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[Preprint]. 2020 Apr 6:2020.04.02.20051417.
doi: 10.1101/2020.04.02.20051417.

Cryptic transmission of SARS-CoV-2 in Washington State

Trevor Bedford  1   2   3 , Alexander L Greninger  1   3 , Pavitra Roychoudhury  1   3 , Lea M Starita  2   3 , Michael Famulare  4 , Meei-Li Huang  3 , Arun Nalla  3 , Gregory Pepper  3 , Adam Reinhardt  3 , Hong Xie  3 , Lasata Shrestha  3 , Truong N Nguyen  3 , Amanda Adler  5 , Elisabeth Brandstetter  3 , Shari Cho  3 , Danielle Giroux  3 , Peter D Han  3 , Kairsten Fay  1 , Chris D Frazar  3 , Misja Ilcisin  1 , Kirsten Lacombe  5 , Jover Lee  1 , Anahita Kiavand  3 , Matthew Richardson  3 , Thomas R Sibley  1 , Melissa Truong  3 , Caitlin R Wolf  3 , Deborah A Nickerson  2   3 , Mark J Rieder  2   3 , Janet A Englund  3   5 ; Seattle Flu Study Investigators; James Hadfield  1 , Emma B Hodcroft  6 , John Huddleston  1   3 , Louise H Moncla  1 , Nicola F Müller  1 , Richard A Neher  6 , Xianding Deng  7 , Wei Gu  7 , Scot Federman  7 , Charles Chiu  7 , Jeff Duchin  3   8 , Romesh Gautom  9 , Geoff Melly  9 , Brian Hiatt  9 , Philip Dykema  9 , Scott Lindquist  9 , Krista Queen  10 , Ying Tao  10 , Anna Uehara  10 , Suxiang Tong  10 , Duncan MacCannell  10 , Gregory L Armstrong  10 , Geoffrey S Baird  3 , Helen Y Chu  2   3 , Jay Shendure  2   3   11 , Keith R Jerome  1   3
Affiliations

Cryptic transmission of SARS-CoV-2 in Washington State

Trevor Bedford et al. medRxiv. .

Update in

  • Cryptic transmission of SARS-CoV-2 in Washington state.
    Bedford T, Greninger AL, Roychoudhury P, Starita LM, Famulare M, Huang ML, Nalla A, Pepper G, Reinhardt A, Xie H, Shrestha L, Nguyen TN, Adler A, Brandstetter E, Cho S, Giroux D, Han PD, Fay K, Frazar CD, Ilcisin M, Lacombe K, Lee J, Kiavand A, Richardson M, Sibley TR, Truong M, Wolf CR, Nickerson DA, Rieder MJ, Englund JA; Seattle Flu Study Investigators; Hadfield J, Hodcroft EB, Huddleston J, Moncla LH, Müller NF, Neher RA, Deng X, Gu W, Federman S, Chiu C, Duchin JS, Gautom R, Melly G, Hiatt B, Dykema P, Lindquist S, Queen K, Tao Y, Uehara A, Tong S, MacCannell D, Armstrong GL, Baird GS, Chu HY, Shendure J, Jerome KR. Bedford T, et al. Science. 2020 Oct 30;370(6516):571-575. doi: 10.1126/science.abc0523. Epub 2020 Sep 10. Science. 2020. PMID: 32913002 Free PMC article.

Abstract

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

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Conflict of interest statement

Competing interests

Janet A. Englund is a consultant for Sanofi Pasteur and Meissa Vaccines, Inc., and receives research support from GlaxoSmithKline, AstraZeneca, and Novavax. Helen Chu is a consultant for Merck and GlaxoSmithKline. Jay Shendure is a consultant with Guardant Health, Maze Therapeutics, Camp4 Therapeutics, Nanostring, Phase Genomics, Adaptive Biotechnologies, and Stratos Genomics, and has a research collaboration with Illumina. Michael Famulare, Lea Starita, Pavitra Roychoudhury, Amanda Adler, Peter Han, Kirsten Lacombe, Elisabeth Brandstetter, Caitlin R. Wolf, Richard A Neher, James Hadfield, Nicola F. Müller, Jover Lee, Thomas Sibley, Kairsten Fay, Deborah A. Nickerson, Mark J. Rieder, and Trevor Bedford declare no competing interests.

Figures

Figure 1.
Figure 1.. Maximum-likelihood resolved phylogeny of WA1 outbreak clade containing 303 SARS-CoV-2 viruses (A) and Bayesian estimates of outbreak ancestor and doubling time (B).
(A) Branch lengths are proportional to the number of substitutions between viruses and the x-axis is labeled with the number of substitutions relative to the root of the overall SARS-CoV-2 phylogeny. Tips on the phylogeny are colored based on location of sampling with viruses from China in blue, viruses from California in green, viruses from the Grand Princess cruise ship in yellow and viruses from Washington State in red. This comb-like phylogenetic structure is consistent with rapid exponential growth of the virus population. (B) Highest posterior density estimates for the date of the common ancestor of viruses from the Washington outbreak clade as well as the doubling time in days of the growth of this clade.
Figure 2.
Figure 2.
Phylogeny of 346 SARS-CoV-2 viruses collected from Washington State (red circles) on a background of globally collected viruses. Clustering of related viruses indicates community transmission after an introduction event. In addition to the estimated January introduction of the large outbreak clade we see later introduction events (marked by arrows) resulting in smaller community outbreaks.
Figure 3.
Figure 3.
Inferences from the transmission model. (A) 500 prevalence trajectories showing the total number of people infected (presymptomatic/exposed and infectious) through time (median trajectory, red). Assumed start date is January 15 and simulations run through 15 March and do not account for impacts of social distancing policies since 5 March. (B) Distribution of simulated prevalences from 1 March 2020 to 15 March 2020.
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