Genomic and healthcare dynamics of nosocomial SARS-CoV-2 transmission
- University of Manchester, United Kingdom
- Manchester University NHS Foundation Trust, United Kingdom
- Manchester Centre for Genomic Medicine, United Kingdom
Abstract
Understanding the effectiveness of infection control methods in reducing and preventing SARS-CoV-2 transmission in healthcare settings is of high importance. We sequenced SARS-CoV-2 genomes for patients and healthcare workers (HCWs) across multiple geographically distinct UK hospitals, obtaining 173 high-quality SARS-CoV-2 genomes. We integrated patient movement and staff location data into the analysis of viral genome data to understand spatial and temporal dynamics of SARS-CoV-2 transmission. We identified eight patient contact clusters (PCC) with significantly increased similarity in genomic variants compared to non-clustered samples. Incorporation of HCW location further increased the number of individuals within PCCs and identified additional links in SARS-CoV-2 transmission pathways. Patients within PCCs carried viruses more genetically identical to HCWs in the same ward location. SARS-CoV-2 genome sequencing integrated with patient and HCW movement data increases identification of outbreak clusters. This dynamic approach can support infection control management strategies within the healthcare setting.
Data availability
All genome sequencing datasets have been shared with COG-UK.
Article and author information
Author details
Jamie M Ellingford
Funding
Health Education England
- Jamie M Ellingford
Manchester Biomedical Research Centre
- William G Newman
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Human subjects: The study was conducted to investigate hospital outbreak investigation/surveillance; individual patient consent or ethical approvals were not required. The study protocol was approved by the Manchester Biomedical Research Centre COVID-19 rapid response group and the Manchester University NHS Foundation Trust Executive Committee. All samples and data collected were part of routine care or hospital operational policy. No patient-identifiable/individual identifiable data are presented.
Copyright
© 2021, Ellingford et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Genomic and healthcare dynamics of nosocomial SARS-CoV-2 transmission
eLife 10:e65453.
https://doi.org/10.7554/eLife.65453
Further reading
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- Medicine
- Microbiology and Infectious Disease
- Epidemiology and Global Health
- Immunology and Inflammation
eLife has published articles on a wide range of infectious diseases, including COVID-19, influenza, tuberculosis, HIV/AIDS, malaria and typhoid fever.
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- Chromosomes and Gene Expression
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Models of nuclear genome organization often propose a binary division into active versus inactive compartments yet typically overlook nuclear bodies. Here, we integrated analysis of sequencing and image-based data to compare genome organization in four human cell types relative to three different nuclear locales: the nuclear lamina, nuclear speckles, and nucleoli. Although gene expression correlates mostly with nuclear speckle proximity, DNA replication timing correlates with proximity to multiple nuclear locales. Speckle attachment regions emerge as DNA replication initiation zones whose replication timing and gene composition vary with their attachment frequency. Most facultative LADs retain a partially repressed state as iLADs, despite their positioning in the nuclear interior. Knock out of two lamina proteins, Lamin A and LBR, causes a shift of H3K9me3-enriched LADs from lamina to nucleolus, and a reciprocal relocation of H3K27me3-enriched partially repressed iLADs from nucleolus to lamina. Thus, these partially repressed iLADs appear to compete with LADs for nuclear lamina attachment with consequences for replication timing. The nuclear organization in adherent cells is polarized with nuclear bodies and genomic regions segregating both radially and relative to the equatorial plane. Together, our results underscore the importance of considering genome organization relative to nuclear locales for a more complete understanding of the spatial and functional organization of the human genome.
