SARS-CoV-2 outbreak in a tri-national urban area is dominated by a B.1 lineage variant linked to a mass gathering event

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Abstract

The first case of SARS-CoV-2 in Basel, Switzerland was detected on February 26 th 2020. We present a phylogenetic study to explore viral introduction and evolution during the exponential early phase of the local COVID-19 outbreak from February 26 th until March 23 rd . We sequenced SARS-CoV-2 naso-oropharyngeal swabs from 746 positive tests that were performed at the University Hospital Basel during the study period. We successfully generated 468 high quality genomes from unique patients and called variants with our COVID-19 Pipeline (COVGAP), and analysed viral genetic diversity using PANGOLIN taxonomic lineages. To identify introduction and dissemination events we incorporated global SARS-CoV-2 genomes and inferred a time-calibrated phylogeny. Epidemiological data from patient questionnaires was used to facilitate the interpretation of phylogenetic observations. The early outbreak in Basel was dominated by lineage B.1 (83·6%), detected first on March 2 nd , although the first sample identified belonged to B.1.1. Within B.1, 68·2% of our samples fall within a clade defined by the SNP C15324T (‘Basel cluster’), including 157 identical sequences at the root of the ‘Basel cluster’, some of which we can specifically trace to regional spreading events. We infer the origin of B.1-C15324T to mid-February in our tri-national region. The other genomes map broadly over the global phylogenetic tree, showing several introduction events from and/or dissemination to other regions of the world via travellers. Family transmissions can also be traced in our data. A single lineage variant dominated the outbreak in the Basel area while other lineages, such as the first (B.1.1), did not propagate. A mass gathering event was the predominant initial source of cases, with travel returners and family transmissions to a lesser extent. We highlight the importance of adding specific questions to epidemiological questionnaires, to obtain data on attendance of large gatherings and their locations, as well as travel history, to effectively identify routes of transmissions in up-coming outbreaks. This phylogenetic analysis in concert with epidemiological and contact tracing data, allows connection and interpretation of events, and can inform public health interventions.

Trial Registration: ClinicalTrials.gov NCT04351503 .

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  1. SciScore for 10.1101/2020.09.01.20186155: (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
    Total nucleic acids (TNAs) were extracted using the MagNA Pure 96 system and the DNA and viral RNA small volume kit (Roche Diagnostics, Rotkreuz, Switzerland) or using the Abbott m2000 Realtime System and the Abbott sample preparation system reagent kit (Abbott, Baar, Switzerland).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)
    Phylogenetic lineage assignment of Basel samples: To assess the phylogenetic diversity of SARS-CoV-2 samples during the early phase of the pandemic we inferred the lineage assignment for each consensus sequence derived from the COVGAP pipeline using PANGOLIN ver.
    COVGAP
    suggested: None
    We calculated Simpson diversity (inverse Simpson concentration) as implemented in the SpadeR package v.0.0.1 45-47, which controls for lineage abundance differences between the countries, which is dependent on available sequence data, and which ranges from 0 (no diversity) to indefinite (large diversity).
    SpadeR
    suggested: None

    Results from OddPub: Thank you for sharing your code and data.


    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    A limitation of the current study is that we are likely to have missed some cases as not all symptomatic people were advised to be tested, especially children younger than 18 years old. Nevertheless, our cohort represents a very high sequencing density per detected case for a city (468 genomes from 746 PCR-confirmed cases in Basel area (62.7%) and from 10,680 PCR-confirmed cases nationwide (4.4%)) for this early phase of the pandemic28. The availability and integration of epidemiological data in the interpretation of phylogenetic clades underlines the validity of instrumentalising those tools for improving the understanding of SARS-CoV-2 outbreak dynamics. Utilizing the clades as the backbone for targeted epidemiological analysis of specific cases helped in grasping how mass gatherings, travel returners, and care facilities may influence an outbreak within a city. The epidemiological data that was collected for the Federal Office of Public Health (FOPH), as requested by law, helped tremendously to verify travel related links; however it was not designed to obtain data on local super-spreading events such as attendance to soccer games, visiting clubs, restaurants, bars, and concerts and future versions could be improved. The classical epidemiological context is very important to further explain molecular epidemiological links especially in a still not very diversified virus. In conclusion, the start of the outbreak of SARS-CoV-2 in the Basel area was characterized by a dominan...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04351503RecruitingA Systems Approach to Predict the Outcome of SARS-CoV-2 in t…


    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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