Spatiotemporal dissemination pattern of SARS-CoV-2 B1.1.28-derived lineages introduced into Uruguay across its southeastern border with Brazil

  1. Natalia Rego
  2. Tamara Fernández-Calero
  3. Ighor Arantes
  4. Verónica Noya
  5. Daiana Mir
  6. Mariana Brandes
  7. Juan Zanetti
  8. Mailen Arleo
  9. Emiliano Pereira
  10. Tania Possi
  11. Odhille Chappos
  12. Lucia Bilbao
  13. Natalia Reyes
  14. Melissa Duquía
  15. Matías Victoria
  16. Pía Techera
  17. María José Benítez-Galeano
  18. Luciana Griffero
  19. Mauricio Méndez
  20. Belén González
  21. Pablo Smircich
  22. Rodney Colina
  23. Cecilia Alonso
  24. Gonzalo Bello
  25. Lucía Spangenberg

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Abstract

During the first nine months of the SARS-CoV-2 pandemic, Uruguay successfully kept it under control, even when our previous studies support a recurrent viral flux across the Uruguayan-Brazilian border that sourced several local outbreaks in Uruguay. However, towards the end of 2020, a remarkable exponential growth was observed and the TETRIS strategy was lost. Here, we aimed to understand the factors that fueled SARS-CoV-2 viral dynamics during the first epidemic wave in the country. We recovered 84 whole viral genomes from patients diagnosed between November, 2020 and February, 2021 in Rocha, a sentinel eastern Uruguayan department bordering Brazil. The lineage B.1.1.28 was the most prevalent in Rocha during November-December 2020, P.2 became the dominant one during January-February 2021, while the first P.1 sequences corresponds to February, 2021. The lineage replacement process agrees with that observed in several Brazilian states, including Rio Grande do Sul (RS). We observed a one to three month delay between the appearance of P.2 and P.1 in RS and their subsequent detection in Rocha. The phylogenetic analysis detected two B.1.1.28 and one P.2 main Uruguayan SARS-CoV-2 clades, introduced from the southern and southeastern Brazilian regions into Rocha between early November and mid December, 2020. One synonymous mutation distinguishes the sequences of the main B.1.1.28 clade in Rocha from those widely distributed in RS. The minor B.1.1.28 cluster, distinguished by several mutations, harbours non-synonymous changes in the Spike protein: Q675H and Q677H, so far not concurrently reported. The convergent appearance of S:Q677H in different viral lineages and its proximity to the S1/S2 cleavage site raise concerns about its functional relevance. The observed S:E484K-VOI P.2 partial replacement of previously circulating lineages in Rocha might have increased transmissibility as suggested by the significant decrease in Ct values. Our study emphasizes the impact of Brazilian SARS-CoV-2 epidemics in Uruguay and the need of reinforcing real-time genomic surveillance on specific Uruguayan border locations, as one of the key elements for achieving long-term COVID-19 epidemic control.

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    SciScore for 10.1101/2021.07.05.21259760: (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
    Real-Time PCR assay and on the other, GeneFinder Covid-19 Plus RealAmp Kit, according to manufacturer’s instructions.
    GeneFinder
    suggested: (GENEFINDER, RRID:SCR_009190)
    We used MinION sequencing platforms (Oxford Nanopore Technologies Ltd., Oxford, UK) as described in detail elsewhere [21] SARS-CoV-2 whole-genome consensus sequences: Whole-genome consensus sequences obtained from ONT were generated using an adaptation of the nCoV-2019 novel coronavirus Artic bioinformatics protocol (https://artic.network/ncov-2019/ncov2019-bioinformatics-sop.html) as in [11] and adjustments made by Ferrés in https://github.com/iferres/ncov2019-artic-nf.
    MinION
    suggested: (MinION, RRID:SCR_017985)
    Alignment was performed with MAFFT v7.471 [26].
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    Maximum likelihood (ML) phylogenetic analysis of final 238 B.1.1.28, P.1 and P.2 sequences was conducted using IQ-TREE version 1.6.12 under the GTR+F+I nucleotide substitution model selected by the built-in ModelFinder option [23].
    IQ-TREE
    suggested: (IQ-TREE, RRID:SCR_017254)
    Phylogenetic trees were estimated in BEAST 1.10 [30] using the GTR+F+I, GTR+F and GTR+F+I nucleotide substitution models for clades UY-IP2, UY-I28, and UY-II28, respectively, the nonparametric Bayesian skyline model as the coalescent tree prior [31], a strict molecular clock model with a uniform substitution rate prior (8−10 × 10−4 substitutions/site/year) and a reversible discrete phylogeographic model [32] with a continuous-time Markov chain (CTMC) rate reference prior [33].
    BEAST
    suggested: (BEAST, RRID:SCR_010228)
    MCMC chains were run for 50 million generations and convergence (Effective Sample Size > 200) in parameter estimates was assessed using TRACER v1.7 [34].
    TRACER
    suggested: (Tracer, RRID:SCR_019121)
    Maximum clade credibility (MCC) trees were summarized with TreeAnnotator v1.10 [35] and visualized using FigTree v1.4.4 (http://tree.bio.ed.ac.uk/software/figtree).
    TreeAnnotator
    suggested: (BEAST2, RRID:SCR_017307)
    FigTree
    suggested: (FigTree, RRID:SCR_008515)
    Additional visualizations were implemented in the R environment with treeio and ggtree Bioconductor packages [36].
    Bioconductor
    suggested: (Bioconductor, RRID:SCR_006442)
    We also determined the mobility index of each period as calculated in https://hdl.handle.net/20.500.12008/27166 based on Google data, and the effective reproductive number (Re) for Rocha (7 day roll-up average) as calculated by the EpiEstim model [37].
    Google
    suggested: (Google, RRID:SCR_017097)

    Results from OddPub: Thank you for sharing your code and 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.
    • No funding statement was detected.
    • No protocol registration statement was detected.

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

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