Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections

CMMID COVID-19 Working Group; The SAFER Investigators and Field Study Team; The Crick COVID-19 Consortium; Joel Hellewell; Timothy W. Russell; Rupert Beale; Gavin Kelly; Catherine Houlihan; Eleni Nastouli; Adam Kucharski; William Edmunds; Stefan Flasche; Frank Sandmann; Mark Jit

doi:10.1186/s12916-021-01982-x

Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections

CMMID COVID-19 Working Group, The SAFER Investigators and Field Study Team, The Crick COVID-19 Consortium, Joel Hellewell^*, Timothy W. Russell, Rupert Beale, Gavin Kelly, Catherine Houlihan, Eleni Nastouli, Adam Kucharski, William Edmunds, Stefan Flasche, Frank Sandmann, Mark Jit

^*Corresponding author for this work

Modelling Economics Unit

Research output: Contribution to journal › Article › peer-review

60 Citations (Scopus)

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Abstract

Background: Routine asymptomatic testing using RT-PCR of people who interact with vulnerable populations, such as medical staff in hospitals or care workers in care homes, has been employed to help prevent outbreaks among vulnerable populations. Although the peak sensitivity of RT-PCR can be high, the probability of detecting an infection will vary throughout the course of an infection. The effectiveness of routine asymptomatic testing will therefore depend on testing frequency and how PCR detection varies over time.

Methods: We fitted a Bayesian statistical model to a dataset of twice weekly PCR tests of UK healthcare workers performed by self-administered nasopharyngeal swab, regardless of symptoms. We jointly estimated times of infection and the probability of a positive PCR test over time following infection; we then compared asymptomatic testing strategies by calculating the probability that a symptomatic infection is detected before symptom onset and the probability that an asymptomatic infection is detected within 7 days of infection.

Results: We estimated that the probability that the PCR test detected infection peaked at 77% (54–88%) 4 days after infection, decreasing to 50% (38–65%) by 10 days after infection. Our results suggest a substantially higher probability of detecting infections 1–3 days after infection than previously published estimates. We estimated that testing every other day would detect 57% (33–76%) of symptomatic cases prior to onset and 94% (75–99%) of asymptomatic cases within 7 days if test results were returned within a day.

Conclusions: Our results suggest that routine asymptomatic testing can enable detection of a high proportion of infected individuals early in their infection, provided that the testing is frequent and the time from testing to notification of results is sufficiently fast.

Original language	English
Article number	106
Number of pages	10
Journal	BMC Medicine
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s12916-021-01982-x
Publication status	Published - 27 Apr 2021

Bibliographical note

Funding Information: The following funding sources are acknowledged as providing funding for the named authors. Wellcome Trust (206250/Z/17/Z: AJK, TWR; 210758/Z/18/Z: JH). AK was supported by the NIHR HPRU in Modelling and Health Economics, a partnership between PHE, Imperial College London and LSHTM (grant code NIHR200908). The views expressed are those of the authors and not necessarily those of the United Kingdom (UK) Department of Health and Social Care, the National Health Service, the National Institute for Health Research (NIHR), or Public Health England (PHE). The SAFER study was funded by MRC UKRI (grant MC_PC_19082) and supported by the UCLH/UCL NIHR BRC.

Wellcome Trust, National Institute for Health Research (NIHR) Health Protection Research Unit, Medical Research Council (UKRI)

Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Publisher Copyright: © The Author(s). 2021.

Citation: Hellewell, J., Russell, T.W., The SAFER Investigators and Field Study Team. et al. Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections. BMC Med 19, 106 (2021).

DOI: https://doi.org/10.1186/s12916-021-01982-x

Keywords

COVID-19
Healthcare workers
PCR testing
Presymptomatic infections
SARS-CoV-2
Test sensitivity

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CMMID COVID-19 Working Group, The SAFER Investigators and Field Study Team, The Crick COVID-19 Consortium, Hellewell, J., Russell, T. W., Beale, R., Kelly, G., Houlihan, C., Nastouli, E., Kucharski, A., Edmunds, W., Flasche, S., Sandmann, F., & Jit, M. (2021). Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections. BMC Medicine, 19(1), Article 106. https://doi.org/10.1186/s12916-021-01982-x

