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

COVID-19 was first reported in December 2019 in Wuhan, China, and has spread around the globe since. The most common tool for tracking and containing the spread of the disease-causing virus-SARS-CoV-2 -are classical epidemiology and contact tracing, which collapse under too high case burdens as seen in this pandemic. However, whole-genome sequencing and phylogenetic analyses of the viral genomes will be crucial to understand the virus evolution and outbreak dynamics to ultimately stop the spread of the disease. Here we combined epidemiological data and whole-genome sequences originating from the time of the arrival of the virus in early 2020 in a typical medium-sized European city, namely Basel-City, Switzerland. On one hand, we identified limited community spread of very distinct viral variants originating from travel returners, which is possibly due to the heightened attention and restrictions imposed on international travellers. On the other hand, we find evidence for large cryptic community spread of a single virus variant in the city, which we infer to have originated around mid-February 2020 in the larger tri-national area around Basel, and which has epidemiological links to a mass gathering event in the region of Alsace, France. 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 center dot 6%), detected first on March 2(nd), although the first sample identified belonged to B.1.1. Within B.1, 68 center dot 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.