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

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, Laing, Kenneth, Monahan, Irene, Kele, Beatrix, Haldenby, Sam, George, Ryan, Bashton, Matthew, Witney, Adam A., Byott, Matthew, Coll, Francesc, Chapman, Michael, Peacock, Sharon J., 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, McCann, Clare, Young, Greg, Nelson, Andrew and The COVID-19 Genomics UK consortium, (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

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Abstract

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' (<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, 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.

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.

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: ClinicalTrials.gov Identifier: NCT04405934.

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