Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection : multicenter, prospective study

Stirrup, Oliver and Blackstone, James and Mapp, Fiona and MacNeil, Alyson and Panca, Monica and Holmes, Alison and Machin, Nicholas and Shin, Gee Yen and Mahungu, Tabitha and Saeed, Kordo and Saluja, Tranprit and Taha, Yusri and Mahida, Nikunj and Pope, Cassie and Chawla, Anu and Cutino-Moguel, Maria-Teresa and Tamuri, Asif and Williams, Rachel and Darby, Alistair and Robertson, David L and Flaviani, Flavia and Nastouli, Eleni and Robson, Samuel and Smith, Darren and Laing, Kenneth and Monahan, Irene and Kele, Beatrix and Haldenby, Sam and George, Ryan and Bashton, Matthew and Witney, Adam A and Byott, Matthew and Coll, Francesc and Chapman, Michael and Peacock, Sharon J and Hughes, Joseph and Nebbia, Gaia and Partridge, David G and Parker, Matthew and Price, James Richard and Peters, Christine and Roy, Sunando and Snell, Luke B and de Silva, Thushan I and Thomson, Emma and Flowers, Paul and Copas, Andrew and Breuer, Judith (2022) Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection : multicenter, prospective study. eLife, 11. e78427. ISSN 2050-084X (https://doi.org/10.7554/elife.78427)

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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.