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[Preprint]. 2020 Aug 25:2020.08.23.20178236.

doi: 10.1101/2020.08.23.20178236.

Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events

Jacob E Lemieux^{1

2}, Katherine J Siddle^{1

3}, Bennett M Shaw^{1

2}, Christine Loreth¹, Stephen F Schaffner^{1

3

4}, Adrianne Gladden-Young¹, Gordon Adams¹, Timelia Fink⁵, Christopher H Tomkins-Tinch^{1

3}, Lydia A Krasilnikova^{1

3}, Katherine C DeRuff¹, Melissa Rudy¹, Matthew R Bauer^{1

6}, Kim A Lagerborg^{1

6}, Erica Normandin^{1

7}, Sinead B Chapman¹, Steven K Reilly^{1

3}, Melis N Anahtar⁸, Aaron E Lin^{1

3}, Amber Carter¹, Cameron Myhrvold^{1

3}, Molly E Kemball^{1

7}, Sushma Chaluvadi¹, Caroline Cusick¹, Katelyn Flowers¹, Anna Neumann¹, Felecia Cerrato¹, Maha Farhat^{9

10}, Damien Slater², Jason B Harris^{2

11}, John Branda⁸, David Hooper², Jessie M Gaeta^{12

13}, Travis P Baggett^{12

14

15}, James O'Connell^{12

14

15}, Andreas Gnirke¹, Tami D Lieberman^{1

16}, Anthony Philippakis¹, Meagan Burns⁵, Catherine M Brown⁵, Jeremy Luban^{1

17

18}, Edward T Ryan^{2

4

15}, Sarah E Turbett^{2

8

15}, Regina C LaRocque^{2

15}, William P Hanage¹⁹, Glen R Gallagher⁵, Lawrence C Madoff^{5

20}, Sandra Smole⁵, Virginia M Pierce^{8

21

22}, Eric Rosenberg^{2

8}, Pardis C Sabeti^{1

3

4

18

23}, Daniel J Park¹, Bronwyn L Maclnnis^{1

4

18}

Affiliations

¹ Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
² Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
³ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
⁴ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁵ Massachusetts Department of Public Health, Boston, MA, USA.
⁶ Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
⁷ Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
⁸ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
⁹ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
¹⁰ Division of Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, USA.
¹¹ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹² lnstitute for Research, Quality, and Policy in Homeless Health Care, Boston Health Care for the Homeless Program, Boston, MA, USA.
¹³ Section of General Internal Medicine, Boston University Medical Center, Boston.
¹⁴ Division of General Internal Medicine, Massachusetts General Hospital, Boston.
¹⁵ Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹⁶ lnstitute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹⁷ Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
¹⁸ Massachusetts Consortium on Pathogen Readiness, Boston, MA, 02115, USA.
¹⁹ Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
²⁰ University of Massachusetts Medical School, Infectious Diseases and Immunology, Worcester, MA 01655.
²¹ Pediatric Infectious Disease Unit, MassGeneral Hospital for Children, Boston, MA, USA.
²² Department of Pathology, Harvard Medical School, Boston, MA, USA.
²³ Howard Hughes Medical Institute, 4000 Jones Bridge Rd, Chevy Chase, MD 20815.

PMID: 32869040
PMCID: PMC7457619
DOI: 10.1101/2020.08.23.20178236

Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events

Jacob E Lemieux et al. medRxiv. 2020.

[Preprint]. 2020 Aug 25:2020.08.23.20178236.

doi: 10.1101/2020.08.23.20178236.

Authors

Affiliations

¹ Broad Institute of Harvard and MIT, 75 Ames Street, Cambridge, MA 02142, USA.
² Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
³ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
⁴ Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁵ Massachusetts Department of Public Health, Boston, MA, USA.
⁶ Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
⁷ Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
⁸ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
⁹ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
¹⁰ Division of Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, USA.
¹¹ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹² lnstitute for Research, Quality, and Policy in Homeless Health Care, Boston Health Care for the Homeless Program, Boston, MA, USA.
¹³ Section of General Internal Medicine, Boston University Medical Center, Boston.
¹⁴ Division of General Internal Medicine, Massachusetts General Hospital, Boston.
¹⁵ Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹⁶ lnstitute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹⁷ Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
¹⁸ Massachusetts Consortium on Pathogen Readiness, Boston, MA, 02115, USA.
¹⁹ Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
²⁰ University of Massachusetts Medical School, Infectious Diseases and Immunology, Worcester, MA 01655.
²¹ Pediatric Infectious Disease Unit, MassGeneral Hospital for Children, Boston, MA, USA.
²² Department of Pathology, Harvard Medical School, Boston, MA, USA.
²³ Howard Hughes Medical Institute, 4000 Jones Bridge Rd, Chevy Chase, MD 20815.

PMID: 32869040
PMCID: PMC7457619
DOI: 10.1101/2020.08.23.20178236

Update in

Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events.
Lemieux JE, Siddle KJ, Shaw BM, Loreth C, Schaffner SF, Gladden-Young A, Adams G, Fink T, Tomkins-Tinch CH, Krasilnikova LA, DeRuff KC, Rudy M, Bauer MR, Lagerborg KA, Normandin E, Chapman SB, Reilly SK, Anahtar MN, Lin AE, Carter A, Myhrvold C, Kemball ME, Chaluvadi S, Cusick C, Flowers K, Neumann A, Cerrato F, Farhat M, Slater D, Harris JB, Branda JA, Hooper D, Gaeta JM, Baggett TP, O'Connell J, Gnirke A, Lieberman TD, Philippakis A, Burns M, Brown CM, Luban J, Ryan ET, Turbett SE, LaRocque RC, Hanage WP, Gallagher GR, Madoff LC, Smole S, Pierce VM, Rosenberg E, Sabeti PC, Park DJ, MacInnis BL. Lemieux JE, et al. Science. 2021 Feb 5;371(6529):eabe3261. doi: 10.1126/science.abe3261. Epub 2020 Dec 10. Science. 2021. PMID: 33303686 Free PMC article.

