Viral genetic sequencing identifies staff transmission of COVID-19 is important in a community hospital outbreak

  1. Jane A.H. Masoli
  2. Aaron Jeffries
  3. Ben Temperton
  4. Cressida Auckland
  5. Michelle Michelsen
  6. Joanna Warwick-Dugdale
  7. Robyn Manley
  8. Audrey Farbos
  9. Sian Ellard
  10. Beatrice Knight
  11. Claire Bewshea
  12. Christine Sambles
  13. James Harrison
  14. Ben Bunce
  15. Alexis Carr
  16. Andrew T. Hattersley
  17. Stephen Ll. Michell
  18. David J. Studholme

Reviewed by

Read the full article See related articles

Listed in

Log in to save this article

Abstract

Background

We have successfully used whole-genome sequencing to provide additional information for transmission pathways in infectious spread. We report and interpret genomic sequencing results in clinical context from a large outbreak of COVID-19 with 46 cases across staff and patients in a community hospital in the UK.

Methods

Following multiple symptomatic cases within a two-week period, all staff and patients were screened by RT-PCR and staff subsequently had serology tests.

Results

Thirty staff (25%) and 16 patients (62%) tested positive for COVID-19. Genomic sequencing data showed significant overlap of viral haplotypes in staff who had overlapping shift patterns. Patient haplotypes were more distinct from each other but had overlap with staff haplotypes.

Conclusions

This study includes clinical and genomic epidemiological detail that demonstrates the value of a combined approach. Viral genetic sequencing has identified that staff transmission of COVID-19 was important in this community hospital outbreak.

Key points

  • Detailed analysis of a large community hospital outbreak in older adults and staff with concurrent clinical and genomic data, including working patterns.

  • Staff transmission was important in this community hospital outbreak.

  • We found plausible associations between staff and patient cases.

Article activity feed

  1. ScreenIT

    SciScore for 10.1101/2021.02.18.21250737: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Sequencing was performed on an Oxford Nanopore MinION.
    MinION
    suggested: (MinION, RRID:SCR_017985)
    Duration of sequencing runs sequenced were 16 to 24 hours, with high-accuracy real-time base calling and demultiplexing (Guppy 3.5.2) and monitoring with MinKNOW v3.6.5 (Oxford Nanopore Technologies) and RAMPART12.
    MinKNOW
    suggested: None
    Sequence Analysis: We aligned genome sequences against the Wuhan-Hu-1 reference genome sequence (GenBank MN908947.313) using MAFFT v7.310. 14 Haplotypes were inferred from the resulting alignment using a custom script (https://github.com/davidjstudholme/get_viral_haplotypes) that identifies genomic sites that show variation and are unambiguously called (i.e. no Ns) across all analysed genome sequences to generate a Nexus-formatted output file.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    A limitation of the study is that viral sequence was not generated in all cases, due to unavailable samples or insufficient sequence, probably reflecting low viral load at testing. This outbreak was prior to widespread testing among healthcare workers or asymptomatic inpatients outside outbreak scenarios and if events repeated now it is likely that testing would have occurred earlier in individual symptomatic cases. A key strength of this study is that it combined viral genomic sequencing with epidemiological clinical analysis, RT-PCR and subsequent serological testing to facilitate full outbreak analysis. The screening of all staff members first by RT-PCR and then by serology testing has given a complete picture in this outbreak. The subsequent antibody testing shows that the majority of cases occurred in the staff during this outbreak. The COG-UK genetic sequencing provides excellent coverage for genomic sequencing in the UK and better clinical corroboration could aid understanding in outbreaks and more generally, such as whether new COVID-19 cases over time in the same setting (e.g. a specific care home) are the same haplotype or if distinct viral haplotypes are being introduced by staff or visitors. This could significantly affect policy, but requires centres having access to both clinical detail and viral genomic sequencing, a particular strength of this study, in which the NHS trust and University teams work in close collaboration. It is particularly challenging to comb...

    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 10.1101/2021.02.18.21250737v1 on medRxiv