Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2020 Sep 30:2020.09.30.20204230.
doi: 10.1101/2020.09.30.20204230.

Viral genomes reveal patterns of the SARS-CoV-2 outbreak in Washington State

Nicola F Müller  1 , Cassia Wagner  1   2 , Chris D Frazar  2 , Pavitra Roychoudhury  1   2 , Jover Lee  1 , Louise H Moncla  1 , Benjamin Pelle  2 , Matthew Richardson  2 , Erica Ryke  2 , Hong Xie  2 , Lasata Shrestha  2 , Amin Addetia  2 , Victoria M Rachleff  1   2 , Nicole A P Lieberman  2 , Meei-Li Huang  2 , Romesh Gautom  3 , Geoff Melly  3 , Brian Hiatt  3 , Philip Dykema  3 , Amanda Adler  4 , Elisabeth Brandstetter  2 , Peter D Han  2 , Kairsten Fay  1 , Misja Llcisin  1 , Kristen Lacombe  4 , Thomas R Sibley  1 , Melissa Truong  2 , Caitlin R Wolf  2 , Michael Boeckh  1   2   5 , Janet A Englund  2   4 , Michael Famulare  6 , Barry R Lutz  2   5 , Mark J Rieder  5 , Matthew Thompson  2 , Jeffrey S Duchin  2   7 , Lea M Starita  2   5 , Helen Y Chu  2   5 , Jay Shendure  2   5   8 , Keith R Jerome  1   2 , Scott Lindquist  3 , Alexander L Greninger  1   2 , Deborah A Nickerson  2   5 , Trevor Bedford  1   2   5
Affiliations

Viral genomes reveal patterns of the SARS-CoV-2 outbreak in Washington State

Nicola F Müller et al. medRxiv. .

Update in

  • Viral genomes reveal patterns of the SARS-CoV-2 outbreak in Washington State.
    Müller NF, Wagner C, Frazar CD, Roychoudhury P, Lee J, Moncla LH, Pelle B, Richardson M, Ryke E, Xie H, Shrestha L, Addetia A, Rachleff VM, Lieberman NAP, Huang ML, Gautom R, Melly G, Hiatt B, Dykema P, Adler A, Brandstetter E, Han PD, Fay K, Ilcisin M, Lacombe K, Sibley TR, Truong M, Wolf CR, Boeckh M, Englund JA, Famulare M, Lutz BR, Rieder MJ, Thompson M, Duchin JS, Starita LM, Chu HY, Shendure J, Jerome KR, Lindquist S, Greninger AL, Nickerson DA, Bedford T. Müller NF, et al. Sci Transl Med. 2021 May 26;13(595):eabf0202. doi: 10.1126/scitranslmed.abf0202. Epub 2021 May 3. Sci Transl Med. 2021. PMID: 33941621 Free PMC article.

Abstract

The rapid spread of SARS-CoV-2 has gravely impacted societies around the world. Outbreaks in different parts of the globe are shaped by repeated introductions of new lineages and subsequent local transmission of those lineages. Here, we sequenced 3940 SARS-CoV-2 viral genomes from Washington State to characterize how the spread of SARS-CoV-2 in Washington State (USA) was shaped by differences in timing of mitigation strategies across counties, as well as by repeated introductions of viral lineages into the state. Additionally, we show that the increase in frequency of a potentially more transmissible viral variant (614G) over time can potentially be explained by regional mobility differences and multiple introductions of 614G, but not the other variant (614D) into the state. At an individual level, we see evidence of higher viral loads in patients infected with the 614G variant. However, using clinical records data, we do not find any evidence that the 614G variant impacts clinical severity or patient outcomes. Overall, this suggests that at least to date, the behavior of individuals has been more important in shaping the course of the pandemic than changes in the virus.

PubMed Disclaimer

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 Boeckh is a consultant for Merck and VirBio. Nicola F. Müller, Cassia Wagner, Chris D. Frazar, Pavitra Roychoudhury, Jover Lee, Louise H. Moncla, Benjamin Pelle, Matthew Richardson, Erica Ryke, Hong Xie, Lasata Shrestha, Amin Addetia, Victoria M. Rachleff, Nicole A. P. Lieberman, Meei-Li Huang, Romesh Gautom, Geoff Melly, Brian Hiatt, Philip Dykema, Amanda Adler, Elisabeth Brandstetter, Peter D. Han, Kairsten Fay, Misja Ilcisin, Kirsten Lacombe, Thomas R. Sibley, Melissa Truong, Caitlin R. Wolf, Michael Famulare, Barry R. Lutz, Mark J. Rieder, Matthew Thompson, Jeffrey S. Duchin, Lea M. Starita, Keith R. Jerome, Scott Lindquist, Alexander L. Greninger, Deborah A. Nickerson, and Trevor Bedford declare no competing interests.

