Protocol for the COG-UK hospital onset COVID-19 infection (HOCI) multicentre interventional clinical study: evaluating the efficacy of rapid genome sequencing of SARS-CoV-2 in limiting the spread of COVID-19 in United Kingdom NHS hospitals

Abstract

Introduction Nosocomial transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a significant cause of mortality in National Health Service (NHS) hospitals during the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study is to evaluate the impact of rapid whole genome sequencing of SARS-CoV-2, supported by a novel probabilistic reporting methodology, to inform infection prevention and control (IPC) practice within NHS hospital settings. Methods and analysis COG-UK HOCI (COG-UK Consortium Hospital-Onset COVID-19 Infections study) is a multicentre, prospective, interventional, superiority study. Eligible patients must be admitted to hospital with first confirmed SARS-CoV-2 PCR positive test result >48h from time of admission, where COVID-19 diagnosis was not suspected upon admission. The projected sample size for 14 participating sites covering all study phases over winter-spring 2020/2021 in the United Kingdom is 2,380 patients. The intervention is the return of a sequence report, within 48 hours in one phase (rapid local lab) and within 5-10 days in a second phase (mimicking central lab use), comparing the viral genome from an eligible study participant with others within and outside the hospital site. The primary outcomes are the incidence of Public Health England (PHE)/IPC-defined SARS-CoV-2 hospital-acquired infection during the baseline and two interventional phases, and proportion of hospital-onset cases with genomic evidence of transmission linkage following implementation of the intervention where such linkage was not suspected by initial IPC investigation. Secondary outcomes include incidence of hospital outbreaks, with and without sequencing data; actual and desirable changes to IPC actions; periods of healthcare worker (HCW) absence. A process evaluation using qualitative interviews with HCWs will be conducted alongside the study and analysis, underpinned by iterative programme theory of the sequence report. Health economic analysis will be conducted to determine cost-benefit of the intervention, and whether this leads to economic advantages within the NHS setting. Ethics and dissemination The protocol has been approved by the National Research Ethics Service Committee (Cambridge South 20/EE/0118). This manuscript is based on version 5.0 of the protocol. The study findings will be disseminated through peer-reviewed publications. Study Registration number ISRCTN50212645 Strengths and limitations of this study - The COG-UK HOCI study harnesses the infrastructure of the UK s existing national COVID-19 genome sequencing platform to evaluate the specific benefit of sequencing to hospital infection control. - The evaluation is thought to be the first interventional study globally to assess effectiveness of genomic sequencing for infection control in an unbiased patient selection in secondary care settings. - A range of institutional settings will participate, from specialist NHS-embedded or academic centres experienced in using pathogen genomics to district general hospitals. - The findings are likely to have wider applicability in future decisions to utilise genome sequencing for infection control of other pathogens (such as influenza, respiratory syncytial virus, norovirus, clostridium difficile and antimicrobial resistant pathogens) in secondary care settings. - The study has been awarded UK NIHR Urgent Public Health status, ensuring prioritised access to NIHR Clinical Research Network (CRN) research staff to recruit patients. - The study does not have a randomised controlled design due to the logistics of managing this against diverse standard practice.