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abstract = "Background: Routine asymptomatic testing using RT-PCR of people who interact with vulnerable populations, such as medical staff in hospitals or care workers in care homes, has been employed to help prevent outbreaks among vulnerable populations. Although the peak sensitivity of RT-PCR can be high, the probability of detecting an infection will vary throughout the course of an infection. The effectiveness of routine asymptomatic testing will therefore depend on testing frequency and how PCR detection varies over time. Methods: We fitted a Bayesian statistical model to a dataset of twice weekly PCR tests of UK healthcare workers performed by self-administered nasopharyngeal swab, regardless of symptoms. We jointly estimated times of infection and the probability of a positive PCR test over time following infection; we then compared asymptomatic testing strategies by calculating the probability that a symptomatic infection is detected before symptom onset and the probability that an asymptomatic infection is detected within 7 days of infection. Results: We estimated that the probability that the PCR test detected infection peaked at 77% (54–88%) 4 days after infection, decreasing to 50% (38–65%) by 10 days after infection. Our results suggest a substantially higher probability of detecting infections 1–3 days after infection than previously published estimates. We estimated that testing every other day would detect 57% (33–76%) of symptomatic cases prior to onset and 94% (75–99%) of asymptomatic cases within 7 days if test results were returned within a day. Conclusions: Our results suggest that routine asymptomatic testing can enable detection of a high proportion of infected individuals early in their infection, provided that the testing is frequent and the time from testing to notification of results is sufficiently fast.",

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note = "Funding Information: The following funding sources are acknowledged as providing funding for the named authors. Wellcome Trust (206250/Z/17/Z: AJK, TWR; 210758/Z/18/Z: JH). AK was supported by the NIHR HPRU in Modelling and Health Economics, a partnership between PHE, Imperial College London and LSHTM (grant code NIHR200908). The views expressed are those of the authors and not necessarily those of the United Kingdom (UK) Department of Health and Social Care, the National Health Service, the National Institute for Health Research (NIHR), or Public Health England (PHE). The SAFER study was funded by MRC UKRI (grant MC_PC_19082) and supported by the UCLH/UCL NIHR BRC. Wellcome Trust, National Institute for Health Research (NIHR) Health Protection Research Unit, Medical Research Council (UKRI) Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Publisher Copyright: {\textcopyright} The Author(s). 2021. Citation: Hellewell, J., Russell, T.W., The SAFER Investigators and Field Study Team. et al. Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections. BMC Med 19, 106 (2021). DOI: https://doi.org/10.1186/s12916-021-01982-x",

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CMMID COVID-19 Working Group, The SAFER Investigators and Field Study Team, The Crick COVID-19 Consortium, Hellewell, J, Russell, TW, Beale, R, Kelly, G, Houlihan, C, Nastouli, E, Kucharski, A, Edmunds, W, Flasche, S, Sandmann, F & Jit, M 2021, 'Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections', BMC Medicine, vol. 19, no. 1, 106. https://doi.org/10.1186/s12916-021-01982-x

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T1 - Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections

AU - CMMID COVID-19 Working Group

AU - The SAFER Investigators and Field Study Team

AU - The Crick COVID-19 Consortium

AU - Hellewell, Joel

AU - Russell, Timothy W.

AU - Matthews, Rebecca

AU - Severn, Abigail

AU - Adam, Sajida

AU - Enfield, Louise

AU - McBride, Angela

AU - Gärtner, Kathleen

AU - Edwards, Sarah

AU - Lorencatto, Fabiana

AU - Michie, Susan

AU - Manley, Ed

AU - Shahmanesh, Maryam

AU - Lukha, Hinal

AU - Prymas, Paulina

AU - McBain, Hazel

AU - Shortman, Robert

AU - Wood, Leigh

AU - Davies, Claudia

AU - Williams, Bethany

AU - Sanchez, Emilie

AU - Frampton, Daniel

AU - Byott, Matthew

AU - Paraskevopoulou, Stavroula M.

AU - Crayton, Elise

AU - Meyer, Carly

AU - Vora, Nina

AU - Gkouleli, Triantafylia

AU - Stoltenberg, Andrea

AU - Ranieri, Veronica

AU - Byrne, Tom

AU - Lewer, Dan

AU - Hayward, Andrew

AU - Gilson, Richard

AU - Walker, Naomi

AU - Ferron, Aaron

AU - Sait, Aaron

AU - Ramaprasad, Abhinay

AU - Perrin, Abigail

AU - Sateriale, Adam

AU - Sullivan, Adrienne E.

