. 2024 May 15;78(5):1204-1213.

doi: 10.1093/cid/ciad738.

Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting

Jocelyn Keehner^{1

2}, Shira R Abeles^{2

3}, Christopher A Longhurst^{4

5}, Lucy E Horton^{2

3

6}, Frank E Myers³, Lindsay Riggs-Rodriguez⁷, Mohammed Ahmad⁸, Sally Baxter⁹, Aaron Boussina¹⁰, Kalen Cantrell¹¹, Priscilla Cardenas¹², Peter De Hoff^{13

14

15}, Robert El-Kareh^{4

16}, Jennifer Holland¹⁷, Daryn Ikeda¹², Kirk Kurashige¹⁷, Louise C Laurent^{13

14

15}; SEARCH Alliance; Andrew Lucas⁸, David Pride^{2

18}, Shashank Sathe^{13

19

14}, Allen R Tran⁸, Tetyana I Vasylyeva², Gene Yeo^{13

19

14}, Rob Knight^{5

20

21

14

22}, Joel O Wertheim², Francesca J Torriani^{2

3}

Collaborators, Affiliations

Collaborators

SEARCH Alliance:
Stefan Aigner, Kristian G Andersen, Catelyn Anderson, Nathan A Baer, Tom Barber, Marco Bauk, Jennifer N Beck, Pedro Belda-Ferre, Maryann Betty, Amanda Birmingham, Anelizze Castro-Martinez, Willi Cheung, Peter De Hoff, Kathleen M Fisch, Karthik Gangavarapu, Isabella Gargano, Abbas Hakim, Shania Harsono, Benjamin Henson, Charlotte Hobbs, Jacqueline Holmes, Kristen Jepsen, Rob Knight, Ezra Kurzban, Louise C Laurent, Clarisse A Marotz, Nathaniel L Matteson, Niema Moshiri, Toan T Ngo, Tyler R Ostrander, Sarah Perkins, Ashley Plascencia, Andrea Rivera, Ariana Rivera, Rodolfo A Salido, Shashank Sathe, Phoebe Seaver, Madison Schwab, Anthony Veder, Gene W Yeo, Mark Zeller

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, University of California-SanFrancisco, San Francisco, California, USA.
² Division of Infectious Diseases and Global Public Health, Department of Medicine, UC San Diego Health, San Diego, California, USA.
³ Infection Prevention and Clinical Epidemiology Unit, UC San Diego Health, San Diego, California, USA.
⁴ Division of Biomedical Informatics, Department of Medicine, UC San Diego Health, La Jolla, California, USA.
⁵ Department of Pediatrics, University of California-San Diego, La Jolla, California, USA.
⁶ Vaccine Research and Development Unit, Pfizer Inc, San Diego, California, USA.
⁷ Population Health Services Organization-Programs and Strategy, UC San Diego Health, San Diego, California, USA.
⁸ Information Services EMR, UC San Diego Health, San Diego, California, USA.
⁹ Division of Biomedical Informatics at the University of California-San Diego, San Diego, California, USA.
¹⁰ Division of Biomedical Informatics, University of California-San Diego, La Jolla, California, USA.
¹¹ Department of Computer Science & Engineering, Jacobs School of Engineering, University of California, San Diego, California, USA.
¹² UC San Diego Health's Contact Tracing Team, Infection Prevention and Clinical Epidemiology Unit, UC San Diego Health, San Diego, California, USA.
¹³ Sanford Consortium of Regenerative Medicine, University of California-San Diego, La Jolla, California, USA.
¹⁴ Expedited COVID Identification Environment Laboratory, Department of Pediatrics, University of California-San Diego, La Jolla, California, USA.
¹⁵ Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego Health, San Diego, California, USA.
¹⁶ Division of Hospital Medicine, Department of Medicine, UC San Diego Health, La Jolla, California, USA.
¹⁷ Analytics and Population Health Department, UC San Diego Health, San Diego, California, USA.
¹⁸ Department of Pathology, UC San Diego Health, La Jolla, California, USA.
¹⁹ Department of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, California, USA.
²⁰ Department of Bioengineering, University of California-San Diego, La Jolla, California, USA.
²¹ Department of Computer Science and Engineering, University of California-San Diego, La Jolla, California, USA.
²² Center for Microbiome Innovation, University of California-San Diego, La Jolla, California, USA.

PMID: 38227643
PMCID: PMC11093679
DOI: 10.1093/cid/ciad738

Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting

Jocelyn Keehner et al. Clin Infect Dis. 2024.

. 2024 May 15;78(5):1204-1213.

doi: 10.1093/cid/ciad738.

Authors

Collaborators

SEARCH Alliance:
Stefan Aigner, Kristian G Andersen, Catelyn Anderson, Nathan A Baer, Tom Barber, Marco Bauk, Jennifer N Beck, Pedro Belda-Ferre, Maryann Betty, Amanda Birmingham, Anelizze Castro-Martinez, Willi Cheung, Peter De Hoff, Kathleen M Fisch, Karthik Gangavarapu, Isabella Gargano, Abbas Hakim, Shania Harsono, Benjamin Henson, Charlotte Hobbs, Jacqueline Holmes, Kristen Jepsen, Rob Knight, Ezra Kurzban, Louise C Laurent, Clarisse A Marotz, Nathaniel L Matteson, Niema Moshiri, Toan T Ngo, Tyler R Ostrander, Sarah Perkins, Ashley Plascencia, Andrea Rivera, Ariana Rivera, Rodolfo A Salido, Shashank Sathe, Phoebe Seaver, Madison Schwab, Anthony Veder, Gene W Yeo, Mark Zeller

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, University of California-SanFrancisco, San Francisco, California, USA.
² Division of Infectious Diseases and Global Public Health, Department of Medicine, UC San Diego Health, San Diego, California, USA.
³ Infection Prevention and Clinical Epidemiology Unit, UC San Diego Health, San Diego, California, USA.
⁴ Division of Biomedical Informatics, Department of Medicine, UC San Diego Health, La Jolla, California, USA.
⁵ Department of Pediatrics, University of California-San Diego, La Jolla, California, USA.
⁶ Vaccine Research and Development Unit, Pfizer Inc, San Diego, California, USA.
⁷ Population Health Services Organization-Programs and Strategy, UC San Diego Health, San Diego, California, USA.
⁸ Information Services EMR, UC San Diego Health, San Diego, California, USA.
⁹ Division of Biomedical Informatics at the University of California-San Diego, San Diego, California, USA.
¹⁰ Division of Biomedical Informatics, University of California-San Diego, La Jolla, California, USA.
¹¹ Department of Computer Science & Engineering, Jacobs School of Engineering, University of California, San Diego, California, USA.
¹² UC San Diego Health's Contact Tracing Team, Infection Prevention and Clinical Epidemiology Unit, UC San Diego Health, San Diego, California, USA.
¹³ Sanford Consortium of Regenerative Medicine, University of California-San Diego, La Jolla, California, USA.
¹⁴ Expedited COVID Identification Environment Laboratory, Department of Pediatrics, University of California-San Diego, La Jolla, California, USA.
¹⁵ Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, UC San Diego Health, San Diego, California, USA.
¹⁶ Division of Hospital Medicine, Department of Medicine, UC San Diego Health, La Jolla, California, USA.
¹⁷ Analytics and Population Health Department, UC San Diego Health, San Diego, California, USA.
¹⁸ Department of Pathology, UC San Diego Health, La Jolla, California, USA.
¹⁹ Department of Cellular and Molecular Medicine, University of California-San Diego, La Jolla, California, USA.
²⁰ Department of Bioengineering, University of California-San Diego, La Jolla, California, USA.
²¹ Department of Computer Science and Engineering, University of California-San Diego, La Jolla, California, USA.
²² Center for Microbiome Innovation, University of California-San Diego, La Jolla, California, USA.

PMID: 38227643
PMCID: PMC11093679
DOI: 10.1093/cid/ciad738

Abstract

Background: Infection prevention (IP) measures are designed to mitigate the transmission of pathogens in healthcare. Using large-scale viral genomic and social network analyses, we determined if IP measures used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic were adequate in protecting healthcare workers (HCWs) and patients from acquiring SARS-CoV-2.

Methods: We performed retrospective cross-sectional analyses of viral genomics from all available SARS-CoV-2 viral samples collected at UC San Diego Health and social network analysis using the electronic medical record to derive temporospatial overlap of infections among related viromes and supplemented with contact tracing data. The outcome measure was any instance of healthcare transmission, defined as cases with closely related viral genomes and epidemiological connection within the healthcare setting during the infection window. Between November 2020 through January 2022, 12 933 viral genomes were obtained from 35 666 patients and HCWs.

Results: Among 5112 SARS-CoV-2 viral samples sequenced from the second and third waves of SARS-CoV-2 (pre-Omicron), 291 pairs were derived from persons with a plausible healthcare overlap. Of these, 34 pairs (12%) were phylogenetically linked: 19 attributable to household and 14 to healthcare transmission. During the Omicron wave, 2106 contact pairs among 7821 sequences resulted in 120 (6%) related pairs among 32 clusters, of which 10 were consistent with healthcare transmission. Transmission was more likely to occur in shared spaces in the older hospital compared with the newer hospital (2.54 vs 0.63 transmission events per 1000 admissions, P < .001).

Conclusions: IP strategies were effective at identifying and preventing healthcare SARS-CoV-2 transmission.

Keywords: SARS-CoV-2 pandemic; healthcare transmission of SARS-CoV-2; infection prevention precautions; social network analyses and contact tracing; whole-genome sequencing.

