Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a generalist virus, infecting and evolving in numerous mammals, including captive and companion animals, free-ranging wildlife, and humans. Transmission among non-human species poses a risk for the establishment of SARS-CoV-2 reservoirs, makes eradication difficult, and provides the virus with opportunities for new evolutionary trajectories, including the selection of adaptive mutations and the emergence of new variant lineages. Here, we use publicly available viral genome sequences and phylogenetic analysis to systematically investigate the transmission of SARS-CoV-2 between human and non-human species and to identify mutations associated with each species. We found the highest frequency of animal-to-human transmission from mink, compared with lower transmission from other sampled species (cat, dog, and deer). Although inferred transmission events could be limited by sampling biases, our results provide a useful baseline for further studies. Using genome-wide association studies, no single nucleotide variants (SNVs) were significantly associated with cats and dogs, potentially due to small sample sizes. However, we identified three SNVs statistically associated with mink and 26 with deer. Of these SNVs, ~⅔ were plausibly introduced into these animal species from local human populations, while the remaining ~⅓ were more likely derived in animal populations and are thus top candidates for experimental studies of species-specific adaptation. Together, our results highlight the importance of studying animal-associated SARS-CoV-2 mutations to assess their potential impact on human and animal health.

Population Genomics Approaches for Genetic Characterization of SARS-CoV-2 Lineages.

The genome of the Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the pathogen that causes coronavirus disease 2019 (COVID-19), has been sequenced at an unprecedented scale leading to a tremendous amount of viral genome sequencing data. To assist in tracing infection pathways and design preventive strategies, a deep understanding of the viral genetic diversity landscape is needed. We present here a set of genomic surveillance tools from population genetics which can be used to better understand the evolution of this virus in humans. To illustrate the utility of this toolbox, we detail an in depth analysis of the genetic diversity of SARS-CoV-2 in first year of the COVID-19 pandemic. We analyzed 329,854 high-quality consensus sequences published in the GISAID database during the pre-vaccination phase. We demonstrate that, compared to standard phylogenetic approaches, haplotype networks can be computed efficiently on much larger datasets. This approach enables real-time lineage identification, a clear description of the relationship between variants of concern, and efficient detection of recurrent mutations. Furthermore, time series change of Tajima's D by haplotype provides a powerful metric of lineage expansion. Finally, principal component analysis (PCA) highlights key steps in variant emergence and facilitates the visualization of genomic variation in the context of SARS-CoV-2 diversity. The computational framework presented here is simple to implement and insightful for real-time genomic surveillance of SARS-CoV-2 and could be applied to any pathogen that threatens the health of populations of humans and other organisms.

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

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.

Outbreak investigation of SARS-CoV-2 transmission in an emergency childcare centre.

OBJECTIVE: To characterize SARS-CoV-2 transmission following a COVID-19 outbreak in an emergency childcare centre (ECCC) in April 2020 in Quebec, Canada. METHODS: The study population consisted of all the children and employees who attended the ECCC as well as household contacts of the confirmed COVID-19 cases. Of the 120 individuals in the study, five cases were confirmed by epidemiological link and 25 were identified as COVID-19 by RT-PCR among which 19 were analyzed by viral whole genome sequencing. Descriptive epidemiology, social network visualization, and phylogenetic analysis were used to characterize viral transmission. RESULTS: Phylogenetic analysis identified two separate introductions of distinct lineages of SARS-CoV-2 and estimated an average effective reproductive number of Re = 1.9 (range 0.9-4.9) with a mean doubling time of 3.2 days (range 2.1-5.2). The first and most prevalent lineage was introduced by two asymptomatic children who were likely infected by their parent, a confirmed COVID-19 case working in a long-term care centre. Among infected household adults, attack rates were significantly higher in mothers than in fathers (risk ratio = 4.5; 95% CI 1.1-18.7). The extent of transmission makes it one of the largest documented outbreaks in a daycare in Canada. CONCLUSION: The analyses carried out showed the probable origin and direction of the transmission of the infection (adult-child, child-adult, and child-child), thus highlighting how asymptomatic children can efficiently transmit SARS-CoV-2.

RéSUMé: OBJECTIF: Caractériser la transmission du SRAS-CoV-2 à la suite d'une éclosion de COVID-19 dans un service de garde d'urgence en milieu scolaire (SGUMS) en avril 2020 au Québec, Canada. MéTHODES: La population à l'étude était composée de tous les enfants et employés ayant fréquenté le SGUMS ainsi que les contacts familiaux des cas confirmés de COVID-19. Sur les 120 personnes à l'étude, cinq cas ont été confirmés par lien épidémiologique et 25 par RT-PCR. Parmi ces derniers, 19 ont été analysés par séquençage viral du génome entier. La caractérisation de la transmission a été réalisée à l'aide d'analyses descriptives et phylogénétiques ainsi que de la visualisation de réseaux sociaux. RéSULTATS: L'analyse phylogénétique a identifié deux introductions de lignées distinctes du SRAS-CoV-2 et un taux de reproduction net Re = 1,9 (étendue 0,9­4,9) avec un temps moyen de doublement de 3,2 jours (étendue 2,1­5,2). La première lignée, et la plus répandue, a été introduite par deux enfants asymptomatiques qui ont probablement été infectés par leur parent, un travailleur de la santé atteint de COVID-19. Dans les noyaux familiaux, les taux d'attaque étaient significativement plus élevés chez les mères que chez les pères (rapport de risque = 4,5 ; IC à 95 % 1,1­18,7). L'ampleur de la transmission en fait de celle-ci la plus importante éclosion documentée dans un service de garde au Canada. CONCLUSION: Cette étude a permis de déterminer l'origine et la direction probables de la transmission de l'infection (adulte-enfant, enfant-adulte et enfant-enfant) et démontrer que les enfants asymptomatiques peuvent transmettre le SRAS-CoV-2.