Figures

Fig. 1.
Fig. 1.. SARS-CoV-2 phylogeny highlighting D614G split and cases through time in Washington State.
(A) Phylogenetic tree of 10,051 sequences from Washington State and around the world. Tips are colored based on sampling location. This is a time-calibrated phylogeny with time shown on the x-axis. The split between 614D sequences (blue) and 614G (orange) sequences is shown as a bar to the right of the phylogeny. (B-E) Confirmed cases and genetic makeup of SARS-CoV-2 across Washington State and individual counties. The green line shows a 7 day moving average of daily confirmed cases. The bar plots show weekly sequenced cases in our dataset. Cases due to the 614D variant are shown in blue and cases due to the 614G variant are shown in orange.
Fig. 2.
Fig. 2.. Regional dynamics of SARS-CoV-2 in Washington State inferred from confirmed cases and pathogen genomes.
(A) Estimates of effective population sizes for the outbreak in Washington State (green interval), as well as for 614D (blue interval) and 614G (orange interval) individually compared to confirmed cases in the state (gray bars). The inner band denotes 50% highest posterior density (HPD) interval and the outer band denotes the 95% HPD interval. (B) Re estimates using a birth death approach for King, for the same groups as in (A). The Re estimates are compared to Google workplace mobility data Pierce, Skagit and Snohomish Counties shown as black solid and dashed lines. Workplace mobility is represented as a 7 day moving average.
Fig. 3.
Fig. 3.. Phylogenetic estimate of the percentage of introductions of the overall cases.
Proportions are estimated as the relative contribution of introductions to the overall number of infections using the multi-tree coalescent. Proportions are shown for the outbreak in Washington State (green interval), as well as for 614D (blue interval) and 614G (orange interval). The inner area denotes the 50% HPD interval, the outer area denotes the 95% HPD interval.
Fig. 4.
Fig. 4.. Factors affecting viral load and disease severity at an individual level.
A Comparison between cycle threshold (Ct) values for viruses from the 614D and 614G clade. B GLM analysis of Ct values using variant, age, and sampling week as predictors. C Odds ratios of being hospitalized given being infected with SARS-CoV-2. Error bars show 95% CI, corrected for multiple hypothesis testing using a Bonferroni Correction. D Proportion of viruses in 614D and 614G clades grouped by sex, immunocompromised status, hospitalization, and severe outcome (requiring critical care or death). Proportion was calculated as the mean of a binary clade variable; error bars show standard error of the mean.
See this image and copyright information in PMC

References

    1. Rambaut A, Phylogenetic analysis of nCoV-2019 genomes Virological (available at http://virological.org/t/phylodynamic-analysis-176-genomes-6-mar-2020/356).
    1. Bedford T., Greninger A. L., Roychoudhury P., Starita L. M., Famulare M., Huang M.-L., Nalla A., Pepper G., Reinhardt A., Xie H., Shrestha L., Nguyen T. N., Adler A., Brandstetter E., Cho S., Giroux D., Han P. D., Fay K., Frazar C. D., Ilcisin M., Lacombe K., Lee J., Kiavand A., Richardson M., Sibley T. R., Truong M., Wolf C. R., Nickerson D. A., Rieder M. J., Englund J. A., Hadfield J., Hodcroft E. B., Huddleston J., Moncla L. H., Müller N. F., Neher R. A., Deng X., Gu W., Federman S., Chiu C., Duchin J., Gautom R., Melly G., Hiatt B., Dykema P., Lindquist S., Queen K., Tao Y., Uehara A., Tong S., MacCannell D., Armstrong G. L., Baird G. S., Chu H. Y., Shendure J., Jerome K. R., Cryptic transmission of SARS-CoV-2 in Washington State, Science, eabc0523 (2020). - PMC - PubMed
    1. Hadfield J., Megill C., Bell S. M., Huddleston J., Potter B., Callender C., Sagulenko P., Bedford T., Neher R. A., Nextstrain: real-time tracking of pathogen evolution, Bioinformatics 34, 4121–4123 (2018). - PMC - PubMed
    1. Korber B., Fischer W. M., Gnanakaran S., Yoon H., Theiler J., Abfalterer W., Hengartner N., Giorgi E. E., Bhattacharya T., Foley B., Hastie K. M., Parker M. D., Partridge D. G., Evans C. M., Freeman T. M., de Silva T. I., McDanal C., Perez L. G., Tang H., Moon-Walker A., Whelan S. P., LaBranche C. C., Saphire E. O., Montefiori D. C., Angyal A., Brown R. L., Carrilero L., Green L. R., Groves D. C., Johnson K. J., Keeley A. J., Lindsey B. B., Parsons P. J., Raza M., Rowland-Jones S., Smith N., Tucker R. M., Wang D., Wyles M. D., Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus Cell (2020), doi: 10.1016/j.cell.2020.06.043. - DOI - PMC - PubMed
    1. Yurkovetskiy L., Pascal K. E., Tompkins-Tinch C., Nyalile T., Wang Y., Baum A., Diehl W. E., Dauphin A., Carbone C., Veinotte K., Egri S. B., Schaffner S. F., Lemieux J. E., Munro J., Sabeti P. C., Kyratsous C., Shen K., Luban J., SARS-CoV-2 Spike protein variant D614G increases infectivity and retains sensitivity to antibodies that target the receptor binding domain, bioRxiv (2020), doi: 10.1016/j.cell.2020.09.032 - DOI - PubMed

Publication types