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

The COVID-19 Genomics UK (COG-UK) Consortium; Oliver Stirrup; James Blackstone; Fiona Mapp; Alyson MacNeil; Monica Panca; Alison Holmes; Nicholas Machin; Gee Yen Shin; Tabitha W. Mahungu; Kordo Saeed; Tranprit Saluja; Yusri Taha; Nikunj Mahida; Cassie F. Pope; Anu Chawla; Maria Teresa Cutino-Moguel; Asif Tamuri; Rachel Williams; Alistair Darby; David L. Robertson; Flavia Flaviani; Eleni Nastouli; Samuel Robson; Darren Smith; Kenneth Laing; Irene M. Monahan; Beatrix Kele; Sam Haldenby; Ryan George; Matthew Bashton; Adam A. Witney; Matthew Byott; Francesc Coll; Michael Chapman; Sharon J. Peacock; Joseph Hughes; Gaia Nebbia; David G. Partridge; Matthew Parker; James Richard Price; Christine Peters; Sunando Roy; Luke B. Snell; Thushan I. de Silva; Emma C. Thomson; Paul Flowers; Andrew Copas; Judith Breuer; Clare McCann; Gregory R. Young; Andrew Nelson

doi:10.7554/eLife.78427

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

The COVID-19 Genomics UK (COG-UK) Consortium, Oliver Stirrup, James Blackstone, Fiona Mapp, Alyson MacNeil, Monica Panca, Alison Holmes, Nicholas Machin, Gee Yen Shin, Tabitha W. Mahungu, Kordo Saeed, Tranprit Saluja, Yusri Taha, Nikunj Mahida, Cassie F. Pope, Anu Chawla, Maria Teresa Cutino-Moguel, Asif Tamuri, Rachel Williams, Alistair DarbyDavid L. Robertson, Flavia Flaviani, Eleni Nastouli, Samuel Robson, Darren Smith, Kenneth Laing, Irene M. Monahan, Beatrix Kele, Sam Haldenby, Ryan George, Matthew Bashton, Adam A. Witney, Matthew Byott, Francesc Coll, Michael Chapman, Sharon J. Peacock, Joseph Hughes, Gaia Nebbia, David G. Partridge, Matthew Parker, James Richard Price, Christine Peters, Sunando Roy, Luke B. Snell, Thushan I. de Silva, Emma C. Thomson, Paul Flowers, Andrew Copas, Judith Breuer^*, Clare McCann, Gregory R. Young, Andrew Nelson

^*Corresponding author for this work

Applied Sciences Department

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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.

Original language	English
Article number	e78427
Number of pages	31
Journal	eLife
Volume	11
Early online date	13 Sept 2022
DOIs	https://doi.org/10.7554/eLife.78427
Publication status	Published - 13 Sept 2022

Keywords

COVID‐19
SARS‐CoV‐2
healthcare‐associated infection
hospital‐acquired infection
infection prevention and control
molecular epidemiology
viral genomics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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elife-78427-v1Accepted author manuscript, 4.55 MBLicence: CC BY
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The COVID-19 Genomics UK (COG-UK) Consortium, Stirrup, O., Blackstone, J., Mapp, F., MacNeil, A., Panca, M., Holmes, A., Machin, N., Shin, G. Y., Mahungu, T. W., Saeed, K., Saluja, T., Taha, Y., Mahida, N., Pope, C. F., Chawla, A., Cutino-Moguel, M. T., Tamuri, A., Williams, R., ... Nelson, A. (2022). Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study. eLife, 11, Article e78427. https://doi.org/10.7554/eLife.78427

@article{e0c3325ac9ea4aa7b33f54483c65e183,

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

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.",

keywords = "COVID‐19, SARS‐CoV‐2, healthcare‐associated infection, hospital‐acquired infection, infection prevention and control, molecular epidemiology, viral genomics",

author = "{The COVID-19 Genomics UK (COG-UK) Consortium} and Oliver Stirrup and James Blackstone and Fiona Mapp and Alyson MacNeil and Monica Panca and Alison Holmes and Nicholas Machin and Shin, {Gee Yen} and Mahungu, {Tabitha W.} and Kordo Saeed and Tranprit Saluja and Yusri Taha and Nikunj Mahida and Pope, {Cassie F.} and Anu Chawla and Cutino-Moguel, {Maria Teresa} and Asif Tamuri and Rachel Williams and Alistair Darby and Robertson, {David L.} and Flavia Flaviani and Eleni Nastouli and Samuel Robson and Darren Smith and Kenneth Laing and Monahan, {Irene M.} and Beatrix Kele and Sam Haldenby and Ryan George and Matthew Bashton and Witney, {Adam A.} and Matthew Byott and Francesc Coll and Michael Chapman and Peacock, {Sharon J.} and Joseph Hughes and Gaia Nebbia and Partridge, {David G.} and Matthew Parker and Price, {James Richard} and Christine Peters and Sunando Roy and Snell, {Luke B.} and {de Silva}, {Thushan I.} and Thomson, {Emma C.} and Paul Flowers and Andrew Copas and Judith Breuer and Clare McCann and Young, {Gregory R.} and Andrew Nelson",

