果冻影院

A phase III prospective, interventional, cohort, superiority study to evaluate the benefit of rapid COVID-19 genomic sequencing (the COVID-19 GENOMICS UK project) on infection control in preventing the spread of the virus in United Kingdom NHS settings

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A first-of-its kind clinical trial led by scientists at 果冻影院, the COG-UK HOCI study will evaluate the use of 鈥榬eal time鈥� viral genomic data to reduce the spread of COVID-19 within hospitals. The study鈥檚 findings could help the NHS reduce further transmission of the virus by determining if an individual caught the virus from someone else within the same hospital.听

The study is being led by Professor Judith Breuer at the Pathogen Genomics Unit, 果冻影院, with the Comprehensive Clinical Trials Unit (CCTU) at 果冻影院 providing study development, coordination, and health economic support. Additionally, colleagues at 果冻影院鈥檚 Institute for Global Health are providing statistical and qualitative research expertise to the study.

Details covering the study鈥檚 design, outcomes, timelines and logistics are provided in the table below.

The National Institute for Health Research鈥檚 Urgent Public Health (NIHR UPH) listing for COG-UK HOCI is available at: .

Trial Information

Countries of Recruitment: United Kingdom

Health Condition(s) or Problem(s) Studied: SARS-CoV-2 nosocomial spread

Intervention(s): The study intervention is delivery of a SARS-CoV-2 genomic sequencing data report either:

• within 48 hours from local sequencing hub 听to the NHS site鈥檚 virology lab for dissemination to Infection Prevention and Control (IPC) teams;
• or the same, delivered within 5-10 days from centralised sequencing facility

Key Inclusion and Exclusion Criteria

Inclusion criteria

• Participants must have confirmed SARS-CoV-2 infection and be a hospital-onset COVID-19 infection (HOCI)
• Participants must have provided a saliva sample or a nasal swab/pharyngeal swab / combined nasal and pharyngeal swab / nasopharyngeal aspirate or broncho alveolar lavage sample for evaluation in the COG-UK project.
• Participants may be of any age to be included in study

Note: in the above criterion a HOCI is an admitted patient at site with first confirmed test for SARS-CoV-2 >48 hours after admission, where they were not suspected to have COVID-19 at time of admission.

Exclusion Criteria

• There are no exclusion criteria for COG-UK HOCI

Study Type: COG-UK HOCI is a phase III prospective, interventional, cohort, superiority study.听
Target Sample Size: A total of 2,000 patients with hospital-onset COVID-19 infection (HOCIs)
Recruitment duration: Anticipated to be 4 months from Q4 2020 to Q1 2021
Participating centres: 18-20 NHS Trusts/Health Boards, United Kingdom-wide.

Outcomes

Primary Outcome(s)

1. Incidence rate of IPC-defined SARS-CoV-2 HAIs, measured as incidence rate of recorded cases per week per 100 inpatients, during each phase of the study based on case report forms.
2. Identification of SARS-CoV-2 nosocomial transmission using sequencing data from HOCIs for whom this was not identified by pre-sequencing IPC evaluation, measured using pre- and post-sequencing case report forms for each enrolled patient during study phases in which the sequence reporting tool is in use.

Key Secondary Outcomes

1. Incidence rate of IPC-defined SARS-CoV-2 hospital outbreaks, defined as cases of hospital transmission linked by location and with intervals between diagnoses no greater than 2 weeks (relevant data extracted from case report forms), measured as incidence rate of outbreak events per week per 100 inpatients during each phase of the study.
2. Incidence rate of IPC+sequencing-defined SARS-CoV-2 hospital outbreaks involving HOCI cases, defined by retrospective review of all available clinical study data for identification of transmission clusters and measured as outbreak events per week per 100 inpatients during study phases in which the sequence reporting tool is in use.
3. Changes to IPC actions implemented following receipt of SARS-CoV-2 sequence report, measured using pre- and post-sequencing case report forms for each enrolled patient during study phases in which the sequence reporting tool is in use.
4. Changes to IPC actions that would ideally have been implemented following receipt of SARS-CoV-2 sequence report, measured using pre- and post-sequencing case report forms for each enrolled patient during study phases in which the sequence reporting tool is in use.
5. Health economic benefit of both standard and rapid sequencing reports to IPC against baseline听
6. The number of HCW periods of sickness/self-isolation as assessed as a proportion of the number of staff usually on those wards impacted by HOCI cases, for all phases of the trial.

