Applying prospective genomic surveillance to support investigation of hospital-onset COVID-19
Authors: William L Hamilton, Tom Fieldman, Aminu Jahun, Ben Warne, Christopher J R Illingworth, Chris Jackson, Beth Blane, Elinor Moore, Michael P Weekes, Sharon J Peacock, Daniela De Angelis, Ian Goodfellow, Theodore Gouliouris, M Estée Török, Martin D Curran, Surendra Parmar, Myra Hosmillo, Yasmin Chaudhry, Malte L Pinckert, Iliana Georgana, Rhys Izuagbe, Mark Ferris, Chris Workman, Nick K Jones, Lucy Rivett, Dominic Sparkes, Matthew Routledge, David Enoch, James Whitehorn, Christine Moody, Liam Brennan, Richard Smith, Rachel Tsui, Rachel Bousfield, Joanna Pocock, Michelle Toleman, Helen Payne, Suny Coscione, Chloe Myers, Katherine Sharrocks, Pooja Ravji, Clare Leong, Isobel Ramsay
Journal: The Lancet Infectious Diseases (2021)

Here, we provide an update on our previous Article,1Meredith LW Hamilton WL Warne B et al.Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.Lancet Infect Dis. 2020; 20: 1263-1271Summary Full Text Full Text PDF PubMed Scopus (264) Google Scholar which described the use of rapid SARS-CoV-2 genome sequencing to investigate hospital-acquired infections (HAIs) at Cambridge University Hospitals NHS Foundation Trust (CUH), Cambridge, UK. CUH experienced a substantial second wave of COVID-19 (figure). Between Nov 2, 2020, and Feb 7, 2021, 162 (14%) of 1178 patients with COVID-19 at CUH had a suspected or definite HAI (as previously defined1Meredith LW Hamilton WL Warne B et al.Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.Lancet Infect Dis. 2020; 20: 1263-1271Summary Full Text Full Text PDF PubMed Scopus (264) Google Scholar), and 465 infected health-care workers (HCWs) were identified via the staff screening programme.2Rivett L Sridhar S Sparkes D et al.Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission.elife. 2020; 9: 1-20Crossref Scopus (392) Google Scholar Nanopore sequencing was attempted for 513 (44%) of 1178 patients, prioritising those with hospital-onset infections, and 324 (70%) of 465 HCWs; 252 (21%) of 1178 patients and 317 (68%) of 465 HCWs had SARS-CoV-2 genomes available after quality control filtering (as previously described1Meredith LW Hamilton WL Warne B et al.Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.Lancet Infect Dis. 2020; 20: 1263-1271Summary Full Text Full Text PDF PubMed Scopus (264) Google Scholar). Patient coverage was lower than in our previous study1Meredith LW Hamilton WL Warne B et al.Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.Lancet Infect Dis. 2020; 20: 1263-1271Summary Full Text Full Text PDF PubMed Scopus (264) Google Scholar and for HCWs, reflecting different diagnostic testing methods and limitations on sequencing capacity. The frequency of the B.1.1.7 PANGO-lineage3Rambaut A Holmes EC O'Toole Á et al.A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology.Nat Microbiol. 2020; 5: 1403-1407Crossref PubMed Scopus (1576) Google Scholar increased from 8% (nine of 109) in November, 2020, to 83% (257 of 311) in January, 2021. As in the first wave, outbreaks of hospital-onset COVID-19 occurred on wards intended for patients without COVID-19, termed green wards. Where genomics were available, cases on these wards were often phylogenetically clustered (virus genomes with zero to one single nucleotide polymorphism differences), consistent with ward-based transmission.1Meredith LW Hamilton WL Warne B et al.Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study.Lancet Infect Dis. 2020; 20: 1263-1271Summary Full Text Full Text PDF PubMed Scopus (264) Google Scholar This transmission occurred despite substantial efforts to reduce HAIs, including universal surgical mask wearing by staff, SARS-CoV-2 screening of all patients at hospital admission and regularly thereafter, cohorting of patients to green, amber, and red wards, and a comprehensive staff screening programme. Continued hospital-based transmission despite these efforts emphasises how challenging it is to limit SARS-CoV-2 transmission in hospitals with limited side-room capacity, given the high infectivity of SARS-CoV-2 and potential for asymptomatic transmission. Genomic data were presented at seven of 11 clinical HAI review meetings and at infection-control meetings, informing decision-making. Staff vaccinations began in January, 2021, and have already had a substantial impact on reducing COVID-19 incidence.4Jones NK Rivett L Seaman S et al.Single-dose BNT162b2 vaccine protects against asymptomatic SARS-CoV-2 infection.eLife. 2021; (published online April 8.)https://doi.org/10.7554/elife.68808Google Scholar Our experience from the first and second epidemic waves of COVID-19 at CUH identified several challenges to applying prospective genomic surveillance to infection control. First, close and efficient working between clinical, infection-control, sequencing, and bioinformatic-analysis teams is crucial. Second, changes in SARS-CoV-2 diagnostic methods resulted in technical difficulties in obtaining sufficient good-quality genetic material for sequencing. Third, the speed from sampling to sequencing to analysis is crucial; for maximum impact, genomic data should be available to inform real-time decision-making. Finally, sustained funding and human resource capacity are essential for consistent service delivery. Nevertheless, we have shown that introducing rapid genomic sequencing and data analysis into hospital outbreak investigations is both feasible and beneficial; the challenge is to translate this from an emergency response into routine clinical practice. CJRI, CJ, and DDA report funding to their institution from MRC. MPW reports grants from Wellcome. SJP reports receiving consulting fees for participating on the Pfizer Coronavirus External Advisory Board and honoraria from SVB Leerink. IG reports grants from Wellcome and MRC. MET reports grants from Academy of Medical Sciences and The Health Foundation, non-financial support from the NIHR Cambridge Biomedical Research Centre, book royalties from Oxford University Press, and honoraria from Wellcome Sanger Institute and University of Cambridge. All other authors declare no competing interests. Download .pdf (.18 MB) Help with pdf files Supplementary appendix Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance studyWe established real-time genomic surveillance of SARS-CoV-2 in a UK hospital and showed the benefit of combined genomic and epidemiological analysis for the investigation of health-care associated COVID-19. This approach enabled us to detect cryptic transmission events and identify opportunities to target infection-control interventions to further reduce health-care associated infections. Our findings have important implications for national public health policy as they enable rapid tracking and investigation of infections in hospital and community settings. Full-Text PDF Open Access