A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage

doi:10.1101/2020.03.27.20044925

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[Preprint]. 2020 Mar 30:2020.03.27.20044925.

doi: 10.1101/2020.03.27.20044925.

A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage

Xianding Deng^{1

2}, Wei Gu^{1

2}, Scot Federman^{1

2}, Louis du Plessis³, Oliver G Pybus³, Nuno Faria³, Candace Wang^{1

2}, Guixia Yu^{1

2}, Chao-Yang Pan⁴, Hugo Guevara⁴, Alicia Sotomayor-Gonzalez^{1

2}, Kelsey Zorn⁵, Allan Gopez¹, Venice Servellita¹, Elaine Hsu¹, Steve Miller¹, Trevor Bedford^{6

7}, Alexander L Greninger^{6

8}, Pavitra Roychoudhury^{6

8}, Lea M Starita^{7

9}, Michael Famulare¹⁰, Helen Y Chu^{7

11}, Jay Shendure^{7

8

12}, Keith R Jerome^{6

8}, Catie Anderson¹³, Karthik Gangavarapu¹³, Mark Zeller¹³, Emily Spencer¹³, Kristian G Andersen¹³, Duncan MacCannell¹⁴, Clinton R Paden¹⁴, Yan Li¹⁴, Jing Zhang¹⁴, Suxiang Tong¹⁴, Gregory Armstrong¹⁴, Scott Morrow¹⁵, Matthew Willis¹⁶, Bela T Matyas¹⁷, Sundari Mase¹⁸, Olivia Kasirye¹⁹, Maggie Park²⁰, Curtis Chan²¹, Alexander T Yu⁴, Shua J Chai^{4

14}, Elsa Villarino²², Brandon Bonin²², Debra A Wadford⁴, Charles Y Chiu^{1

2

23}

Affiliations

¹ Department of Laboratory Medicine, University of California, San Francisco, California, USA.
² UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, California, USA.
³ Department of Zoology, University of Oxford, Oxford, UK.
⁴ California Department of Public Health, Richmond, California, USA.
⁵ Department of Biochemistry and Biophysics, San Francisco, California, USA.
⁶ Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁷ Brotman Baty Institute for Precision Medicine, Seattle, Washington, USA.
⁸ Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
⁹ Department of Genome Sciences, University of Washington, Seattle, WA, USA.
¹⁰ Institute for Disease Modeling, Bellevue, WA, USA.
¹¹ Department of Medicine, University of Washington, Seattle, WA, USA.
¹² Howards Hughes Medical Institute, Seattle, WA, USA.
¹³ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
¹⁴ United States Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
¹⁵ San Mateo County Department of Public Health, San Mateo, California, USA.
¹⁶ Marin County Division of Public Health, San Rafael, California, USA.
¹⁷ Solano County Department of Public Health, Fairfield, California, USA.
¹⁸ Sonoma County Department of Public Health, Santa Rosa, California, USA.
¹⁹ Sacramento County Division of Public Health, Sacramento, California, USA.
²⁰ San Joaquin County Department of Public Health, Stockton, California, USA.
²¹ San Francisco County Department of Public Health, San Francisco, California, USA.
²² Santa Clara County Department of Public Health, Santa Clara, California, USA.
²³ Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, California, USA.

PMID: 32511579
PMCID: PMC7276006
DOI: 10.1101/2020.03.27.20044925

A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage

Xianding Deng et al. medRxiv. 2020.

[Preprint]. 2020 Mar 30:2020.03.27.20044925.

doi: 10.1101/2020.03.27.20044925.