Key exploratory Outcomes

1. Summaries of results from generated sequence reports:

• Number of close sequence matches in same unit
• Reported probability of infection source within the unit
• Number of close sequence matches in rest of hospital
• Reported probability of linked infection somewhere else in the hospital
• Likelihood of infection from a visitor听
• Likelihood of infection in the community听
• Whether any HCWs are reported among the close sequence matches returned

2. An understanding of how the rapid genome sequencing intervention worked in practice across different sites during the HOCI trial including descriptions of:

• Intervention context
• The problem the intervention was designed to addressed
• The key intervention components and mechanisms of action
• Implementation actions of the IPC teams and hospital planners

3. The links between the intervention and the trial outcomes

Publications

• Monica Panca, James Blackstone, Oliver Stirrup, Maria-Teresa Cutino-Moguel, Emma Thomson, Christine Peters, Luke B. Snell, Gaia Nebbia, Alison Holmes, Anu Chawla, Nicholas Machin, Yusri Taha, Tabitha Mahungu, Tranprit Saluja, Thushan I. de Silva, Kordo Saeed, Cassie Pope, Gee Yen Shin, Rachel Williams, Alistair Darby, Darren L. Smith, Matthew Loose, Samuel C. Robson, Kenneth Laing, David G. Partridge, James R. Price, Judith Breuer听|听听|听Journal of Hospital Infection 2023听|听ISSN 0195-6701听|听.
• Flowers, P., Leiser, R., Mapp, F., McLeod, J., Stirrup, O., Illingworth, C. J. R., Blackstone, J., & Breuer, J. (2023). British Journal of Health Psychology, 00, 1鈥� 25.
• Hayley Colton, Matthew D. Parker, Oliver Stirrup, James Blackstone, Matthew Loose, C. Patrick McClure, Sunando Roy, Charlotte Williams, Julie McLeod, Darren Smith, Yusri Taha, Peijun Zhang, Sharon Nienyun Hsu, Beatrix Kele, Kathryn Harris, Fiona Mapp, Rachel Williams, Paul Flowers, Judith Breuer, David G. Partridge, Thushan I. de Silva |听 |听Journal of Hospital Infection, 2022,听ISSN 0195-6701,听.
• Oliver Stirrup,听James Blackstone,听Fiona Mapp,听Alyson MacNeil,听Monica Panca,听Alison Holmes,听Nicholas Machin,听Gee Yen Shin,听Tabitha Mahungu,听Kordo Saeed,听Tranprit Saluja,听Yusri Taha,听Nikunj Mahida,听Cassie Pope,听Anu Chawla,听Maria-Teresa Cutino-Moguel,听Asif听Tamuri,听Rachel听Williams,听Alistair听Darby,听David听L听Robertson,听Flavia听Flaviani,听Eleni听Nastouli,听Samuel Robson,听Darren Smith,听Kenneth Laing,听Irene听Monahan,听Beatrix Kele,听Sam Haldenby,听Ryan George,听Matthew Bashton,听Adam A Witney,听Matthew Byott,听Francesc Coll,听Michael Chapman,听Sharon J Peacock,听COG鈥怳K HOCI Investigators,听The COVID鈥�19 Genomics UK (COG鈥怳K) Consortium,听Joseph Hughes,听Gaia Nebbia,听David G Partridge,听Matthew Parker,听James Richard Price,听Christine Peters,听Sunando Roy,听Luke B Snell,听Thushan I de Silva,听Emma Thomson,听Paul Flowers,听Andrew Copas,听Judith Breuer |听 |听eLife听11:e78427.
• James Blackstone, Oliver Stirrup, Fiona Mapp, Monica Panca, Andrew Copas, Paul Flowers, Leanne Hockey, James Price, David Partridge, Christine Peters, Thushan de Silva, Gaia Nebbia, Luke B Snell, Rachel McComish, The COVID-19 Genomics UK (COG-UK) Consortium, Judith Breuer |听s |听doi: 10.1136/bmjopen-2021-052514
• Stirrup O, Boshier F, Venturini C, Freemantle N, et al听|听听|听BMJ Open Respiratory Research 2021;8:e001029.
• Oliver Stirrup, Joseph Hughes, Matthew Parker, David G Partridge, James G Shepherd, James Blackstone, Francesc Coll, Alexander Keeley, Benjamin B Lindsey, Aleksandra Marek, Christine Peters, Joshua B Singer, The COVID-19 Genomics UK (COG-UK) consortium, Asif Tamuri, Thushan I de Silva, Emma C Thomson, Judith Breuer听| | eLife 2021;10:e65828 DOI: 10.7554/eLife.65828

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