Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study
Authors: Stirrup Oliver , Blackstone James , Mapp Fiona , MacNeil Alyson , Panca Monica , Holmes Alison , Machin Nicholas , Shin Gee Yen , Mahungu Tabitha , Saeed Kordo , Saluja Tranprit , Taha Yusri , Mahida Nikunj , Pope Cassie , Chawla Anu , Cutino-Moguel Maria-Teresa , Tamuri Asif , Williams Rachel , Darby Alistair , Robertson David L , Flaviani Flavia , Nastouli Eleni , Robson Samuel , Smith Darren , Loose Matthew , Laing Kenneth , Monahan Irene , Kele Beatrix , Haldenby Sam , George Ryan , Bashton Matthew , Witney Adam A , Byott Matthew , Coll Francesc , Chapman Michael , Peacock Sharon J ,   COG-UK HOCI Investigators,   The COVID-19 Genomics UK (COG-UK) consortium, Hughes Joseph , Nebbia Gaia , Partridge David G , Parker Matthew , Price James Richard , Peters Christine , Roy Sunando , Snell Luke B , de Silva Thushan I , Thomson Emma , Flowers Paul , Copas Andrew , Breuer Judith 
Published: September 2022

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_PC_19027), and Genome Research Limited, operating as the Wellcome Sanger Institute.Clinical trial number:NCT04405934.