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

Using genomic epidemiology, we investigated the arrival of SARS-CoV-2 to Québec, the Canadian province most impacted by COVID-19, with >280,000 positive cases and >10,000 deaths in a population of 8.5 million as of March 1st, 2021. We report 2,921 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 spatio-temporal spread of the virus. Conservatively, we estimated at least 500 independent introduction events, the majority of which happened from spring break until two weeks after the Canadian border closed for non-essential travel. Subsequent mass repatriations did not generate large transmission lineages (>50 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. Fewer than 100 viral introductions arrived during spring break, of which 5-10 led to the largest transmission lineages of the first wave (accounting for 36-58% of all sequenced infections). These successful viral transmission lineages dispersed widely across the province, consistent with founder effects and superspreading dynamics. Transmission lineage size was greatly reduced after March 11th, when a quarantine order for returning travelers was enacted. While this suggests the effectiveness of early public health measures, the biggest transmission lineages had already been ignited prior to this order. 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The work was supported by the McGill Genome Center and the Canadian Center for Computational Genomics, two Genomics Technology Platforms (GTPs) supported by the Canadian Government through Genome Canada and a CFI grant 33408 to JR and GB. This study was also funded by the Sentinelle COVID Quebec variant network led by the Laboratoire de Sante Publique du Quebec (LSPQ) in collaboration with Fonds de la Recherche du Quebec-Sante (FRQS) and Genome Quebec, and supported by the Ministere de la Sante et des Services Sociaux (MSSS), the Ministere de l'Economie et Innovation (MEI) and Genome Canada to SM and MR under the umbrella of the Canadian COVID Genomic Network (CanCOGeN). Data analyses were enabled by compute and storage resources provided by Compute Canada and Calcul Quebec. The funders played no role in the study design. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This investigation was carried out in accordance with the legal mandate granted to public health authorities by the Public Health Act (LRQ, chapter S-2.2. Article 1; ) as part of a public health intervention. All data was treated confidentially and analysed without nominal identification in accordance with the Policy on Information Protection and Security (PO-04-2014) of the National Public Health Institute of Quebec (INSPQ). The INSPQ therefore deemed this study exempt from ethical oversight according to provincial legislation. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All reported genome sequences have been deposited in GISAID under accession numbers listed in Table S1.