Authors

Affiliations

¹ Department of Laboratory Medicine, University of California, San Francisco, California, USA.
² UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, California, USA.
³ Department of Zoology, University of Oxford, Oxford, UK.
⁴ California Department of Public Health, Richmond, California, USA.
⁵ Department of Biochemistry and Biophysics, San Francisco, California, USA.
⁶ Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
⁷ Brotman Baty Institute for Precision Medicine, Seattle, Washington, USA.
⁸ Department of Laboratory Medicine, University of Washington, Seattle, WA, USA.
⁹ Department of Genome Sciences, University of Washington, Seattle, WA, USA.
¹⁰ Institute for Disease Modeling, Bellevue, WA, USA.
¹¹ Department of Medicine, University of Washington, Seattle, WA, USA.
¹² Howards Hughes Medical Institute, Seattle, WA, USA.
¹³ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA, USA.
¹⁴ United States Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
¹⁵ San Mateo County Department of Public Health, San Mateo, California, USA.
¹⁶ Marin County Division of Public Health, San Rafael, California, USA.
¹⁷ Solano County Department of Public Health, Fairfield, California, USA.
¹⁸ Sonoma County Department of Public Health, Santa Rosa, California, USA.
¹⁹ Sacramento County Division of Public Health, Sacramento, California, USA.
²⁰ San Joaquin County Department of Public Health, Stockton, California, USA.
²¹ San Francisco County Department of Public Health, San Francisco, California, USA.
²² Santa Clara County Department of Public Health, Santa Clara, California, USA.
²³ Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, California, USA.

PMID: 32511579
PMCID: PMC7276006
DOI: 10.1101/2020.03.27.20044925

Update in

Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California.
Deng X, Gu W, Federman S, du Plessis L, Pybus OG, Faria NR, Wang C, Yu G, Bushnell B, Pan CY, Guevara H, Sotomayor-Gonzalez A, Zorn K, Gopez A, Servellita V, Hsu E, Miller S, Bedford T, Greninger AL, Roychoudhury P, Starita LM, Famulare M, Chu HY, Shendure J, Jerome KR, Anderson C, Gangavarapu K, Zeller M, Spencer E, Andersen KG, MacCannell D, Paden CR, Li Y, Zhang J, Tong S, Armstrong G, Morrow S, Willis M, Matyas BT, Mase S, Kasirye O, Park M, Masinde G, Chan C, Yu AT, Chai SJ, Villarino E, Bonin B, Wadford DA, Chiu CY. Deng X, et al. Science. 2020 Jul 31;369(6503):582-587. doi: 10.1126/science.abb9263. Epub 2020 Jun 8. Science. 2020. PMID: 32513865 Free PMC article.

Abstract

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

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Figures

**Figure 1.. Genomic survey of SARS-CoV-2 genomes in Northern California.**
**(A)** Analysis workflow. **(B)** Map of the Northern California survey region. The pie charts for each county are subdivided according to the number of patients whose viral genome was sequenced, and the color corresponds to the viral lineage as determined by phylogenetic analysis. Passengers who were on the Grand Princess ship during the first cruise to Mexico are denoted by an asterisk.

**Figure 2.. Phylogeny of SARS-CoV-2 lineages in California.**
**(A)** Phylogenetic tree of 342 SARS-CoV2 genomes along with the 29 genomes in this survey. Multiple sequence alignment of all available SARS-CoV-2 genomes in GISAID as of March 22nd, 2020, was performed using MAFFT (24), followed by tree constructions using PhyML (25). Viral lineages from California or Washington State are colored, while those outside of California and Washington are shown in gray. **(B)** A zoomed view of individual phylogenetic clusters corresponding to the WA1 lineage (1), Santa Clara County cluster (2), and Solano County cluster (3).

**Figure 3:. Multiple sequence alignment of all SARS-CoV-2 genomes reported across 9 counties and 1 cruise ship.**
Single nucleotide variants (SNVs) with respect to the reference strain (NC_045512) are shown in vertical red lines. Cases that are grouped into the WA1 cluster (defined as containing the C8782T, C18060T, T28144C SNVs) include the first identified case of COVID-19 infection (WA1) in the United States on January 15^th, 2020, 9 passengers and crew members aboard the Grand Princess cruise ship, and 4 Northern California counties. Two additional SNVs, C17747T and A17858G, are common to SARS-CoV-2 viruses associated with the Grand Princess cruise ship. Single SNV variants C9924T and G29711T define groups of infected individuals in the Solano County (UC2, UC3, and UC4) and Santa Clara County (UC14, UC16, and UC17) clusters, respectively.

