Rapid implementation of SARS-CoV-2 sequencing to investigate cases of health-care associated COVID-19: a prospective genomic surveillance study

Abstract

Background: The burden and influence of health-care associated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unknown. We aimed to examine the use of rapid SARS-CoV-2 sequencing combined with detailed epidemiological analysis to investigate health-care associated SARS-CoV-2 infections and inform infection control measures.

Methods: In this prospective surveillance study, we set up rapid SARS-CoV-2 nanopore sequencing from PCR-positive diagnostic samples collected from our hospital (Cambridge, UK) and a random selection from hospitals in the East of England, enabling sample-to-sequence in less than 24 h. We established a weekly review and reporting system with integration of genomic and epidemiological data to investigate suspected health-care associated COVID-19 cases.

Findings: Between March 13 and April 24, 2020, we collected clinical data and samples from 5613 patients with COVID-19 from across the East of England. We sequenced 1000 samples producing 747 high-quality genomes. We combined epidemiological and genomic analysis of the 299 patients from our hospital and identified 35 clusters of identical viruses involving 159 patients. 92 (58%) of 159 patients had strong epidemiological links and 32 (20%) patients had plausible epidemiological links. These results were fed back to clinical, infection control, and hospital management teams, leading to infection-control interventions and informing patient safety reporting.

Interpretation: We 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.

Funding: COVID-19 Genomics UK funded by the Department of Health and Social Care, UK Research and Innovation, and the Wellcome Sanger Institute.

Figure 1

Study profile We prioritised CUH samples for nanopore sequencing on site for quick turnaround to investigate health-care associated infections. Of the 166 samples that did not pass quality control, two were removed as their genomes were less than 29 kb and 164 were removed as they had more than 2990 undefined nucleotides. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. CUH=Cambridge University Hospitals National Health Service Foundation Trust. *Of 3891 samples assigned for sequencing, 2940 were uploaded to the CLIMB server, as have all of the 1000 genomes sequenced on site, for national COVID-19 Genomics UK analyses. †The 37 health-care workers were identified through a CUH screening programme. In addition, nine self-presented to CUH admission units and are counted as patients (n=46).

Figure 2

Epidemic curve of COVID-19 at CUH Data for 374 patients tested at CUH. Classification of infection: (1) community onset, community associated; (2) community onset, suspected health-care associated; (3) hospital onset, indeterminate health-care associated; (4) hospital onset, suspected health-care associated; (5) hospital onset, health-care associated; (6) health-care worker. These data do not include 37 health-care workers identified through the CUH screening programme, but do include nine health-care workers that self-presented for testing. Note that data for week commencing April 20, 2020, stops at 8 AM on April 24, 2020, so does not include the weekend. CUH=Cambridge University Hospitals National Health Service Foundation Trust.

Figure 3

SARS-CoV-2 lineages identified in the East of England and CUH Map of the East of England region (A) showing the breakdown of SARS-CoV-2 lineages by collecting hospital site. Lineage B.1 was the most prevalent lineage throughout the region (B). SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. CUH=Cambridge University Hospitals National Health Service Foundation Trust.

Figure 4

Phylogenetic tree of SARS-CoV-2 genomes from CUH Phylogenetic tree of 299 SARS-CoV-2 genomes form CUH and 30 international genomes. The tree is rooted on a December, 2019, genome from Wuhan, China. The left-hand column highlights several hospital and community associated clusters in different colours. Wards A, B, and C all had clusters of hospital-acquired infections cases with viruses of less than two single nucleotide polymorphisms different. Eight ward C cases are contained within one of the largest clusters of identical viruses. Genomic clusters containing the cases for wards B and C, the dialysis unit, and care home A all included health-care workers. The right hand column shows the classification of infection, also shown in figure 2. Classification of infection: (1) community onset, community associated; (2) community onset, suspected health-care associated; (3) hospital onset, indeterminate health-care associated; (4) hospital onset, suspected health-care associated; (5) hospital onset, health-care associated; (6) health-care worker; (7) unable to determine or missing. See appendix pp 23–24 for GISAID identification codes of included reference genomes, and appendix p 13 for their position on the East of England phylogenetic tree. SARS-CoV-2=severe acute respiratory syndrome coronavirus 2. CUH=Cambridge University Hospitals National Health Service Foundation Trust.

Figure 5

Epidemiological timeline of ward A cluster Six patients on ward A were diagnosed with COVID-19. All had been admitted for more than 7 days before their specimen date and were considered likely to have hospital-acquired infections. The date of the first positive sample collection is shown with a red box and patient death date indicated with a solid black bar. Five of the viral genomes (patients A to E) had zero single nucleotide polymorphism differences between them, and one of the viral genomes (patient F) differed by one single nucleotide polymorphism.