CT threshold values, a proxy for viral load in community sars-cov-2 cases, demonstrate wide variation across populations and over time

A. Sarah Walker; Emma Pritchard; Thomas House; Julie Robotham; Paul Birrell; Iain Bell; John I. Bell; John N. Newton; Jeremy Farrar; Ian Diamond; Ruth Studley; Jodie Hay; Karina Doris Vihta; Timothy E.A. Peto; Nicole Stoesser; Philippa C. Matthews; David W. Eyre; Koen Pouwels

doi:10.7554/eLife.64683

CT threshold values, a proxy for viral load in community sars-cov-2 cases, demonstrate wide variation across populations and over time

A. Sarah Walker^*, Emma Pritchard, Thomas House, Julie Robotham, Paul Birrell, Iain Bell, John I. Bell, John N. Newton, Jeremy Farrar, Ian Diamond, Ruth Studley, Jodie Hay, Karina Doris Vihta, Timothy E.A. Peto, Nicole Stoesser, Philippa C. Matthews, David W. Eyre, Koen Pouwels

^*Corresponding author for this work

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Abstract

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.

Original language	English
Article number	e64683
Journal	eLife
Volume	10
DOIs	https://doi.org/10.7554/eLife.64683
Publication status	Published - 12 Jul 2021

Bibliographical note

Funding Information: This study is funded by the Department of Health and Social
Care. ASW, EP, JVR, TEAP, NS, DE, KBP are supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with Public Health England (PHE) (NIHR200915). ASW and TEAP are also supported by the NIHR Oxford Biomedical Research Centre. EP and KBP are also supported by the Huo Family Foundation. ASW is also supported by core support from the Medical Research Council UK to the MRC Clinical Trials Unit [MC_UU_12023/22] and is an NIHR Senior Investigator. PCM is funded by Wellcome (intermediate fellowship, grant ref 110110/Z/15/Z) and holds an NIHR BRC Senior Fellowship award. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, Department of Health, or PHE. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
David W Eyre: declares lecture fees from Gilead, outside the submitted work. The other authors declare that no competing interests exist.

Open Access: This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Publisher Copyright: Copyright Walker et al.

Citation: Sarah, Walker A., et al. "Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time." eLife 10 (2021).

DOI: https://doi.org/10.7554/eLife.64683

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Walker, A. S., Pritchard, E., House, T., Robotham, J., Birrell, P., Bell, I., Bell, J. I., Newton, J. N., Farrar, J., Diamond, I., Studley, R., Hay, J., Vihta, K. D., Peto, T. E. A., Stoesser, N., Matthews, P. C., Eyre, D. W., & Pouwels, K. (2021). CT threshold values, a proxy for viral load in community sars-cov-2 cases, demonstrate wide variation across populations and over time. eLife, 10, Article e64683. https://doi.org/10.7554/eLife.64683

@article{340be74c899a4ee7b1d7268f734217ac,

title = "CT threshold values, a proxy for viral load in community sars-cov-2 cases, demonstrate wide variation across populations and over time",

abstract = "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{\textquoteright}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.",

author = "Walker, {A. Sarah} and Emma Pritchard and Thomas House and Julie Robotham and Paul Birrell and Iain Bell and Bell, {John I.} and Newton, {John N.} and Jeremy Farrar and Ian Diamond and Ruth Studley and Jodie Hay and Vihta, {Karina Doris} and Peto, {Timothy E.A.} and Nicole Stoesser and Matthews, {Philippa C.} and Eyre, {David W.} and Koen Pouwels",

note = "Funding Information: This study is funded by the Department of Health and Social Care. ASW, EP, JVR, TEAP, NS, DE, KBP are supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with Public Health England (PHE) (NIHR200915). ASW and TEAP are also supported by the NIHR Oxford Biomedical Research Centre. EP and KBP are also supported by the Huo Family Foundation. ASW is also supported by core support from the Medical Research Council UK to the MRC Clinical Trials Unit [MC_UU_12023/22] and is an NIHR Senior Investigator. PCM is funded by Wellcome (intermediate fellowship, grant ref 110110/Z/15/Z) and holds an NIHR BRC Senior Fellowship award. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, Department of Health, or PHE. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. David W Eyre: declares lecture fees from Gilead, outside the submitted work. The other authors declare that no competing interests exist. Open Access: This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Publisher Copyright: Copyright Walker et al. Citation: Sarah, Walker A., et al. {"}Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time.{"} eLife 10 (2021). DOI: https://doi.org/10.7554/eLife.64683",

year = "2021",

month = jul,

day = "12",

doi = "10.7554/eLife.64683",

language = "English",

volume = "10",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

Walker, AS, Pritchard, E, House, T, Robotham, J , Birrell, P, Bell, I, Bell, JI, Newton, JN, Farrar, J, Diamond, I, Studley, R, Hay, J, Vihta, KD, Peto, TEA, Stoesser, N, Matthews, PC, Eyre, DW & Pouwels, K 2021, 'CT threshold values, a proxy for viral load in community sars-cov-2 cases, demonstrate wide variation across populations and over time', eLife, vol. 10, e64683. https://doi.org/10.7554/eLife.64683

TY - JOUR

T1 - CT threshold values, a proxy for viral load in community sars-cov-2 cases, demonstrate wide variation across populations and over time

AU - Walker, A. Sarah

AU - Pritchard, Emma

AU - House, Thomas

AU - Robotham, Julie

AU - Birrell, Paul

AU - Bell, Iain

AU - Bell, John I.

AU - Newton, John N.

AU - Farrar, Jeremy

AU - Diamond, Ian

AU - Studley, Ruth

AU - Hay, Jodie

AU - Vihta, Karina Doris

AU - Peto, Timothy E.A.

AU - Stoesser, Nicole

AU - Matthews, Philippa C.

AU - Eyre, David W.

AU - Pouwels, Koen

N1 - Funding Information: This study is funded by the Department of Health and Social Care. ASW, EP, JVR, TEAP, NS, DE, KBP are supported by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at the University of Oxford in partnership with Public Health England (PHE) (NIHR200915). ASW and TEAP are also supported by the NIHR Oxford Biomedical Research Centre. EP and KBP are also supported by the Huo Family Foundation. ASW is also supported by core support from the Medical Research Council UK to the MRC Clinical Trials Unit [MC_UU_12023/22] and is an NIHR Senior Investigator. PCM is funded by Wellcome (intermediate fellowship, grant ref 110110/Z/15/Z) and holds an NIHR BRC Senior Fellowship award. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR, Department of Health, or PHE. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. David W Eyre: declares lecture fees from Gilead, outside the submitted work. The other authors declare that no competing interests exist. Open Access: This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. Publisher Copyright: Copyright Walker et al. Citation: Sarah, Walker A., et al. "Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time." eLife 10 (2021). DOI: https://doi.org/10.7554/eLife.64683

PY - 2021/7/12

Y1 - 2021/7/12

N2 - 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.

AB - 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.

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U2 - 10.7554/eLife.64683

DO - 10.7554/eLife.64683

M3 - Article

AN - SCOPUS:85111329823

SN - 2050-084X

VL - 10

JO - eLife

JF - eLife

M1 - e64683

ER -

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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