On-demand, hospital-based, severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic epidemiology to support nosocomial outbreak investigations: A prospective molecular epidemiology study

Abstract

Objectives: We evaluated the added value of infection control-guided, on demand, and locally performed severe acute respiratory coronavirus virus 2 (SARS-CoV-2) genomic sequencing to support outbreak investigation and control in acute-care settings. Design and setting: This 18-month prospective molecular epidemiology study was conducted at a tertiary-care hospital in Montreal, Canada. When nosocomial transmission was suspected by local infection control, viral genomic sequencing was performed locally for all putative outbreak cases. Molecular and conventional epidemiology data were correlated on a just-in-time basis to improve understanding of coronavirus disease 2019 (COVID-19) transmission and reinforce or adapt control measures. Results: Between April 2020 and October 2021, 6 outbreaks including 59 nosocomial infections (per the epidemiological definition) were investigated. Genomic data supported 7 distinct transmission clusters involving 6 patients and 26 healthcare workers. We identified multiple distinct modes of transmission, which led to reinforcement and adaptation of infection control measures. Molecular epidemiology data also refuted (n = 14) suspected transmission events in favor of community acquired but institutionally clustered cases. Conclusion: SARS-CoV-2 genomic sequencing can refute or strengthen transmission hypotheses from conventional nosocomial epidemiological investigations, and guide implementation of setting-specific control strategies. Our study represents a template for prospective, on site, outbreak-focused SARS-CoV-2 sequencing. This approach may become increasingly relevant in a COVID-19 endemic state where systematic sequencing within centralized surveillance programs is not available. Trial registration: clinicaltrials.gov identifier: NCT05411562

The utility of whole-genome sequencing to inform epidemiologic investigations of SARS-CoV-2 clusters in acute-care hospitals

“…In a single-center, 18-month trial using “on-demand” reactive WGS to characterize 6 outbreaks, WGS commonly refuted epidemiologic hypotheses for transmission (29% of outbreaks) and informed infection prevention measures, changing practice in 5 of 6 (83%) outbreaks. 30 However, this approach was not selective because it used defined criteria to trigger investigations of outbreaks with WGS, and did not describe epidemiologic investigation characteristics that may have indicated where WGS was most useful. In our investigation, we attempted to characterize the hypothesis generation about transmission pathways that preceded requests for WGS.…”

“…[8][9][10][11][12] For COVID-19 disease, approaches have included both WGS of all hospital-onset isolates ("WGS surveillance") to identify transmission events and reactive sequencing to investigate potential outbreaks. 2,[13][14][15] WGS surveillance identifies genetically related viruses in individuals without epidemiologic links in as many as 11%-22% of sequenced specimens. 8 Although WGS surveillance may identify all genetically related COVID-19 cases, it has practical limitations including resource costs, experienced staff, and availability.…”