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.

Deep mutational scanning of SARS-CoV-2 receptor binding domain reveals constraints on folding and ACE2 binding

“…Vast numbers of viral genomes have been sequenced in almost real-time during the SARS-CoV-2 pandemic. These genomic sequences have been useful for understanding viral emergence and spread (Andersen et al, 2020;Bedford et al, 2020;Fauver et al, 2020), but the lack of corresponding highthroughput functional characterization means that speculation has greatly outpaced experimental data when it comes to understanding the phenotypic consequences of mutations. Here, we take a step toward providing phenotypic maps commensurate with the scale of genomic data by experimentally characterizing how all amino-acid mutations to the RBD affect the expression of folded protein and its affinity for ACE2, two key factors for viral fitness.…”

Introductions and early spread of SARS-CoV-2 in France

“…A set of 100 SARS-CoV-2 sequences generated in this study (97 from France, 3 from Algeria) was complemented with 338 genomes published or freely available sequences on GenBank or the GISAID database. From the latter, only published sequences were chosen (Deng, Gu et al 2020, Fauver, Petrone et al 2020) (Supplementary material, Table S2). A total of 438 full genome sequences were analyzed with augur and auspice as implemented in the Nextstrain pipeline (Hadfield, Megill et al 2018) version from March 20, 2020 (https://github.com/nextstrain/ncov).…”

SARS-CoV-2 infection of the placenta

“…SARS-CoV-2 RNA from the placenta was sequenced using the portable MinION platform. The sequenced data was processed and used for phylogenetic analysis as described 8 .…”