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Conflict of interest statement

Potential conflicts of interest. K. G. A. reports consulting fees from Adagio Therapeutics (consulting and Scientific Advisory Board (SAB)) and Ring Therapeutics (consulting); a role of SAB for Adagio Therapeutics; stock or stock options with Ring Therapeutics; and grants or contracts from National National Center for Advancing Translational Sciences, NIAID, Prebys 211—Prebys Foundation, Bill & Melinda Gates Foundation, 2016 Pew Scholar—Pew Charitable Trust, National Institute of General Medical Sciences, and CDC. C. A. L. reports serving as equity holder and advisor (unrelated to this work) for Doximity. L. E. H. reports consulting fees from Gilead; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, the Infectious Diseases Association of California, the Medical Education Speakers Network, and CME consultants; support for attending meetings and/or travel from AstraZeneca; stock or stock options from Pfizer; and is a salaried employee of Pfizer. S. B. reports an NIH and an unrestricted departmental grant from Research to Prevent Blindness (no role in design of the study and no payment) and receipt of equipment, materials, drugs, medical writing, gifts, or other services from Optomed and Topcon. L. C. L. reports stock or stock options from Illumina, Inc and equipment and reagents for sequencing purchased from Illumina via UCSD Institute for Genomic Medicine. R. K. reports consulting fees from DayTwo (consultant and SAB member), Cybele (stock and consultant), and Biomesense (stock, consultant, SAB member); participation on a data safety monitoring board or advisory board from Gencirq (stock and SAB member) and Micronoma (stock, SAB member, and cofounder); and owning stock and serving as cofounder of Biota. J. O. W. reports grants or contracts to their institution from the CDC and consulting fees as an expert witness (consulting fees paid to author) from Charles Russell Speechlys, LLP. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

**Graphical Abstract**
This graphical abstract is also available at Tidbit: https://tidbitapp.io/tidbits/integrated-genomic-and-social-network-analyses-of-sars-cov-2-transmission-in-the-healthcare-setting-1d3824e5-4e59-4391-a778-4f9205ecca0a

**Figure 1.**
Clusters of people with links in the electronic contact records (ECRs) on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) phylogeny. A, SARS-CoV-2 maximum likelihood phylogeny from the second and third pandemic waves. Tip shapes indicate that the viral genome came from a person with an ECR. Green indicates that these genomes were not linked. Blue indicates that they were genetically linked. B–E, Expanded view of clusters 1, 2, 4, and 5 from the second and third pandemic waves. Shape denotes patients (triangles) and HCWs (squares). F, SARS-CoV-2 maximum likelihood phylogeny from the BA.1 Omicron wave, shown on the same scale as the second and third waves and expanded for greater resolution (in the gray box). Abbreviation: HCW, healthcare worker.

**Figure 2.**
Contacts in the electronic contact records (ECRs) that are consistent with viral transmission based on severe acute respiratory syndrome coronavirus 2 phylogenetic analysis. A, Contacts during the second and third waves. B, Contacts during the BA.1 Omicron wave. The larger, lighter-colored pie represents links in the ECR. The smaller, darker-colored pie represents phylogenetic links. Color denotes the type of link: healthcare worker-to-healthcare worker in blue, healthcare worker-to-patient in green, and patient-to-patient in red. The area of the pies is proportional to the number of links represented.

**Figure 3.**
Expected and observed linked pairs during the BA.1 Omicron wave. A, Healthcare worker-to-healthcare worker genetically linked pairs. B, Healthcare worker-to-patient genetically linked pairs. C, Patient-to-patient genetically linked pairs. Number of observed linked pairs is indicated by the colored bars. Number of expected linked pairs based on 10 000 permutations is shown in gray.

See this image and copyright information in PMC

References

1. Spencer J, Jewett C. Lost on the frontline: our key findings about US healthcare worker deaths to date. Guardian 2021. Available at: https://www.theguardian.com/us-news/2021/apr/08/us-health-workers-deaths.... Accessed December 2023.
1. Nguyen LH, Drew DA, Graham MS, et al. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. Lancet Public Health 2020; 5:e475–83. - PMC - PubMed
1. Çelebi G, Pişkin N, Çelik Bekleviç A, et al. Specific risk factors for SARS-CoV-2 transmission among health care workers in a university hospital. Am J Infect Control 2020; 48:1225–30. - PMC - PubMed
1. Wang X, Ferro EG, Zhou G, Hashimoto D, Bhatt DL. Association between universal masking in a health care system and SARS-CoV-2 positivity among health care workers. JAMA 2020; 324:703–4. - PMC - PubMed
1. Denny TN, Andrews L, Bonsignori M, et al. Implementation of a pooled surveillance testing program for asymptomatic SARS-CoV-2 infections on a college campus—Duke University, Durham, North Carolina, August 2–October 11, 2020. MMWR Morb Mortal Wkly Rep 2020; 69:1743–7. - PMC - PubMed

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Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting

Collaborators

Affiliations

Integrated Genomic and Social Network Analyses of SARS-CoV-2 Transmission in the Healthcare Setting

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

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