Genomic epidemiology of COVID-19 in care homes in the East of England
- University of Cambridge, United Kingdom
- Wellcome Sanger Institute, United Kingdom
- Cambridgeshire County Council, United Kingdom
- University College London Hospitals NHS Foundation Trust, United Kingdom
- Public Health England, United Kingdom
- Public Health England (PHE), United Kingdom
- MRC-Laboratory of Molecular Biology, United Kingdom
- University of Oxford, United Kingdom
- Wellcome Trust Sanger Institute, United Kingdom
Abstract
COVID-19 poses a major challenge to care homes, as SARS-CoV-2 is readily transmitted and causes disproportionately severe disease in older people. Here, 1,167 residents from 337 care homes were identified from a dataset of 6,600 COVID-19 cases from the East of England. Older age and being a care home resident were associated with increased mortality. SARS-CoV-2 genomes were available for 700 residents from 292 care homes. By integrating genomic and temporal data, 409 viral clusters within the 292 homes were identified, indicating two different patterns - outbreaks among care home residents and independent introductions with limited onward transmission. Approximately 70% of residents in the genomic analysis were admitted to hospital during the study, providing extensive opportunities for transmission between care homes and hospitals. Limiting viral transmission within care homes should be a key target for infection control to reduce COVID-19 mortality in this population.
Data availability
The main analysis set comprised 700 genomes from care home residents. Additionally, a randomised selection of 700 genomes from non-care home residents was used for comparing lineage composition, and genomes from 76 healthcare workers tested at CUH were included for the analysis of care home resident-HCW transmission. Consensus fasta sequences for the 1,476 genomes are publicly accessible through the COG-UK website data section (https://www.cogconsortium.uk/data/). COG-UK also regularly deposits data into public databases such as GISAID (https://www.gisaid.org/). GISAID accession IDs and virus names are included in the Supplementary Materials. 13 samples were not added to GISAID as they did not pass GISAID's quality control filtering, but these fasta sequences are available in the COG-UK database.Sequences have associated public metadata (also available via the COG-UK website or GISAID), including patient age, sex, collection date (if available), and location to the level of UK county. However, not all of the metadata used in this study can be released publicly. COG-UK samples are sequenced under statutory powers granted to the UK Public Health Agencies. Matched patient data is securely released to the COG-UK consortium under a data sharing framework which strictly controls the handling of patient data. The status of individuals living in a care home and groups of such care home patients are both on the consortium restricted data list. This means that this data cannot be publicly released linked to sequencing identifiers, sampling date and UK counties. This is because of the risk of deductive disclosure. If a research scientist would like to repeat our analysis using these data fields, they should write to the corresponding authors to discuss the process of signing a data sharing agreement that will allow them to access the data securely.
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COVID-19 Genomics Consortium UKCOGUK, see Supplementary File 1 for identifiers.
Article and author information
Author details
Charlotte J Houldcroft
Michael Spencer Chapman
Funding
Medical Research Council (COG-UK grant to SJP)
- Sharon J Peacock
National Institute for Health Research (COG-UK grant to SJP)
- William L Hamilton
- Emily R Smith
- Sharon J Peacock
Genome Research Ltd (COG-UK grant to SJP)
- Sharon J Peacock
The Wellcome Trust (Senior Fellowship 097997/Z/11/Z)
- Ian G Goodfellow
Academy of Medical Sciences (Clinician Scientist Fellowship to MET)
- M Estee Torok
Health Foundation (Clinician Scientist Fellowship to MET)
- M Estee Torok
NIHR Cambridge Biomedical Research Centre
- Ben Warne
- Gordon Dougan
- M Estee Torok
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Amy Wesolowski, Johns Hopkins Bloomberg School of Public Health, United States
Ethics
Human subjects: This study was conducted as part of surveillance for COVID-19 infections under the auspices of Section 251 of the NHS Act 2006. It therefore did not require individual patient consent or ethical approval. The COG-UK study protocol was approved by the Public Health England Research Ethics Governance Group (reference: R&D NR0195).
Version history
- Received: November 4, 2020
- Accepted: February 25, 2021
- Accepted Manuscript published: March 2, 2021 (version 1)
- Version of Record published: March 26, 2021 (version 2)
- Version of Record updated: September 2, 2021 (version 3)
Copyright
© 2021, Hamilton 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 epidemiology of COVID-19 in care homes in the East of England
eLife 10:e64618.
https://doi.org/10.7554/eLife.64618
Further reading
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- Epidemiology and Global Health
Background:
The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission.
Methods:
To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018.
Results:
Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes.
Conclusions:
Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors.
Funding:
This research was funded by the National Institutes of Health, grants R01AI121558, R01AI137395, R01AI155730, F30AI143172, and K24AI134990. Funding was also contributed from the Swedish Research Council, Erling-Persson Family Foundation, and the Yang Fund. RV acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. RV also acknowledges funding by Community Jameel.
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.
Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.
Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
