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.

Nanopore sequencing for real-time genomic surveillance ofPlasmodium falciparum

“…While our study does not address this question, it demonstrates that Nanopore is an effective method for genotyping SNPs in the csp CTR as part of a multiplex surveillance panel, and identifies several high-frequency non-synonymous SNPs present in Ghana relative to the vaccine reference sequence. The SNP frequencies identified using ONT are very consistent with whole genome sequence data generated Experience with SARS-CoV-2 has shown that prompt turnaround time is a key factor for genomic epidemiology to be useful in clinical and public health applications [48][49][50]93]. Results are available faster if sequencing can be performed in-country, without requiring the ethical, legal and logistical framework to transport samples outside of national borders.…”

“…Experience with SARS-CoV-2 has shown that prompt turnaround time is a key factor for genomic epidemiology to be useful in clinical and public health applications [48–50,93]. Results are available faster if sequencing can be performed in-country, without requiring the ethical, legal and logistical framework to transport samples outside of national borders.…”

Multiple pathways of SARS-CoV-2 nosocomial transmission uncovered by integrated genomic and epidemiological analyses during the second wave of the COVID-19 pandemic in the UK

“…Rapid turnaround WGS and application of tools that we have used in this investigation, such as A2B Covid, genomic clustering and phylogenetics, could enable outbreaks to be disentangled in precise detail within the week that they are initiated, which may enable precise control measures to be put in place soon enough to contain the outbreak quickly. Such rapid feedback from WGS has been trialed during the second wave of COVID-19 in the UK through the Hospital Onset COVID-19 Infection (HOCI) study, which shows the effectiveness of rapid genotyping of patient infections and identification of linked cases for impacting Infection Control Procedures (Stirrup et al 2021;Stirrup et al, 2022). The limitations of this approach are that it requires easy access to WGS and specialist knowledge of bioinformatics, which may not be readily available within all hospital settings.…”

“…In addition, genomic data have been used to inform the governmental implementation of nonpharmaceutical interventions, such as national lockdown measures, to prevent viral transmission. These datasets have also been used to investigate SARS-CoV-2 transmission in hospitals and other healthcare settings, both as a rapidturnaround service to inform infection control when an outbreak occurs (Blackstone et al, 2021;Stirrup et al, 2021;Stirrup et al, 2022) and on a retrospective basis to understand the dynamics of nosocomial transmission at a larger scale (Illingworth et al, 2021;Lumley et al, 2021;Snell et al, 2022).…”

Combining viral genomics and clinical data to assess risk factors for severe COVID-19 (mortality, ICU admission, or intubation) amongst hospital patients in a large acute UK NHS hospital Trust

“…Large-scale SARS-CoV-2 sequencing programs throughout the pandemic have allowed researchers to explore the role of viral genomics and different variants of the virus. However, whilst genomic epidemiology has been used in a number of studies to understand viral transmission in settings such as hospitals [14][15][16][17], long-term care facilities [18][19][20][21][22], and army barracks [23,24], well-powered studies of patient outcomes with high numbers of cases currently remain limited [25][26][27][28][29][30][31]. One of the largest studies looking at large-scale effects of viral genomics on patient outcomes are papers from the Hospital Onset COVID-19 Infections (HOCI) study in the UK [25,26,28].…”