Abstract

SARS-CoV-2 has caused a severe, ongoing outbreak of COVID-19 in Massachusetts with 111,070 confirmed cases and 8,433 deaths as of August 1, 2020. To investigate the introduction, spread, and epidemiology of COVID-19 in the Boston area, we sequenced and analyzed 772 complete SARS-CoV-2 genomes from the region, including nearly all confirmed cases within the first week of the epidemic and hundreds of cases from major outbreaks at a conference, a nursing facility, and among homeless shelter guests and staff. The data reveal over 80 introductions into the Boston area, predominantly from elsewhere in the United States and Europe. We studied two superspreading events covered by the data, events that led to very different outcomes because of the timing and populations involved. One produced rapid spread in a vulnerable population but little onward transmission, while the other was a major contributor to sustained community transmission, including outbreaks in homeless populations, and was exported to several other domestic and international sites. The same two events differed significantly in the number of new mutations seen, raising the possibility that SARS-CoV-2 superspreading might encompass disparate transmission dynamics. Our results highlight the failure of measures to prevent importation into MA early in the outbreak, underscore the role of superspreading in amplifying an outbreak in a major urban area, and lay a foundation for contact tracing informed by genetic data.

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Conflict of interest statement

Competing interests: J.E.L. has received consulting fees from Sherlock Biosciences. J.B. has been a consultant for T2 Biosystems, DiaSorin, and Roche Diagnostics. A.P. is a Venture Partner at Google Ventures. P.C.S. is a co-founder and shareholder of Sherlock Biosciences, and a Board member and shareholder of Danaher Corporation.

Figures

**Fig 1.. Epidemiology of SARS-CoV-2 in Massachusetts and of sequenced viral genomes.**
A. Cumulative confirmed and presumed cases reported state-wide in MA (7) from March 1 through May 1, 2020, and the number of these cases that were processed (orange) and successfully yielded complete genomes with >98% coverage (green) in this study. B. Cumulative proportion of all MA confirmed positive cases with complete genome sequences from unique individuals that are part of this dataset over time. C. Daily reported cases across MA from March 1 through June 15 statewide (blue) and at MGH (orange). D. Total number of cases compared to cases per 100,000 people for cities across MA. Cities in blue are highly represented in the genome dataset. E. Distribution of MA cases with sequenced viral genomes by county. F. As in E but showing only Middlesex and Suffolk counties, the two counties with the highest number of sequenced samples, by zip code. Cases associated with congregate living environments were excluded from the maps in E and F.

**Fig 2.. A.**
A. Time tree of 772 MA genomes and a global set of 4,011 high-quality genomes from GISAID. The embedded panel shows the C2416T clade in detail (outlined in gray on the main tree). To view an interactive version of this tree and for more information on specific sub-groupings within the MA dataset see auspice.broadinstitute.org. B. Estimated allele frequency in sequenced genomes over time for major Boston-area lineages. C. Frequency of the C2416T allele in 58,043 GISAID samples reported through July 14, 2020. D. Proportion of genomes that were inferred as imported (ancestral state as not from MA) in the early (prior to March 28, 2020), middle (March 28 - April 14, 2020) and late (after April 15, 2020) time periods of the MA epidemic.

**Fig 3.. A.**
A. Time-measured maximum-likelihood phylogeny of 772 MA genomes. B. Maximum clade credibility tree with tips labeled by clade. Nodes with posterior support > 0.8 are labeled. C. Violin plots of tMRCA for the major Boston-area clades.

**Fig 4.. SARS-CoV-2 superspreading events.**
A. Haplotype network of SARS-CoV-2 haplotypes in the MA dataset with major known superspreading events highlighted. **B, C.** Gene graphs showing clusters of highly similar sequences among viral genomes from the SNF **(B)** and BHCHP **(C)** cohorts. Sequences are clustered when they are separated by < 4 SNPs, and the lengths of lines between points reflect genetic distance. D. Detection of common respiratory viruses from metagenomic sequencing data. Samples with >10 reads mapped to at least 1 of these viruses using Kraken2 are shown in red. Enterovirus and Rhinovirus species have been grouped due to difficulty in discriminating at the sequence level.

See this image and copyright information in PMC

References

1. Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU), COVID-19 Dashboard, (available at https://coronavirus.jhu.edu/map.html). - PMC - PubMed
1. MA Department of Public Health, Man returning from Wuhan, China is first case of 2019 Novel Coronavirus confirmed in Massachusetts (2020), (available at https://www.mass.gov/news/man-returning-from-wuhan-china-is-first-case-o...).
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This is a preprint.

Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events

Affiliations

Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and superspreading events

Authors

Affiliations

Update in

Abstract

Conflict of interest statement

Figures

References

Publication types

Grants and funding

LinkOut - more resources

Full Text Sources

Miscellaneous