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Stability of SARS-CoV-2 phylogenies.
Turakhia Y, De Maio N, Thornlow B, Gozashti L, Lanfear R, Walker CR, Hinrichs AS, Fernandes JD, Borges R, Slodkowicz G, Weilguny L, Haussler D, Goldman N, Corbett-Detig R. Turakhia Y, et al. PLoS Genet. 2020 Nov 18;16(11):e1009175. doi: 10.1371/journal.pgen.1009175. eCollection 2020 Nov. PLoS Genet. 2020. PMID: 33206635 Free PMC article.
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References

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[1] Dong E., Du H., Gardner L., An interactive web-based dashboard to track COVID-19 in real time. The Lancet Infectious Diseases (2020), doi: 10.1016/S1473-3099(20)30120-1 - DOI - PMC - PubMed

[2] Dong E., Du H., Gardner L., An interactive web-based dashboard to track COVID-19 in real time. The Lancet Infectious Diseases (2020), doi: 10.1016/S1473-3099(20)30120-1 - DOI - PMC - PubMed

[3] Li R., Pei S., Chen B., Song Y., Zhang T., Yang W., Shaman J., Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2). Science (2020), doi: 10.1126/science.abb3221 - DOI - PMC - PubMed

[4] Li R., Pei S., Chen B., Song Y., Zhang T., Yang W., Shaman J., Substantial undocumented infection facilitates the rapid dissemination of novel coronavirus (SARS-CoV2). Science (2020), doi: 10.1126/science.abb3221 - DOI - PMC - PubMed

[5] Chan J. F.-W., Yuan S., Kok K.-H., To K. K.-W., Chu H., Yang J., Xing F., Liu J., Yip C. C.-Y., Poon R. W.-S., Tsoi H.-W., Lo S. K.-F., Chan K.-H., Poon V. K.-M., Chan W.-M., Ip J. D., Cai J.-P., Cheng V. C.-C., Chen H., Hui C. K.-M., Yuen K.-Y., A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 395, 514–523 (2020). - PMC - PubMed

[6] Chan J. F.-W., Yuan S., Kok K.-H., To K. K.-W., Chu H., Yang J., Xing F., Liu J., Yip C. C.-Y., Poon R. W.-S., Tsoi H.-W., Lo S. K.-F., Chan K.-H., Poon V. K.-M., Chan W.-M., Ip J. D., Cai J.-P., Cheng V. C.-C., Chen H., Hui C. K.-M., Yuen K.-Y., A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. The Lancet. 395, 514–523 (2020). - PMC - PubMed

[7] Lu X., Zhang L., Du H., Zhang J., Li Y. Y., Qu J., Zhang W., Wang Y., Bao S., Li Y., Wu C., Liu H., Liu D., Shao J., Peng X., Yang Y., Liu Z., Xiang Y., Zhang F., Silva R. M., Pinkerton K. E., Shen K., Xiao H., Xu S., Wong G. W. K., New England Journal of Medicine, in press, doi: 10.1056/NEJMc2005073 - DOI

[8] Lu X., Zhang L., Du H., Zhang J., Li Y. Y., Qu J., Zhang W., Wang Y., Bao S., Li Y., Wu C., Liu H., Liu D., Shao J., Peng X., Yang Y., Liu Z., Xiang Y., Zhang F., Silva R. M., Pinkerton K. E., Shen K., Xiao H., Xu S., Wong G. W. K., New England Journal of Medicine, in press, doi: 10.1056/NEJMc2005073 - DOI

[9] Otani A., Santilli P., The Week That Wiped $3.6 Trillion Off the Stock Market. Wall Street Journal (2020).

[10] Otani A., Santilli P., The Week That Wiped $3.6 Trillion Off the Stock Market. Wall Street Journal (2020).

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This is a preprint.

A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage

Affiliations

A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage

Authors

Affiliations

Update in

Abstract

Figures

Similar articles

Cited by

References

Publication types

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous