Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States

Abstract

The novel coronavirus SARS-CoV-2 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 United States, 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 effects of federal travel restrictions. This study provides evidence of widespread sustained transmission of SARS-CoV-2 within the United States and highlights the critical need for local surveillance.

Keywords: COVID-19; MinION sequencing; SARS-CoV-2; coronavirus; genomic epidemiology; phylogenetics; travel risk.

Graphical abstract

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. The number of SARS-CoV-2 genomes used in this phylogenetic tree from each location is shown in parentheses. (B) We enlarged the United States clade consisting primarily of SARS-CoV-2 sequences from Washington state and Connecticut. The map shows the location and number of SARS-CoV-2 genomes that cluster within this clade. The MinION sequencing statistics are enumerated in Data S1, and the SARS-CoV-2 sequences used and author acknowledgments can be found in Data S2. A root-to-tip plot showing the genetic diversity and substitution rate of the data can be found in Figure S1. The genomic data can be visualized and interacted with at https://nextstrain.org/community/grubaughlab/CT-SARS-CoV-2/paper1.

Figure 2

Domestic Outbreaks and Travel Are a Rising Source of SARS-CoV-2 Importation Risk (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 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 and D) The cumulative number of daily COVID-19 cases were divided by 100,000 population to calculate normalized disease prevalence for each international location (China, Italy, Iran, Spain, and Germany) (C). The cumulative number of daily COVID-19 cases were divided by 100,000 population to calculate normalized disease prevalence for each international location (Washington, California, Florida, Illinois, and Louisiana) (D). (E) We calculated importation risk by modeling 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. The data, criteria, and analyses used to create this figure can be found in Data S3.

Figure S1

Root-to-Tip Plot Showing the Evolutionary Rate of the SARS-CoV-2 Genomes in Our Dataset, Related to Figure 1