̽��ֱ�� of Cambridge - Estee Torok

Genomics study identifies routes of transmission of coronavirus in care homes

cjb250 — Wed, 03 Mar 2021 09:27:53 +0000

Care homes are at high risk of experiencing outbreaks of COVID-19, the disease caused by SARS-CoV-2. Older people and those affected by heart disease, respiratory disease and type 2 diabetes – all of which increase with age – are at greatest risk of severe disease and even death, making the care home population especially vulnerable.

Care homes are known to be high-risk settings for infectious diseases, owing to a combination of the underlying vulnerability of residents who are often frail and elderly, the shared living environment with multiple communal spaces, and the high number of contacts between residents, staff and visitors in an enclosed space.

In research published today in eLife, a team led by scientists at the ̽��ֱ�� of Cambridge and Wellcome Sanger Institute used a combination of genome sequencing and detailed epidemiological information to examine the impact of COVID-19 on care homes and to look at how the virus spreads in these settings.

SARS-CoV-2 is an RNA virus and as such its genetic code is prone to errors each time it replicates. It is currently estimated that the virus mutates at a rate of 2.5 nucleotides (the A, C, G and U of its genetic code) per month. Reading – or ‘sequencing’ – the genetic code of the virus can provide valuable information on its biology and transmission. It allows researchers to create ‘family trees’ – known as phylogenetic trees – that show how samples relate to each other.

Scientists and clinicians in Cambridge have pioneered the use of genome sequencing and epidemiological information to trace outbreaks and transmission networks in hospitals and community-based healthcare settings, helping inform infection control measures and break the chains of transmission. Since March 2020, they have been applying this method to SARS-CoV-2 as part of the COVID-19 Genomics UK (COG-UK) Consortium.

In this new study, researchers analysed samples collected from 6,600 patients between 26 February and 10 May 2020 and tested at the Public Health England (PHE) Laboratory in Cambridge. Out of all the cases, 1,167 (18%) were care home residents from 337 care homes, 193 of which were residential homes and 144 nursing homes, the majority in the East of England. ̽��ֱ��median age of care home residents was 86 years.

While the median number of cases per care home was two, the ten care homes with the largest number of cases accounted for 164 cases. There was a slight trend for nursing homes to have more cases per home than residential homes, with a median of three cases.

Compared with non-care home residents admitted to hospital with COVID-19, hospitalised care home residents were less likely to be admitted to intensive care units (less than 7% versus 21%) and more likely to die (47% versus 20%).

̽��ֱ��researchers also explored links between care homes and hospitals. 68% of care home residents were admitted to hospital during the study period. 57% were admitted with COVID-19, 6% of cases had suspected hospital-acquired infection, and 33% were discharged from hospital within 7 days of a positive test. These findings highlight the ample opportunities for SARS-CoV-2 transmission between hospital and care home settings.

When the researchers examined the viral sequences, they found that for several of the care homes with the highest number of cases, all of the cases clustered closely together on a phylogenetic tree with either identical genomes or just one base pair difference. This was consistent with a single outbreak spreading within the care home.

By contrast, for several other care homes, cases were distributed across the phylogenetic tree, with more widespread genetic differences, suggesting that each of these cases was independent and not related to a shared transmission source.

“Older people, particularly those in care homes who may be frail, are at particular risk from COVID-19, so it’s essential we do all that we can to protect them,” said Dr Estée Török, an Honorary Consultant at Addenbrooke's Hospital, Cambridge ̽��ֱ�� Hospitals (CUH), and an Honorary Senior Visiting Fellow at the ̽��ֱ�� of Cambridge.

“Preventing the introduction of new infections into care homes should be a key priority to limit outbreaks, alongside infection control efforts to limit transmission within care homes, including once an outbreak has been identified.”

̽��ֱ��team found two clusters that were linked to healthcare workers. One of these involved care home residents, a carer from that home and another from an unknown care home, paramedics and people living with them. ̽��ֱ��second involved several care home residents and acute medical staff at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust who cared for at least one of the residents. It was not possible to say where these clusters originated from and how the virus spread.

