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Negative SARS-CoV-2 PCR or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study

BACKGROUND: A considerable proportion of SARS-CoV-2 transmission occurs from asymptomatic and pre-symptomatic cases. Therefore, different polymerase chain reaction (PCR)- or rapid antigen test (RAT)-based approaches are being discussed and applied to identify infectious individuals that would have o...

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Autores principales: Krumkamp, Ralf, Kreuels, Benno, Jaeger, Veronika K., May, Jürgen, Mikolajczyk, Rafael, Karch, André
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353420/
https://www.ncbi.nlm.nih.gov/pubmed/34376152
http://dx.doi.org/10.1186/s12874-021-01361-3
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author Krumkamp, Ralf
Kreuels, Benno
Jaeger, Veronika K.
May, Jürgen
Mikolajczyk, Rafael
Karch, André
author_facet Krumkamp, Ralf
Kreuels, Benno
Jaeger, Veronika K.
May, Jürgen
Mikolajczyk, Rafael
Karch, André
author_sort Krumkamp, Ralf
collection PubMed
description BACKGROUND: A considerable proportion of SARS-CoV-2 transmission occurs from asymptomatic and pre-symptomatic cases. Therefore, different polymerase chain reaction (PCR)- or rapid antigen test (RAT)-based approaches are being discussed and applied to identify infectious individuals that would have otherwise gone undetected. In this article, we provide a framework to estimate the time-dependent risk of being infectious after a negative SARS-CoV-2 test, and we simulate the number of expected infectious individuals over time in populations who initially tested negative. METHODS: A Monte Carlo approach is used to simulate asymptomatic infections over a 10-days period in populations of 1000 individuals following a negative SARS-CoV-2 test. Parameters representing the application of PCR tests or RATs are utilized, and SARS-CoV-2 cumulative 7-day incidences between 25 and 200 per 100,000 people are considered. Simulation results are compared to case numbers predicted via a mathematical equation. RESULTS: The simulations showed a continuous increase in infectious individuals over time in populations of individuals who initially tested SARS-CoV-2 negative. The interplay between false negative rates of PCR tests or RATs, and the time that has passed since testing determines the number of infectious individuals. The simulated and the mathematically predicted number of infectious individuals were comparable. However, Monte Carlo simulations highlight that, due to random variation, theoretically observed infectious individuals can considerably exceed predicted case numbers even shortly after a test was conducted. CONCLUSIONS: This study demonstrates that the number of infectious individuals in a screened group of asymptomatic people can be effectively reduced, and this effect can be described mathematically. However, the false negative rate of a test, the time since the negative test and the underlying SARS-CoV-2 incidence are critical parameters in determining the observed subsequent number of cases in tested population groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12874-021-01361-3.
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spelling pubmed-83534202021-08-10 Negative SARS-CoV-2 PCR or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study Krumkamp, Ralf Kreuels, Benno Jaeger, Veronika K. May, Jürgen Mikolajczyk, Rafael Karch, André BMC Med Res Methodol Research Article BACKGROUND: A considerable proportion of SARS-CoV-2 transmission occurs from asymptomatic and pre-symptomatic cases. Therefore, different polymerase chain reaction (PCR)- or rapid antigen test (RAT)-based approaches are being discussed and applied to identify infectious individuals that would have otherwise gone undetected. In this article, we provide a framework to estimate the time-dependent risk of being infectious after a negative SARS-CoV-2 test, and we simulate the number of expected infectious individuals over time in populations who initially tested negative. METHODS: A Monte Carlo approach is used to simulate asymptomatic infections over a 10-days period in populations of 1000 individuals following a negative SARS-CoV-2 test. Parameters representing the application of PCR tests or RATs are utilized, and SARS-CoV-2 cumulative 7-day incidences between 25 and 200 per 100,000 people are considered. Simulation results are compared to case numbers predicted via a mathematical equation. RESULTS: The simulations showed a continuous increase in infectious individuals over time in populations of individuals who initially tested SARS-CoV-2 negative. The interplay between false negative rates of PCR tests or RATs, and the time that has passed since testing determines the number of infectious individuals. The simulated and the mathematically predicted number of infectious individuals were comparable. However, Monte Carlo simulations highlight that, due to random variation, theoretically observed infectious individuals can considerably exceed predicted case numbers even shortly after a test was conducted. CONCLUSIONS: This study demonstrates that the number of infectious individuals in a screened group of asymptomatic people can be effectively reduced, and this effect can be described mathematically. However, the false negative rate of a test, the time since the negative test and the underlying SARS-CoV-2 incidence are critical parameters in determining the observed subsequent number of cases in tested population groups. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12874-021-01361-3. BioMed Central 2021-08-10 /pmc/articles/PMC8353420/ /pubmed/34376152 http://dx.doi.org/10.1186/s12874-021-01361-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://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.
spellingShingle Research Article
Krumkamp, Ralf
Kreuels, Benno
Jaeger, Veronika K.
May, Jürgen
Mikolajczyk, Rafael
Karch, André
Negative SARS-CoV-2 PCR or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study
title Negative SARS-CoV-2 PCR or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study
title_full Negative SARS-CoV-2 PCR or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study
title_fullStr Negative SARS-CoV-2 PCR or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study
title_full_unstemmed Negative SARS-CoV-2 PCR or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study
title_short Negative SARS-CoV-2 PCR or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study
title_sort negative sars-cov-2 pcr or rapid antigen test result and the subsequent risk of being infectious: a mathematical simulation study
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8353420/
https://www.ncbi.nlm.nih.gov/pubmed/34376152
http://dx.doi.org/10.1186/s12874-021-01361-3
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