The emergence of SARS-CoV-2 in Europe and the US

Abstract

Accurate understanding of the global spread of emerging viruses is critically important for public health response and for anticipating and preventing future outbreaks. Here, we elucidate when, where and how the earliest sustained SARS-CoV-2 transmission networks became established in Europe and the United States (US). Our results refute prior findings erroneously linking cases in January 2020 with outbreaks that occurred weeks later. Instead, rapid interventions successfully prevented onward transmission of those early cases in Germany and Washington State. Other, later introductions of the virus from China to both Italy and Washington State founded the earliest sustained European and US transmission networks. Our analyses reveal an extended period of missed opportunity when intensive testing and contact tracing could have prevented SARS-CoV-2 from becoming established in the US and Europe.

Fig. 1.. Schematic showing a hypothetical path along which the key mutations in the WA outbreak could have taken in a susceptible population, alongside the inferred phylogeny.

(A) Scenario where a hypothetical mutation occurs from WA1-like genomes (B) A hypothetical phylogeny where A17747 and C17858 from the original WA1 virus are maintained in the population and sampled at the end. (C) Hypothetical scenario where a virus one mutation (A17747C) different from WA1 is maintained in the population. (D) The observed tree from the WA outbreak.

Fig. 2.. Epidemic simulation workflow.

(1) FAVITES generates the contact network and (1a) runs an SIR model (1b) to simulate spread through the contact network and (2) produce a transmission network. (3) FAVITES outputs a viral time tree based on the infected individuals in the transmission network from which (4) individuals are subsampled to match the dates of the original epidemic (e.g., WA outbreak clade). (5) Evolutionary rates are applied to the time tree based on the number of variant sites from the original alignment, converting the branches from years to substitutions/site (μ). (6) Genetic sequences at variant sites are evolved over the subsampled tree using Pyvolve, starting with the ancestral sequence (e.g., WA1), based on GTR parameters inferred from the original alignment. (7) The ancestral sequence and invariant sites are added to the sequence data so (8) a maximum likelihood phylogeny can be inferred in IQ-TREE2.

Fig. 3.. Potential phylogenetic relationships between WA1 and the Washington outbreak clade and their occurrence frequencies in 1000 epidemic simulations.

(A) Observed pattern where the WA1 genome is the direct ancestor of the outbreak clade, separated by at least two mutations. (B) Identical sequence to WA1. (C) Sequence that is one mutation divergent from WA1. (D) Lineage forming a basal polytomy with WA1 and the outbreak clade. (E) Sibling lineage to the outbreak clade experiencing only a single mutation from WA1 before divergence. Frequency each relationship was observed in 1000 simulations reported in gray box.

Fig. 4.. MCC tree of SARS-CoV-2 entry into Washington State.

A subtree of the maximum clade credibility (MCC) tree depicting the evolutionary relationships inferred between (i) the first identified SARS-CoV-2 case in the US (WA1); (ii) the clade associated with the Washington State outbreak (including WA2); and (iii) closely related viruses that were identified in multiple locations in Asia. Circles at the tips represent observed taxa and are shaded by location. Branches and internal node circles are shaded similarly by posterior modal location state. Dotted lines represent branches associated with unsampled taxa assigned to Hubei, China (CN). Circle sizes for internal nodes are proportional to posterior clade support. Posterior location state probabilities are shown for three well-supported key nodes.

Fig. 5.. MCC tree of SARS-CoV-2 entry into Europe.

A subtree inferred for viruses from (i) the first outbreak in Europe (Germany, BatPat1), (ii) outbreaks in Italy and New York, and (iii) other locations in Europe. Dotted lines represent branches associated with unsampled taxa assigned to Italy and Hubei, China (CN). Country codes are shown at tips for genomes sampled from travellers returning from Italy. Other features as described in Figure 4.

Fig. 6.. SARS-CoV-2 introductions to Europe and the US.

Pierce projection mapping early and apparently ‘dead-end’ introductions of SARS-CoV-2 to Europe and the US (dashed arrows). These were followed by a series of dispersals (solid arrows) all likely taking place in February 2020: from Hubei Province, China to Northern Italy, from Hubei to Washington State, then from Europe (as the Italian outbreak spread more widely) to New York City.