Whole-genome sequencing of SARS-CoV-2 in the Republic of Ireland during waves 1 and 2 of the pandemic

  1. P.W.G. Mallon
  2. F. Crispie
  3. G. Gonzalez
  4. W. Tinago
  5. A.A. Garcia Leon
  6. M. McCabe
  7. E. de Barra
  8. O. Yousif
  9. J.S. Lambert
  10. C.J. Walsh
  11. J.G. Kenny
  12. E. Feeney
  13. M. Carr
  14. P. Doran
  15. P.D. Cotter

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Abstract

Background

Whole-genome sequencing (WGS) of SARS-CoV-2 laboratory-confirmed cases can provide insights into viral transmission and genetic diversity at a population level. However, less is known about the impact of non-pharmaceutical interventions (NPIs), including ‘lockdowns’, on circulating SARS-CoV-2 lineages and variants of concern, the relative contribution of travel to re-emergence of pandemic waves within communities or how different lineages and variants contribute to disease severity.

Methods

We have conducted an analysis within a prospective, multicentre observational study of individuals attending four hospitals in the South-East of Ireland with COVID-19. Samples underwent WGS from which lineages and variants were assigned, lineage frequency was plotted over time and phylogenetic analysis was employed to determine the origin of variants detected post-lockdown. Univariate and multivariate analyses assessed relationships between viral lineage/variant and COVID-19 disease severity.

Results

We analysed 225 genome sequences across two SARS-CoV-2 waves, 134 (59.6%) from wave 1 (March to June) and 91 (40.4%) from wave 2 (July to December), representing 15.2% of COVID-19 admissions to these hospitals during the sampling periods. Four variants (B.1.1.162, B1.1.70, B.1.1.267 and B.1.1) comprised 68% of variants detected during wave 1. Of these variants, only a single B.1.1.70 sequence was detected in wave 2, while the B.1.177 lineage emerged and contributed to 82.3% of lineages detected. Phylogenetic analysis suggested multiple introductions of wave 2 variants from outside Ireland. We found no consistent association between SARS-CoV-2 lineages and disease severity.

Conclusions

These data suggest elimination of common SARS-CoV-2 lineages from hospitalised cases associated with effective NPIs and that importation of new viral variants through travel was a significant contributor to the re-emergence of the pandemic in the second wave in Ireland. Our findings highlight the importance of genomic surveillance in identifying circulating viral genetic diversity and variants of concern and, also, modelling the disease burden of SARS-CoV-2.

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  1. ScreenIT

    SciScore for 10.1101/2021.02.09.21251402: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: Subjects provide consent for use of routine clinical and laboratory data for research, including demographic characteristics, symptom history, comorbidities, disease severity, clinical outcome, epidemiological risk and treatments, along with results of routine laboratory and radiological investigations.
    IRB: The AIID Cohort is approved by local institutional review boards and all participants provide written, informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The adaptor-ligated libraries were then cleaned using Ampure beads and pooled libraries loaded on flowcells and sequenced on either the MinION or GridION devices (ONT) for 24-72 hrs.
    MinION
    suggested: (MinION, RRID:SCR_017985)
    Subsequently, 310 sequences with the earliest sampling dates were chosen and multiple sequences aligned to the reference (MN908947) and 71 AIID B.1.177 genomic sequences with MAFFT [16].
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    A phylogenetic tree was inferred from this multiple sequence alignment with RAxML [17] with the general time reversible model of substitution allowing for heterogeneity among sites (GTRCAT).
    RAxML
    suggested: (RAxML, RRID:SCR_006086)
    Bubble charts were created in R with ggplot2 packages [18].
    ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    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:
    This study does have limitations. Although our study contains a relatively small sample size compared to the overall reported cases in Ireland and from only one region in Ireland (the South East), it does include a significant proportion of hospitalised cases (15.2% overall) from major hospitals in a geographical location where the majority of SARS-CoV-2 cases in Ireland have been reported. As we only sequenced samples with Cq values of 30 or below, viral genetic lineages with lower viral loads theoretically may be unrepresented, although this technical limitation would apply to all analyses of WGS of SARS-CoV-2. Whole genome sequencing studies in SARS-CoV-2 are also prone to sampling bias, with greater sampling of outbreaks or to detect variants of interest. However, as the AIID cohort took an unselected approach to sampling and did not pre-screen for variants of interest, the impact of any sampling bias would have been less evident. In conclusion, we have described disappearances of viral lineages from hospitalised COVID-19 cases during wave 1 of the pandemic in Ireland occurring alongside lockdown restrictions, and emergence of different SARS-CoV-2 lineages contributing to hospitalisations during wave 2, with phylogenetic analysis pointing to importation through travel as an important source. These findings show the utility of SARS-CoV-2 genomic epidemiology in providing insights into viral genetic lineages and variants of concern and have significant implications for refl...

    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.

    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 10.1101/2021.02.09.21251402v1 on medRxiv