RESUMEN
Wastewater-based epidemiology has emerged as a promising tool to monitor pathogens in a population, particularly when clinical diagnostic capacities become overwhelmed. During the ongoing COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), several jurisdictions have tracked viral concentrations in wastewater to inform public health authorities. While some studies have also sequenced SARS-CoV-2 genomes from wastewater, there have been relatively few direct comparisons between viral genetic diversity in wastewater and matched clinical samples from the same region and time period. Here we report sequencing and inference of SARS-CoV-2 mutations and variant lineages (including variants of concern) in 936 wastewater samples and thousands of matched clinical sequences collected between March 2020 and July 2021 in the cities of Montreal, Quebec City, and Laval, representing almost half the population of the Canadian province of Quebec. We benchmarked our sequencing and variant-calling methods on known viral genome sequences to establish thresholds for inferring variants in wastewater with confidence. We found that variant frequency estimates in wastewater and clinical samples are correlated over time in each city, with similar dates of first detection. Across all variant lineages, wastewater detection is more concordant with targeted outbreak sequencing than with semi-random clinical swab sampling. Most variants were first observed in clinical and outbreak data due to higher sequencing rate. However, wastewater sequencing is highly efficient, detecting more variants for a given sampling effort. This shows the potential for wastewater sequencing to provide useful public health data, especially at places or times when sufficient clinical sampling is infrequent or infeasible.
RESUMEN
Using genomic epidemiology, we investigated the arrival of SARS-CoV-2 to Quebec, 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 Quebec, 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.