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Nosocomial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have severely affected bed capacity and patient flow. We utilized whole-genome sequencing (WGS) to identify outbreaks and focus infection control resources and intervention during the United Kingdom's second pandemic wave in late 2020. Phylogenetic analysis of WGS and epidemiological data pinpointed an initial transmission event to an admission ward, with immediate prior community infection linkage documented. High incidence of asymptomatic staff infection with genetically identical viral sequences was also observed, which may have contributed to the propagation of the outbreak. WGS allowed timely nosocomial transmission intervention measures, including admissions ward point-of-care testing and introduction of portable HEPA14 filters. Conversely, WGS excluded nosocomial transmission in 2 instances with temporospatial linkage, conserving time and resources. In summary, WGS significantly enhanced understanding of SARS-CoV-2 clusters in a hospital setting, both identifying high-risk areas and conversely validating existing control measures in other units, maintaining clinical service overall. [ABSTRACT FROM AUTHOR]

Background: 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' (<48 hr) and 4 weeks of 'longer-turnaround' (5-10 days) sequencing using a sequence reporting tool (SRT). Data were collected on all hospital-onset COVID-19 infections (HOCIs; detected ≥48 hr from admission). The impact of the sequencing intervention on IPC knowledge and actions, and on the incidence of probable/definite hospital-acquired infections (HAIs), was evaluated., Results: A total of 2170 HOCI cases were recorded from October 2020 to April 2021, corresponding to a period of extreme strain on the health service, 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 (incidence rate ratio 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. Capacity to respond effectively to insights from sequencing was breached in most sites by the volume of cases and limited resources., Conclusions: 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., Funding: COG-UK is supported by funding from the Medical Research Council (MRC) part of UK Research & Innovation (UKRI), the National Institute of Health Research (NIHR) (grant code: MC&#95;PC&#95;19027), and Genome Research Limited, operating as the Wellcome Sanger Institute., Clinical Trial Number: NCT04405934., Competing Interests: OS, JB, FM, AM, MP, AH, NM, TM, KS, TS, YT, NM, CP, AC, AT, RW, AD, DR, FF, SR, ML, KL, IM, BK, SH, RG, MB, AW, MB, MC, JH, GN, DP, MP, JP, CP, SR, LS, Td, ET, AC, JB No competing interests declared, GS has an unpaid role as Deputy Chair, British Medical Association London Regional Council. The author has no other competing interests to declare, MC received payment for anonymous interview conducted by Adkins Research Group. The author has no other competing interests to declare, EN holds grants by NIHR, EPSRC, MRC-UKRI , H2020, ViiV Healthcare, Pfizer and Amfar, and has received grants to attend meetings from H2020 and ViiV Healthcare, DS holds the following grants that are not specifically for the present work: COG-UK, PHE test and trace funded the sequencing aspect. HOCI funded a technician to support sequencing during study period. The author has no other competing interests to declare, FC received consulting fees from Next Gen Diagnostics LLC (during 2018/2019), received payment or honoria for lectures from University of Cambridge and Wellcome Genome Campus Advanced Courses, and received support for attending meeting and/or travel to meetings from European Congress of Clinical Microbiology &amp; Infectious Diseases (ECCMID), The American Society for Microbiology (ASM), Microbiology Society, European Congress of Clinical Microbiology &amp; Infectious Diseases (ECCMID), and the British Infection Association (BIA). The author has no other competing interests to declare, SP received consultancy fees from Pfizer (Coronavirus External Advisory Board) and Melinta Therapeutics, received payment from SVB Leerink for a round table meeting and for Mary Strauss Distinguished Public Lecture from the Fralin Biomedical Research Institute, US, and support for attending ICPIC conference, Geneva and World Health Summit, Berlin in 2021, and hold stocks or stock options in Specific Technologies (European Union Scientific Advisory Board) and Next Gen Diagnostics (Scientific Advisory Board). SP also serves as Chair, Medical Advisory Committee, Sir Jules Thorn Charitable Trust, Board member of the Wellcome SEDRIC (Surveillance and Epidemiology of Drug Resistant Consortium), and Non-Executive Director of Cambridge University Hospitals NHS Foundation Trust. The author has no other competing interests to declare, PF is a member of the SAGE hospital onset covid working group 2020-2022. The author has no other competing interests to declare, (© 2022, Stirrup et al.)