Insights into the implementation of a whole genome sequencing report form (SRF) to reduce nosocomial SARS-CoV-2 within UK hospitals: a qualitative process evaluation using normalisation process theory (preprint)

Background Here we report on a process evaluation conducted as part of a large multisite non-randomised trial of the effectiveness of a whole genome sequence report form (SRF) to reduce nosocomial SARS-CoV-2 through changing infection prevention and control (IPC) behaviours during the COVID − 19 pandemic. We detail how the SRF was implemented across a heterogeneous purposive sub-sample of hospital trial sites (n = 5/14). Methods We conducted in-depth interviews from diverse professional staff (N = 39). Inductive thematic analysis initially explored participants’ accounts of implementing the SRF. The resulting data driven themes, concerning the way the SRF was used within sites, were then coded in relation to the key tenets of normalisation process theory (NPT). Results Factors that enabled the implementation of the SRF included: elements of the context such as health care professional passion; the existence of whole genome sequencing (WGS) infrastructure; effective communication channels, the creation of new connections across professionals and teams; the integration of SRF-led discussions within pre-existing meetings and the ability of a site to achieve a rapid turnaround time. In contrast, we found factors that constrained the use of the SRF included elements of the context such as the impact of the Alpha-variant overwhelming hospitals. In turn, dealing with COVID-19 breached the limited capacity of infection prevention and control (IPC) to respond to the SRF and ensure its routinisation. Conclusion We show preliminary support for the SRF being an acceptable, useable and potentially scalable way of enhancing existing IPC activities. However, the context of both the trial and the alpha wave of COVID-19 limit these insights. Clinical trial number https://www.isrctn.com/ISRCTN50212645, Registration date 20/05/2020

A qualitative process evaluation using the behaviour change wheel approach: Did a whole genome sequence report form (SRF) used to reduce nosocomial SARS-CoV-2 within UK hospitals operate as anticipated? (preprint)

PurposeTo conduct a process evaluation of a whole genome sequence report form (SRF) used to reduce nosocomial SARS-CoV-2 through changing infection prevention and control (IPC) behaviours. Here using qualitative behavioural analyses we report how the SRF worked. MethodsPrior to a multisite non-randomised trial of its effectiveness, the SRF was coded in relation to its putative behaviour change content (using the theoretical domains framework (TDF), the behaviour change wheel (BCW) and the behaviour change technique taxonomy (BCTTv1)). After the SRF had been used, through the peak of the Alpha variant, we conducted in-depth interviews from diverse professional staff (N=39) from a heterogeneous purposive sub-sample of hospital trial sites (n=5/14). Deductive thematic analysis explored participants accounts of using the SRF according to its putative content in addition to inductive exploration of their experiences. ResultsWe found empirical support for the putative theoretical mechanisms of Knowledge and Behavioural regulation, as well as for intervention functions of Education and Persuasion and Enablement, and for particular BCTs 1.2 Problem solving, 2.6 Biofeedback, 2.7 Feedback on outcomes of behaviour, and 7.1 Prompts and cues. Most participants found the SRF useful and believed it could shape IPC behaviour. ConclusionsOur process evaluation of the SRF provided granular and general support for the SRF working to change IPC behaviours. Our analysis highlighted useful SRF content. However, we also note that, without complementary work on systematically embedding the SRF within routine practice and wider hospital systems, it may not reach its full potential to reduce nosocomial infection. What is already known on this subject?O_LIHealth psychology remains under-exploited within infection prevention and control (IPC) interventions C_LIO_LIFor genomic insights to be understood by a range of health care professionals and elicit changes in IPC behaviour, ways of translating complex genomic insights into a simple format are needed. These simple translation tools can be described as whole genome sequence report forms (SRFs) C_LIO_LINothing is currently known about the use of SRFs, for SARS-CoV-2 or other infections, to change hospital-based IPC behaviour. C_LIO_LIHealth psychological tools such as the behaviour change wheel (BCW), the theoretical domains framework (TDF), and the behaviour change technique taxonomy (BCTTv1) are widely used to develop behaviour change interventions but are rarely used to evaluate them C_LIO_LIContemporary guidance on conducting process evaluations highlights the value of explicitly theorising how an intervention is intended to work before systematically examining how it actually worked in practice C_LI What does this study add?O_LIThe paper presents a novel worked example of using tools from health psychology within a qualitative process evaluation of using an SRF during the COVID-19 pandemic in UK hospitals C_LIO_LIThis paper is the first to report how people experienced using whole genome sequence report forms (SRFs) in order to change hospital-based IPC behaviour C_LIO_LIWe provide qualitative evidence detailing empirical support for much of the SRFs putative content, including casual mechanisms Knowledge and Behavioural regulation, intervention functions such as Education and Enablement, and for particular BCTs: 1.2 Problem solving, 2.6 Biofeedback, 2.7 Feedback on outcomes of behaviour, and 7.1 Prompts and cues C_LI