“Using this technique of ‘genomic surveillance’ can help institutions such as care homes and hospitals better understand the transmission networks that allow the spread of COVID-19,” added Dr William Hamilton from the ̽��ֱ�� of Cambridge and CUH. “This can then inform infection control measures, helping ensure that these places are as safe as possible for residents, patients, staff and visitors.”

̽��ֱ��absolute number of diagnosed COVID-19 cases from care home residents declined more slowly in April than for non-care home residents, increasing the proportion of cases from care homes and contributing to the slow rate of decline in total case numbers during April and early May 2020.

“Our data suggest that care home transmission was more resistant to lockdown measures than non-care home settings. This may reflect the underlying vulnerability of the care home population, and the infection control challenges of nursing multiple residents who may also share communal living spaces,” said Gerry Tonkin-Hill from the Wellcome Sanger Institute.

̽��ֱ��team found no new viral lineages from outside the UK, which may reflect the success of travel restrictions in limiting new viral introductions into the general population during the first epidemic wave and lockdown period.

This work was funded by COG-UK, Wellcome, the Academy of Medical Sciences, the Health Foundation and the NIHR Cambridge Biomedical Research Centre.

Reference
Hamilton, W et al. COVID-19 infection dynamics in care homes in the East of England: a retrospective genomic epidemiology study. eLife; 2 March 2021; DIO: 10.7554/eLife.64618

Genomic surveillance – using information about genetic differences between virus samples – can help identify how SARS-CoV-2 spreads in care home settings, whose residents are at particular risk, according to new research published today.

Older people, particularly those in care homes who may be frail, are at particular risk from COVID-19, so it’s essential we do all that we can to protect them

Estee Torok

National Cancer Institute

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̽��ֱ��text in this work is licensed under a Creative Commons Attribution 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Reflections on a year of fighting COVID-19

cjb250 — Fri, 11 Dec 2020 09:30:35 +0000

2020 will be forever remembered for COVID-19. As the year draws to a close, Dr Estée Török looks back at how colleagues across the NHS and the research community worked tirelessly to fight back.

“We’re in it for the long haul”

cjb250 — Wed, 21 Oct 2020 07:46:34 +0000

In late 2019, a new institute opened on the Cambridge Biomedical Campus. Its timing could not have been better - as the COVID-19 pandemic sent Britain into lockdown several months later, the institute found itself at the heart of the ̽��ֱ��’s response to this unprecedented challenge.

Rapid genome sequencing and screening help hospital manage COVID-19 outbreaks

cjb250 — Tue, 14 Jul 2020 22:30:00 +0000

Since the start of the UK pandemic, when the virus was spreading between people, a team of scientists and clinicians at the ̽��ֱ�� of Cambridge and Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust (CUH) have been reading the genetic code of the virus to see if cases within the hospital are connected. This has enabled the hospital to fully investigate these outbreaks and to improve infection control measures to reduce the risk of further infections.

In addition, the introduction of a screening programme that involved repeat testing of staff, has helped the hospital to investigate clusters of COVID-19 infections, informing infection control measures and breaking chains of transmission. This has helped reduce the number of hospital-acquired infections, ensuring maximum safety for patients and staff as the NHS aims to re-start other services.

Researchers have published details of these investigations in two peer-reviewed journals, Lancet Infectious Diseases and eLife.

Genomic surveillance

Researchers in Cambridge have previously pioneered the use of genome sequencing as a way of managing hospital infections such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE) and Clostridium difficile. They have also used real-time sequencing to rapidly identify transmission chains in epidemics such as the Ebola epidemic in Sierra Leone.

̽��ֱ��researchers have now turned their attention to COVID-19.

SARS-CoV-2, the coronavirus that causes COVID-19, is an RNA virus and as such its genetic code is prone to errors each time it replicates. It is currently estimated that the virus mutates at a rate of 2.5 nucleotides (the A, C, G and T of genetic code) per month. Reading – or ‘sequencing’ – the genetic code of the virus can provide valuable information on its biology and transmission.

As part of the COVID-19 Genomics UK (COG-UK) Consortium, researchers have been sequencing all available positive samples from patients admitted to the hospital with COVID-19 infection as well as a selection of samples collected from patients in regional hospitals across the East of England.

In a five week period from mid-March to late April, the team sequenced over 1,000 viral genomes. They used phylogenetic trees – akin to a ‘family tree’ – to look at how clusters of virus samples might be related, allowing them to help pinpoint particular wards or locations where the disease was spreading.

Dr Estée Török from the Department of Medicine at the ̽��ֱ�� of Cambridge said: “Genome sequencing gives us a rapid and reliable way of identifying cases of COVID-19 infection that are closely related within the hospital. This approach can provide vital information to help us to investigate the possible routes of transmission and to improve infection control measures to limit the spread of infection.”

̽��ֱ��researchers analysed 299 COVID-19 patients and found 35 clusters of genetically identical viruses involving 159 patients. By examining the patients’ medical records and ward location data researchers identified strong links between 58% of cases and plausible links between 20% of cases. ̽��ֱ��epidemiological and genomic data were fed back to the hospital infection control and management teams resulting in implementation of a range of measures to prevent further transmission, including isolation of infected patients, revised procedures for ward cleaning, enhanced use of personal protective equipment (PPE) and changes in staff social distancing behaviour.

As an example, six dialysis patients were admitted to different locations in the hospital with COVID-19 infection over a three-week period. Sequencing revealed that their viral genomes were identical. Epidemiological investigation showed that the patients dialysed at the same outpatient dialysis unit on the same days of the week and identified shared patient transportation and neighbouring dialysis chairs as risk factors for transmission. This enabled the infection control team to enhance infection control measures and prevented additional cases.

Professor Ian Goodfellow, from the Department of Pathology at the ̽��ֱ�� of Cambridge, said: “We’re able to combine genomic data with patients’ medical records to provide real time information to help the hospital review its infection control on a weekly basis. It’s also highlighted possible transmission networks less well documented, such as care homes, outpatient units and ambulance services.”

̽��ֱ��COVID-19 Genomics UK Consortium is supported by funding from the Medical Research Council, part of UK Research & Innovation (UKRI), the National Institute of Health Research and the Wellcome Sanger Institute.

Screening asymptomatic and symptomatic healthcare workers

In addition to genomic surveillance, CUH has implemented a screening programme in which all staff – both symptomatic and asymptomatic – are screened.

In May, Cambridge researchers reported that of the more than 1,000 staff members reporting fit for duty during April, 3% tested positive for the coronavirus.

Now, in a follow-up study published in eLife, they have found that, alongside a decline in patient admissions with COVID-19, the proportion of both asymptomatic and symptomatic healthcare workers testing positive declined rapidly throughout the following month.

̽��ֱ��team performed 3,388 tests at CUH between 25 April and 24 May. These included 2,611 tests on asymptomatic healthcare workers. ̽��ֱ��samples were analysed using a technique called PCR to detect genetic information from the virus on the swab.

̽��ֱ��researchers found that just 21 (0.8%) of the 2,611 tests carried out on asymptomatic healthcare workers returned positive, a large drop compared to the previous month.

Of the 771 tests carried out on symptomatic healthcare workers or those living with someone with possible infection, just 13 (1.7%) were positive – compared to 13% the previous month.

Dr Mike Weekes, from the Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), said: “Screening all staff at the hospital regardless of whether they are showing symptoms has helped us see a dramatic fall in the number of hospital-acquired infections. It means we’re able to spot new outbreaks faster, limiting their opportunity to spread.

“It’s important not to be complacent, though. There will inevitably be new outbreaks that occur – that is, unfortunately, the nature of a pandemic. But we hope our approach will help reassure both staff and patients that the hospital remains a safe place to give and receive care.”

In their report, the team give an example of where four symptomatic staff from the same general medical ward tested positive. In response, the team was able to carry out targeted screening of staff on the ward, allowing them to identify a cluster of infections and prevent further onward transmission.

“ ̽��ֱ��existence of clusters of infection in specific areas of the hospital shows the potential for staff and patients to become infected within the hospital environment,” said Professor Steve Baker from CITIID. “If left unchecked, these clusters could lead to self-sustaining outbreaks. Frequent testing at CUH allowed us to spot these clusters quickly and stop any further transmission.”

