SARS-CoV-2 within-host diversity and transmission

  1. Katrina A. Lythgoe
  2. Matthew Hall
  3. Luca Ferretti
  4. Mariateresa de Cesare
  5. George MacIntyre-Cockett
  6. Amy Trebes
  7. Monique Andersson
  8. Newton Otecko
  9. Emma L. Wise
  10. Nathan Moore
  11. Jessica Lynch
  12. Stephen Kidd
  13. Nicholas Cortes
  14. Matilde Mori
  15. Rebecca Williams
  16. Gabrielle Vernet
  17. Anita Justice
  18. Angie Green
  19. Samuel M. Nicholls
  20. M. Azim Ansari
  21. Lucie Abeler-Dörner
  22. Catrin E. Moore
  23. Timothy E. A. Peto
  24. David W. Eyre
  25. Robert Shaw
  26. Peter Simmonds
  27. David Buck
  28. John A. Todd
  29. on behalf of the Oxford Virus Sequencing Analysis Group (OVSG)
  30. Thomas R. Connor
  31. Shirin Ashraf
  32. Ana da Silva Filipe
  33. James Shepherd
  34. Emma C. Thomson
  35. The COVID-19 Genomics UK (COG-UK) Consortium
  36. David Bonsall
  37. Christophe Fraser
  38. Tanya Golubchik

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Abstract

A year into the severe acute respiratory syndrome coronavirus 2 pandemic, we are experiencing waves of new variants emerging. Some of these variants have worrying functional implications, such as increased transmissibility or antibody treatment escape. Lythgoe et al. have undertaken in-depth sequencing of more than 1000 hospital patients' isolates to find out how the virus is mutating within individuals. Overall, there seem to be consistent and reproducible patterns of within-host virus diversity. The authors observed only one or two variants in most samples, but a few carried many variants. Although the evidence indicates strong purifying selection, including in the spike protein responsible for viral entry, the authors also saw evidence for transmission clusters associated with households and other possible superspreader events. After transmission, most variants fizzled out, but occasionally some initiated ongoing transmission and wider dissemination.

Science , this issue p. eabg0821

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  1. Version published to 10.1126/science.abg0821
  2. ScreenIT

    SciScore for 10.1101/2020.05.28.118992: (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
    Bioinformatics processing: De-multiplexed sequence read pairs were classified by Kraken v2 (39) using a custom database containing the human genome (GRCh38 build) and the full RefSeq set of bacterial and viral genomes (pulled May 2020)
    Kraken
    suggested: (Kraken, RRID:SCR_005484)
    Remaining reads, comprised of viral and unclassified reads, were trimmed in two stages: first to remove the random hexamer primers from the forward read and SMARTer TSO from the reverse read, and then to remove Illumina adapter sequences using Trimmomatic v0.36(40), with the ILLUMINACLIP options set to “2:10:7:1:true MINLEN:80”.
    Trimmomatic
    suggested: (Trimmomatic, RRID:SCR_011848)
    Trimmed reads were mapped to the SARS-CoV-2 RefSeq genome of isolate Wuhan-Hu-1 (NC_045512.2), using shiver (41) v1.5.7, with either smalt(42) or bowtie2 (43) as the mapper.
    bowtie2
    suggested: (Bowtie 2, RRID:SCR_016368)
    The resulting set, along with the reference genome Wuhan-Hu-1 (RefSeq ID NC_045512), were aligned using MAFFT (46), with some manual improvement of the algorithmic alignment and removal of problematic sequences performed as a post-processing step.
    RefSeq
    suggested: (RefSeq, RRID:SCR_003496)
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    Phylogenetic association of iSNVs and SNPs: Where an iSNV corresponded to a consensus SNP (by the base pair involved, not simply the site), we performed ancestral state reconstruction on the consensus trees using ClonalFrameML (48) to identify all branches upon which that substitution was involved.
    ClonalFrameML
    suggested: (Clonalframe, RRID:SCR_016060)

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

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  3. Version published to 10.1101/2020.05.28.118992v4 on bioRxiv
  4. Version published to 10.1101/2020.05.28.118992v3 on bioRxiv
  5. Version published to 10.1101/2020.05.28.118992v2 on bioRxiv
  6. Version published to 10.1101/2020.05.28.118992v1 on bioRxiv