note = "Funding information: 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. Matthew Bashton, Andrew Nelson, Darren Smith, Greg Young and Clare McCann are members of the COVID-19 Genomics UK consortium.",

year = "2022",

month = sep,

day = "13",

doi = "10.7554/eLife.78427",

language = "English",

volume = "11",

journal = "eLife",

issn = "2050-084X",

publisher = "eLife Sciences Publications",

}

The COVID-19 Genomics UK (COG-UK) Consortium, Stirrup, O, Blackstone, J, Mapp, F, MacNeil, A, Panca, M, Holmes, A, Machin, N, Shin, GY, Mahungu, TW, Saeed, K, Saluja, T, Taha, Y, Mahida, N, Pope, CF, Chawla, A, Cutino-Moguel, MT, Tamuri, A, Williams, R, Darby, A, Robertson, DL, Flaviani, F, Nastouli, E, Robson, S, Smith, D, Laing, K, Monahan, IM, Kele, B, Haldenby, S, George, R, Bashton, M, Witney, AA, Byott, M, Coll, F, Chapman, M, Peacock, SJ, Hughes, J, Nebbia, G, Partridge, DG, Parker, M, Price, JR, Peters, C, Roy, S, Snell, LB, de Silva, TI, Thomson, EC, Flowers, P, Copas, A, Breuer, J, McCann, C, Young, GR & Nelson, A 2022, 'Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection: Multicentre, prospective study', eLife, vol. 11, e78427. https://doi.org/10.7554/eLife.78427

TY - JOUR

T1 - Effectiveness of rapid SARS-CoV-2 genome sequencing in supporting infection control for hospital-onset COVID-19 infection

T2 - Multicentre, prospective study

AU - The COVID-19 Genomics UK (COG-UK) Consortium

AU - Stirrup, Oliver

AU - Blackstone, James

AU - Mapp, Fiona

AU - MacNeil, Alyson

AU - Panca, Monica

AU - Holmes, Alison

AU - Machin, Nicholas

AU - Shin, Gee Yen

AU - Mahungu, Tabitha W.

AU - Saeed, Kordo

AU - Saluja, Tranprit

AU - Taha, Yusri

AU - Mahida, Nikunj

AU - Pope, Cassie F.

AU - Chawla, Anu

AU - Cutino-Moguel, Maria Teresa

AU - Tamuri, Asif

AU - Williams, Rachel

AU - Darby, Alistair

AU - Robertson, David L.

AU - Flaviani, Flavia

AU - Nastouli, Eleni

AU - Robson, Samuel

AU - Smith, Darren

AU - Laing, Kenneth

AU - Monahan, Irene M.

AU - Kele, Beatrix

AU - Haldenby, Sam

AU - George, Ryan

AU - Bashton, Matthew

AU - Witney, Adam A.

AU - Byott, Matthew

AU - Coll, Francesc

AU - Chapman, Michael

AU - Peacock, Sharon J.

AU - Hughes, Joseph

AU - Nebbia, Gaia

AU - Partridge, David G.

AU - Parker, Matthew

AU - Price, James Richard

AU - Peters, Christine

AU - Roy, Sunando

AU - Snell, Luke B.

AU - de Silva, Thushan I.

AU - Thomson, Emma C.

AU - Flowers, Paul

AU - Copas, Andrew

AU - Breuer, Judith

AU - McCann, Clare

AU - Young, Gregory R.

AU - Nelson, Andrew

N1 - Funding information: 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. Matthew Bashton, Andrew Nelson, Darren Smith, Greg Young and Clare McCann are members of the COVID-19 Genomics UK consortium.

PY - 2022/9/13

Y1 - 2022/9/13

N2 - 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.

AB - 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.

KW - COVID‐19

KW - SARS‐CoV‐2

KW - healthcare‐associated infection

KW - hospital‐acquired infection

KW - infection prevention and control

KW - molecular epidemiology

KW - viral genomics

UR - http://www.scopus.com/inward/record.url?scp=85140855893&partnerID=8YFLogxK

U2 - 10.7554/eLife.78427

DO - 10.7554/eLife.78427

M3 - Article

C2 - 36098502

SN - 2050-084X

VL - 11

JO - eLife

JF - eLife

M1 - e78427

ER -

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

Abstract

Keywords

UN SDGs

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