridge University NHS Hospitals Foundation Trust, Cambridge, United Kingdom
    2. Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    Contribution
    Resources, Data curation
    Competing interests
    No competing interests declared
    1. Amy Amory
    2. Stephen Baker
    3. Emma Bateman
    4. Aklima Begum
    5. Moushima Begum
    6. John Bradley
    7. Michael Brennan
    8. Helen Burn
    9. Caroline Crofts
    10. Afzal Chaudhry
    11. Yasmin Chaudhry
    12. Daniel J Cooper
    13. Sharon Dawson
    14. Gordon Dougan
    15. Renny Feather
    16. Louise Free
    17. Katie Friel
    18. Claire Gildea
    19. Iliana Georgana
    20. Lizz Grimwade
    21. Ravi Gupta
    22. Susan Hall
    23. Sophie Hannan
    24. James Hayes
    25. Aleksandra Hosaja
    26. Myra Hosmillo
    27. Rhys Izuagbe
    28. Aminu Jahun
    29. Lidia James
    30. Jill Jardin
    31. Nathalie Kingston
    32. Sara Lear
    33. Paul A Lyons
    34. Patrick H Maxwell
    35. Sue Mott
    36. Sarah Mugavin
    37. Joyce Mwiya
    38. Sharon Peacock
    39. Ravi Prakash Nallattil
    40. Kazeem Oloyede
    41. Willem H Ouwehand
    42. Elle Page
    43. Marina Perez
    44. Tim Raine
    45. Matthew Routledge
    46. Caroline Saunders
    47. Kenneth GC Smith
    48. Dominic Sparkes
    49. Maria Stafford
    50. Charlotte Summers
    51. Despiona Tatsi
    52. James ED Thaventhiran
    53. Sharon Thomas Johnson
    54. M Estée Török
    55. Mark Toshner
    56. Lesley Turner
    57. Kate Wall
    58. Karis Watson
  12. Ian G Goodfellow

    Division of Virology, Department of Pathology, University of Cambridge, Cambridge, United Kingdom
    Contribution
    Formal analysis, Investigation, Writing - review and editing
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9483-510X
  13. Paul J Lehner

    1. Cambridge University NHS Hospitals Foundation Trust, Cambridge, United Kingdom
    2. Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, United Kingdom
    3. Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    Contribution
    Conceptualization, Methodology, Writing - review and editing
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9383-1054
  14. Rob Howes

    Cambridge COVID-19 Testing Centre and AstraZeneca, Anne McLaren Building, Cambridge, United Kingdom
    Contribution
    Data curation, Investigation, Methodology, Project administration, Writing - review and editing
    Competing interests
    Dr Howes was employed by AstraZeneca PLC during the period of study and preparation of this manuscript.
  15. Giles Wright

    Occupational Health and Wellbeing, Cambridge Biomedical Campus, Cambridge, United Kingdom
    Contribution
    Supervision, Investigation, Methodology, Project administration, Writing - review and editing
    Competing interests
    No competing interests declared
  16. Nicholas J Matheson

    1. Cambridge University NHS Hospitals Foundation Trust, Cambridge, United Kingdom
    2. Cambridge Institute of Therapeutic Immunology & Infectious Disease, University of Cambridge, Cambridge, United Kingdom
    3. Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    4. NHS Blood and Transplant, Cambridge, United Kingdom
    Contribution
    Conceptualization, Formal analysis, Investigation, Methodology, Writing - review and editing
    Contributed equally with
    Michael P Weekes
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3318-1851
  17. Michael P Weekes

    1. Cambridge University NHS Hospitals Foundation Trust, Cambridge, United Kingdom
    2. Department of Medicine, University of Cambridge, Cambridge, United Kingdom
    3. Cambridge Institute for Medical Research, University of Cambridge, Cambridge, United Kingdom
    Contribution
    Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing - original draft, Project administration
    Contributed equally with
    Nicholas J Matheson
    For correspondence
    mpw1001@cam.ac.uk
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3196-5545

Funding

Wellcome Trust (108070/Z/15/Z)

  • Michael P Weekes

Wellcome Trust (207498/Z/17/Z)

  • Ian G Goodfellow

Wellcome Trust (210688/Z/18/Z)

  • Paul J Lehner

Medical Research Council (MR/P008801/1)

  • Nicholas J Matheson

NHS Blood and Transplant (WPA15-02)

  • Nicholas J Matheson

EPSRC (EP/P031447/1)

  • Richard J Samworth

Medical Research Council (MC_UU_00002/10)

  • Shaun Seaman

EPSRC (EP/N031938/1)

  • Richard J Samworth

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Acknowledgements

This work was funded in part by Wellcome Senior Clinical Research Fellowships (Grant numbers 108070/Z/15/Z to MPW, 207498/Z/17/Z to IGG), a Wellcome Principal Research Fellowship to PJL (210688/Z/18/Z), an MRC Clinician Scientist Fellowship (MR/P008801/1) and NHSBT workpackage (WPA15-02) to NJM, EPSRC grants to RJS (EP/P031447/1,EP/N031938/1), and an MRC grant to SS (MC_UU_00002/10). The sequencing costs were funded by the COVID-19 Genomics UK (COG-UK) Consortium, which is supported by funding from the Medical Research Council (MRC) part of UK Research and Innovation (UKRI), the National Institute of Health Research (NIHR), and Genome Research Limited, operating as the Wellcome Sanger Institute. Funding was also received from Addenbrooke’s Charitable Trust and the NIHR Cambridge Biomedical Research Centre. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. We also acknowledge contributions from all staff at CUHNFT Occupational Health and Wellbeing, the COVID-19 vaccination programme and the Cambridge COVID-19 Testing Centre.

Ethics

Human subjects: This study was conducted as a service evaluation of the CUHNFT staff testing and vaccination services (CUHNFT clinical project ID ID3682). As a study of healthcare-associated infections, this investigation is exempt from requiring ethical approval under Section 251 of the NHS Act 2006 (see also the NHS Health Research Authority algorithm, available at http://www.hra-decisiontools.org.uk/research/, which concludes that no formal ethical approval is required).

Version history

  1. Received: March 26, 2021
  2. Accepted: April 7, 2021
  3. Accepted Manuscript published: April 8, 2021 (version 1)
  4. Version of Record published: April 23, 2021 (version 2)

Copyright

© 2021, Jones et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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  1. Nick K Jones
  2. Lucy Rivett
  3. Shaun Seaman
  4. Richard J Samworth
  5. Ben Warne
  6. Chris Workman
  7. Mark Ferris
  8. Jo Wright
  9. Natalie Quinnell
  10. Ashley Shaw
  11. Cambridge COVID-19 Collaboration
  12. Ian G Goodfellow
  13. Paul J Lehner
  14. Rob Howes
  15. Giles Wright
  16. Nicholas J Matheson
  17. Michael P Weekes
(2021)
Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection
eLife 10:e68808.
https://doi.org/10.7554/eLife.68808

Share this article

https://doi.org/10.7554/eLife.68808

Further reading

    1. Epidemiology and Global Health
    2. Medicine
    Nick K Jones, Lucy Rivett ... Michael P Weekes
    Research Advance Updated

    Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to near-zero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK ‘lockdown’. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent ‘hubs’ of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely.

    1. Epidemiology and Global Health
    2. Medicine
    Lucy Rivett, Sushmita Sridhar ... Michael P Weekes
    Research Article Updated

    Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.