Ct threshold values, a proxy for viral load in community SARS-CoV-2 cases, demonstrate wide variation across populations and over time
- University of Oxford, United Kingdom
- University of Manchester, United Kingdom
- Public Health England, United Kingdom
- Office for National Statistics, United Kingdom
- The Wellcome Trust, United Kingdom
- University of Glasgow, United Kingdom
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 6,550(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 6,189 participants with IgG S-antibody tests post-first RT-PCR-positive, 4,808(78%) were ever antibody-positive; Cts were significantly higher in those remaining antibody-negative.
Conclusions: Marked variation in community SARS-CoV-2 Ct values suggest 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.
Data availability
De-identified study data are available for access by accredited researchers in the ONS Secure Research Service (SRS) for accredited research purposes under part 5, chapter 5 of the Digital Economy Act 2017. Individuals can apply to be an accredited researcher using the short form on https://researchaccreditationservice.ons.gov.uk/ons/ONS_registration.ofml. Accreditation requires completion of a short free course on accessing the SRS. To request access to data in the SRS, researchers must submit a research project application for accreditation in the Research Accreditation Service (RAS). Research project applications are considered by the project team and the Research Accreditation Panel (RAP) established by the UK Statistics Authority. Project application example guidance and an exemplar of a research project application are available. A complete record of accredited researchers and their projects is published on the UK Statistics Authority website to ensure transparency of access to research data. For further information about accreditation, contact Research.Support@ons.gov.uk or visit the SRS website.Data points underlying Figures are provided in Supplementary File 4 and Stata code in Supplementary File 3.
Article and author information
Author details
Philippa C Matthews
Funding
Department of Health and Social Care (-)
- A Sarah Walker
- Emma Pritchard
- Thomas House
- Iain Bell
- Ian Diamond
- Ruth Studley
- Jodie Hay
- Karina-Doris Vihta
- Koen Pouwels
National Institutes of Health Research (NIHR200915)
- A Sarah Walker
- Emma Pritchard
- Julie V Robotham
- Karina-Doris Vihta
- Timothy EA Peto
- Nicole Stoesser
- David W Eyre
- Koen Pouwels
Huo Family Foundation
- Emma Pritchard
- Koen Pouwels
Medical Research Council (MC_UU_12023/22)
- A Sarah Walker
Wellcome Trust (110110/Z/15/Z)
- Philippa C Matthews
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: Written informed consent was obtained from participants aged 16 years and older, and from parents/carers for those aged 2-15 years; those aged 10-15 years provided written assent. The study received ethical approval from the South Central Berkshire B Research Ethics Committee (20/SC/0195).
Copyright
© 2021, Walker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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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
eLife 10:e64683.
https://doi.org/10.7554/eLife.64683
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Background:
Approximately one-third of patients with HER2-positive breast cancer experienced recurrence within 10 years after receiving 1 year of adjuvant trastuzumab. The ExteNET study showed that 1 year of extended adjuvant neratinib after trastuzumab-based adjuvant therapy could reduce invasive disease-free survival (iDFS) events compared with placebo. This study investigated the efficacy and safety of pyrotinib, an irreversible pan-HER receptor tyrosine kinase inhibitor, after trastuzumab-based adjuvant therapy in patients with high-risk, HER2-positive early or locally advanced breast cancer.
Methods:
This multicenter phase II trial was conducted at 23 centers in China. After enrollment, patients received 1 year of extended adjuvant pyrotinib (400 mg/day), which should be initiated within 6 months after the completion of 1-year adjuvant therapy (trastuzumab alone or plus pertuzumab). The primary endpoint was 2-year iDFS rate.
Results:
Between January 2019 and February 2022, 141 eligible women were enrolled and treated. As of October 10, 2022, the median follow-up was 24 (interquartile range, 18.0–34.0) months. The 2-year iDFS rate was 94.59% (95% confidence interval [CI]: 88.97–97.38) in all patients, 94.90% (95% CI: 86.97–98.06) in patients who completed 1-year treatment, 90.32% (95% CI: 72.93–96.77) in patients who completed only 6-month treatment, 96.74% (95% CI: 87.57–99.18) in the hormone receptor (HR)-positive subgroup, 92.77% (95% CI: 83.48–96.93) in the HR-negative subgroup, 96.88% (95% CI: 79.82–99.55) in the lymph node-negative subgroup, 93.85% (95% CI: 86.81–97.20) in the lymph node-positive subgroup, 97.30% (95% CI: 82.32–99.61) in patients with adjuvant trastuzumab plus pertuzumab, and 93.48% (95% CI: 86.06–97.02) in patients with adjuvant trastuzumab. The most common adverse events were diarrhea (79.4%), fatigue (36.9%), lymphocyte count decreased (36.9%), nausea (33.3%), and hand-foot syndrome (33.3%).
Conclusions:
Extended adjuvant pyrotinib administrated after trastuzumab-based adjuvant therapy showed promising efficacy in patients with high-risk HER2-positive breast cancer. The follow-up is ongoing to determine the long-term benefit.
Funding:
No external funding was received for this work.
Clinical trial number:
ClinicalTrials.gov: NCT05880927