AU - Nelson, Aileen

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AU - Gaiba, Alessandra

AU - Beale, Rupert

AU - Kelly, Gavin

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AU - Nastouli, Eleni

AU - Kucharski, Adam

AU - Edmunds, William

AU - Flasche, Stefan

AU - Sandmann, Frank

AU - Jit, Mark

N1 - Funding Information: The following funding sources are acknowledged as providing funding for the named authors. Wellcome Trust (206250/Z/17/Z: AJK, TWR; 210758/Z/18/Z: JH). AK was supported by the NIHR HPRU in Modelling and Health Economics, a partnership between PHE, Imperial College London and LSHTM (grant code NIHR200908). The views expressed are those of the authors and not necessarily those of the United Kingdom (UK) Department of Health and Social Care, the National Health Service, the National Institute for Health Research (NIHR), or Public Health England (PHE). The SAFER study was funded by MRC UKRI (grant MC_PC_19082) and supported by the UCLH/UCL NIHR BRC. Wellcome Trust, National Institute for Health Research (NIHR) Health Protection Research Unit, Medical Research Council (UKRI) Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Publisher Copyright: © The Author(s). 2021. Citation: Hellewell, J., Russell, T.W., The SAFER Investigators and Field Study Team. et al. Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections. BMC Med 19, 106 (2021). DOI: https://doi.org/10.1186/s12916-021-01982-x

PY - 2021/4/27

Y1 - 2021/4/27

N2 - Background: Routine asymptomatic testing using RT-PCR of people who interact with vulnerable populations, such as medical staff in hospitals or care workers in care homes, has been employed to help prevent outbreaks among vulnerable populations. Although the peak sensitivity of RT-PCR can be high, the probability of detecting an infection will vary throughout the course of an infection. The effectiveness of routine asymptomatic testing will therefore depend on testing frequency and how PCR detection varies over time. Methods: We fitted a Bayesian statistical model to a dataset of twice weekly PCR tests of UK healthcare workers performed by self-administered nasopharyngeal swab, regardless of symptoms. We jointly estimated times of infection and the probability of a positive PCR test over time following infection; we then compared asymptomatic testing strategies by calculating the probability that a symptomatic infection is detected before symptom onset and the probability that an asymptomatic infection is detected within 7 days of infection. Results: We estimated that the probability that the PCR test detected infection peaked at 77% (54–88%) 4 days after infection, decreasing to 50% (38–65%) by 10 days after infection. Our results suggest a substantially higher probability of detecting infections 1–3 days after infection than previously published estimates. We estimated that testing every other day would detect 57% (33–76%) of symptomatic cases prior to onset and 94% (75–99%) of asymptomatic cases within 7 days if test results were returned within a day. Conclusions: Our results suggest that routine asymptomatic testing can enable detection of a high proportion of infected individuals early in their infection, provided that the testing is frequent and the time from testing to notification of results is sufficiently fast.

AB - Background: Routine asymptomatic testing using RT-PCR of people who interact with vulnerable populations, such as medical staff in hospitals or care workers in care homes, has been employed to help prevent outbreaks among vulnerable populations. Although the peak sensitivity of RT-PCR can be high, the probability of detecting an infection will vary throughout the course of an infection. The effectiveness of routine asymptomatic testing will therefore depend on testing frequency and how PCR detection varies over time. Methods: We fitted a Bayesian statistical model to a dataset of twice weekly PCR tests of UK healthcare workers performed by self-administered nasopharyngeal swab, regardless of symptoms. We jointly estimated times of infection and the probability of a positive PCR test over time following infection; we then compared asymptomatic testing strategies by calculating the probability that a symptomatic infection is detected before symptom onset and the probability that an asymptomatic infection is detected within 7 days of infection. Results: We estimated that the probability that the PCR test detected infection peaked at 77% (54–88%) 4 days after infection, decreasing to 50% (38–65%) by 10 days after infection. Our results suggest a substantially higher probability of detecting infections 1–3 days after infection than previously published estimates. We estimated that testing every other day would detect 57% (33–76%) of symptomatic cases prior to onset and 94% (75–99%) of asymptomatic cases within 7 days if test results were returned within a day. Conclusions: Our results suggest that routine asymptomatic testing can enable detection of a high proportion of infected individuals early in their infection, provided that the testing is frequent and the time from testing to notification of results is sufficiently fast.

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KW - Healthcare workers

KW - PCR testing

KW - Presymptomatic infections

KW - SARS-CoV-2

KW - Test sensitivity

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Estimating the effectiveness of routine asymptomatic PCR testing at different frequencies for the detection of SARS-CoV-2 infections

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