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At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data

BACKGROUND: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for inf...

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Autores principales: Mallett, Sue, Allen, A. Joy, Graziadio, Sara, Taylor, Stuart A., Sakai, Naomi S., Green, Kile, Suklan, Jana, Hyde, Chris, Shinkins, Bethany, Zhelev, Zhivko, Peters, Jaime, Turner, Philip J., Roberts, Nia W., di Ruffano, Lavinia Ferrante, Wolff, Robert, Whiting, Penny, Winter, Amanda, Bhatnagar, Gauraang, Nicholson, Brian D., Halligan, Steve
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609379/
https://www.ncbi.nlm.nih.gov/pubmed/33143712
http://dx.doi.org/10.1186/s12916-020-01810-8
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author Mallett, Sue
Allen, A. Joy
Graziadio, Sara
Taylor, Stuart A.
Sakai, Naomi S.
Green, Kile
Suklan, Jana
Hyde, Chris
Shinkins, Bethany
Zhelev, Zhivko
Peters, Jaime
Turner, Philip J.
Roberts, Nia W.
di Ruffano, Lavinia Ferrante
Wolff, Robert
Whiting, Penny
Winter, Amanda
Bhatnagar, Gauraang
Nicholson, Brian D.
Halligan, Steve
author_facet Mallett, Sue
Allen, A. Joy
Graziadio, Sara
Taylor, Stuart A.
Sakai, Naomi S.
Green, Kile
Suklan, Jana
Hyde, Chris
Shinkins, Bethany
Zhelev, Zhivko
Peters, Jaime
Turner, Philip J.
Roberts, Nia W.
di Ruffano, Lavinia Ferrante
Wolff, Robert
Whiting, Penny
Winter, Amanda
Bhatnagar, Gauraang
Nicholson, Brian D.
Halligan, Steve
author_sort Mallett, Sue
collection PubMed
description BACKGROUND: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. METHODS: We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. RESULTS: Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from − 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. CONCLUSIONS: RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.
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spelling pubmed-76093792020-11-05 At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data Mallett, Sue Allen, A. Joy Graziadio, Sara Taylor, Stuart A. Sakai, Naomi S. Green, Kile Suklan, Jana Hyde, Chris Shinkins, Bethany Zhelev, Zhivko Peters, Jaime Turner, Philip J. Roberts, Nia W. di Ruffano, Lavinia Ferrante Wolff, Robert Whiting, Penny Winter, Amanda Bhatnagar, Gauraang Nicholson, Brian D. Halligan, Steve BMC Med Research Article BACKGROUND: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity. METHODS: We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites. RESULTS: Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from − 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset. CONCLUSIONS: RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated. BioMed Central 2020-11-04 /pmc/articles/PMC7609379/ /pubmed/33143712 http://dx.doi.org/10.1186/s12916-020-01810-8 Text en © The Author(s) 2020 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/. 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.
spellingShingle Research Article
Mallett, Sue
Allen, A. Joy
Graziadio, Sara
Taylor, Stuart A.
Sakai, Naomi S.
Green, Kile
Suklan, Jana
Hyde, Chris
Shinkins, Bethany
Zhelev, Zhivko
Peters, Jaime
Turner, Philip J.
Roberts, Nia W.
di Ruffano, Lavinia Ferrante
Wolff, Robert
Whiting, Penny
Winter, Amanda
Bhatnagar, Gauraang
Nicholson, Brian D.
Halligan, Steve
At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data
title At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data
title_full At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data
title_fullStr At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data
title_full_unstemmed At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data
title_short At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data
title_sort at what times during infection is sars-cov-2 detectable and no longer detectable using rt-pcr-based tests? a systematic review of individual participant data
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609379/
https://www.ncbi.nlm.nih.gov/pubmed/33143712
http://dx.doi.org/10.1186/s12916-020-01810-8
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