The emergence of SARS-CoV-2 in Europe and North America

Abstract

Accurate understanding of the global spread of emerging viruses is critical for public health responses and for anticipating and preventing future outbreaks. Here we elucidate when, where, and how the earliest sustained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission networks became established in Europe and North America. Our results suggest that rapid early interventions successfully prevented early introductions of the virus from taking hold in Germany and the United States. Other, later introductions of the virus from China to both Italy and Washington state, United States, founded the earliest sustained European and North America transmission networks. Our analyses demonstrate the effectiveness of public health measures in preventing onward transmission and show that intensive testing and contact tracing could have prevented SARS-CoV-2 outbreaks from becoming established in these regions.

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

(A) Scenario in which a hypothetical mutation occurs from WA1-like genomes. (B) Hypothetical phylogeny in which A17747 and C17858 from the original WA1 virus are maintained in the population and sampled at the end. (C) Hypothetical scenario in which a virus that differs from WA1 by one mutation (A17858G) is maintained in the population. (D) Observed tree from the WA outbreak.

Fig. 2. Potential phylogenetic relationships between WA1 and the WA outbreak clade and their occurrence probabilities.

(A) Observed pattern in which the WA1 genome is the direct ancestor of the outbreak clade, separated by at least two mutations. (B) Identical sequence to that of WA1. (C) Sequence that diverges from the WA1 sequence by one mutation. (D) Lineage forming a basal polytomy with WA1 and the outbreak clade. (E) Sibling lineage to the outbreak clade, with fewer than two mutations from WA1 before divergence. The frequency of each relationship across 1000 simulations is reported in the gray box.

Fig. 3. Phylogeny of representative sequences, showing connections between sequences that share derived mutations despite differences at the key site 17747.

Derived mutations from ancestral states (relative to the reference sequence hCoV-19/Wuhan/Hu-1/2019|EPI_ISL_402125) are shown above each branch, with position numbers indicated. Branches are connected to taxon names with horizontal dotted lines. The taxon names include a two-letter state or province code, as well as the GISAID accession number. In cases for which more than one sequence is represented, the total number of additional, identical sequences is indicated after the “+” symbol. Sequences that share derived mutations are connected with colored lines on the right, with colors indicating the locations where the connected sequences were sampled. Some lines on the right are dashed for clarity. Names of sequences that contain the derived nucleotide at site 17747 are shaded in gray.

Fig. 4. Hypothesis of SARS-CoV-2 entry into Washington state.

A subtree of the maximum clade credibility (MCC) tree is shown, depicting the evolutionary relationships inferred between (i) the first identified SARS-CoV-2 case in the United States (WA1); (ii) the clade associated with the Washington state outbreak (including WA2) and related viruses (WA-S566 and a virus from New York); and (iii) closely related viruses that were identified in multiple locations in Asia. Genome sequences sampled at the tips of the phylogeny are represented by circles shaded according to sampling location. Internal node circles, representing posterior clade support values, and branches are shaded similarly by location. Dotted lines represent branches associated with unsampled taxa assigned to Hubei and Zhejiang, China. Posterior location state probabilities are shown for three well-supported key nodes (circle color indicates inferred location state). The inset bar chart summarizes the probability by location for a second introduction giving rise to the WA outbreak clade. The mean date and 95% HPD intervals represent estimated time of introduction from Hubei.

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

A subtree was inferred for viruses from (i) the first outbreak in Europe (Germany, BavPat) and identical viruses from China, (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. Country codes are shown at branch tips for genomes sampled from travelers returning from Italy (BR, Brazil; FL, Finland; DE, Germany; NG, Nigeria; MX, Mexico; GB, United Kingdom of Great Britain and Northern Ireland). The inset bar chart summarizes the probability distribution for the location state ancestral to the Italian clade. Other features as described in Fig. 4.

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

Pierce projection mapping of early and apparently “dead-end” introductions of SARS-CoV-2 to Europe and the United States. Successful dispersals between late January and mid-February are shown with solid arrows: from Hubei Province, China, to Northern Italy; from China to Washington state; and later from Europe (as the Italian outbreak spread more widely) to NYC and from China to California. Dashed arrows indicate dead-end introductions.