Progressing in sequence: next-generation sequencing to support nosocomial outbreak investigations

This MD thesis offers an insight into the role of state-of-the art next-generation sequencing (NGS) for the identification and analysis of healthcare-associated pathogens, with emphasis on its role in nosocomial outbreak investigations.

We provide a detailed genomic-epidemiological analysis of a complex outbreak of SARS-CoV-2, centred on the overcrowded Emergency Department of a tertiary referral hospital, which informed Infection Prevention and Control (IPC) responses and hospital policy during the acute phase of the COVID-19 pandemic. We also demonstrate the value of NGS to elucidate a protracted outbreak of a previously un-characterised Carbapenemase-Producing Enterobacterales (CPE) species, which failed to identify by conventional microbiological techniques. These examples highlight the utility of NGS for the precise genomic characterisation of viral transmission networks and multi-drug resistant bacteria and, to our knowledge, represent the first published experiences of nanopore sequencing performed on-site in an Irish hospital diagnostic laboratory, for local nosocomial outbreak investigations.

Through a comprehensive systematic review of literature describing the use of WGS to investigate nosocomial SARS-CoV-2 transmission, we highlight the current limitations of pathogen genomics for outbreak investigations, along with infrastructural challenges to be overcome for successful integration into hospital workflows. Comparing experiences internationally, this much-needed analysis addresses a number of important knowledge gaps with respect to the use of WGS as an IPC intervention and, combined with our experiences of on-site NGS at UHL, will serve as an important resource to the scientific and healthcare communities.

In summary, the work presented throughout this MD provides valuable insights into the benefits of NGS to inform nosocomial outbreak investigations, as well as the practical and technical aspects of implementing genomic surveillance in an acute hospital setting. This has the potential to impact healthcare policy, enhance our understanding of hospital microbial ecosystems, and ultimately improve patient care.