A2B-COVID: A Tool for Rapidly Evaluating Potential SARS-CoV-2 Transmission Events

Author:

Illingworth Christopher J R1234ORCID,Hamilton William L56,Jackson Christopher2,Warne Ben56,Popay Ashley7,Meredith Luke8,Hosmillo Myra8,Jahun Aminu8,Fieldman Tom56,Routledge Matthew69,Houldcroft Charlotte J5ORCID,Caller Laura10,Caddy Sarah11,Yakovleva Anna8,Hall Grant8,Khokhar Fahad A8,Feltwell Theresa5,Pinckert Malte L8,Georgana Iliana8,Chaudhry Yasmin8,Curran Martin9,Parmar Surendra9,Sparkes Dominic69,Rivett Lucy69,Jones Nick K69,Sridhar Sushmita51112,Forrest Sally10,Dymond Tom6,Grainger Kayleigh6,Workman Chris6,Gkrania-Klotsas Effrossyni61314,Brown Nicholas M69ORCID,Weekes Michael P511,Baker Stephen511ORCID,Peacock Sharon J512ORCID,Gouliouris Theodore59,Goodfellow Ian8,Angelis Daniela De215,Török M Estée56

Affiliation:

1. MRC-University of Glasgow Centre for Virus Research, Glasgow, United Kingdom

2. MRC Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom

3. Department of Applied Mathematics and Theoretical Physics, University of Cambridge, Cambridge, United Kingdom

4. Institut für Biologische Physik, Universität zu Köln, Köln, Germany

5. Department of Medicine, University of Cambridge, Cambridge, United Kingdom

6. Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom

7. Public Health England Field Epidemiology Unit, Cambridge Institute of Public Health, Cambridge, United Kingdom

8. Department of Pathology, Division of Virology, University of Cambridge, Cambridge, United Kingdom

9. Clinical Microbiology and Public Health Laboratory, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom

10. Francis Crick Institute, London, United Kingdom

11. Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge, United Kingdom

12. Wellcome Sanger Institute, Hinxton, United Kingdom

13. MRC Epidemiology Unit, University of Cambridge, Level 3 Institute of Metabolic Science, Cambridge, United Kingdom

14. School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom

15. Public Health England, National Infection Service, London, United Kingdom

Abstract

AbstractIdentifying linked cases of infection is a critical component of the public health response to viral infectious diseases. In a clinical context, there is a need to make rapid assessments of whether cases of infection have arrived independently onto a ward, or are potentially linked via direct transmission. Viral genome sequence data are of great value in making these assessments, but are often not the only form of data available. Here, we describe A2B-COVID, a method for the rapid identification of potentially linked cases of COVID-19 infection designed for clinical settings. Our method combines knowledge about infection dynamics, data describing the movements of individuals, and evolutionary analysis of genome sequences to assess whether data collected from cases of infection are consistent or inconsistent with linkage via direct transmission. A retrospective analysis of data from two wards at Cambridge University Hospitals NHS Foundation Trust during the first wave of the pandemic showed qualitatively different patterns of linkage between cases on designated COVID-19 and non-COVID-19 wards. The subsequent real-time application of our method to data from the second epidemic wave highlights its value for monitoring cases of infection in a clinical context.

Funder

Medical Research Council

UK Research & Innovation

National Institute of Health Research (NIHR) and Genome Research Limited

Wellcome Sanger Institute; We also acknowledge the support from the Wellcome [Senior Clinical Fellowship

Senior Research Fellowship

Senior Fellowship

Collaborative Grant

Academy of Medical Sciences & the Health Foundation (Clinician Scientist Fellowship

NIHR Cambridge Biomedical Research Centre

NIHR Clinical Research Network Greenshoots

Deutsche Forschungsgemeinschaft

UKRI through the JUNIPER modeling consortium

UKRI Medical Research Council funding (Unit Programme

NIHR Health Protection Units in Behavioural Science and Evaluation

Publisher

Oxford University Press (OUP)

Subject

Genetics,Molecular Biology,Ecology, Evolution, Behavior and Systematics

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