Increased infections, but not viral burden, with a new SARS-CoV-2 variant

  1. A. Sarah Walker
  2. Karina-Doris Vihta
  3. Owen Gethings
  4. Emma Pritchard
  5. Joel Jones
  6. Thomas House
  7. Iain Bell
  8. John I Bell
  9. John N Newton
  10. Jeremy Farrar
  11. Ian Diamond
  12. Ruth Studley
  13. Emma Rourke
  14. Jodie Hay
  15. Susan Hopkins
  16. Derrick Crook
  17. Tim Peto
  18. Philippa C. Matthews
  19. David W. Eyre
  20. Nicole Stoesser
  21. Koen B. Pouwels
  22. COVID-19 Infection Survey team

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Abstract

Background

A new variant of SARS-CoV-2, B.1.1.7/VOC202012/01, was identified in the UK in December-2020. Direct estimates of its potential to enhance transmission are limited.

Methods

Nose and throat swabs from 28-September-2020 to 2-January-2021 in the UK’s nationally representative surveillance study were tested by RT-PCR for three genes (N, S and ORF1ab). Those positive only on ORF1ab+N, S-gene target failures (SGTF), are compatible with B.1.1.7/VOC202012/01. We investigated cycle threshold (Ct) values (a proxy for viral load), percentage of positives, population positivity and growth rates in SGTF vs non-SGTF positives.

Results

15,166(0.98%) of 1,553,687 swabs were PCR-positive, 8,545(56%) with three genes detected and 3,531(23%) SGTF. SGTF comprised an increasing, and triple-gene positives a decreasing, percentage of infections from late-November in most UK regions/countries, e.g. from 15% to 38% to 81% over 1.5 months in London. SGTF Ct values correspondingly declined substantially to similar levels to triple-gene positives. Population-level SGTF positivity remained low (<0.25%) in all regions/countries until late-November, when marked increases with and without self-reported symptoms occurred in southern England (to 1.5-3%), despite stable rates of non-SGTF cases. SGTF positivity rates increased on average 6% more rapidly than rates of non-SGTF positives (95% CI 4-9%) supporting addition rather than replacement with B.1.1.7/VOC202012/01. Excess growth rates for SGTF vs non-SGTF positives were similar in those up to high school age (5% (1-8%)) and older individuals (6% (4-9%)).

Conclusions

Direct population-representative estimates show that the B.1.1.7/VOC202012/01 SARS-CoV-2 variant leads to higher infection rates, but does not seem particularly adapted to any age group.

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    SciScore for 10.1101/2021.01.13.21249721: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Following verbal agreement to participate, a study worker visited each household to take written informed consent, which was obtained from parents/carers for those 2-15 years; those aged 10-15 years provided written assent.
    IRB: The study received ethical approval from the South Central Berkshire B Research Ethics Committee (20/SC/0195).
    RandomizationThe survey randomly selects private households on a continuous basis from address lists and previous surveys to provide a representative UK sample.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    RT-PCR for three SARS-CoV-2 genes (N protein, S protein and ORF1ab) used the Thermo Fisher TaqPath RT-PCR COVID-19 Kit, and analysed using UgenTec FastFinder 3.300.5, with an assay-specific algorithm and decision mechanism that allows conversion of amplification assay raw data from the ABI 7500 Fast into test results with minimal manual intervention.
    UgenTec FastFinder
    suggested: None

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    The main limitation is that not all SGTF will be B.1.1.7/VOC202012/01, even in the most recent period, as illustrated by varying Ct in SGTF by region (Figure 1B). Rather, we model SGTF in their entirety to estimate a “background” rate on which we can assess when B.1.1.7/VOC202012/01 might have arisen, as indicated by evidence for a change in trend using ISR. Enhanced whole genome sequencing for survey positives started mid-December, but was previously sparse. Preliminary data support B.1.1.7/VOC202012/01 comprising most SGTF in the survey from mid-November, and >88% of SGTF in the national symptomatic testing program are B.1.1.7/VOC202012/01 from this time8. However, conversely, some “non-SGTF” single N-gene or ORF1ab only positives (with high Ct13) could also be B.1.1.7/VOC202012/01. ISR does not identify “optimal” changepoints, and therefore does not correspond exactly to MRP, but this would be expected to lead to dilution bias. Analyses by participant do not account for within-household clustering; however, results were similar in household-level analyses (Supplementary Figure 4). Our analysis is based on regions, although there were some local differences in restrictions on hospitality and socialising within regions. However, mathematical models including only changes in behaviour/contact patterns poorly fitted observed data, suggesting this may have had less effect6. In summary, direct representative population-level estimates of positivity across ages show that the new ...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    ISRCTN21086382NANA

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

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  2. Version published to 10.1101/2021.01.13.21249721 on medRxiv