̽��ֱ��research was supported by Wellcome, the Addenbrooke’s Charitable Trust, the Medical Research Council, NHS Blood and Transfusion, National Institute for Health Research Cambridge Biomedical Research Centre and Cancer Research UK.

Reference

Meredith, LW, Hamilton, WL, et al. Rapid implementation of real-time SARS-CoV-2 sequencing to investigate healthcare-associated COVID-19 infections. Lancet ID; 14 July 2020; DOI: 10.1016/S1473-3099(20)30562-4

Jones, NK, Rivett, L, Sparkes, D, and Forrest, S et al. Effective control of healthcare worker SARS-CoV-2 transmission in a period of declining community prevalence of COVID-19. eLife; 19 June 2020; DOI: 0.7554/eLife.59391

Cambridge researchers have shown how rapid genome sequencing of virus samples and enhanced testing of hospital staff can help to identify clusters of healthcare-associated COVID-19 infections.

This approach can provide vital information to help us to investigate the possible routes of transmission and to improve infection control measures to limit the spread of infection

Estee Torok

Spc. Miguel Pena

Taking a swab to test for SARS-CoV-2 (COVID-19)

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Tackling COVID-19: Dr Estée Török

jg533 — Thu, 09 Jul 2020 07:00:40 +0000

This article is part of a series in which we speak to some of the many Cambridge researchers tackling COVID-19. For other articles about our latest COVID-19-related research, click here.

I’m a clinical academic working in the Department of Medicine at the ̽��ֱ�� of Cambridge and at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust. With most of my research team I have continued to work at Addenbrooke’s during lockdown, but we’ve all worked much longer hours than usual. In fact, until recently I hadn’t had a day off for six weeks.

My clinical experience and research interests are in infectious diseases, microbiology and genomics. I have been involved in clinical trials of infectious diseases - including TB, HIV, viral hepatitis, Staphylococcus aureus and multidrug-resistant bacteria - in the UK and in Southeast Asia for nearly 20 years. Since moving to Cambridge my research has focussed on using genome sequencing to investigate transmission of pathogens in hospital and community settings. These skills have prepared me to respond to the COVID-19 pandemic response efforts in Cambridge.

As a clinician I’m interested in understanding the epidemiology of infectious diseases and how best to treat them. I have used my clinical trials experience to contribute to the RECOVERY trial, a randomised controlled trial of various treatments for COVID-19, as a study doctor. To date this is the world’s biggest trial of drugs to treat COVID-19 patients, and the results are regularly reviewed so that any effective treatment can be quickly made available to patients. A preliminary analysis has found that dexamethasone (a steroid drug), a cheap and readily available treatment, reduces mortality in patients with COVID-19 requiring respiratory support.

I also set up and led a novel coronavirus vaccine trial, the ‘COV002’ trial, in Cambridge. This is a phase 2/3 trial of the vaccine developed by the ̽��ֱ�� of Oxford, which is being tested in over 10,000 healthy volunteers in 19 UK centres. We rapidly assembled a team of over 70 research staff in three NHS Trusts (Cambridge ̽��ֱ�� Hospitals, Royal Papworth Hospital and Cambridgeshire and Peterborough NHS Foundation Trust) in Cambridgeshire. We screened over 500 healthcare workers and vaccinated over 300 of them in just over three weeks. ̽��ֱ��results of this trial will also give us vital information on the safety and efficacy of this vaccine, production of which is already being scaled up by AstraZeneca.

I used rapid sequencing of SARS-CoV-2 virus to investigate patients with COVID-19 infections at Addenbrooke’s Hospital. This work was done in collaboration with the Department of Pathology and the Public Health England Clinical Microbiology and Public Health Laboratory, as part of the COVID-19 Genomics Consortium UK. We set up and implemented a system to rapidly sequence clinical samples and to investigate healthcare-associated COVID-19 infections by analysing epidemiological and genomic data. This information was fed back to the hospital infection control and hospital management teams to investigate suspected outbreaks and improve infection control. ̽��ֱ��data we gather will help to guide UK public health interventions and policies.

