. 2021 Feb 5;371(6529):eabe3261.

doi: 10.1126/science.abe3261. Epub 2020 Dec 10.

Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events

Jacob E Lemieux^#^{1

2}, Katherine J Siddle^#^{3

4}, Bennett M Shaw^{3

2}, Christine Loreth³, Stephen F Schaffner^{3

4

5}, Adrianne Gladden-Young³, Gordon Adams³, Timelia Fink⁶, Christopher H Tomkins-Tinch^{3

4}, Lydia A Krasilnikova^{3

4}, Katherine C DeRuff³, Melissa Rudy³, Matthew R Bauer^{3

7}, Kim A Lagerborg^{3

7}, Erica Normandin^{3

8}, Sinéad B Chapman³, Steven K Reilly^{3

4}, Melis N Anahtar⁹, Aaron E Lin^{3

4}, Amber Carter³, Cameron Myhrvold^{3

4}, Molly E Kemball^{3

8}, Sushma Chaluvadi³, Caroline Cusick³, Katelyn Flowers³, Anna Neumann³, Felecia Cerrato³, Maha Farhat^{10

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

12}, John A Branda⁹, David Hooper², Jessie M Gaeta^{13

14}, Travis P Baggett^{13

15

16}, James O'Connell^{13

15

16}, Andreas Gnirke³, Tami D Lieberman^{3

17}, Anthony Philippakis³, Meagan Burns⁶, Catherine M Brown⁶, Jeremy Luban^{3

18

19}, Edward T Ryan^{2

5

16}, Sarah E Turbett^{2

9

16}, Regina C LaRocque^{2

16}, William P Hanage²⁰, Glen R Gallagher^#⁶, Lawrence C Madoff^#^{6

21}, Sandra Smole^#⁶, Virginia M Pierce^#^{9

22

23}, Eric Rosenberg^#^{2

9}, Pardis C Sabeti^#^{1

4

5

19

24}, Daniel J Park^#³, Bronwyn L MacInnis^#^{1

5

19}

Affiliations

¹ Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA. lemieux@broadinstitute.org pardis@broadinstitute.org bronwyn@broadinstitute.org.
² Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
³ Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
⁴ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
⁵ Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁶ Massachusetts Department of Public Health, Boston, MA, USA.
⁷ Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
⁸ Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
⁹ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
¹¹ Division of Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, USA.
¹² Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹³ Institute for Research, Quality, and Policy in Homeless Health Care, Boston Health Care for the Homeless Program, Boston, MA, USA.
¹⁴ Section of General Internal Medicine, Boston University Medical Center, Boston, MA, USA.
¹⁵ Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁶ Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹⁷ Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹⁸ Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
¹⁹ Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.
²⁰ Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
²¹ University of Massachusetts Medical School, Infectious Diseases and Immunology, Worcester, MA 01655, USA.
²² Pediatric Infectious Disease Unit, Massachusetts General Hospital for Children, Boston, MA, USA.
²³ Department of Pathology, Harvard Medical School, Boston, MA, USA.
²⁴ Howard Hughes Medical Institute, 4000 Jones Bridge Rd, Chevy Chase, MD 20815, USA.

^# Contributed equally.

PMID: 33303686
PMCID: PMC7857412
DOI: 10.1126/science.abe3261

Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events

Jacob E Lemieux et al. Science. 2021.

. 2021 Feb 5;371(6529):eabe3261.

doi: 10.1126/science.abe3261. Epub 2020 Dec 10.

