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

Joseph R Fauver; Mary E. Petrone; Emma B Hodcroft; Kayoko Shioda; Hanna Y Ehrlich; Alexander G. Watts; Chantal B.F. Vogels; Anderson F. Brito; Tara Alpert; Anthony Muyombwe; Jafar Razeq; Randy Downing; Nagarjuna R. Cheemarla; Anne L Wyllie; Chaney C. Kalinich; Isabel Ott; Josh Quick; Nicholas J. Loman; Karla M. Neugebauer; Alexander L. Greninger; Keith R. Jerome; Pavitra Roychoundhury; Hong Xie; Lasata Shrestha; Meei-Li Huang; Virginia E. Pitzer; Akiko Iwasaki; Saad B. Omer; Kamran Khan; Isaac Bogoch; Richard A. Martinello; Ellen F. Foxman; Marie-Louise Landry; Richard A Neher; Albert I Ko; Nathan D. Grubaugh

We built phylogenetic trees using a maximum likelihood reconstruction approach, and we used shared nucleotide substitutions to assess clade support ( Figure 1 ). Our first nine SARS-CoV-2 genomes clustered into three distinct phylogenetic clades, indicating multiple independent virus introductions into Connecticut. Two of the genomes, CT-Yale-001 and CT-Yale-006, clustered primarily with viruses from China and Europe, respectively ( Figure 1A ). However, neither of the corresponding COVID-19 cases were travel-associated, which indicates that these patients were part of domestic transmission chains that stemmed from recent international virus introductions. The other seven SARS-CoV-2 genomes clustered with a large, primarily U.S. clade, within which the majority of genomes were sequenced from cases in Washington state ( Figure 1B ). Due to a paucity of SARS-CoV-2 genomes from other regions within the U.S., we could not determine the exact domestic origin of these viruses in Connecticut. We also cannot yet determine whether the higher number of substitutions observed in CT-Yale-007 and CT-Yale-008 ( Figure 1B ) compared to the other Connecticut virus genomes within this clade was the result of multiple introductions or of significant undersampling. Importantly, however, our data indicate that by early to mid March there had already been interstate spread during the early COVID-19 epidemic in the U.S. 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 . CC-BY-NC-ND 4.0 International license It is made available under a author/funder, who has granted medRxiv a license to display the preprint in perpetuity.