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Quantifying the Impact of Nasopharyngeal Specimen Quality on Severe Acute Respiratory Syndrome Coronavirus 2 Test Performance

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) has been used to estimate quantitative viral load, with the goal of targeting isolation precautions for individuals with coronavirus disease 2019...

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Autores principales: Richard-Greenblatt, Melissa, Ziegler, Matthew J, Bromberg, Valerie, Huang, Elizabeth, Abdallah, Hatem, Tolomeo, Pam, Lautenbach, Ebbing, Glaser, Laurel, Kelly, Brendan J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136075/
https://www.ncbi.nlm.nih.gov/pubmed/34095340
http://dx.doi.org/10.1093/ofid/ofab235
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author Richard-Greenblatt, Melissa
Ziegler, Matthew J
Bromberg, Valerie
Huang, Elizabeth
Abdallah, Hatem
Tolomeo, Pam
Lautenbach, Ebbing
Glaser, Laurel
Kelly, Brendan J
author_facet Richard-Greenblatt, Melissa
Ziegler, Matthew J
Bromberg, Valerie
Huang, Elizabeth
Abdallah, Hatem
Tolomeo, Pam
Lautenbach, Ebbing
Glaser, Laurel
Kelly, Brendan J
author_sort Richard-Greenblatt, Melissa
collection PubMed
description BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) has been used to estimate quantitative viral load, with the goal of targeting isolation precautions for individuals with coronavirus disease 2019 (COVID-19) and guiding public health interventions. However, variability in specimen quality can alter the Ct values obtained from SARS-CoV-2 clinical assays. We sought to define how variable nasopharyngeal (NP) swab quality impacts clinical SARS-CoV-2 test sensitivity. METHODS: We performed amplification of a human gene target (β-actin) in parallel with a clinical RT-PCR targeting the SARS-CoV-2 ORF1ab gene for 1282 NP specimens collected from patients with clinical concern for COVID-19. We evaluated the relationship between NP specimen quality, characterized by late Ct values for the human gene target β-actin Ct, and the probability of SARS-CoV-2 detection via logistic regression, as well as the linear relationship between SARS-CoV-2 and β-actin Ct. RESULTS: Low-quality NP swabs are less likely to detect SARS-CoV-2 (odds ratio, 0.607 [95% credible interval {CrI}, .487–.753]). We observed a positive linear relationship between SARS-CoV-2 and β-actin Ct values (slope, 0.181 [95% CrI, .097–.264]), consistent with a reduction in detection of 0.181 cycles for each additional cycle of the β-actin target. COVID-19 disease severity was not associated with β-actin Ct values. CONCLUSIONS: Variability in NP specimen quality significantly impacts the performance of clinical SARS-CoV-2 assays, and caution should be taken when interpreting quantitative SARS-CoV-2 Ct results. If unrecognized, low-quality NP specimens, which are characterized by a low level of amplifiable human DNA target, may limit the successful application of SARS-CoV-2 Ct values to direct infection control and public health interventions.
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spelling pubmed-81360752021-05-21 Quantifying the Impact of Nasopharyngeal Specimen Quality on Severe Acute Respiratory Syndrome Coronavirus 2 Test Performance Richard-Greenblatt, Melissa Ziegler, Matthew J Bromberg, Valerie Huang, Elizabeth Abdallah, Hatem Tolomeo, Pam Lautenbach, Ebbing Glaser, Laurel Kelly, Brendan J Open Forum Infect Dis Major Articles BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) has been used to estimate quantitative viral load, with the goal of targeting isolation precautions for individuals with coronavirus disease 2019 (COVID-19) and guiding public health interventions. However, variability in specimen quality can alter the Ct values obtained from SARS-CoV-2 clinical assays. We sought to define how variable nasopharyngeal (NP) swab quality impacts clinical SARS-CoV-2 test sensitivity. METHODS: We performed amplification of a human gene target (β-actin) in parallel with a clinical RT-PCR targeting the SARS-CoV-2 ORF1ab gene for 1282 NP specimens collected from patients with clinical concern for COVID-19. We evaluated the relationship between NP specimen quality, characterized by late Ct values for the human gene target β-actin Ct, and the probability of SARS-CoV-2 detection via logistic regression, as well as the linear relationship between SARS-CoV-2 and β-actin Ct. RESULTS: Low-quality NP swabs are less likely to detect SARS-CoV-2 (odds ratio, 0.607 [95% credible interval {CrI}, .487–.753]). We observed a positive linear relationship between SARS-CoV-2 and β-actin Ct values (slope, 0.181 [95% CrI, .097–.264]), consistent with a reduction in detection of 0.181 cycles for each additional cycle of the β-actin target. COVID-19 disease severity was not associated with β-actin Ct values. CONCLUSIONS: Variability in NP specimen quality significantly impacts the performance of clinical SARS-CoV-2 assays, and caution should be taken when interpreting quantitative SARS-CoV-2 Ct results. If unrecognized, low-quality NP specimens, which are characterized by a low level of amplifiable human DNA target, may limit the successful application of SARS-CoV-2 Ct values to direct infection control and public health interventions. Oxford University Press 2021-05-12 /pmc/articles/PMC8136075/ /pubmed/34095340 http://dx.doi.org/10.1093/ofid/ofab235 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) ), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Major Articles
Richard-Greenblatt, Melissa
Ziegler, Matthew J
Bromberg, Valerie
Huang, Elizabeth
Abdallah, Hatem
Tolomeo, Pam
Lautenbach, Ebbing
Glaser, Laurel
Kelly, Brendan J
Quantifying the Impact of Nasopharyngeal Specimen Quality on Severe Acute Respiratory Syndrome Coronavirus 2 Test Performance
title Quantifying the Impact of Nasopharyngeal Specimen Quality on Severe Acute Respiratory Syndrome Coronavirus 2 Test Performance
title_full Quantifying the Impact of Nasopharyngeal Specimen Quality on Severe Acute Respiratory Syndrome Coronavirus 2 Test Performance
title_fullStr Quantifying the Impact of Nasopharyngeal Specimen Quality on Severe Acute Respiratory Syndrome Coronavirus 2 Test Performance
title_full_unstemmed Quantifying the Impact of Nasopharyngeal Specimen Quality on Severe Acute Respiratory Syndrome Coronavirus 2 Test Performance
title_short Quantifying the Impact of Nasopharyngeal Specimen Quality on Severe Acute Respiratory Syndrome Coronavirus 2 Test Performance
title_sort quantifying the impact of nasopharyngeal specimen quality on severe acute respiratory syndrome coronavirus 2 test performance
topic Major Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136075/
https://www.ncbi.nlm.nih.gov/pubmed/34095340
http://dx.doi.org/10.1093/ofid/ofab235
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