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Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing

BACKGROUND: As SARS-CoV-2 testing expands, particularly to widespread asymptomatic testing, high sensitivity point-of-care PCR platforms may optimise potential benefits from pooling multiple patients’ samples. METHOD: We tested patients and asymptomatic citizens for SARS-CoV-2, exploring the efficie...

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Autores principales: Burdett, Alison, Toumazou, Christofer, Sahoo, Rashmita, Mujan, Adam, Hon, Tsz-Kin, Bedzo-Nutakor, Judith, Casali, Nicola, Karvela, Maria, Sohbati, Mohammadreza, Cooke, Graham S., Davies, Gary W., Moore, Luke S. P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265726/
https://www.ncbi.nlm.nih.gov/pubmed/34238234
http://dx.doi.org/10.1186/s12879-021-06316-z
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author Burdett, Alison
Toumazou, Christofer
Sahoo, Rashmita
Mujan, Adam
Hon, Tsz-Kin
Bedzo-Nutakor, Judith
Casali, Nicola
Karvela, Maria
Sohbati, Mohammadreza
Cooke, Graham S.
Davies, Gary W.
Moore, Luke S. P.
author_facet Burdett, Alison
Toumazou, Christofer
Sahoo, Rashmita
Mujan, Adam
Hon, Tsz-Kin
Bedzo-Nutakor, Judith
Casali, Nicola
Karvela, Maria
Sohbati, Mohammadreza
Cooke, Graham S.
Davies, Gary W.
Moore, Luke S. P.
author_sort Burdett, Alison
collection PubMed
description BACKGROUND: As SARS-CoV-2 testing expands, particularly to widespread asymptomatic testing, high sensitivity point-of-care PCR platforms may optimise potential benefits from pooling multiple patients’ samples. METHOD: We tested patients and asymptomatic citizens for SARS-CoV-2, exploring the efficiency and utility of CovidNudge (i) for detection in individuals’ sputum (compared to nasopharyngeal swabs), (ii) for detection in pooled sputum samples, and (iii) by modelling roll out scenarios for pooled sputum testing. RESULTS: Across 295 paired samples, we find no difference (p = 0.1236) in signal strength for sputum (mean amplified replicates (MAR) 25.2, standard deviation (SD) 14.2, range 0–60) compared to nasopharyngeal swabs (MAR 27.8, SD 12.4, range 6–56). At 10-sample pool size we find some drop in absolute strength of signal (individual sputum MAR 42.1, SD 11.8, range 13–60 vs. pooled sputum MAR 25.3, SD 14.6, range 1–54; p < 0.0001), but only marginal drop in sensitivity (51/53,96%). We determine a limit of detection of 250 copies/ml for an individual test, rising only four-fold to 1000copies/ml for a 10-sample pool. We find optimal pooled testing efficiency to be a 12–3-1-sample model, yet as prevalence increases, pool size should decrease; at 5% prevalence to maintain a 75% probability of negative first test, 5-sample pools are optimal. CONCLUSION: We describe for the first time the use of sequentially dipped sputum samples for rapid pooled point of care SARS-CoV-2 PCR testing. The potential to screen asymptomatic cohorts rapidly, at the point-of-care, with PCR, offers the potential to quickly identify and isolate positive individuals within a population “bubble”. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06316-z.
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spelling pubmed-82657262021-07-09 Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing Burdett, Alison Toumazou, Christofer Sahoo, Rashmita Mujan, Adam Hon, Tsz-Kin Bedzo-Nutakor, Judith Casali, Nicola Karvela, Maria Sohbati, Mohammadreza Cooke, Graham S. Davies, Gary W. Moore, Luke S. P. BMC Infect Dis Research Article BACKGROUND: As SARS-CoV-2 testing expands, particularly to widespread asymptomatic testing, high sensitivity point-of-care PCR platforms may optimise potential benefits from pooling multiple patients’ samples. METHOD: We tested patients and asymptomatic citizens for SARS-CoV-2, exploring the efficiency and utility of CovidNudge (i) for detection in individuals’ sputum (compared to nasopharyngeal swabs), (ii) for detection in pooled sputum samples, and (iii) by modelling roll out scenarios for pooled sputum testing. RESULTS: Across 295 paired samples, we find no difference (p = 0.1236) in signal strength for sputum (mean amplified replicates (MAR) 25.2, standard deviation (SD) 14.2, range 0–60) compared to nasopharyngeal swabs (MAR 27.8, SD 12.4, range 6–56). At 10-sample pool size we find some drop in absolute strength of signal (individual sputum MAR 42.1, SD 11.8, range 13–60 vs. pooled sputum MAR 25.3, SD 14.6, range 1–54; p < 0.0001), but only marginal drop in sensitivity (51/53,96%). We determine a limit of detection of 250 copies/ml for an individual test, rising only four-fold to 1000copies/ml for a 10-sample pool. We find optimal pooled testing efficiency to be a 12–3-1-sample model, yet as prevalence increases, pool size should decrease; at 5% prevalence to maintain a 75% probability of negative first test, 5-sample pools are optimal. CONCLUSION: We describe for the first time the use of sequentially dipped sputum samples for rapid pooled point of care SARS-CoV-2 PCR testing. The potential to screen asymptomatic cohorts rapidly, at the point-of-care, with PCR, offers the potential to quickly identify and isolate positive individuals within a population “bubble”. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-021-06316-z. BioMed Central 2021-07-08 /pmc/articles/PMC8265726/ /pubmed/34238234 http://dx.doi.org/10.1186/s12879-021-06316-z 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
Burdett, Alison
Toumazou, Christofer
Sahoo, Rashmita
Mujan, Adam
Hon, Tsz-Kin
Bedzo-Nutakor, Judith
Casali, Nicola
Karvela, Maria
Sohbati, Mohammadreza
Cooke, Graham S.
Davies, Gary W.
Moore, Luke S. P.
Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing
title Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing
title_full Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing
title_fullStr Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing
title_full_unstemmed Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing
title_short Pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular SARS-CoV-2 testing
title_sort pooled sputum to optimise the efficiency and utility of rapid, point-of-care molecular sars-cov-2 testing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265726/
https://www.ncbi.nlm.nih.gov/pubmed/34238234
http://dx.doi.org/10.1186/s12879-021-06316-z
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