A small number of early introductions seeded widespread transmission of SARS-CoV-2 in Québec, Canada

  1. Carmen Lía Murall
  2. Eric Fournier
  3. Jose Hector Galvez
  4. Arnaud N’Guessan
  5. Sarah J. Reiling
  6. Pierre-Olivier Quirion
  7. Sana Naderi
  8. Anne-Marie Roy
  9. Shu-Huang Chen
  10. Paul Stretenowich
  11. Mathieu Bourgey
  12. David Bujold
  13. Romain Gregoire
  14. Pierre Lepage
  15. Janick St-Cyr
  16. Patrick Willet
  17. Réjean Dion
  18. Hugues Charest
  19. Mark Lathrop
  20. Michel Roger
  21. Guillaume Bourque
  22. Jiannis Ragoussis
  23. B. Jesse Shapiro
  24. Sandrine Moreira

Reviewed by

Read the full article See related articles

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

Background

Québec was the Canadian province most impacted by COVID-19, with 401,462 cases as of September 24th, 2021, and 11,347 deaths due mostly to a very severe first pandemic wave. In April 2020, we assembled the Coronavirus Sequencing in Québec (CoVSeQ) consortium to sequence SARS-CoV-2 genomes in Québec to track viral introduction events and transmission within the province.

Methods

Using genomic epidemiology, we investigated the arrival of SARS-CoV-2 to Québec. We report 2921 high-quality SARS-CoV-2 genomes in the context of > 12,000 publicly available genomes sampled globally over the first pandemic wave (up to June 1st, 2020). By combining phylogenetic and phylodynamic analyses with epidemiological data, we quantify the number of introduction events into Québec, identify their origins, and characterize the spatiotemporal spread of the virus.

Results

Conservatively, we estimated approximately 600 independent introduction events, the majority of which happened from spring break until 2 weeks after the Canadian border closed for non-essential travel. Subsequent mass repatriations did not generate large transmission lineages (> 50 sequenced cases), likely due to mandatory quarantine measures in place at the time. Consistent with common spring break and “snowbird” destinations, most of the introductions were inferred to have originated from Europe via the Americas. Once introduced into Québec, viral lineage sizes were overdispersed, with a few lineages giving rise to most infections. Consistent with founder effects, the earliest lineages to arrive tended to spread most successfully. Fewer than 100 viral introductions arrived during spring break, of which 7–12 led to the largest transmission lineages of the first wave (accounting for 52–75% of all sequenced infections). These successful transmission lineages dispersed widely across the province. Transmission lineage size was greatly reduced after March 11th, when a quarantine order for returning travellers was enacted. While this suggests the effectiveness of early public health measures, the biggest transmission lineages had already been ignited prior to this order.

Conclusions

Combined, our results reinforce how, in the absence of tight travel restrictions or quarantine measures, fewer than 100 viral introductions in a week can ensure the establishment of extended transmission chains.

Article activity feed

  1. Version published to 10.1186/s13073-021-00986-9
  2. ScreenIT

    SciScore for 10.1101/2021.03.20.21253835: (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
    Plate 9 was sequenced using both Nanopore and Illumina technologies, as well as by applying the Cleanplex assay by Paragon Genomics, followed by MGI sequencing.
    Nanopore
    suggested: None
    To do so, reads were aligned to a hybrid reference including SARS-CoV-2 (MN908947.3) and GRCh38 using bwa-mem (v0.7.17).
    SARS-CoV-2
    suggested: (Active Motif Cat# 91351, RRID:AB_2847848)
    Samtools (v1.9) was used to produce a pileup which was then used as input by iVar (v1.3) to create a consensus sequence for regions with a minimum of 10x depth, using reads with a Q score >20 and a minimum allele frequency of 0.75.
    Samtools
    suggested: (SAMTOOLS, RRID:SCR_002105)
    Nanopolish (v0.13.1) was used to call variants in regions with a minimum depth of 16x and a flank of 10bp.
    Nanopolish
    suggested: (Nanopolish, RRID:SCR_016157)
    The Augur/align module was then called to execute the multiple sequence alignment with MAFFT (https://github.com/GSLBiotech/mafft, version v7.463) using Wuhan-1 (Genbank accession MN908947) as a reference genome.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    We used IQ-TREE (http://www.iqtree.org/, version 1.6.12) to construct a phylogenetic tree of Québec only sequences and another tree of Québec and global context sequences, with the GTR substitution model.
    IQ-TREE
    suggested: (IQ-TREE, RRID:SCR_017254)
    Phylodynamics: The molecular clock signal was assessed by plotting the root-to-tip phylogenetic distance against time using TempEst (Rambaut et al. 2016).
    TempEst
    suggested: (TempEst, RRID:SCR_017304)
    The largest (>50 cases) QC transmission lineages were analyzed using Bayesian phylogenetic tree reconstruction with Markov chain Monte Carlo (MCMC) implemented in BEAST v2.6.2 (Bouckaert et al. 2019) with the Birth-Death Skyline (BDSKY) model, assuming a gamma distributed Hasegawa-Kishino-Yano (HYK) nucleotide substitution model (with a uniform distribution 0.25 [0,1] of the nucleotide frequencies, a lognormal 2 [0, ∞] for ϰ, and a γ count of 4 with an exponential distribution 0.5 [-∞, ∞]) and a strict molecular clock (0.8 x 10−3 substitutions/site/year).
    BEAST
    suggested: (BEAST, RRID:SCR_010228)

    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.

    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.

  3. Version published to 10.1101/2021.03.20.21253835 on medRxiv