Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time

Background: Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load). Methods: We included all positive nose and throat swabs 26 April 2020 to 13 March 2021 from the UK’s national COVID-19 Infection Survey, teste...

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Autores principales:	A Sarah Walker, Emma Pritchard, Thomas House, Julie V Robotham, Paul J Birrell, Iain Bell, John I Bell, John N Newton, Jeremy Farrar, Ian Diamond, Ruth Studley, Jodie Hay, Karina-Doris Vihta, Timothy EA Peto, Nicole Stoesser, Philippa C Matthews, David W Eyre, Koen B Pouwels, COVID-19 Infection Survey team
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	SARS-CoV-2 community viral load symptoms Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fb7c41c3ebf6484aa04bcf7f4a824a45
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spelling	oai:doaj.org-article:fb7c41c3ebf6484aa04bcf7f4a824a452021-11-15T14:41:28ZCt threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time10.7554/eLife.646832050-084Xe64683https://doaj.org/article/fb7c41c3ebf6484aa04bcf7f4a824a452021-07-01T00:00:00Zhttps://elifesciences.org/articles/64683https://doaj.org/toc/2050-084XBackground: Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load). Methods: We included all positive nose and throat swabs 26 April 2020 to 13 March 2021 from the UK’s national COVID-19 Infection Survey, tested by RT-PCR for the N, S, and ORF1ab genes. We investigated predictors of median Ct value using quantile regression. Results: Of 3,312,159 nose and throat swabs, 27,902 (0.83%) were RT-PCR-positive, 10,317 (37%), 11,012 (40%), and 6550 (23%) for 3, 2, or 1 of the N, S, and ORF1ab genes, respectively, with median Ct = 29.2 (~215 copies/ml; IQR Ct = 21.9–32.8, 14–56,400 copies/ml). Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity, and age. Single-gene positives almost invariably had Ct > 30, but Cts varied widely in triple-gene positives, including without symptoms. Population-level Cts changed over time, with declining Ct preceding increasing SARS-CoV-2 positivity. Of 6189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4808 (78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody negative. Conclusions: Marked variation in community SARS-CoV-2 Ct values suggests that they could be a useful epidemiological early-warning indicator. Funding: Department of Health and Social Care, National Institutes of Health Research, Huo Family Foundation, Medical Research Council UK; Wellcome Trust.A Sarah WalkerEmma PritchardThomas HouseJulie V RobothamPaul J BirrellIain BellJohn I BellJohn N NewtonJeremy FarrarIan DiamondRuth StudleyJodie HayKarina-Doris VihtaTimothy EA PetoNicole StoesserPhilippa C MatthewsDavid W EyreKoen B PouwelsCOVID-19 Infection Survey teameLife Sciences Publications LtdarticleSARS-CoV-2communityviral loadsymptomsMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SARS-CoV-2 community viral load symptoms Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	SARS-CoV-2 community viral load symptoms Medicine R Science Q Biology (General) QH301-705.5 A Sarah Walker Emma Pritchard Thomas House Julie V Robotham Paul J Birrell Iain Bell John I Bell John N Newton Jeremy Farrar Ian Diamond Ruth Studley Jodie Hay Karina-Doris Vihta Timothy EA Peto Nicole Stoesser Philippa C Matthews David W Eyre Koen B Pouwels COVID-19 Infection Survey team Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
description	Background: Information on SARS-CoV-2 in representative community surveillance is limited, particularly cycle threshold (Ct) values (a proxy for viral load). Methods: We included all positive nose and throat swabs 26 April 2020 to 13 March 2021 from the UK’s national COVID-19 Infection Survey, tested by RT-PCR for the N, S, and ORF1ab genes. We investigated predictors of median Ct value using quantile regression. Results: Of 3,312,159 nose and throat swabs, 27,902 (0.83%) were RT-PCR-positive, 10,317 (37%), 11,012 (40%), and 6550 (23%) for 3, 2, or 1 of the N, S, and ORF1ab genes, respectively, with median Ct = 29.2 (~215 copies/ml; IQR Ct = 21.9–32.8, 14–56,400 copies/ml). Independent predictors of lower Cts (i.e. higher viral load) included self-reported symptoms and more genes detected, with at most small effects of sex, ethnicity, and age. Single-gene positives almost invariably had Ct > 30, but Cts varied widely in triple-gene positives, including without symptoms. Population-level Cts changed over time, with declining Ct preceding increasing SARS-CoV-2 positivity. Of 6189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4808 (78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody negative. Conclusions: Marked variation in community SARS-CoV-2 Ct values suggests that they could be a useful epidemiological early-warning indicator. Funding: Department of Health and Social Care, National Institutes of Health Research, Huo Family Foundation, Medical Research Council UK; Wellcome Trust.
format	article
author	A Sarah Walker Emma Pritchard Thomas House Julie V Robotham Paul J Birrell Iain Bell John I Bell John N Newton Jeremy Farrar Ian Diamond Ruth Studley Jodie Hay Karina-Doris Vihta Timothy EA Peto Nicole Stoesser Philippa C Matthews David W Eyre Koen B Pouwels COVID-19 Infection Survey team
author_facet	A Sarah Walker Emma Pritchard Thomas House Julie V Robotham Paul J Birrell Iain Bell John I Bell John N Newton Jeremy Farrar Ian Diamond Ruth Studley Jodie Hay Karina-Doris Vihta Timothy EA Peto Nicole Stoesser Philippa C Matthews David W Eyre Koen B Pouwels COVID-19 Infection Survey team
author_sort	A Sarah Walker
title	Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
title_short	Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
title_full	Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
title_fullStr	Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
title_full_unstemmed	Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
title_sort	ct threshold values, a proxy for viral load in community sars-cov-2 cases, demonstrate wide variation across populations and over time
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/fb7c41c3ebf6484aa04bcf7f4a824a45
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Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time

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