COG-UK HOCI COVID-19 Urgent Public Health Clinical Study
4 November 2020
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
Sponsor: University College London
A first-of-its kind clinical trial led by scientists at UCL, the COG-UK HOCI study will evaluate the use of ‘real time’ viral genomic data to reduce the spread of COVID-19 within hospitals. The study’s 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.
The study is being led by Professor Judith Breuer at the Pathogen Genomics Unit, UCL, with the Comprehensive Clinical Trials Unit (CCTU) at UCL providing study development, coordination, and health economic support. Additionally, colleagues at UCL’s Institute for Global Health are providing statistical and qualitative research expertise to the study.
Details covering the study’s design, outcomes, timelines and logistics are provided in the table below.
The National Institute for Health Research’s Urgent Public Health (NIHR UPH) listing for COG-UK HOCI is available at: https://www.nihr.ac.uk/covid-studies/study-detail.htm?entryId=283014.
- 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 to the NHS site’s 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
- 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.
- There are no exclusion criteria for COG-UK HOCI
Study Type: COG-UK HOCI is a phase III prospective, interventional, cohort, superiority study.
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.
- 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.
- 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
- 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.
- 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.
- 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.
- 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.
- Health economic benefit of both standard and rapid sequencing reports to IPC against baseline
- 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
- Likelihood of infection in the community
- 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
- Stirrup O, Boshier F, Venturini C, Freemantle N, et al | SARS-CoV-2 lineage B.1.1.7 is associated with greater disease severity among hospitalised women but not men: multicentre cohort study | 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 | Rapid feedback on hospital onset SARS-CoV-2 infections combining epidemiological and sequencing data | eLife 2021;10:e65828 DOI: 10.7554/eLife.65828