Coast-to-coast spread of SARS-CoV-2 in the United States revealed by genomic epidemiology

Abstract

Since its emergence and detection in Wuhan, China in late 2019, the novel coronavirus SARS-CoV-2 has spread to nearly every country around the world, resulting in hundreds of thousands of infections to date. The virus was first detected in the Pacific Northwest region of the United States in January, 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the U.S., we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated impacts of federal travel restrictions. This study provides evidence for widespread, sustained transmission of SARS-CoV-2 within the U.S. and highlights the critical need for local surveillance.

Keywords: COVID-19; Coronavirus; Genomic epidemiology; MinION sequencing; Phylogenetics; SARS-CoV-2; Travel Risk.

Figure 1.. The COVID-19 outbreak in Connecticut is phylogenetically linked to SARS-CoV-2 from Washington.

(A) We constructed a maximum-likelihood tree using 168 global SARS-CoV-2 protein coding sequences, including 9 sequences from COVID-19 patients identified in Connecticut from March 6–14, 2020. The total number of nucleotide differences from the root of the tree quantifies evolution since the putative SARS-CoV-2 ancestor. We included clade-defining nucleotide substitutions to directly show the evidence supporting phylogenetic clustering. (B) We enlarged the U.S. clade consisting primarily of SARS-CoV-2 sequences from Washington state and Connecticut. The MinION sequencing statistics are enumerated in Data S1, and the SARS-CoV-2 sequences used and author acknowledgements can be found in Data S2. The genomic data can be visualized and interacted with at: https://nextstrain.org/community/grubaughlab/CT-SARS-CoV-2.

Figure 2.. Domestic outbreaks and travel are a rising source of SARS-CoV-2 importations.

(A) To compare the relative risks of SARS-CoV-2 importations from domestic and international sources, we selected five international (China, Italy, Iran, Spain, and Germany) and out-of-region U.S. states (Washington, California, Florida, Illinois, and Louisiana) with the highest number of reported COVID-19 cases as of March 19, 2020. (B) We selected three international airports in the region that are commonly used by Connecticut residents: Hartford (BDL), Boston (BOS), and New York (JFK). We used data from January to March, 2019, to estimate relative differences in daily air passenger volumes from the selected origins to the airport destinations. These daily estimates were then combined by either international or domestic travel. (C–D) The cumulative number of daily COVID-19 cases were divided by 100,000 population to calculate normalized disease prevalence for each location. (E) We calculated importation risk by modelling the number of daily prevalent COVID-19 cases in each potential importation source and then estimating the number of infected travelers using the daily air travel volume from each location. Data, criteria, and analyses used to create this figure can be found in Data S3.