How acceptable is rapid whole genome sequencing for infectious disease management in hospitals? Perspectives of those involved in managing nosocomial SARS-CoV-2 (preprint)

Structured summary Background Whole genome sequencing (WGS) for managing healthcare associated infections (HCAIs) has developed considerably through experiences with SARS-CoV-2. We interviewed various healthcare professionals (HCPs) with direct experience of using WGS in hospitals (within the COG-UK Hospital Onset COVID-19 Infection (HOCI) study) to explore its acceptability and future use. Method An exploratory, cross-sectional, qualitative design employed semi-structured interviews with 39 diverse HCPs between December 2020 and June 2021. Participants were recruited from five sites within the larger clinical study of a novel genome sequencing reporting tool for SARS-CoV-2 (the HOCI study). All had experience, in their diverse roles, of using sequencing data to manage nosocomial SARS-CoV-2 infection. Deductive and inductive thematic analysis identified themes exploring aspects of the acceptability of sequencing. Findings The analysis highlighted the overall acceptability of rapid WGS for infectious disease using SARS-CoV-2 as a case study. Diverse professionals were largely very positive about its future use and believed that it could become a valuable and routine tool for managing HCAIs. We identified three key themes ‘1) ‘Proof of concept achieved’; 2) ‘Novel insights and implications’; and 3) ‘Challenges and demands’. Conclusion Our qualitative analysis, drawn from five diverse hospitals, shows the broad acceptability of rapid sequencing and its potential. Participants believed it could and should become an everyday technology capable of being embedded within typical hospital processes and systems. However, its future integration into existing healthcare systems will not be without challenges (e.g., resource, multi-level change) warranting further mixed methods research.

Evaluating the effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control teams: the COG-UK hospital-onset COVID-19 infection study (preprint)

Introduction Viral sequencing of SARS-CoV-2 has been used for outbreak investigation, but there is limited evidence supporting routine use for infection prevention and control (IPC) within hospital settings. Methods We conducted a prospective non-randomised trial of sequencing at 14 acute UK hospital trusts. Sites each had a 4-week baseline data-collection period, followed by intervention periods comprising 8 weeks of 'rapid' (<48h) and 4 weeks of 'longer-turnaround' (5-10 day) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital onset COVID-19 infections (HOCIs; detected [≥]48h from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on incidence of probable/definite hospital-acquired infections (HAIs) was evaluated. Results A total of 2170 HOCI cases were recorded from October 2020-April 2021, with sequence reports returned for 650/1320 (49.2%) during intervention phases. We did not detect a statistically significant change in weekly incidence of HAIs in longer-turnaround (IRR 1.60, 95%CI 0.85-3.01; P=0.14) or rapid (0.85, 0.48-1.50; P=0.54) intervention phases compared to baseline phase. However, IPC practice was changed in 7.8% and 7.4% of all HOCI cases in rapid and longer-turnaround phases, respectively, and 17.2% and 11.6% of cases where the report was returned. In a per-protocol sensitivity analysis there was an impact on IPC actions in 20.7% of HOCI cases when the SRT report was returned within 5 days. Conclusion While we did not demonstrate a direct impact of sequencing on the incidence of nosocomial transmission, our results suggest that sequencing can inform IPC response to HOCIs, particularly when returned within 5 days.

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 (preprint)

IntroductionNosocomial 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 analysisCOG-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 disseminationThe 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 numberISRCTN50212645 Strengths and limitations of this studyO_LIThe COG-UK HOCI study harnesses the infrastructure of the UKs existing national COVID-19 genome sequencing platform to evaluate the specific benefit of sequencing to hospital infection control. C_LIO_LIThe 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. C_LIO_LIA range of institutional settings will participate, from specialist NHS-embedded or academic centres experienced in using pathogen genomics to district general hospitals. C_LIO_LIThe 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. C_LIO_LIThe study has been awarded UK NIHR Urgent Public Health status, ensuring prioritised access to NIHR Clinical Research Network (CRN) research staff to recruit patients. C_LIO_LIThe study does not have a randomised controlled design due to the logistics of managing this against diverse standard practice. C_LI