Estimating the increase in reproduction number associated with the Delta variant using local area dynamics in England

  1. Sam Abbott
  2. CMMID COVID-19 Working Group
  3. Adam J. Kucharski
  4. Sebastian Funk

Reviewed by

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

Background

Local estimates of the time-varying effective reproduction number ( R t ) of COVID-19 in England became increasingly heterogeneous during April and May 2021. This may have been attributable to the spread of the Delta SARS-CoV-2 variant. This paper documents real-time analysis that aimed to investigate the association between changes in the proportion of positive cases that were S-gene positive, an indicator of the Delta variant against a background of the previously predominant Alpha variant, and the estimated time-varying R t at the level of upper-tier local authorities (UTLA).

Method

We explored the relationship between the proportion of samples that were S-gene positive and the R t of test-positive cases over time from the 23 February 2021 to the 25 May 2021. Effective reproduction numbers were estimated using the EpiNow2 R package independently for each local authority using two different estimates of the generation time. We then fit a range of regression models to estimate a multiplicative relationship between S-gene positivity and weekly mean R t estimate.

Results

We found evidence of an association between increased mean R t estimates and the proportion of S-gene positives across all models evaluated with the magnitude of the effect increasing as model flexibility was decreased. Models that adjusted for either national level or NHS region level time-varying residuals were found to fit the data better, suggesting potential unexplained confounding.

Conclusions

Our results indicated that even after adjusting for time-varying residuals between NHS regions, S-gene positivity was associated with an increase in the effective reproduction number of COVID-19. These findings were robust across a range of models and generation time assumptions, though the specific effect size was variable depending on the assumptions used. The lower bound of the estimated effect indicated that the reproduction number of Delta was above 1 in almost all local authorities throughout the period of investigation.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.11.30.21267056: (What is this?)

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

    Table 1: Rigor

    NIH rigor criteria are not applicable to paper type.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    reopening phase 1/2) is in place and 0 otherwise, Gikt is the relative mobility in context k (home, workplace, public transport) at time t in UTLA i as measured by Google, and s(t) is a time-varying component, modelled either as a region-specific thin-plate regression spline (“Regional time-varying”), the sum of a static regional parameter and a national spline (“National time-varying”), or only a static regional parameter (“Regional static”).
    Google
    suggested: (Google, RRID:SCR_017097)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Our results should be treated with caution as several caveats apply: we assumed that S-gene positive and negative cases had the same generation interval, while a complementary hypothesis might be that the new variant shortened the generation interval, affecting our estimates[18]. We assumed that the effect of tiers and lockdown applied uniformly across the country. While we did allow for a flexible regional-level behaviour through our use of UTLA level intercepts and region-specific regression splines as sensitivity analysis, there may be UTLA level, potentially spatial structured, variation that we did not capture in doing so. If this could explain some of the sub-regional differences in reproduction numbers, our estimate for the increased reproduction number could be biased. In addition, we did not include case importation between UTLAs or cases linked to international travel which may have particularly biased initial estimates. Our estimates are also likely to be overly precise as we fitted the model only to the mean estimated reproduction numbers and therefore ignored uncertainty in these estimates as well as in the proportion of S-gene positives observed in every UTLA per week, which were treated as fixed-point estimates and naively referenced to the week of infection using an assumed delay of one week. Improving our inference method to incorporate these uncertainties is a future aim of our research[19]. Our estimates may also be biased as S-gene status is only a proxy f...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.11.30.21267056 on medRxiv