Authors

Affiliations

¹ Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA. lemieux@broadinstitute.org pardis@broadinstitute.org bronwyn@broadinstitute.org.
² Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.
³ Broad Institute of Harvard and MIT, 415 Main Street, Cambridge, MA 02142, USA.
⁴ Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA 02138, USA.
⁵ Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Harvard University, Boston, MA, USA.
⁶ Massachusetts Department of Public Health, Boston, MA, USA.
⁷ Harvard Program in Biological and Biomedical Sciences, Harvard Medical School, Boston, MA 02115, USA.
⁸ Department of Systems Biology, Harvard Medical School, Boston, MA, USA.
⁹ Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.
¹⁰ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
¹¹ Division of Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, USA.
¹² Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
¹³ Institute for Research, Quality, and Policy in Homeless Health Care, Boston Health Care for the Homeless Program, Boston, MA, USA.
¹⁴ Section of General Internal Medicine, Boston University Medical Center, Boston, MA, USA.
¹⁵ Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.
¹⁶ Department of Medicine, Harvard Medical School, Boston, MA, USA.
¹⁷ Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹⁸ Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
¹⁹ Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA.
²⁰ Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
²¹ University of Massachusetts Medical School, Infectious Diseases and Immunology, Worcester, MA 01655, USA.
²² Pediatric Infectious Disease Unit, Massachusetts General Hospital for Children, Boston, MA, USA.
²³ Department of Pathology, Harvard Medical School, Boston, MA, USA.
²⁴ Howard Hughes Medical Institute, 4000 Jones Bridge Rd, Chevy Chase, MD 20815, USA.

^# Contributed equally.

PMID: 33303686
PMCID: PMC7857412
DOI: 10.1126/science.abe3261

Abstract

Analysis of 772 complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from early in the Boston-area epidemic revealed numerous introductions of the virus, a small number of which led to most cases. The data revealed two superspreading events. One, in a skilled nursing facility, led to rapid transmission and significant mortality in this vulnerable population but little broader spread, whereas other introductions into the facility had little effect. The second, at an international business conference, produced sustained community transmission and was exported, resulting in extensive regional, national, and international spread. The two events also differed substantially in the genetic variation they generated, suggesting varying transmission dynamics in superspreading events. Our results show how genomic epidemiology can help to understand the link between individual clusters and wider community spread.

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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 (10) from March 1 through May 1, 2020, and the number of these cases that 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) Total number of cases compared to cases in this study by MA county. Points are colored by state as shown in the state map. Suffolk and Middlesex counties are shown in detail to the right with counts from this study shown by zip code. (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 owing to the difficulty in discriminating at the sequence level.

**Fig. 2. Introductions of SARS-CoV-2 into Massachusetts.**
(A) Time tree of 772 MA genomes and a global set of 4,011 high-quality genomes from GISAID. 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) 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. (C) The proportion of importation events and cases that were associated with singleton introductions (importation events associated with a single case in MA) into the Boston area over sub-sampled trees. (D) Allele frequency of the C2416T mutation by state. (E) Allele frequency of the C2416T and C26233T alleles in 159,043 GISAID samples reported through October 17, 2020. The vertical black line denotes the end of the business conference on February 27th. (F) Time tree of all sequences containing the C2416T variant collected before September 30th 2020

**Fig. 3. SARS-CoV-2 spread in the Boston area.**
(A) Time-measured maximum clade credibility tree of 772 MA genomes with tips labeled by clade. Nodes with posterior support > 0.8 are labeled. (B) Violin plots of tMRCA for the major Boston-area clades. (C) Estimated allele frequency in sequenced genomes over time for major Boston-area clades. We use the following abbreviations; Boston Healthcare for the Homeless Program (BHCHP); Skilled Nursing Facility (SNF); large international business conference (Conference).

**Fig. 4. SARS-CoV-2 superspreading events.**
(A) Minimal spanning network showing genetic similarity of SARS-CoV-2 genomes in the MA dataset, with genomes from major known superspreading events highlighted. (B and 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.

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Update of

Phylogenetic analysis of SARS-CoV-2 in the Boston area highlights the role of recurrent importation and 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 J, 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, Maclnnis BL. Lemieux JE, et al. medRxiv [Preprint]. 2020 Aug 25:2020.08.23.20178236. doi: 10.1101/2020.08.23.20178236. medRxiv. 2020. Update in: Science. 2021 Feb 5;371(6529):eabe3261. doi: 10.1126/science.abe3261. PMID: 32869040 Free PMC article. Updated. Preprint.

Comment in

Superspreading genomes.
Alizon S. Alizon S. Science. 2021 Feb 5;371(6529):574-575. doi: 10.1126/science.abg0100. Science. 2021. PMID: 33542127 No abstract available.

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Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events

Affiliations

Phylogenetic analysis of SARS-CoV-2 in Boston highlights the impact of superspreading events

Authors

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Figures

Update of

Comment in

References

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