Emergence and spread of a SARS-CoV-2 lineage A variant (A.23.1) with altered spike protein in Uganda

  1. Daniel Lule Bugembe
  2. My V. T. Phan
  3. Isaac Ssewanyana
  4. Patrick Semanda
  5. Hellen Nansumba
  6. Beatrice Dhaala
  7. Susan Nabadda
  8. Áine Niamh O’Toole
  9. Andrew Rambaut
  10. Pontiano Kaleebu
  11. Matthew Cotten

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Abstract

Here, we report SARS-CoV-2 genomic surveillance from March 2020 until January 2021 in Uganda, a landlocked East African country with a population of approximately 40 million people. We report 322 full SARS-CoV-2 genomes from 39,424 reported SARS-CoV-2 infections, thus representing 0.8% of the reported cases. Phylogenetic analyses of these sequences revealed the emergence of lineage A.23.1 from lineage A.23. Lineage A.23.1 represented 88% of the genomes observed in December 2020, then 100% of the genomes observed in January 2021. The A.23.1 lineage was also reported in 26 other countries. Although the precise changes in A.23.1 differ from those reported in the first three SARS-CoV-2 variants of concern (VOCs), the A.23.1 spike-protein-coding region has changes similar to VOCs including a change at position 613, a change in the furin cleavage site that extends the basic amino acid motif and multiple changes in the immunogenic N-terminal domain. In addition, the A.23.1 lineage has changes in non-spike proteins including nsp6, ORF8 and ORF9 that are also altered in other VOCs. The clinical impact of the A.23.1 variant is not yet clear and it has not been designated as a VOC. However, our findings of emergence and spread of this variant indicate that careful monitoring of this variant, together with assessment of the consequences of the spike protein changes for COVID-19 vaccine performance, are advisable.

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  1. Version published to 10.1038/s41564-021-00933-9
  2. Version published to 10.1101/2021.02.08.21251393v2 on medRxiv
  3. ScreenIT

    SciScore for 10.1101/2021.02.08.21251393: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: Ethical approvals: This study was approved by the Uganda Virus Research Institute-Research and Ethics Committee (UVRI-REC
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    The nucleic acid was converted to cDNA and amplified using SARS-CoV specific 1500bp-amplicon spanning the entire genome as previously described(11).
    SARS-CoV
    suggested: (SARS-CoV RNA SSS, RRID:SCR_007912)
    The resulting DNA amplicons were used to prepare sequencing libraries, barcoded individually and then pooled to sequence on MinION R.9.4.1 flowcells, following the standard manufacturer’s protocol.
    MinION
    suggested: (MinION, RRID:SCR_017985)
    Adapters and primers sequences were removed using Porechop (https://github.com/rrwick/Porechop) and the resulting reads were mapped to the reference genome Wuhan-1 (GenBank NC_045512.2) using minimap2(34) and consensus genomes were generated in Geneious (Biomatters
    Porechop
    suggested: (Porechop, RRID:SCR_016967)
    These global lineage A.23 and A.23.1 genomes combining with Ugandan A.23 and A.23.1 genomes (N = 97) and an outgroup of this A.23 lineage (Uganda strain UG053) were aligned using MAFFT and manually checked in AliView, followed by trimming 5’ and 3’ UTRs.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    AliView
    suggested: (AliView, RRID:SCR_002780)
    The global and Ugandan A.23 and A.23.1 genomes were used to construct a ML tree under the GTR+F+I model as best-fitted substitution model according to AIC determined by ModelFinder and run for 100 pseudo-replicates in IQTREE.
    ModelFinder
    suggested: None
    Resulting trees were visualised in Figtree and rooted using the strain UG053.
    Figtree
    suggested: (FigTree, RRID:SCR_008515)

    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: 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 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.

  4. Version published to 10.1101/2021.02.08.21251393v1 on medRxiv