̽��ֱ��biggest challenges we face relating to this pandemic are to prevent people from becoming infected with SARS-CoV-2, and to find treatments that can prevent the development of severe COVID-19 disease and save lives. Developing an effective vaccine really is key to controlling the pandemic.

COVID-19 is a global public health emergency that requires national and international collaborative efforts. I feel very fortunate to have been able work with outstanding clinical and academic colleagues in three NHS Trusts in Cambridgeshire, different clinical and ̽��ֱ�� departments, and other UK institutions to contribute to these efforts.

With a dedicated and enthusiastic team it’s possible to achieve extraordinary things in a short period of time. It is important to recognise what is clinically and scientifically important, and to focus all your efforts on this.

I was due to get married in June. When the pandemic is over, I’m looking forward to seeing my friends and family, getting back to triathlon training, and getting married!

Estée Török is Clinician Scientist Fellow and a Senior Research Associate in the Department of Medicine at the ̽��ֱ�� of Cambridge, and an Honorary Consultant in Infectious Diseases and Microbiology at Addenbrooke’s Hospital.

How you can support Cambridge’s COVID-19 research

Long hours running COVID-19 vaccine and drugs trials have left little time for Estée Török to contemplate her postponed wedding. With over 20 years' clinical research experience in infectious diseases in the UK and south-east Asia, she has a great deal to contribute to tackling the pandemic.

Estee Torok

Estee Torok (centre, in black) with team at Addenbrooke's Hospital

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Recruitment underway as Cambridgeshire NHS trusts join COVID-19 vaccine trial

Anonymous — Thu, 11 Jun 2020 07:49:43 +0000

̽��ֱ��COV002 trial, developed by the ̽��ֱ�� of Oxford, aims to assess how well people across a broad range of ages could be protected from COVID-19 using a new vaccine called ChAdOx1 nCoV-19. It will also provide valuable information on safety of the vaccine and its ability to generate good immune responses against the virus.

Cambridgeshire and Peterborough NHS Foundation Trust (CPFT), Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust and Royal Papworth Hospital NHS Foundation Trust are recruiting healthy staff aged between 18-55 years old who have not been infected with coronavirus but have regular face-to-face contact with COVID-19 patients, to take part in the trial.

Eligible participants will be randomised to receive one dose of either the trial vaccine (ChAdOx1 nCoV-19) or a licensed meningitis vaccine (MenACWY) that will be used as a ‘control’ for comparison. Following vaccination, participants will be followed up over 12 months.

Dr Estée Török from the Department of Medicine at the ̽��ֱ�� of Cambridge and Principal Investigator at Cambridge ̽��ֱ�� Hospitals NHS Foundation Trust, said: “Developing an effective vaccine is key to controlling the COVID-19 pandemic. We are delighted to be working with CPFT and Royal Papworth on this UK national priority vaccine trial. We are looking for healthy volunteers at high risk of COVID-19 infection at CUH to participate in this study and are most grateful to them for doing so.”

Dr Ben Underwood, Deputy Medical Director and Principal Investigator (study lead) at CPFT said: “We are grateful to all our staff for their brilliant response to the coronavirus pandemic. Our research teams are playing a vital role in international efforts to secure a vaccine, which we hope will protect those most at risk, save more lives and minimise the disruption caused by the virus. Thank you to all volunteers who take part and make clinical trials possible.”

Dr Robert Rintoul, Director, Papworth Trials Unit Collaboration, and Reader in Thoracic Oncology at the Department of Oncology, ̽��ֱ�� of Cambridge, said: “We at Royal Papworth Hospital are proud to be supporting research into possible vaccines and treatments for COVID-19. I would like to thank our staff members who have chosen to participate in this important public health project.”

Adapted from a press release by Cambridge ̽��ֱ�� Health Partners.

Recruitment has begun at three leading Cambridgeshire NHS Trusts for volunteers to take part in the nationwide COVID-19 vaccine trial.

Developing an effective vaccine is key to controlling the COVID-19 pandemic

Estee Torok

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